D. Craig Miller, M.D.

All Publications

• In Memoriam: Randall B. Griepp (1940-2022): Master Surgeon, Innovator, Scientist, Teacher, and Sailor. The Annals of thoracic surgery Lansman, S. L., Miller, D. C. 2023

  Abstract

  Dr Randall B.Griepp's career spanned the founding age of cardiovascular and thoracic aortic surgery, the era he called "the golden age of cardiac surgery." He made groundbreaking contributions in cardiac transplantation while at Stanford and in the surgical technique and the methods of cerebral and spinal cord protection for thoracic and thoracoabdominal aortic surgery throughout his years as chairman of cardiothoracic surgery at The Mount Sinai Medical Center in New York. His commitment to honesty and his personal ethic and stature served as a role model for a generation of trainees, many of whom went on to leadership roles in cardiovascular surgery.

  View details for DOI 10.1016/j.athoracsur.2023.01.020

  View details for PubMedID 36690198

• Association of Thoracic Aortic Aneurysm Size With Long-term Patient Outcomes: The KP-TAA Study. JAMA cardiology Solomon, M. D., Leong, T., Sung, S. H., Lee, C., Allen, J. G., Huh, J., LaPunzina, P., Lee, H., Mason, D., Melikian, V., Pellegrini, D., Scoville, D., Sheikh, A. Y., Mendoza, D., Naderi, S., Sheridan, A., Hu, X., Cirimele, W., Gisslow, A., Leung, S., Padilla, K., Bloom, M., Chung, J., Topic, A., Vafaei, P., Chang, R., Miller, D. C., Liang, D. H., Go, A. S., Kaiser Permanente Northern California Center for Thoracic Aortic Disease, Chow, N., Chen, E., Dawson, K., Manace, L., Urbania, T., Yang, S., Pompili, M., Cain, B., Yano, O., Hua, H., Wu, B., Sharma, G., Baker, A., Sivamurthy, N., Garg, J., Madriz, T., Hui, H. 2022

  Abstract

  Importance: The risk of adverse events from ascending thoracic aorta aneurysm (TAA) is poorly understood but drives clinical decision-making.Objective: To evaluate the association of TAA size with outcomes in nonsyndromic patients in a large non-referral-based health care delivery system.Design, Setting, and Participants: The Kaiser Permanente Thoracic Aortic Aneurysm (KP-TAA) cohort study was a retrospective cohort study at Kaiser Permanente Northern California, a fully integrated health care delivery system insuring and providing care for more than 4.5 million persons. Nonsyndromic patients from a regional TAA safety net tracking system were included. Imaging data including maximum TAA size were merged with electronic health record (EHR) and comprehensive death data to obtain demographic characteristics, comorbidities, medications, laboratory values, vital signs, and subsequent outcomes. Unadjusted rates were calculated and the association of TAA size with outcomes was evaluated in multivariable competing risk models that categorized TAA size as a baseline and time-updated variable and accounted for potential confounders. Data were analyzed from January 2018 to August 2021.Exposures: TAA size.Main Outcomes and Measures: Aortic dissection (AD), all-cause death, and elective aortic surgery.Results: Of 6372 patients with TAA identified between 2000 and 2016 (mean [SD] age, 68.6 [13.0] years; 2050 female individuals [32.2%] and 4322 male individuals [67.8%]), mean (SD) initial TAA size was 4.4 (0.5) cm (828 individuals [13.0% of cohort] had initial TAA size 5.0 cm or larger and 280 [4.4%] 5.5 cm or larger). Rates of AD were low across a mean (SD) 3.7 (2.5) years of follow-up (44 individuals [0.7% of cohort]; incidence 0.22 events per 100 person-years). Larger initial aortic size was associated with higher risk of AD and all-cause death in multivariable models, with an inflection point in risk at 6.0 cm. Estimated adjusted risks of AD within 5 years were 0.3% (95% CI, 0.3-0.7), 0.6% (95% CI, 0.4-1.3), 1.5% (95% CI, 1.2-3.9), 3.6% (95% CI, 1.8-12.8), and 10.5% (95% CI, 2.7-44.3) in patients with TAA size of 4.0 to 4.4 cm, 4.5 to 4.9 cm, 5.0 to 5.4 cm, 5.5 to 5.9 cm, and 6.0 cm or larger, respectively, in time-updated models. Rates of the composite outcome of AD and all-cause death were higher than for AD alone, but a similar inflection point for increased risk was observed at 6.0 cm.Conclusions and Relevance: In a large sociodemographically diverse cohort of patients with TAA, absolute risk of aortic dissection was low but increased with larger aortic sizes after adjustment for potential confounders and competing risks. Our data support current consensus guidelines recommending prophylactic surgery in nonsyndromic individuals with TAA at a 5.5-cm threshold.

  View details for DOI 10.1001/jamacardio.2022.3305

  View details for PubMedID 36197675

• Midterm outcomes of aortic root surgery in patients with Marfan syndrome: A prospective, multicenter, comparative study. The Journal of thoracic and cardiovascular surgery Coselli, J. S., Volguina, I. V., LeMaire, S. A., Connolly, H. M., Sundt, T. M., Milewicz, D. M., Dietz, H. C., Amarasekara, H. S., Green, S. Y., Zhang, Q., Schaff, H. V., Miller, D. C., Aortic Valve Operative Outcomes in Marfan Patients Study Group 2021

  Abstract

  OBJECTIVE: The objective of this study was to compare midterm outcomes of aortic valve-replacing root replacement (AVR) and aortic valve-sparing root replacement (AVS) operations in patients with Marfan syndrome.METHODS: Patients who met strict Ghent diagnostic criteria for Marfan syndrome and who underwent either AVR or AVS between March 1, 2005 and December 31, 2010 were enrolled in a 3-year follow-up prospective, multicenter, international registry study; the study was subsequently amended to include 20-year follow-up. Enrollees were followed clinically and echocardiographically.RESULTS: Of the 316 patients enrolled, 77 underwent AVR and 239 underwent AVS; 214 gave reconsent for 20-year follow-up. The median clinical follow-up time for surviving patients was 64months (interquartile range, 42-66months). Survival rates for the AVR and AVS groups were similar at 88.2%±4.4% and 95.0%±1.5%, respectively (P=.1). Propensity score-adjusted competing risk modeling showed associations between AVS and higher cumulative incidences of major adverse valve-related events, valve-related morbidity, combined structural valve deterioration and nonstructural valve dysfunction, and aortic regurgitation ≥2+ (all P<.01). No differences were found for reintervention (P=.7), bleeding (P=.2), embolism (P=.3), or valve-related mortality (P=.8).CONCLUSIONS: Five years postoperatively, major adverse valve-related events and valve-related morbidity were more frequent after AVS than after AVR procedures, primarily because of more frequent aortic valve dysfunction. No between-group differences were found in rates of survival, valve-related mortality, reintervention on the aortic valve, or bleeding. We plan to follow this homogenous cohort for 20years after aortic root replacement.

  View details for DOI 10.1016/j.jtcvs.2021.08.064

  View details for PubMedID 34629178

• Rational Dispersion of TAVR: Failed Expectations and Unintended Consequences. Journal of the American College of Cardiology Holmes, D. R., Miller, D. C. 2021; 78 (8): 807-810

  View details for DOI 10.1016/j.jacc.2021.07.008

  View details for PubMedID 34412814

• Structural Deterioration of Transcatheter Versus Surgical Aortic Valve Bioprostheses in the PARTNER-2 Trial. Journal of the American College of Cardiology Pibarot, P., Ternacle, J., Jaber, W. A., Salaun, E., Dahou, A., Asch, F. M., Weissman, N. J., Rodriguez, L., Xu, K., Annabi, M., Guzzetti, E., Beaudoin, J., Bernier, M., Leipsic, J., Blanke, P., Clavel, M., Rogers, E., Alu, M. C., Douglas, P. S., Makkar, R., Miller, D. C., Kapadia, S. R., Mack, M. J., Webb, J. G., Kodali, S. K., Smith, C. R., Herrmann, H. C., Thourani, V. H., Leon, M. B., Hahn, R. T., PARTNER 2 Investigators 2020; 76 (16): 1830–43

  Abstract

  BACKGROUND: It is unknown whether transcatheter valves will have similar durability as surgical bioprosthetic valves. Definitions of structural valve deterioration (SVD), based on valve related reintervention or death, underestimate the incidence of SVD.OBJECTIVES: This study sought to determine and compare the 5-year incidence of SVD, using new standardized definitions based on echocardiographic follow-up of valve function, in intermediate-risk patients with severe aortic stenosis given transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) in the PARTNER (Placement of Aortic Transcatheter Valves) 2A trial and registry.METHODS: In the PARTNER 2A trial, patients were randomly assigned to receive either TAVR with the SAPIEN XT or SAVR, whereas in the SAPIEN 3 registry, patients were assigned to TAVR with the SAPIEN 3. The primary endpoint was the incidence of SVD, that is, the composite of SVD-related hemodynamic valve deterioration during echocardiographic follow-up and/or SVD-related bioprosthetic valve failure (BVF) at 5 years.RESULTS: Compared with SAVR, the SAPIEN-XT TAVR cohort had a significantly higher 5-year exposure adjusted incidence rates (per 100 patient-years) of SVD (1.61 ± 0.24% vs. 0.63 ± 0.16%), SVD-related BVF (0.58 ± 0.14% vs. 0.12 ± 0.07%), and all-cause (structural or nonstructural) BVF (0.81 ± 0.16% vs. 0.27 ± 0.10%) (p≤ 0.01 for all). The 5-year rates of SVD (0.68 ± 0.18% vs. 0.60 ± 0.17%; p=0.71), SVD-related BVF (0.29 ± 0.12% vs. 0.14 ± 0.08%; p=0.25), and all-cause BVF (0.60 ± 0.15% vs. 0.32 ± 0.11%; p=0.32) in SAPIEN 3 TAVR were not significantly different to a propensity score matched SAVR cohort. The 5-year rates of SVD and SVD-related BVF were significantly lower in SAPIEN 3 versus SAPIEN XT TAVR matched cohorts.CONCLUSIONS: Compared with SAVR, the second-generation SAPIEN XT balloon-expandable valve has a higher 5-year rate of SVD, whereas the third-generation SAPIEN 3 has a rate of SVD that was not different from SAVR. (The PARTNER II Trial: Placement of AoRTic TraNscathetER Valves - PII A [PARTNERII A]; NCT01314313; The PARTNER II Trial: Placement of AoRTic TraNscathetER Valves II - PARTNER II - PARTNERII - S3 Intermediate [PARTNERII S3i]; NCT03222128).

  View details for DOI 10.1016/j.jacc.2020.08.049

  View details for PubMedID 33059828

• Five-Year Outcomes of Transcatheter or Surgical Aortic-Valve Replacement. The New England journal of medicine Makkar, R. R., Thourani, V. H., Mack, M. J., Kodali, S. K., Kapadia, S., Webb, J. G., Yoon, S., Trento, A., Svensson, L. G., Herrmann, H. C., Szeto, W. Y., Miller, D. C., Satler, L., Cohen, D. J., Dewey, T. M., Babaliaros, V., Williams, M. R., Kereiakes, D. J., Zajarias, A., Greason, K. L., Whisenant, B. K., Hodson, R. W., Brown, D. L., Fearon, W. F., Russo, M. J., Pibarot, P., Hahn, R. T., Jaber, W. A., Rogers, E., Xu, K., Wheeler, J., Alu, M. C., Smith, C. R., Leon, M. B., PARTNER 2 Investigators 2020; 382 (9)

  Abstract

  BACKGROUND: There are scant data on long-term clinical outcomes and bioprosthetic-valve function after transcatheter aortic-valve replacement (TAVR) as compared with surgical aortic-valve replacement in patients with severe aortic stenosis and intermediate surgical risk.METHODS: We enrolled 2032 intermediate-risk patients with severe, symptomatic aortic stenosis at 57 centers. Patients were stratified according to intended transfemoral or transthoracic access (76.3% and 23.7%, respectively) and were randomly assigned to undergo either TAVR or surgical replacement. Clinical, echocardiographic, and health-status outcomes were followed for 5 years. The primary end point was death from any cause or disabling stroke.RESULTS: At 5 years, there was no significant difference in the incidence of death from any cause or disabling stroke between the TAVR group and the surgery group (47.9% and 43.4%, respectively; hazard ratio, 1.09; 95% confidence interval [CI], 0.95 to 1.25; P=0.21). Results were similar for the transfemoral-access cohort (44.5% and 42.0%, respectively; hazard ratio, 1.02; 95% CI, 0.87 to 1.20), but the incidence of death or disabling stroke was higher after TAVR than after surgery in the transthoracic-access cohort (59.3% vs. 48.3%; hazard ratio, 1.32; 95% CI, 1.02 to 1.71). At 5 years, more patients in the TAVR group than in the surgery group had at least mild paravalvular aortic regurgitation (33.3% vs. 6.3%). Repeat hospitalizations were more frequent after TAVR than after surgery (33.3% vs. 25.2%), as were aortic-valve reinterventions (3.2% vs. 0.8%). Improvement in health status at 5 years was similar for TAVR and surgery.CONCLUSIONS: Among patients with aortic stenosis who were at intermediate surgical risk, there was no significant difference in the incidence of death or disabling stroke at 5 years after TAVR as compared with surgical aortic-valve replacement. (Funded by Edwards Lifesciences; PARTNER 2 ClinicalTrials.gov number, NCT01314313.).

  View details for DOI 10.1056/NEJMoa1910555

  View details for PubMedID 31995682

• Type A Aortic Dissection-Experience Over 5 Decades: JACC Historical Breakthroughs in Perspective. Journal of the American College of Cardiology Zhu, Y. n., Lingala, B. n., Baiocchi, M. n., Tao, J. J., Toro Arana, V. n., Khoo, J. W., Williams, K. M., Traboulsi, A. A., Hammond, H. C., Lee, A. M., Hiesinger, W. n., Boyd, J. n., Oyer, P. E., Stinson, E. B., Reitz, B. A., Mitchell, R. S., Miller, D. C., Fischbein, M. P., Woo, Y. J. 2020; 76 (14): 1703–13

  Abstract

  The Stanford classification of aortic dissection was described in 1970. The classification proposed that type A aortic dissection should be surgically repaired immediately, whereas type B aortic dissection can be treated medically. Since then, diagnostic tools and management of acute type A aortic dissection (ATAAD) have undergone substantial evolution. This paper evaluated historical changes of ATAAD repair at Stanford University since the establishment of the aortic dissection classification 50 years ago. The surgical approaches to the proximal and distal extent of the aorta, cerebral perfusion methods, and cannulation strategies were reviewed. Additional analyses using patients who underwent ATAAD repair at Stanford University from 1967 through December 2019 were performed to further illustrate the Stanford experience in the management of ATAAD. While technical complexity increased over time, post-operative survival continued to improve. Further investigation is warranted to delineate factors associated with the improved outcomes observed in this study.

  View details for DOI 10.1016/j.jacc.2020.07.061

  View details for PubMedID 33004136

• Do annuloplasty rings designed to treat ischemic/functional mitral regurgitation alter left-ventricular dimensions in the acutely ischemic ovine heart? JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Bothe, W., Kvitting, J., Rausch, M. K., Timek, T. A., Swanson, J. C., Liang, D. H., Walther, M., Kuhl, E., Ingels, N. B., Miller, D. 2019; 158 (4): 1058–68

  View details for DOI 10.1016/j.jtcvs.2018.12.077

  View details for Web of Science ID 000486317100031

• Quality of Life of Patients With Marfan Syndrome After Valve-Sparing or Valve-Replacement Operations. Mayo Clinic proceedings Helder, M. R., Schaff, H. V., Lahr, B. D., Miller, D. C., Connolly, H. M. 2019; 94 (9): 1906–9

  View details for DOI 10.1016/j.mayocp.2019.04.045

  View details for PubMedID 31486387

• Inter- and intrasite variability of mortality and stroke for sites performing both surgical and transcatheter aortic valve replacement for aortic valve stenosis in intermediate-risk patients. The Journal of thoracic and cardiovascular surgery Greason, K. L., Blackstone, E. H., Rajeswaran, J., Lowry, A. M., Svensson, L. G., Webb, J. G., Tuzcu, E. M., Smith, C. R., Makkar, R. R., Mack, M. J., Thourani, V. H., Kodali, S. K., Leon, M. B., Miller, D. C. 2019

  Abstract

  OBJECTIVES: Multisite procedure-based randomized trials may be confounded by performance variability and variability among sites. Therefore, we studied variability in mortality and stroke after patients were randomized to surgical (SAVR) or transcatheter aortic valve replacement (TAVR) in the Placement of Aortic Transcatheter Valves-2A (PARTNER-2A) randomized trial.METHODS: Patients at intermediate risk for SAVR were randomized to SAVR (n=1017) or TAVR (n=1011) with a SAPIEN XT device (Edwards Lifesciences, Irvine, Calif) at 54 sites. Patients were followed to 2years. A mixed-effect model quantified variability at intersite and intrasite levels.RESULTS: There were 336 deaths (SAVR 170, TAVR 166) and 176 strokes (SAVR 85, TAVR 91). Intersite variability for mortality was similar across sites for SAVR (hazard ratios ranging from 0.52-1.93 among sites) and TAVR (hazard ratios ranging from 0.49-2.03), but intersite variability for stroke was greater for SAVR (hazard ratios ranging from 0.44-2.26) than for TAVR (no detectable variability). Case mix and lower site trial volume accounted for 37% of mortality intersite variability for SAVR and 73% for TAVR, but only 14% for stroke for SAVR. Intrasite mortality hazard ratios demonstrated all but 1 site's 95% confidence interval overlapped 1.0, indicating generally similar SAVR and TAVR mortalities within sites.CONCLUSIONS: Intersite variability was similar for mortality in SAVR and TAVR, but variability for stroke was greater for SAVR than for TAVR. Intrasite events were similar for both SAVR and TAVR. These findings suggest that in performance-based trials, site variability and its sources should be taken into account in analyzing and interpreting trial results.

  View details for DOI 10.1016/j.jtcvs.2019.04.112

  View details for PubMedID 31350027

• Characterization of 3-dimensional papillary muscle displacement in in vivo ovine models of ischemic/functional mitral regurgitation JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Bothe, W., Timek, T. A., Tibayan, F. A., Walther, M., Daughters, G. T., Ingels, N. B., Miller, D. 2019; 157 (4): 1444–49

  View details for DOI 10.1016/j.jtcvs.2018.09.069

  View details for Web of Science ID 000461717300072

• Endovascular Versus Open Repair of Intact Descending Thoracic Aortic Aneurysms JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Chiu, P., Goldstone, A. B., Schaffer, J. M., Lingala, B., Miller, D., Mitchell, R., Woo, Y., Fischbein, M. P., Dake, M. D. 2019; 73 (6): 643–51

  Abstract

  For the management of descending thoracic aortic aneurysms, recent evidence has suggested that outcomes of open surgical repair may surpass thoracic endovascular aortic repair (TEVAR) in as early as 2 years.The purpose of this study was to evaluate the comparative effectiveness of TEVAR and open surgical repair in the treatment of intact descending thoracic aortic aneurysms.Using the Medicare database, a retrospective study using regression discontinuity design and propensity score matching was performed on patients with intact descending thoracic aortic aneurysms who underwent TEVAR or open surgical repair between 1999 and 2010 with follow-up through 2014. Survival was assessed with restricted mean survival time. Perioperative mortality was assessed with logistic regression. Reintervention was evaluated as a secondary outcome.Matching created comparable groups with 1,235 open surgical repair patients matched to 2,470 TEVAR patients. The odds of perioperative mortality were greater for open surgical repair: high-volume center, odds ratio (OR): 1.97 (95% confidence interval [CI]: 1.53 to 2.61); low-volume center, OR: 3.62 (95% CI: 2.88 to 4.51). The restricted mean survival time difference favored TEVAR at 9 years, -209.2 days (95% CI: -298.7 to -119.7 days; p < 0.001) for open surgical repair. Risk of reintervention was lower for open surgical repair, hazard ratio: 0.40 (95% CI: 0.34 to 0.60; p < 0.001).Open surgical repair was associated with increased odds of early postoperative mortality but reduced late hazard of death. Despite the late advantage of open repair, mean survival was superior for TEVAR. TEVAR should be considered the first line for repair of intact descending thoracic aortic aneurysms in Medicare beneficiaries.

  View details for PubMedID 30765029

• 3-Year Outcomes After Valve-in-Valve Transcatheter Aortic Valve Replacement for Degenerated Bioprostheses: The PARTNER 2 Registry. Journal of the American College of Cardiology Webb, J. G., Murdoch, D. J., Alu, M. C., Cheung, A. n., Crowley, A. n., Dvir, D. n., Herrmann, H. C., Kodali, S. K., Leipsic, J. n., Miller, D. C., Pibarot, P. n., Suri, R. M., Wood, D. n., Leon, M. B., Mack, M. J. 2019; 73 (21): 2647–55

  Abstract

  Transcatheter aortic valve replacement (TAVR) for degenerated surgical bioprosthetic aortic valves is associated with favorable early outcomes. However, little is known about the durability and longer-term outcomes associated with this therapy.The aim of this study was to examine late outcomes after valve-in-valve TAVR.Patients with symptomatic degeneration of surgical aortic bioprostheses at high risk (≥50% major morbidity or mortality) for reoperative surgery were prospectively enrolled in the multicenter PARTNER (Placement of Aortic Transcatheter Valves) 2 valve-in-valve and continued access registries. Three-year clinical and echocardiographic follow-up was obtained.Valve-in-valve procedures were performed in 365 patients. The mean age was 78.9 ± 10.2 years, and the mean Society of Thoracic Surgeons score was 9.1 ± 4.7%. At 3 years, the overall Kaplan-Meier estimate of all-cause mortality was 32.7%. Aortic valve re-replacement was required in 1.9%. Mean transaortic gradient was 35.0 mm Hg at baseline, decreasing to 17.8 mm Hg at 30-day follow-up and 16.6 mm Hg at 3-year follow-up. Baseline effective orifice area was 0.93 cm2, increasing to 1.13 and 1.15 cm2 at 30 days and 3 years, respectively. Moderate to severe aortic regurgitation was reduced from 45.1% at pre-TAVR baseline to 2.5% at 3 years. Importantly, moderate or severe mitral and tricuspid regurgitation also decreased (33.7% vs. 8.6% [p < 0.0001] and 29.7% vs. 18.8% [p = 0.002], respectively). Baseline left ventricular ejection fraction was 50.7%, increasing to 54.7% at 3 years (p < 0.0001), while left ventricular mass index was 136.4 g/m2, decreasing to 109.1 g/m2 at 3 years (p < 0.0001). New York Heart Association functional class improved, with 90.4% in class III or IV at baseline and 14.1% at 3 years (p < 0.0001), and Kansas City Cardiomyopathy Questionnaire overall score increased (43.1 to 73.1; p < 0.0001).At 3-year follow-up, TAVR for bioprosthetic aortic valve failure was associated with favorable survival, sustained improved hemodynamic status, and excellent functional and quality-of-life outcomes. (The PARTNER II Trial: Placement of Aortic Transcatheter Valves II - PARTNER II - Nested Registry 3/Valve-in-Valve [PII NR3/ViV]; NCT03225001).

  View details for DOI 10.1016/j.jacc.2019.03.483

  View details for PubMedID 31146808

• Characterization of 3-dimensional papillary muscle displacement in invivo ovine models of ischemic/functional mitral regurgitation. The Journal of thoracic and cardiovascular surgery Bothe, W., Timek, T. A., Tibayan, F. A., Walther, M., Daughters, G. T., Ingels, N. B., Miller, D. C. 2018

  Abstract

  OBJECTIVE: Papillary muscle (PM) displacement contributes to ischemic/functional mitral regurgitation (IMR/FMR). The displaced PMs pull the mitral leaflets into the left ventricle (ie, toward the apex) thus hampering leaflet coaptation. Intuitively apical leaflet tethering results from apical PM displacement. The 3-dimensional directions of PM displacement are, however, incompletely characterized.METHODS: Data from invivo ovine models of IMR (6-8weeks of posterolateral infarction, n=12) and FMR (9-21days of rapid left ventricular pacing, n=11) were analyzed. All sheep had radiopaque markers implanted on the anterior and posterior PM (PPM) tips, around the mitral annulus, and on the left ventricular apex. To explore 3-dimensional PM displacement directions, differences in marker coordinates were calculated at end-systole before and during IMR/FMR using a right-handed coordinate system centered on the mitral annular "saddle horn" with the y-axis passing through the apical marker.RESULTS: No apical PM displacement was observed during either IMR or FMR. The anterior PM displaced laterally during FMR. Posterolateral PPM displacement was observed during IMR and FMR.CONCLUSIONS: Experimental invivo ovine models suggest posterolateral PPM displacement as a predominant pathomechanism leading to apical leaflet tethering during IMR/FMR.

  View details for PubMedID 30447965

• Observed to expected 30-day mortality as a benchmark for transcatheter aortic valve replacement. The Journal of thoracic and cardiovascular surgery Henn, M. C., Zajarias, A., Quader, N., Sintek, M., Lasala, J. M., Koogler, K., Damiano, M. S., Kachroo, P., Miller, D. C., King, C. R., Melby, S. J., Moon, M. R., Damiano, R. J., Maniar, H. S. 2018

  Abstract

  OBJECTIVE: The observed-to-expected 30-day mortality ratio (O:E ratio) is a standard metric by which transcatheter aortic valve replacement (TAVR) trials have been evaluated. Early TAVR trials consistently demonstrated O:E ratio less than 0.6 after TAVR when based on the Society for Thoracic Surgery Predicted Risk of Mortality (STS-PROM) for surgical aortic valve replacement. Recent published results from the Transcatheter Valve Therapy (TVT) Registry have demonstrated O:E ratios of 1.0. We evaluated our own O:E ratios for TAVR to investigate this discordance.METHODS: Data were collected prospectively for TAVR patients from 2008 through 2015 (N=546) and were reviewed retrospectively. The observed mortality and STS-PROM were calculated to formulate O:E ratios and were compared over a variety of subgroups.RESULTS: Overall, the O:E ratio for 30-day mortality was 0.4 and significantly less than 1 (P<.001; 95% confidence interval, 0.25-0.63). The O:E ratio relationship remained less than 0.5 for patients with low (STS-PROM<4), moderate (STS-PROM=4-8) and high risk (STS-PROM>8). The O:E ratio was significantly higher for transapical patients (O:E ratio=0.8) when compared with transfemoral patients (O:E ratio=0.2). Lastly, O:E ratios for both commercial (O:E ratio=0.5) and research (O:E ratio=0.3) patients were similar (P=.337), and both were significantly less than 1 (P=.007 and P<.001, respectively).CONCLUSIONS: The STS-PROM consistently overestimated 30-day mortality after TAVR. Achieving an O:E ratio less than 0.6 may be a realistic goal for all TAVR programs. While an accurate and specific risk calculator for 30-day mortality after TAVR remains to be established, our data suggest that current TVT results are not acceptable for commercial TAVR and that programs with an O:E ratio greater than 0.6, based on the STS-PROM, should reevaluate internal processes to improve their results.

  View details for PubMedID 30454980

• Acute Limited Intimal Tears of the Thoracic Aorta. Journal of the American College of Cardiology Chin, A. S., Willemink, M. J., Kino, A. n., Hinostroza, V. n., Sailer, A. M., Fischbein, M. P., Mitchell, R. S., Berry, G. J., Miller, D. C., Fleischmann, D. n. 2018; 71 (24): 2773–85

  Abstract

  Limited intimal tears (LITs) of the aorta (Class 3 dissection variant) are the least common form of aortic pathology in patients presenting with acute aortic syndrome (AAS). LITs are difficult to detect on imaging and may be underappreciated.This study sought to describe the frequency, pathology, treatment, and outcome of LITs compared with other AAS, and to demonstrate that LITs can be detected pre-operatively by contemporary imaging.The authors retrospectively reviewed 497 patients admitted for 513 AAS events at a single academic aortic center between 2003 and 2012. AAS were classified into classic dissection (AD), intramural hematoma, LIT, penetrating atherosclerotic ulcer, and rupturing thoracic aortic aneurysm. The prevalence, pertinent risk factors, and detailed imaging findings with surgical and pathological correlation of LITs are described. Management, early outcomes, and late mortality are reported.Among 497 patients with AAS, the authors identified 24 LITs (4.8% of AAS) in 16 men and 8 women (17 type A, 7 type B). Patients with LITs were older than those with AD, and type A LITs had similarly dilated ascending aortas as type A AD. Three patients presented with rupture. Eleven patients underwent urgent surgical aortic replacement, and 2 patients underwent endovascular repair. Medial degeneration was present in all surgical specimens. In-hospital mortality was 4% (1 of 24), and in total, 5 patients with LIT died subsequently at 1.5 years (interquartile range [IQR]: 0.3 to 2.5 years). Computed tomography imaging detected all but 1 LIT, best visualized on volume-rendered images.LITs are rare acute aortic lesions within the dissection spectrum, with similar presentation, complications, and outcomes compared with AD and intramural hematoma. Awareness of this lesion allows pre-operative diagnosis using high-quality computed tomography angiography.

  View details for PubMedID 29903350

• Longitudinal Hemodynamics of Transcatheter and Surgical Aortic Valves in the PARTNER Trial JAMA CARDIOLOGY Douglas, P. S., Leon, M. B., Mack, M. J., Svensson, L. G., Webb, J. G., Hahn, R. T., Pibarot, P., Weissman, N. J., Miller, C., Kapadia, S., Herrmann, H. C., Kodali, S. K., Makkar, R. R., Thourani, V. H., Lerakis, S., Lowry, A. M., Rajeswaran, J., Finn, M. T., Alu, M. C., Smith, C. R., Blackstone, E. H., PARTNER Trial Investigators 2017; 2 (11): 1197–1206

  Abstract

  Use of transcatheter aortic valve replacement (TAVR) for severe aortic stenosis is growing rapidly. However, to our knowledge, the durability of these prostheses is incompletely defined.To determine the midterm hemodynamic performance of balloon-expandable transcatheter heart valves.In this study, we analyzed core laboratory-generated data from echocardiograms of all patients enrolled in the Placement of Aortic Transcatheter Valves (PARTNER) 1 Trial with successful TAVR or surgical AVR (SAVR) obtained preimplantation and at 7 days, 1 and 6 months, and 1, 2, 3, 4, and 5 years postimplantation. Patients from continued access observational studies were included for comparison.Successful implantation after randomization to TAVR vs SAVR (PARTNER 1A; TAVR, n = 321; SAVR, n = 313), TAVR vs medical treatment (PARTNER 1B; TAVR, n = 165), and continued access (TAVR, n = 1996). Five-year echocardiogram data were available for 424 patients after TAVR and 49 after SAVR.Death or reintervention for aortic valve structural indications, measured using aortic valve mean gradient, effective orifice area, Doppler velocity index, and evidence of hemodynamic deterioration by reintervention, adverse hemodynamics, or transvalvular regurgitation.Of 2795 included patients, the mean (SD) age was 84.5 (7.1) years, and 1313 (47.0%) were female. Population hemodynamic trends derived from nonlinear mixed-effects models showed small early favorable changes in the first few months post-TAVR, with a decrease of -2.9 mm Hg in aortic valve mean gradient, an increase of 0.028 in Doppler velocity index, and an increase of 0.09 cm2 in effective orifice area. There was relative stability at a median follow-up of 3.1 (maximum, 5) years. Moderate/severe transvalvular regurgitation was noted in 89 patients (3.7%) after TAVR and increased over time. Patients with SAVR showed no significant changes. In TAVR, death/reintervention was associated with lower ejection fraction, stroke volume index, and aortic valve mean gradient up to 3 years, with no association with Doppler velocity index or valve area. Reintervention occurred in 20 patients (0.8%) after TAVR and in 1 (0.3%) after SAVR and became less frequent over time. Reintervention was caused by structural deterioration of transcatheter heart valves in only 5 patients. Severely abnormal hemodynamics on echocardiograms were also infrequent and not associated with excess death or reintervention for either TAVR or SAVR.This large, core laboratory-based study of transcatheter heart valves revealed excellent durability of the transcatheter heart valves and SAVR. Abnormal findings in individual patients, suggestive of valve thrombosis or structural deterioration, were rare in this protocol-driven database and require further investigation.clinicaltrials.gov Identifier: NCT00530894.

  View details for PubMedID 28973520

• Effect of Sapien-3 Transcatheter Valve Implant on Health Status in Patients with Severe Aortic Stenosis at Intermediate Surgical Risk: Results from the PARTNER S3i Trial Baron, S., Alu, M., Thourani, V., Kodali, S., Arnold, S., Chinnakondepali, K., Magnuson, E., Wang, K., Pichard, A., Babaliaros, V., George, I., Miller, D., Tuzcu, E., Greason, K., Herrmann, H., Smith, C., Leon, M., Cohen, D. ELSEVIER SCIENCE INC. 2016: B14

  View details for DOI 10.1016/j.jacc.2016.09.056

  View details for Web of Science ID 000397332900035

• Aortic Valve-Sparing Surgery Yes, But Not for Every Patient and Select the Center Very Carefully JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Miller, D. 2016; 68 (17): 1848–50

  View details for PubMedID 27765187

• Evolution of surgical therapy for Stanford acute type A aortic dissection. Annals of cardiothoracic surgery Chiu, P., Miller, D. C. 2016; 5 (4): 275-295

  Abstract

  Acute type A aortic dissection (AcA-AoD) is a surgical emergency associated with very high morbidity and mortality. Unfortunately, the early outcome of emergency surgical repair has not improved substantially over the last 20 years. Many of the same debates occur repeatedly regarding operative extent and optimal conduct of the operation. The question remains: are patients suffering from too large an operation or too small? The pendulum favoring routine aortic valve resuspension, when feasible, has swung towards frequent aortic root replacement. This already aggressive approach is now being challenged with the even more extensive valve-sparing aortic root replacement (V-SARR) in selected patients. Distally, open replacement of most of the transverse arch is best in most patients. The need for late aortic re-intervention has not been shown to be affected by more extensive distal operative procedures, but the contemporary enthusiasm for a distal frozen elephant trunk (FET) only seems to build. It must be remembered that the first and foremost goal of the operation is to have an operative survivor; additional measures to reduce late morbidity are secondary aspirations. With increasing experience, true contraindications to emergency surgical operation have dwindled, but patients with advanced age, multiple comorbidities, and major neurological deficits do not fare well. The endovascular revolution, moreover, has spawned innovative options for modern practice, including ascending stent graft and adaptations of the old flap fenestration technique. Despite the increasingly complex operations and ever expanding therapies, this life-threatening disease remains a stubborn challenge for all cardiovascular surgeons. Development of specialized thoracic aortic teams and regionalization of care for patients with AcA-AoD offers the most promise to improve overall results.

  View details for DOI 10.21037/acs.2016.05.05

  View details for PubMedID 27563541

• 5-year outcomes of transcatheter aortic valve replacement compared with standard treatment for patients with inoperable aortic stenosis (PARTNER 1): a randomised controlled trial LANCET Kapadia, S. R., Leon, M. B., Makkar, R. R., Tuzcu, E. M., Svensson, L. G., Kodali, S., Webb, J. G., Mack, M. J., Douglas, P. S., Thourani, V. H., Babaliaros, V. C., Herrmann, H. C., Szeto, W. Y., Pichard, A. D., Williams, M. R., Fontana, G. P., Miller, D. C., Anderson, W. N., Akin, J. J., Davidson, M. J., Smith, C. R. 2015; 385 (9986): 2485-2491

  Abstract

  Based on the early results of the Placement of Aortic Transcatheter Valves (PARTNER) trial, transcatheter aortic valve replacement (TAVR) is an accepted treatment for patients with severe aortic stenosis who are not suitable for surgery. However, little information is available about the late clinical outcomes in such patients.We did this randomised controlled trial at 21 experienced valve centres in Canada, Germany, and the USA. We enrolled patients with severe symptomatic inoperable aortic stenosis and randomly assigned (1:1) them to transfemoral TAVR or to standard treatment, which often included balloon aortic valvuloplasty. Patients and their treating physicians were not masked to treatment allocation. The randomisation was done centrally, and sites learned of the assignment only after a patient had been screened, consented, and entered into the database. The primary outcome of the trial was all-cause mortality at 1 year in the intention-to-treat population, here we present the prespecified findings after 5 years. This study is registered with ClinicalTrials.gov, number NCT00530894.We screened 3015 patients, of whom 358 were enrolled (mean age 83 years, Society of Thoracic Surgeons Predicted Risk of Mortality 11·7%, 54% female). 179 were assigned to TAVR treatment and 179 were assigned to standard treatment. 20 patients crossed over from the standard treatment group and ten withdrew from study, leaving only six patients at 5 years, of whom five had aortic valve replacement treatment outside of the study. The risk of all-cause mortality at 5 years was 71·8% in the TAVR group versus 93·6% in the standard treatment group (hazard ratio 0·50, 95% CI 0·39-0·65; p<0·0001). At 5 years, 42 (86%) of 49 survivors in the TAVR group had New York Heart Association class 1 or 2 symptoms compared with three (60%) of five in the standard treatment group. Echocardiography after TAVR showed durable haemodynamic benefit (aortic valve area 1·52 cm(2) at 5 years, mean gradient 10·6 mm Hg at 5 years), with no evidence of structural valve deterioration.TAVR is more beneficial than standard treatment for treatment of inoperable aortic stenosis. TAVR should be strongly considered for patients who are not surgical candidates for aortic valve replacement to improve their survival and functional status. Appropriate selection of patients will help to maximise the benefit of TAVR and reduce mortality from severe comorbidities.Edwards Lifesciences.

  View details for DOI 10.1016/S0140-6736(15)60290-2

  View details for PubMedID 25788231

• 5-year outcomes of transcatheter aortic valve replacement or surgical aortic valve replacement for high surgical risk patients with aortic stenosis (PARTNER 1): a randomised controlled trial LANCET Mack, M. J., Leon, M. B., Smith, C. R., Miller, D. C., Moses, J. W., Tuzcu, E. M., Webb, J. G., Douglas, P. S., Anderson, W. N., Blackstone, E. H., Kodali, S. K., Makkar, R. R., Fontana, G. P., Kapadia, S., Bavaria, J., Hahn, R. T., Thourani, V. H., Babaliaros, V., Pichard, A., Herrmann, H. C., Brown, D. L., Williams, M., Akin, J., Davidson, M. J., Svensson, L. G. 2015; 385 (9986): 2477-2484

  Abstract

  The Placement of Aortic Transcatheter Valves (PARTNER) trial showed that mortality at 1 year, 2 years, and 3 years is much the same with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) for high-risk patients with aortic stenosis. We report here the 5-year outcomes.We did this randomised controlled trial at 25 hospitals, in Canada (two), Germany (one), and the USA (23). We used a computer-generated randomisation sequence to randomly assign high-risk patients with severe aortic stenosis to either SAVR or TAVR with a balloon-expandable bovine pericardial tissue valve by either a transfemoral or transapical approach. Patients and their treating physicians were not masked to treatment allocation. The primary outcome of the trial was all-cause mortality in the intention-to-treat population at 1 year, we present here predefined outcomes at 5 years. The study is registered with ClinicalTrials.gov, number NCT00530894.We screened 3105 patients, of whom 699 were enrolled (348 assigned to TAVR, 351 assigned to SAVR). Overall mean Society of Thoracic Surgeons Predicted Risk of Mortality score was 11·7%. At 5 years, risk of death was 67·8% in the TAVR group compared with 62·4% in the SAVR group (hazard ratio 1·04, 95% CI 0·86-1·24; p=0·76). We recorded no structural valve deterioration requiring surgical valve replacement in either group. Moderate or severe aortic regurgitation occurred in 40 (14%) of 280 patients in the TAVR group and two (1%) of 228 in the SAVR group (p<0·0001), and was associated with increased 5-year risk of mortality in the TAVR group (72·4% for moderate or severe aortic regurgitation vs 56·6% for those with mild aortic regurgitation or less; p=0·003).Our findings show that TAVR as an alternative to surgery for patients with high surgical risk results in similar clinical outcomes.Edwards Lifesciences.

  View details for DOI 10.1016/S0140-6736(15)60308-7

  View details for PubMedID 25788234

• Rationale and results of the Stanford modification of the David V reimplantation technique for valve-sparing aortic root replacement JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Miller, D. C. 2015; 149 (1): 112-114

  View details for DOI 10.1016/j.jtcvs.2014.08.077

  View details for PubMedID 25308121

• Defining "Severe" Secondary Mitral Regurgitation Emphasizing an Integrated Approach JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Grayburn, P. A., Carabello, B., Hung, J., Gillam, L. D., Liang, D., Mack, M. J., McCarthy, P. M., Miller, D. C., Trento, A., Siegel, R. J. 2014; 64 (25): 2792-2801

  Abstract

  Secondary mitral regurgitation (MR) is associated with poor outcomes, but its correction does not reverse the underlying left ventricular (LV) pathology or improve the prognosis. The recently published American Heart Association/American College of Cardiology guidelines on valvular heart disease generated considerable controversy by revising the definition of severe secondary MR from an effective regurgitant orifice area (EROA) of 0.4 to 0.2 cm(2), and from a regurgitant volume (RVol) of 60 to 30 ml. This paper reviews hydrodynamic determinants of MR severity, showing that EROA and RVol values associated with severe MR depend on LV volume. This explains disparities in the evidence associating a lower EROA threshold with suboptimal survival. Redefining MR severity purely on EROA or RVol may cause significant clinical problems. As the guidelines emphasize, defining severe MR requires careful integration of all echocardiographic and clinical data, as measurement of EROA is imprecise and poorly reproducible.

  View details for DOI 10.1016/j.jacc.2014.10.016

  View details for Web of Science ID 000346734900012

• Tirone David procedure for bicuspid aortic valve disease: impact of root geometry and valve type on mid-term outcomes†. Interactive cardiovascular and thoracic surgery Kari, F. A., Kvitting, J. E., Stephens, E. H., Liang, D. H., Merk, D. R., Fischbein, M. P., Mitchell, R. S., Miller, D. C. 2014; 19 (3): 375-381

  Abstract

  A 180/180° configuration has been reported to increase repair durability after valve-sparing aortic root replacement (V-SARR) for bicuspid aortic valve (BAV) disease. We studied the impact of commissural angular configuration (CAC) and of BAV type on valve performance after V-SARR.A total of 85 BAV patients (68 males, age 44 ± 11 years) underwent Tirone David-V V-SARR between 1997 and 2013. BAV type was documented intraoperatively, and CAC determined from pre- and postoperative computed tomography scans as the angle subtended by the non-fused cusp. Transthoracic echocardiogram was performed at 6 ± 3 days and at 2.9 ± 2.1 years. Functional end-points included freedom from aortic regurgitation (AR) 1+, AR 2+ and freedom from AR progression (0 to 1+, or 1+ to 2+). Tested variables included preoperative CAC (>160 vs <160°) and changes in CAC after V-SARR (Δ > 30° vs Δ < 30°) and Sievers' BAV type (SØ or S1).CAC in SØ-BAV (n = 26) changed minimally from 164 ± 12 to 171 ± 11° (mean Δ = 7.2 ± 16°, P = 0.044), whereas in S1-BAV (n = 59) CAC changed substantially from 132 ± 19 to 156 ± 18° (mean Δ = 27 ± 21°, P < 0.001). Larger postoperative CAC angles were not linked to better mid-term valve performance, but Sievers' BAV type had a major effect on valve performance: mild AR in S1/i BAV progressed more often (76 vs 32% at 4 years, P = 0.017) and 1+ AR was more frequent (70 vs 36% at 4 years, P = 0.008) compared with SØ-BAV.BAV type, including number of raphes, sinuses and commissures (SØ superior to S1) but not commissure geometry within the neoroot alone, appears to be linked to functional outcomes after V-SARR for BAV.

  View details for DOI 10.1093/icvts/ivu123

  View details for PubMedID 24903440

• Early and 1-year outcomes of aortic root surgery in patients with Marfan syndrome: A prospective, multicenter, comparative study JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Coselli, J. S., Volguina, I. V., LeMaire, S. A., Sundt, T. M., Connolly, H. M., Stephens, E. H., Schaff, H. V., Milewicz, D. M., Vricella, L. A., Dietz, H. C., Minard, C. G., Miller, D. C. 2014; 147 (6): 1758-1766

  Abstract

  To compare the 1-year results after aortic valve-sparing (AVS) or valve-replacing (AVR) aortic root replacement from a prospective, international registry of 316 patients with Marfan syndrome (MFS).Patients underwent AVS (n = 239, 76%) or AVR (n = 77, 24%) aortic root replacement at 19 participating centers from 2005 to 2010. One-year follow-up data were complete for 312 patients (99%), with imaging findings available for 293 (94%). The time-to-events were compared between groups using Kaplan-Meier curves and Cox proportional hazards models.Two patients (0.6%)--1 in each group--died within 30 days. No significant differences were found in early major adverse valve-related events (MAVRE; P = .6). Two AVS patients required early reoperation for coronary artery complications. The 1-year survival rates were similar in the AVR (97%) and AVS (98%) groups; the procedure type was not significantly associated with any valve-related events. At 1 year and beyond, aortic regurgitation of at least moderate severity (≥2+) was present in 16 patients in the AVS group (7%) but in no patients in the AVR group (P = .02). One AVS patient required late AVR.AVS aortic root replacement was not associated with greater 30-day mortality or morbidity rates than AVR root replacement. At 1 year, no differences were found in survival, valve-related morbidity, or MAVRE between the AVS and AVR groups. Of concern, 7% of AVS patients developed grade ≥2+ aortic regurgitation, emphasizing the importance of 5 to 10 years of follow-up to learn the long-term durability of AVS versus AVR root replacement in patients with MFS.

  View details for DOI 10.1016/j.jtcvs.2014.02.021

  View details for PubMedID 24655904

• Another Meiosis in the Specialty of Cardiovascular and Thoracic Surgery Birth of the Purebred "Thoracic Aortic Surgeon"? JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Miller, D. 2014; 63 (17): 1804–6

  View details for PubMedID 24365716

• Incidence and progression of mild aortic regurgitation after Tirone David reimplantation valve-sparing aortic root replacement JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Stephens, E. H., Liang, D. H., Kvitting, J. E., Kari, F. A., Fischbein, M. P., Mitchell, R. S., Miller, D. C. 2014; 147 (1): 169-?

  Abstract

  The study objective was to determine whether recurrent or residual mild aortic regurgitation, which occurs after valve-sparing aortic root replacement, progresses over time.Between 2003 and 2008, 154 patients underwent Tirone David-V valve-sparing aortic root replacement; 96 patients (62%) had both 1-year (median, 12 ± 4 months) and mid-term (62 ± 22 months) transthoracic echocardiograms available for analysis. Age of patients averaged 38 ± 13 years, 71% were male, 31% had a bicuspid aortic valve, 41% had Marfan syndrome, and 51% underwent aortic valve repair, predominantly cusp free margin shortening.Forty-one patients (43%) had mild aortic regurgitation on 1-year echocardiogram. In 85% of patients (n = 35), mild aortic regurgitation remained stable on the most recent echocardiogram (median, 57 ± 20 months); progression to moderate aortic regurgitation occurred in 5 patients (12%) at a median of 28 ± 18 months and remained stable thereafter; severe aortic regurgitation developed in 1 patient, eventually requiring reoperation. Five patients (5%) had moderate aortic regurgitation at 1 year, which did not progress subsequently. Two patients (2%) had more than moderate aortic regurgitation at 1 year, and both ultimately required reoperation.Although mild aortic regurgitation occurs frequently after valve-sparing aortic root replacement, it is unlikely to progress over the next 5 years and should not be interpreted as failure of the valve-preservation concept. Further, we suggest that mild aortic regurgitation should not be considered nonstructural valve dysfunction, as the 2008 valve reporting guidelines would indicate. We need 10- to 15-year follow-up to learn the long-term clinical consequences of mild aortic regurgitation early after valve-sparing aortic root replacement.

  View details for DOI 10.1016/j.jtcvs.2013.09.009

  View details for PubMedID 24176278

• Evaluation of Marfan patients status post valve-sparing aortic root replacement with 4D flow MAGNETIC RESONANCE IMAGING Hope, T. A., Kvitting, J. E., Hope, M. D., Miller, D. C., Markl, M., Herfkens, R. J. 2013; 31 (9): 1479-1484

  Abstract

  BACKGROUND: Over the past two decades elective valve-sparing aortic root replacement (V-SARR) has become more common in the treatment of patients with aortic root and ascending aortic aneurysms. Currently there are little data available to predict complications in the post-operative population. The study goal was to determine if altered flow patterns in the thoracic aorta, as measured by MRI, are associated with complications after V-SARR. METHODS: Time-resolved three-dimensional phase-contrast MRI (4D flow) was used to image 12 patients with Marfan syndrome after V-SARR. The patients were followed up for an average of 5.8years after imaging and 8.2years after surgery. Additionally 5 volunteers were imaged for comparison. Flow profiles were visualized during peak systole using streamlines. Wall shear stress estimates and normalized flow displacement were evaluated at multiple planes in the thoracic aorta. RESULTS: During the follow-up period, a single patient developed a Stanford Type B aortic dissection. At initial imaging, prior to the development of the dissection, the patient had altered flow patterns, wall shear stress estimates, and increased normalized flow displacement in the thoracic aorta in comparison to the remaining V-SARR patients and volunteers. CONCLUSIONS: This is the first follow-up study of patients after 4D flow imaging. An aortic dissection developed in one patient with altered flow patterns and hemodynamic stresses in the thoracic aorta. These results suggest that flow and altered hemodynamics may play a role in the development of post-operative intramural hematomas and dissections.

  View details for DOI 10.1016/j.mri.2013.04.003

  View details for PubMedID 23706513

• Predictors of Mortality and Outcomes of Therapy in Low-Flow Severe Aortic Stenosis: A Placement of Aortic Transcatheter Valves (PARTNER) Trial Analysis CIRCULATION Herrmann, H. C., Pibarot, P., Hueter, I., Gertz, Z. M., Stewart, W. J., Kapadia, S., Tuzcu, E. M., Babaliaros, V., Thourani, V., Szeto, W. Y., Bavaria, J. E., Kodali, S., Hahn, R. T., Williams, M., Miller, D. C., Douglas, P. S., Leon, M. B. 2013; 127 (23): 2316-2326

  Abstract

  The prognosis and treatment of patients with low-flow (LF) severe aortic stenosis are controversial.The Placement of Aortic Transcatheter Valves (PARTNER) trial randomized patients with severe aortic stenosis to medical management versus transcatheter aortic valve replacement (TAVR; inoperable cohort) and surgical aortic valve replacement versus TAVR (high-risk cohort). Among 971 patients with evaluable echocardiograms (92%), LF (stroke volume index ≤35 mL/m(2)) was observed in 530 (55%); LF and low ejection fraction (<50%) in 225 (23%); and LF, low ejection fraction, and low mean gradient (<40 mm Hg) in 147 (15%). Two-year mortality was significantly higher in patients with LF compared with those with normal stroke volume index (47% versus 34%; hazard ratio, 1.5; 95% confidence interval, 1.25-1.89; P=0.006). In the inoperable cohort, patients with LF had higher mortality than those with normal flow, but both groups improved with TAVR (46% versus 76% with LF and 38% versus 53% with normal flow; P<0.001). In the high-risk cohort, there was no difference between TAVR and surgical aortic valve replacement. In patients with paradoxical LF and low gradient (preserved ejection fraction), TAVR reduced 1-year mortality from 66% to 35% (hazard ratio, 0.38; P=0.02). LF was an independent predictor of mortality in all patient cohorts (hazard ratio, ≈1.5), whereas ejection fraction and gradient were not.LF is common in severe aortic stenosis and independently predicts mortality. Survival is improved with TAVR compared with medical management and similar with TAVR and surgical aortic valve replacement. A measure of flow (stroke volume index) should be included in the evaluation and therapeutic decision making of patients with severe aortic stenosis.URL: http://www.clinicaltrial.gov. Unique identifier: NCT0053089.4.

  View details for DOI 10.1161/CIRCULATIONAHA.112.001290

  View details for Web of Science ID 000320156900020

  View details for PubMedID 23661722

• Aortic Valve and Ascending Aorta Guidelines for Management and Quality Measures ANNALS OF THORACIC SURGERY Svensson, L. G., Adams, D. H., Bonow, R. O., Kouchoukos, N. T., Miller, D. C., O'Gara, P. T., Shahian, D. M., Schaff, H. V., Akins, C. W., Bavaria, J. E., Blackstone, E. H., David, T. E., Desai, N. D., Dewey, T. M., D'Agostino, R. S., Gleason, T. G., Harrington, K. B., Kodali, S., Kapadia, S., Leon, M. B., Lima, B., Lytle, B. W., Mack, M. J., Reardon, M., Reece, T. B., Reiss, G. R., Roselli, E. E., Smith, C. R., Thourani, V. H., Tuzcu, E. M., Webb, J., Williams, M. R. 2013; 95 (6): S1-S66

  View details for DOI 10.1016/j.athoracsur.2013.01.083

  View details for Web of Science ID 000320303900001

  View details for PubMedID 23688839

• Sizing for Mitral Annuloplasty: Where Does Science Stop and Voodoo Begin? ANNALS OF THORACIC SURGERY Bothe, W., Miller, D. C., Doenst, T. 2013; 95 (4): 1475-1483

  Abstract

  The implantation of an improperly sized annuloplasty ring may result in an incompetent valve after surgical mitral valve repair. Consequently, the procedure of ring size selection is considered critical. Although a plethora of sizing strategies are described, the opinions on how to select the appropriate ring size differ widely and often appear arbitrary (ie, without scientific justification). These inconsistencies raise the question where, with respect to ring sizing, science stops and voodoo begins.

  View details for DOI 10.1016/j.athoracsur.2012.10.023

  View details for Web of Science ID 000317150600061

  View details for PubMedID 23481703

• Tirone David valve-sparing aortic root replacement and cusp repair for bicuspid aortic valve disease JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Kari, F. A., Liang, D. H., Kvitting, J. E., Stephens, E. H., Mitchell, R. S., Fischbein, M. P., Miller, D. C. 2013; 145 (3): S35-?

  Abstract

  The durability of valve-sparing aortic root replacement with or without cusp repair in patients with bicuspid aortic valve (BAV) disease is questioned. We analyzed the results of 75 patients with a BAV undergoing Tirone David reimplantation valve-sparing aortic root replacement.Average age was 45 ± 10 years; 80% were male; 31% had 2+ or greater aortic regurgitation (AR); annular diameter averaged 28 ± 3 mm; 32% had a Sievers' type 0 BAV, and 66% underwent concomitant cusp repair (usually cusp free margin shortening) to correct prolapse. Early (6 ± 3 days) and late (2.9 ± 1.7, 1-10 years) postoperative echocardiographic results were compared (cumulative echocardiographic follow-up, 190 patient-years; median late interval, 2 years [interquartile range, 0.68, 4.2]). Seven patients remained at risk beyond 6 years. Clinical outcome and valve function were analyzed using log-rank calculations.Actuarial survival was 99% ± 2%; freedom from reoperation was 90% ± 5%, infection 98% ± 2%, and stroke 100% at 6 years. After initial improvement in degree of AR (P < .001), minor subclinical progression of AR was observed (P > .5); however, freedom from AR of more than 2+ was 100%. Cusp free margin shortening was not associated with valve deterioration, but commissural suspensory polytetrafluoroethylene neochord creation (n = 4) portended a higher probability of recurrent AR (P = .025).After David procedure and cusp repair in patients with a BAV, midterm clinical and valve function outcomes were favorable out to 6 years. More follow-up is required to determine long-term valve durability and the hazard of other clinically important late adverse events, including eventual reoperation, to beyond 10 years.

  View details for DOI 10.1016/j.jtcvs.2012.11.043

  View details for PubMedID 23260433

• Through the looking glass: The first 20 years of thoracic aortic stent-grafting JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Miller, D. C. 2013; 145 (3): S142-S148

  View details for DOI 10.1016/j.jtcvs.2012.11.076

  View details for PubMedID 23410771

• David valve-sparing aortic root replacement: Equivalent mid-term outcome for different valve types with or without connective tissue disorder JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Kvitting, J. E., Kari, F. A., Fischbein, M. P., Liang, D. H., Beraud, A., Stephens, E. H., Mitchell, R. S., Miller, D. C. 2013; 145 (1): 117-?

  Abstract

  Although implicitly accepted by many that the durability of valve-sparing aortic root replacement in patients with bicuspid aortic valve disease and connective tissue disorders will be inferior, this hypothesis has not been rigorously investigated.From 1993 to 2009, 233 patients (27% bicuspid aortic valve, 40% Marfan syndrome) underwent Tirone David valve-sparing aortic root replacement. Follow-up averaged 4.7 ± 3.3 years (1102 patient-years). Freedom from adverse outcomes was determined using log-rank calculations.Survival at 5 and 10 years was 98.7% ± 0.7% and 93.5% ± 5.1%, respectively. Freedom from reoperation (all causes) on the aortic root was 92.2% ± 3.6% at 10 years; 3 reoperations were aortic valve replacement owing to structural valve deterioration. Freedom from structural valve deterioration at 10 years was 96.1% ± 2.1%. No significant differences were found in survival (P = .805, P = .793, respectively), reoperation (P = .179, P = .973, respectively), structural valve deterioration (P = .639, P = .982, respectively), or any other functional or clinical endpoints when patients were stratified by valve type (tricuspid aortic valve vs bicuspid aortic valve) or associated connective tissue disorder. At the latest echocardiographic follow-up (95% complete), 202 patients (94.8%) had none or trace aortic regurgitation, 10 (4.7%) mild, 0 had moderate to severe, and 1 (0.5%) had severe aortic regurgitation. Freedom from greater than 2+ aortic regurgitation at 10 years was 95.3% ± 2.5%. Six patients sustained acute type B aortic dissection (freedom at 10 years, 90.4% ± 5.0%).Tirone David reimplantation valve-sparing aortic root replacement in carefully selected young patients was associated with excellent clinical and echocardiographic outcome in patients with either a tricuspid aortic valve or bicuspid aortic valve. No demonstrable adverse influence was found for Marfan syndrome or connective tissue disorder on durability, clinical outcome, or echocardiographic results.

  View details for DOI 10.1016/j.jtcvs.2012.09.013

  View details for PubMedID 23083792

• Transcatheter (TAVR) versus surgical (AVR) aortic valve replacement: Occurrence, hazard, risk factors, and consequences of neurologic events in the PARTNER trial 91st Annual Meeting of the American-Association-for-Thoracic-Surgery Miller, D. C., Blackstone, E. H., Mack, M. J., Svensson, L. G., Kodali, S. K., Kapadia, S., Rajeswaran, J., Anderson, W. N., Moses, J. W., Tuzcu, E. M., Webb, J. G., Leon, M. B., Smith, C. R. MOSBY-ELSEVIER. 2012: 832–U368

  Abstract

  All neurologic events in the PARTNER randomized trial comparing transcatheter aortic valve replacement (TAVR) with surgical aortic valve replacement (AVR) were analyzed.High-risk patients with aortic stenosis were stratified into transfemoral (TF, n = 461) or transapical (TA, n = 196) strata based on their arterial anatomy and randomized: 657 received treatment assigned ("as treated"), 313 underwent AVR, and 344 TAVR. Neurologic events were prospectively adjudicated by an independent Clinical Events Committee. Multivariable, multiphase hazard analysis elucidated factors associated with increased likelihood of neurologic events.Forty-nine neurologic events (15 transient ischemic attacks, 34 strokes) occurred in 47 patients (TAVR, n = 31; AVR, n = 16). An early peaking high hazard phase occurred within the first week, which declined to a constant late hazard phase out to 2 years. The risk in the early phase was higher after TAVR than AVR, and in the TAVR arm in patients with a smaller aortic valve area index. In the late risk phase, the likelihood of neurologic event was linked to patient-related factors in both arms ("non-TF candidate," history of recent stroke or transient ischemic attack, and advanced functional disability), but not by treatment (TAVR vs AVR) or any intraprocedural variables. The likelihood of sustaining a neurologic event was lowest in the AVR subgroup in the TF stratum during all available follow-up.After either treatment, there were 2 distinct hazard phases for neurologic events that were driven by different risk factors. Neurologic complications occurred more frequently after TAVR than AVR early, but thereafter the risk was influenced by patient- and disease-related factors.

  View details for DOI 10.1016/j.jtcvs.2012.01.055

  View details for PubMedID 22424519

• Transcatheter versus Surgical Aortic-Valve Replacement in High-Risk Patients NEW ENGLAND JOURNAL OF MEDICINE Smith, C. R., Leon, M. B., Mack, M. J., Miller, C., Moses, J. W., Svensson, L. G., Tuzcu, E. M., Webb, J. G., Fontana, G. P., Makkar, R. R., Williams, M., Dewey, T., Kapadia, S., Babaliaros, V., Thourani, V. H., Corso, P., Pichard, A. D., Bavaria, J. E., Herrmann, H. C., Akin, J. J., Anderson, W. N., Wang, D., Pocock, S. J. 2011; 364 (23): 2187-2198

  Abstract

  The use of transcatheter aortic-valve replacement has been shown to reduce mortality among high-risk patients with aortic stenosis who are not candidates for surgical replacement. However, the two procedures have not been compared in a randomized trial involving high-risk patients who are still candidates for surgical replacement.At 25 centers, we randomly assigned 699 high-risk patients with severe aortic stenosis to undergo either transcatheter aortic-valve replacement with a balloon-expandable bovine pericardial valve (either a transfemoral or a transapical approach) or surgical replacement. The primary end point was death from any cause at 1 year. The primary hypothesis was that transcatheter replacement is not inferior to surgical replacement.The rates of death from any cause were 3.4% in the transcatheter group and 6.5% in the surgical group at 30 days (P=0.07) and 24.2% and 26.8%, respectively, at 1 year (P=0.44), a reduction of 2.6 percentage points in the transcatheter group (upper limit of the 95% confidence interval, 3.0 percentage points; predefined margin, 7.5 percentage points; P=0.001 for noninferiority). The rates of major stroke were 3.8% in the transcatheter group and 2.1% in the surgical group at 30 days (P=0.20) and 5.1% and 2.4%, respectively, at 1 year (P=0.07). At 30 days, major vascular complications were significantly more frequent with transcatheter replacement (11.0% vs. 3.2%, P<0.001); adverse events that were more frequent after surgical replacement included major bleeding (9.3% vs. 19.5%, P<0.001) and new-onset atrial fibrillation (8.6% vs. 16.0%, P=0.006). More patients undergoing transcatheter replacement had an improvement in symptoms at 30 days, but by 1 year, there was not a significant between-group difference.In high-risk patients with severe aortic stenosis, transcatheter and surgical procedures for aortic-valve replacement were associated with similar rates of survival at 1 year, although there were important differences in periprocedural risks. (Funded by Edwards Lifesciences; Clinical Trials.gov number, NCT00530894.).

  View details for Web of Science ID 000291392100005

  View details for PubMedID 21639811

• Report on the results of thoracic endovascular aortic repair for acute, complicated, type B aortic dissection at 30 days and 1 year from a multidisciplinary subcommittee of the Society for Vascular Surgery Outcomes Committee JOURNAL OF VASCULAR SURGERY White, R. A., Miller, D. C., Criado, F. J., Dake, M. D., Diethrich, E. B., Greenberg, R. K., Piccolo, R. S., Siami, F. S. 2011; 53 (4): 1082-1090

  Abstract

  This study analyzed 1-year outcome after thoracic endovascular aortic repair (TEVAR) in patients with complicated type B aortic dissection (cTBAoD) who had rupture or malperfusion and symptom onset ≤14 days (acute), 15 to 30 days (subacute), and 31 to 90 days (chronic) until required intervention. The main focus of this report is primarily on the acute cohort.Clinical data were systematically collected from five physician-sponsored investigational device exemption (IDE) clinical trials between 2000 and 2008 using standardized definitions and forms. Adverse events were reported early (≤30 days) and late (>30 days) by body system. Major adverse events included death, stroke, myocardial infarction, renal failure, respiratory failure, paralysis, and bowel ischemia.There were 99 cTBAoD patients: 85 were acute, 11 were subacute, and 3 were chronic. Among the acute patients, 31.8% had rupture and 71.8% had malperfusion, including 55.7% lower extremity, 36.1% renal, 19.7% visceral, 8.2% other, and 3.3% spinal cord (patients may have more than one source). Rupture and malperfusion were both reported for three acute patients. Additional findings for the acute cohort included pain (76.5%), hypertension (43.5%), and bleeding (8.2%); comorbidities included hypertension (83.5%), current/past smoking history (69.8%), and diabetes (12.9%). The main focus of this analysis was the acute cohort (n = 85). Age averaged 59 years (72.9% male). Early adverse events included pulmonary (36.5%), vascular (28.2%), renal (25.9%), and neurologic (23.5%). Early major adverse events occurred in 37.6% of patients, including death (10.6%), stroke (9.4%), renal failure (9.4%), and paralysis (9.4%); late adverse events included vascular (15.8%), cardiac (10.5%), gastrointestinal (6.6%), and hemorrhage (5.3%). The point-estimate mortality rate was 10.8 (95% confidence interval [CI], 4.1-17.5) at 30 days and 29.4 (95% CI, 18.4-40.4) at 1 year, when 34 patients remained at risk.Emergency TEVAR for patients with cTBAoD (malperfusion or rupture) provided acceptable mortality and morbidity results out to 1 year. Manufacturers can use this 30-day mortality point-estimate of 10.8 (95% CI, 4.1-17.5) for the acute cohort to establish a performance goal for use in single-arm commercial IDE trials if the Food and Drug Administration and other regulatory bodies concur.

  View details for DOI 10.1016/j.jvs.2010.11.124

  View details for Web of Science ID 000289012600028

  View details for PubMedID 21334174

• Transcatheter Aortic-Valve Implantation for Aortic Stenosis in Patients Who Cannot Undergo Surgery. NEW ENGLAND JOURNAL OF MEDICINE Leon, M. B., Smith, C. R., Mack, M., Miller, D. C., Moses, J. W., Svensson, L. G., Tuzcu, E. M., Webb, J. G., Fontana, G. P., Makkar, R. R., Brown, D. L., Block, P. C., Guyton, R. A., Pichard, A. D., Bavaria, J. E., Herrmann, H. C., Douglas, P. S., Petersen, J. L., Akin, J. J., Anderson, W. N., Wang, D., Pocock, S. 2010; 363 (17): 1597-1607

  Abstract

  Many patients with severe aortic stenosis and coexisting conditions are not candidates for surgical replacement of the aortic valve. Recently, transcatheter aortic-valve implantation (TAVI) has been suggested as a less invasive treatment for high-risk patients with aortic stenosis.We randomly assigned patients with severe aortic stenosis, whom surgeons considered not to be suitable candidates for surgery, to standard therapy (including balloon aortic valvuloplasty) or transfemoral transcatheter implantation of a balloon-expandable bovine pericardial valve. The primary end point was the rate of death from any cause.A total of 358 patients with aortic stenosis who were not considered to be suitable candidates for surgery underwent randomization at 21 centers (17 in the United States). At 1 year, the rate of death from any cause (Kaplan–Meier analysis) was 30.7% with TAVI, as compared with 50.7% with standard therapy (hazard ratio with TAVI, 0.55; 95% confidence interval [CI], 0.40 to 0.74; P<0.001). The rate of the composite end point of death from any cause or repeat hospitalization was 42.5% with TAVI as compared with 71.6% with standard therapy (hazard ratio, 0.46; 95% CI, 0.35 to 0.59; P<0.001). Among survivors at 1 year, the rate of cardiac symptoms (New York Heart Association class III or IV) was lower among patients who had undergone TAVI than among those who had received standard therapy (25.2% vs. 58.0%, P<0.001). At 30 days, TAVI, as compared with standard therapy, was associated with a higher incidence of major strokes (5.0% vs. 1.1%, P=0.06) and major vascular complications (16.2% vs. 1.1%, P<0.001). In the year after TAVI, there was no deterioration in the functioning of the bioprosthetic valve, as assessed by evidence of stenosis or regurgitation on an echocardiogram.In patients with severe aortic stenosis who were not suitable candidates for surgery, TAVI, as compared with standard therapy, significantly reduced the rates of death from any cause, the composite end point of death from any cause or repeat hospitalization, and cardiac symptoms, despite the higher incidence of major strokes and major vascular events. (Funded by Edwards Lifesciences; ClinicalTrials.gov number, NCT00530894.).

  View details for DOI 10.1056/NEJMoa1008232

  View details for Web of Science ID 000283242700004

  View details for PubMedID 20961243

• Myofiber angle distributions in the ovine left Ventricle do not conform to computationally optimized predictions JOURNAL OF BIOMECHANICS Ennis, D. B., Nguyen, T. C., Riboh, J. C., Wigstroem, L., Harrington, K. B., Daughters, G. T., Ingels, N. B., Miller, D. C. 2008; 41 (15): 3219-3224

  Abstract

  Recent computational models of optimized left ventricular (LV) myofiber geometry that minimize the spatial variance in sarcomere length, stress, and ATP consumption have predicted that a midwall myofiber angle of 20 degrees and transmural myofiber angle gradient of 140 degrees from epicardium to endocardium is a functionally optimal LV myofiber geometry. In order to test the extent to which actual fiber angle distributions conform to this prediction, we measured local myofiber angles at an average of nine transmural depths in each of 32 sites (4 short-axis levels, 8 circumferentially distributed blocks in each level) in five normal ovine LVs. We found: (1) a mean midwall myofiber angle of -7 degrees (SD 9), but with spatial heterogeneity (averaging 0 degrees in the posterolateral and anterolateral wall near the papillary muscles, and -9 degrees in all other regions); and (2) an average transmural gradient of 93 degrees (SD 21), but with spatial heterogeneity (averaging a low of 51 degrees in the basal posterior sector and a high of 130 degrees in the mid-equatorial anterolateral sector). We conclude that midwall myofiber angles and transmural myofiber angle gradients in the ovine heart are regionally non-uniform and differ significantly from the predictions of present-day computationally optimized LV myofiber models. Myofiber geometry in the ovine heart may differ from other species, but model assumptions also underlie the discrepancy between experimental and computational results. To test the predictive capability of the current computational model would we propose using an ovine specific LV geometry and comparing the computed myofiber orientations to those we report herein.

  View details for DOI 10.1016/j.jbiomech.2008.08.007

  View details for PubMedID 18805536

• Heterogeneity of left ventricular wall thickening mechanisms 78th Annual Scientific Session of the American-Heart-Association Cheng, A., Nguyen, T. C., Malinowski, M., Daughters, G. T., Miller, D. C., Ingels, N. B. LIPPINCOTT WILLIAMS & WILKINS. 2008: 713–21

  Abstract

  Myocardial fibers are grouped into lamina (or sheets) 3 to 4 cells thick. Fiber shortening produces systolic left ventricular (LV) wall thickening primarily by laminar extension, thickening, and shear, but the regional variability and transmural distribution of these 3 mechanisms are incompletely understood.Nine sheep had transmural radiopaque markers inserted into the anterior basal and lateral equatorial LV. Four-dimensional marker dynamics were studied with biplane videofluoroscopy to measure circumferential, longitudinal, and radial systolic strains in the epicardium, midwall, and endocardium. Fiber and sheet angles from quantitative histology allowed transformation of these strains into transmural contributions of sheet extension, thickening, and shear to systolic wall thickening. At all depths, systolic wall thickening in the anterior basal region was 1.6 to 1.9 times that in the lateral equatorial region. Interestingly, however, systolic fiber shortening was identical at each transmural depth in these regions. Endocardial anterior basal sheet thickening was >2 times greater than in the lateral equatorial region (epicardium, 0.16+/-0.15 versus 0.03+/-0.06; endocardium, 0.45+/-0.40 versus 0.17+/-0.09). Midwall sheet extension was >2 times that in the lateral wall (0.22+/-0.12 versus 0.09+/-0.06). Epicardial and midwall sheet shears in the anterior wall were approximately 2 times higher than in the lateral wall (epicardium, 0.14+/-0.07 versus 0.05+/-0.03; midwall, 0.21+/-0.12 versus 0.12+/-0.06).These data demonstrate fundamentally different regional contributions of laminar mechanisms for amplifying fiber shortening to systolic wall thickening. Systolic fiber shortening was identical at each transmural depth in both the anterior and lateral LV sites. However, systolic wall thickening of the anterior site was much greater than that of the lateral site. Fiber shortening drives systolic wall thickening, but sheet dynamics and orientations are of great importance to systolic wall thickening. LV wall thickening and its clinical implications pivot on different wall thickening mechanisms in various LV regions. Attempts to implant healthy contractile cells into diseased hearts or to surgically manipulate LV geometry need to take into account not only cardiomyocyte contraction but also transmural LV intercellular architecture and geometry.

  View details for DOI 10.1161/CIRCULATIONAHA.107.744623

  View details for PubMedID 18663088

• The aortopathy of bicuspid aortic valve disease has distinctive patterns and usually involves the transverse aortic arch 33rd Annual Meeting of the Western-Thoracic-Surgical-Association Fazel, S. S., Mallidi, H. R., Lee, R. S., Sheehan, M. P., Liang, D., Fleischman, D., Herfkens, R., Mitchell, S., Miller, D. C. MOSBY-ELSEVIER. 2008: 901–U54

  Abstract

  Bicuspid aortic valves are associated with a poorly characterized connective tissue disorder that predisposes to aortic catastrophes. Because no criterion exists dictating the appropriate extent of aortic resection in aneurysmal disease of the bicuspid aortic valve, we studied the patterns of aortic dilation in this population.Sixty-four patients with bicuspid aortic valves who underwent computed tomographic or magnetic resonance angiography and echocardiography were retrospectively identified between January 2002 and March 2006. Orthonormal 2-dimensional or 3-dimensional aortic diameters were measured at 10 levels. Agglomerative hierarchic clustering with centered correlation distance measurements and complete linkage analysis was used to detect distinct patterns of aortic dilatation.Mean aortic diameter was 28.1 +/- 0.7 mm at the annulus and 21.7 +/- 0.4 mm at the diaphragmatic hiatus. The aorta was largest in the tubular ascending aorta (45.9 +/- 1.0 mm). Compared with the descending aorta, the transverse aortic arch was also dilated (P < .01). Cluster analysis showed 4 patterns of aortic dilatation: cluster I, aortic root alone (n = 8, 13%); cluster II, tubular ascending aorta alone (n = 9, 14%); cluster III, tubular portion and transverse arch (n = 18, 28%); and, cluster IV, aortic root and tubular portion with tapering across the transverse arch (n = 29, 45%).Distinct patterns of aortic dilatation in patients with bicuspid aortic valves call for an individualized degree of aortic replacement to minimize late aortic complications and reoperation. Patients in clusters III and IV should have transverse arch replacement (plus concomitant root replacement in cluster IV). Patients in cluster I should undergo complete aortic root replacement, whereas in patients in cluster II supracommissural ascending aortic grafting is adequate.

  View details for DOI 10.1016/j.jtcvs.2008.01.022

  View details for PubMedID 18374778

• Expert consensus document on the treatment of descending thoracic aortic disease using endovascular stent-grafts ANNALS OF THORACIC SURGERY Svensson, L. G., Kouchoukos, N. T., Miller, D. C., Bavaria, J. E., Coselli, J. S., Curi, M. A., Eggebrecht, H., Elefteriades, J. A., Erbel, R., Gleason, T. G., Lytle, B. W., Mitchell, R. S., Nienaber, C. A., Roselli, E. E., Safi, H. J., Shemin, R. J., Sicard, G. A., Sundt, T. M., Szeto, W. Y., Wheatley, G. H. 2008; 85 (1): S1-S41

  Abstract

  Between 43,000 and 47,000 people die annually in the United States from diseases of the aorta and its branches and continues to increase. For the thoracic aorta, these diseases are increasingly treated by stent-grafting. No prospective randomized study exists comparing stent-grafting and open surgical treatment, including for disease subgroups. Currently, one stent-graft device is approved by the Food and Drug Administration for descending thoracic aortic aneurysms although two new devices are expected to obtain FDA approval in 2008. Stent-graft devices are used "off label" or under physician Investigational Device Exemption studies for other indications such as traumatic rupture of the aorta and aortic dissection. Early first-generation devices suffered from problems such as stroke with insertion, ascending aortic dissection or aortic penetration from struts, vascular injury, graft collapse, endovascular leaks, graft material failure, continued aneurysm expansion or rupture, and migration or kinking; however, the newer iterations coming to market have been considerably improved. Although the devices have been tested in pulse duplicators out to 10 years, long-term durability is not known, particularly in young patients. The long-term consequences of repeated computed tomography scans for checking device integrity and positioning on the risk of irradiation-induced cancer remains of concern in young patients. This document (1) reviews the natural history of aortic disease, indications for repair, outcomes after conventional open surgery, currently available devices, and insights from outcomes of randomized studies using stent-grafts for abdominal aortic aneurysm surgery, the latter having been treated for a longer time by stent-grafts; and (2) offers suggestions for treatment.

  View details for DOI 10.1016/j.athoracsur.2007.10.099

  View details for Web of Science ID 000252451700001

  View details for PubMedID 18083364

• Aortic root dynamics and surgery: from craft to science PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES Cheng, A., Dagum, P., Miller, D. C. 2007; 362 (1484): 1407-1419

  Abstract

  Since the fifteenth century beginning with Leonardo da Vinci's studies, the precise structure and functional dynamics of the aortic root throughout the cardiac cycle continues to elude investigators. The last five decades of experimental work have contributed substantially to our current understanding of aortic root dynamics. In this article, we review and summarize the relevant structural analyses, using radiopaque markers and sonomicrometric crystals, concerning aortic root three-dimensional deformations and describe aortic root dynamics in detail throughout the cardiac cycle. We then compare data between different studies and discuss the mechanisms responsible for the modes of aortic root deformation, including the haemodynamics, anatomical and temporal determinants of those deformations. These modes of aortic root deformation are closely coupled to maximize ejection, optimize transvalvular ejection haemodynamics and-perhaps most importantly-reduce stress on the aortic valve cusps by optimal diastolic load sharing and minimizing transvalvular turbulence throughout the cardiac cycle. This more comprehensive understanding of aortic root mechanics and physiology will contribute to improved medical and surgical treatment methods, enhanced therapeutic decision making and better post-intervention care of patients. With a better understanding of aortic root physiology, future research on aortic valve repair and replacement should take into account the integrated structural and functional asymmetry of aortic root dynamics to minimize stress on the aortic cusps in order to prevent premature structural valve deterioration.

  View details for DOI 10.1098/rstb.2007.2124

  View details for PubMedID 17594968

• Valve-sparing aortic root replacement: Current state of the art and where are we headed? Aortic Surgery Symposium X Miller, D. C. ELSEVIER SCIENCE INC. 2007: S736–S739

  View details for DOI 10.1016/j.athoracsur.2006.10.001

  View details for PubMedID 17257918

• Direct measurement of transmural laminar architecture in the anterolateral wall of the ovine left ventricle: new implications for wall thickening mechanics AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Harrington, K. B., Rodriguez, F., Cheng, A., Langer, F., Ashikaga, H., Daughters, G. T., Criscione, J. C., Ingels, N. B., Miller, D. C. 2005; 288 (3): H1324-H1330

  Abstract

  Laminar, or sheet, architecture of the left ventricle (LV) is a structural basis for normal systolic and diastolic LV dynamics, but transmural sheet orientations remain incompletely characterized. We directly measured the transmural distribution of sheet angles in the ovine anterolateral LV wall. Ten Dorsett-hybrid sheep hearts were perfusion fixed in situ with 5% buffered glutaraldehyde at end diastole and stored in 10% formalin. Transmural blocks of myocardial tissue were excised, with the edges cut parallel to local circumferential, longitudinal, and radial axes, and sliced into 1-mm-thick sections parallel to the epicardial tangent plane from epicardium to endocardium. Mean fiber directions were determined in each section from five measurements of fiber angles. Each section was then cut transverse to the fiber direction, and five sheet angles (beta) were measured and averaged. Mean fiber angles progressed nearly linearly from -41 degrees (SD 11) at the epicardium to +42 degrees (SD 16) at the endocardium. Two families of sheets were identified at approximately +45 degrees (beta(+)) and -45 degrees (beta(-)). In the lateral region (n = 5), near the epicardium, sheets belonged to the beta(+) family; in the midwall, to the beta(-) family; and near the endocardium, to the beta(+) family. This pattern was reversed in the basal anterior region (n = 4). Sheets were uniformly beta(-) over the anterior papillary muscle (n = 2). These direct measurements of sheet angles reveal, for the first time, alternating transmural families of predominant sheet angles. This may have important implications in understanding wall mechanics in the normal and the failing heart.

  View details for DOI 10.1152/ajpherat.00813.2004

  View details for PubMedID 15550521

• Simple modification of "T. David-V" valve-sparing aortic root replacement to create graft pseudosinuses ANNALS OF THORACIC SURGERY Demers, P., Miller, D. C. 2004; 78 (4): 1479-1481

  Abstract

  The absence of sinuses of Valsalva is postulated to perturb coronary flow patterns and to create abnormal leaflet stresses, which theoretically may limit the long-term durability of valve-sparing aortic root replacement with the original Tirone David-I reimplantation technique with a cylindrical tube graft. David developed the "T. David-V" procedure in 2001; it creates large billowing Dacron pseudosinuses while retaining the reimplantation concept. To illustrate a simple modification of the T. David-V technique, we describe a patient with Marfan's syndrome who underwent valve-sparing aortic root replacement with 1 large and 1 small graft to create pseudosinuses in the Dacron graft, to facilitate suturing the valve inside the graft, and to make the distal graft-to-aorta anastomosis a better size match.

  View details for DOI 10.1016/j.athoracsur.2003.08.032

  View details for PubMedID 15464530

• Midterm results of endovascular repair of descending thoracic aortic aneurysms with first-generation stent grafts 29th Annual Meeting of the Western-Thoracic-Surgical-Association Demers, P., Miller, D. C., Mitchell, R. S., Kee, S. T., Sze, D., Razavi, M. K., Dake, M. D. MOSBY-ELSEVIER. 2004: 664–73

  Abstract

  Five years after reporting our initial stent-graft repair of descending thoracic aortic aneurysms experience, we determined the 5- to 10-year results of stent-graft treatment and identified risk factors for adverse late outcomes.Between 1992 and 1997, 103 patients (mean age 69 +/- 12 years) underwent repair using first-generation (custom-fabricated) stent grafts. Sixty-two patients (60%) were unsuitable candidates for conventional open surgical repair ("inoperable"). Follow-up was 100% complete (mean 4.5 +/- 2.5 years; maximum 10 years). Outcome variables included death and treatment failure (endoleak, aortic rupture, reintervention, and/or aortic-related or sudden death).Overall actuarial survival was 82% +/- 4%, 49% +/- 5%, and 27% +/- 6% at 1, 5, and 8 years. Survival in open surgical candidates was 93% +/- 4% and 78% +/- 6% and at 1 and 5 years compared with 74% +/- 6% and 31% +/- 6% in those deemed inoperable (P <.001). Independent risk factors for death were older age (hazard ratio = 1.1; P =.008), previous stroke (hazard ratio = 2.8; P =.003), and being designated an inoperable candidate (hazard ratio = 1.9; P =.04). Actuarial freedom from aortic reintervention and treatment failure at 8 years was 70% +/- 6% and 39% +/- 8%, respectively. Earlier operative year (hazard ratio = 1.2; P =.07), larger distal landing zone diameter (hazard ratio = 1.1; P =.001), and transposition of the left subclavian artery (hazard ratio = 3.3; P =.008) were determinants of treatment failure.Survival after aneurysm repair using crude, first-generation stent grafts was satisfactory in good operative candidates but bleak in the inoperable cohort, raising the question of whether asymptomatic patients should have even been treated. Late aortic complications were detected in many patients, reemphasizing the importance of serial imaging surveillance.

  View details for DOI 10.1016/j.jtcvs.2003.10.047

  View details for PubMedID 15001894

• Does septal-lateral annular cinching work for chronic ischemic mitral regurgitation? 29th Annual Meeting of the Western-Thoracic-Surgical-Association Tibayan, F. A., Rodriguez, F., Langer, F., Zasio, M. K., Bailey, L., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. MOSBY-ELSEVIER. 2004: 654–63

  Abstract

  Ring annuloplasty, the current treatment of choice for chronic ischemic mitral regurgitation, abolishes dynamic annular motion and immobilizes the posterior leaflet. In a model of chronic ischemic mitral regurgitation, we tested septal-lateral annular cinching aimed at maintaining normal annular and leaflet dynamics.Twenty-five sheep had radiopaque markers placed on the mitral annulus and anterior and posterior mitral leaflets. A transannular suture was anchored to the midseptal mitral annulus and externalized through the midlateral mitral annulus. After 7 days, biplane cinefluoroscopy provided 3-dimensional marker data (baseline) prior to creating inferior myocardial infarction by snare occlusion of obtuse marginal branches. After 7 weeks, the 9 animals that developed chronic ischemic mitral regurgitation were restudied before and after septal-lateral annular cinching. Anterior and posterior mitral leaflet angular excursion and annular septal-lateral and commissure-commissure dimensions and percent shortening were computed.Septal-lateral annular cinching reduced septal-lateral dimension (baseline: 3.0 +/- 0.2; chronic ischemic mitral regurgitation: 3.5 +/- 0.4 [P <.05 vs baseline by repeated measures analysis of variance and Dunnett's test]; septal-lateral annular cinching: 2.4 +/- 0.3 cm; maximum dimension) and eliminated chronic ischemic mitral regurgitation (baseline: 0.6 +/- 0.5; chronic ischemic mitral regurgitation: 2.3 +/- 1.0 [P <.05 vs baseline by repeated measures analysis of variance and Dunnett's test]; septal-lateral annular cinching: 0.6 +/- 0.6; mitral regurgitation grade [0 to 4+]) but did not alter dynamic annular shortening (baseline: 7 +/- 3; chronic ischemic mitral regurgitation: 10 +/- 5; septal-lateral annular cinching: 6 +/- 2, percent septal-lateral shortening) or posterior mitral leaflet excursion (baseline: 46 degrees +/- 8 degrees; chronic ischemic mitral regurgitation: 41 degrees +/- 13 degrees; septal-lateral annular cinching: 46 degrees +/- 8 degrees ).In this model, septal-lateral annular cinching decreased chronic ischemic mitral regurgitation, reduced annular septal-lateral diameter (but not commissure-commissure diameter), and maintained normal annular and leaflet dynamics. These findings provide additional insight into the treatment of chronic ischemic mitral regurgitation.

  View details for DOI 10.1016/j.jtcvs.2003.09.036

  View details for PubMedID 15001893

• Acute type A aortic dissection complicated by aortic regurgitation: Composite valve graft versus separate valve graft versus conservative valve repair 28th Annual Meeting of the Western-Thoracic-Surgical-Association Lai, D. T., Miller, D. C., Mitchell, R. S., Oyer, P. E., Moore, K. A., Robbins, R. C., Shumway, N. E., Reitz, B. A. MOSBY-ELSEVIER. 2003: 1978–86

  Abstract

  To clarify the merits of various surgical approaches, we studied the outcome after composite valve graft versus separate valve and graft replacement versus conservative valve treatment with replacement of the ascending aorta in patients with acute type A aortic dissection complicated by aortic regurgitation.Between 1967 and 1999, 123 patients (mean age 56 +/- 15 years) underwent composite valve graft replacement (n = 21), separate valve and graft replacement (n = 20), or conservative valve treatment (n = 82 [commissural resuspension in 46]); follow-up averaged 6.5 years (95% complete).The 30-day, 1-year, and 6-year survival estimates of 85% +/- 4%, 79% +/- 5%, and 69% +/- 5% (+/-1 standard error of mean), respectively, after conservative valve treatment were similar to 86% +/- 8%, 81% +/- 9%, and 65% +/- 16%, respectively, with composite valve graft replacement and better (but insignificantly so) than 70% +/- 10%, 70% +/- 10%, and 45% +/- 11%, respectively, with separate valve and graft replacement. The 6-year freedom from proximal reoperation was 95% +/- 3%, 89% +/- 10%, and 100% in conservative valve graft, separate valve and graft, and composite valve graft subgroups, respectively (P = not significant). Cox regression multivariable analysis identified that previous sternotomy (hazard ratio [or e(beta)] 95% confidence interval 1.4-10.9, P =.006), hypertension (0.99-2.9, P =.05), cardiac tamponade (1.1-4.0, P =.03), and stroke (1.7-7.0, P =.001) increased the hazard of death. No factors predicting a higher likelihood of late proximal reoperation were identified.In patients with acute type A aortic dissection and aortic regurgitation, there was no significant difference in overall survival or reoperation rates among these surgical approaches. We try to save the valve whenever possible unless the aortic root is pathologically dilated (eg, Marfan syndrome or annuloaortic ectasia) or destroyed by the dissection process, when composite valve graft or valve-sparing aortic root replacement is indicated.

  View details for DOI 10.1016/S0022-5223(03)01279-0

  View details for PubMedID 14688716

• Images in cardiovascular medicine. Simultaneous "Tirone David-V" valve-sparing aortic root replacement and radical mitral valve repair for the Marfan syndrome with Barlow syndrome. Circulation Demers, P., Liang, D., Miller, D. C. 2003; 108 (16): e116-7

  View details for PubMedID 14568889

• Geometric distortions of the mitral valvular-ventricular complex in chronic ischemic mitral regurgitation. Circulation Tibayan, F. A., Rodriguez, F., Zasio, M. K., Bailey, L., Liang, D., Daughters, G. T., Langer, F., Ingels, N. B., Miller, D. C. 2003; 108: II116-21

  Abstract

  Better understanding of the precise 3-dimensional geometric changes of the mitral valvular-ventricular complex in chronic ischemic mitral regurgitation (CIMR) is needed in order to devise better surgical repair techniques. We hypothesized that changes after inferior myocardial infarction would be different in hearts that developed CIMR compared with those that did not.Twenty-four sheep underwent coronary snare and marker placement (annulus, papillary muscles, and anterior and posterior leaflets). After 8 days, cinefluoroscopy provided 3-dimensional marker data, and snare occlusion of obtuse marginal branches created inferior myocardial infarction, including the posterior papillary muscle. After 7 weeks, the 16 surviving animals were studied again and grouped by mitral regurgitation grade (>or= 2+, n=10 versus

  View details for PubMedID 12970219

• Valve-sparing aortic root replacement in patients with the Marfan syndrome JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Miller, D. C. 2003; 125 (4): 773-778

  View details for DOI 10.1067/mtc.2003.162

  View details for Web of Science ID 000182327700001

  View details for PubMedID 12698136

• Is medical therapy still the optimal treatment strategy for patients with acute type B aortic dissections? 27th Annual Meeting of the Western-Thoracic-Surgical-Association Umana, J. P., Lai, D. T., Mitchell, R. S., Moore, K. A., Rodriguez, F., Robbins, R. C., Oyer, P. E., Dake, M. D., Shumway, N. E., Reitz, B. A., Miller, D. C. MOSBY-ELSEVIER. 2002: 896–910

  Abstract

  The optimal treatment of patients with acute type B dissections continues to be debated.A 36-year clinical experience of medical and surgical treatments in 189 patients was retrospectively analyzed (multivariable Cox proportional hazards model) with respect to three outcome end points: all deaths, freedom from reoperation, and freedom from late aortic complications or death. Propensity score analysis identified 2 quintiles (quintiles I and II, consisting of 142 comparable patients) for further comparison of the effects of surgical versus medical treatment.Shock (hazard ratio 14.5, 95% confidence interval 4.7-44.5, P <.001) and visceral ischemia (hazard ratio 10.9, 95% confidence interval 3.9-30.3, P <.001) largely predominated as determinants of death, along with 6 other risk factors (arch involvement, rupture, stroke, previous sternotomy, and coronary or lung disease), which roughly doubled the hazard of death. Female sex was a significant but weaker predictor of death. Renal dysfunction, year of presentation, age, and mode of therapy (medical vs surgical) had no important bearing on overall survival. The actuarial survival estimates for all patients were 71%, 60%, 35%, and 17% at 1, 5, 10, and 15 years, respectively, and were similar for the medical and surgical patients. Reoperation and late aortic complications were predicted by the presence of Marfan syndrome. For the propensity-matched patients in quintiles I and II, survival, freedom from reoperation, and freedom from aortic complications were almost identical in the medically treated and surgical subsets.The prognosis for patients with acute type B aortic dissection is bleak and determined primarily by dissection-related and patient-specific risk factors, which do not appear to be readily modifiable.

  View details for DOI 10.1067/mtc.2002.123131

  View details for PubMedID 12407372

• Does profound hypothermic circulatory arrest improve survival in patients with acute type a aortic dissection? Circulation Lai, D. T., Robbins, R. C., Mitchell, R. S., Moore, K. A., Oyer, P. E., Shumway, N. E., Reitz, B. A., Miller, D. C. 2002; 106 (12): I218-28

  Abstract

  No evidence exists that profound hypothermic circulatory arrest (PHCA) improves survival or reduces the likelihood of distal aortic reoperation in patients with acute type A aortic dissection.Records of 307 patients with acute type A aortic dissection from 1967 to 1999 were retrospectively reviewed. The influence of repair using PHCA (n=121) versus without PHCA (n=186) on death and freedom from distal aortic reoperation was analyzed using multivariable Cox regression models. Propensity score analysis identified a subset of 152 comparable patients in 3 quintiles (QIII-V) in which the effects of PHCA (n=113) versus no PHCA (n=39) were further compared.For all patients, 30-day, 1-year, and 5-year survival estimates were 81+/-2%, 74+/-3%, and 63+/-3% (+/-1 SE). Survival rates and actual freedom from distal aortic reoperation was not significantly different between treatment methods in the entire patient cohort nor in the matched patients in quintiles III-V. Treatment method was not associated with differences in early major complications, late survival, or distal aortic reoperation rates in the entire patient sample or in quintiles III-V.Aortic repair with or without circulatory arrest was associated with comparable early complications, survival, and distal aortic reoperation rates in patients with acute type A aortic dissection. Despite the lack of concrete evidence favoring the use of PHCA, it does no harm, and most of our group uses PHCA regularly because of its practical technical advantages and theoretical potential merit.

  View details for PubMedID 12354737

• Prognosis of aortic intramural hematoma with and without penetrating atherosclerotic ulcer - A clinical and radiological analysis CIRCULATION Ganaha, F., Miller, C., Sugimoto, K., Do, Y. S., Minamiguchi, H., Saito, H., Mitchell, R. S., Dake, M. D. 2002; 106 (3): 342-348

  Abstract

  Advances in imaging techniques have increased the recognition of aortic intramural hematomas (IMHs) and penetrating atherosclerotic ulcers (PAUs); however, distinction between IMH and PAU remains unclear. We intended to clarify differences between IMH coexisting with PAU and IMH not associated with PAU by comparisons of clinical features, imaging findings, and patient outcome to derive the optimal therapeutic approach.We performed a retrospective analysis of 65 symptomatic patients with aortic IMH. There were 34 patients with IMH associated with PAU (group 1) and 31 patients with IMH unaccompanied by PAU (group 2). Involvement of the ascending aorta (type A) was more frequent in group 2 (8 of 31, 26%), whereas most of the patients in group 1 had exclusive involvement of the descending aorta (type B) (31of 34, 91%). Patients were subdivided into 2 categories, those with clinical progression and those with stable disease. Forty-eight percent of patients in group 1 and 8% in group 2 were in the progressive category (P=0.002). Clinical and radiological findings were compared between those group 1 patients who had a progressive disease course (n=12) and those who were stable (n=13). Sustained or recurrent pain (P<0.0001), increasing pleural effusion (P=0.0003), and both the maximum diameter (P=0.004) and maximum depth (P=0.003) of the PAU were reliable predictors of disease progression.This study suggests a difference in disease behavior that argues for the prognostic importance of making a clear distinction between IMH caused by PAU and IMH not associated with PAU. IMH with PAU was significantly associated with a progressive disease course, whereas IMH without PAU typically had a stable course, especially when limited to the descending thoracic aorta.

  View details for DOI 10.1161/01.CIR.0000022164.26075.5A

  View details for PubMedID 12119251

• Septal-lateral annular cinching abolishes acute ischemic mitral regurgitation JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Timek, T. A., Lai, D. T., Tibayan, F., Liang, D., Daughters, G. T., Dagum, P., Ingels, N. B., Miller, D. C. 2002; 123 (5): 881-888

  Abstract

  Ring annuloplasty prevents acute ischemic mitral regurgitation in sheep, but it also abolishes normal mitral annular and posterior leaflet dynamics. We investigated a novel surgical approach of simple septal-lateral annular cinching with sutures to treat acute ischemic mitral regurgitation.Nine adult sheep underwent implantation of multiple radiopaque markers on the left ventricle, mitral anulus, and mitral leaflets. A septal-lateral transannular suture was anchored to the midseptal mitral anulus and externalized to a tourniquet through the midlateral mitral anulus and left ventricular wall. Open-chest animals were studied immediately postoperatively. Acute ischemic mitral regurgitation was induced by means of proximal left circumflex artery snare occlusion, and 3 progressive steps of septal-lateral annular cinching (each 2-3 mm suture tightening for 5 seconds) were performed with the transannular suture. Biplane videofluoroscopy for 3-dimensional marker coordinates and transesophageal echocardiography were performed continuously before and during left circumflex ischemia and septal-lateral annular cinching.Acute left circumflex ischemia caused ischemic mitral regurgitation (+0.5 +/- 0.4 [baseline] vs +2.0 +/- 0.7 [ischemia]; P =.005; scale, +0-4), which decreased progressively with each step of septal-lateral annular cinching and was eliminated during the third step (ischemic mitral regurgitation, +0.6 +/- 0.5; P = not significant vs baseline). The third step of septal-lateral annular cinching decreased the septal-lateral diameter by 6.0 +/- 2.6 mm (P =.005); however, mitral anulus area reduction (8.5% +/- 1.0% and 6.9% +/- 1.9% for ischemic mitral regurgitation and septal-lateral annular cinching step 3, respectively; P =.006) and posterior leaflet excursion (50 degrees +/- 9 degrees and 44 degrees +/- 11 degrees for regurgitation and annular cinching step 3, respectively; P =.002) throughout the cardiac cycle were affected only mildly. Normal mitral annular 3-dimensional shape was maintained with septal-lateral annular cinching.Isolated 22% +/- 10% reduction in mitral annular septal-lateral dimension abolished acute ischemic mitral regurgitation in normal sheep hearts while allowing near-normal mitral annular and posterior leaflet dynamic motion. Septal-lateral annular cinching may represent a simple method for the surgical treatment of ischemic mitral regurgitation, either as an adjunctive technique or alone, which helps preserve physiologic annular and leaflet function.

  View details for DOI 10.1067/mtc.2002.122296

  View details for PubMedID 12019372

• Torsion dynamics in the evolution from acute to chronic mitral regurgitation 1st Biennial Meeting of the Society-for-Heart-Valve-Disease Tibayan, F. A., Yun, K. L., Lai, D. T., Timek, T. A., Daughters, G. T., Ingels, N. B., Miller, D. C. I C R PUBLISHERS. 2002: 39–46

  Abstract

  Left ventricular (LV) torsion reduces transmural fiber strain gradients during systole, and torsional recoil in early diastole is thought to assist LV filling. To test the hypothesis that deterioration of torsional dynamics accompanied LV dysfunction during the evolution of mitral regurgitation (MR), torsion was measured during the progression from acute to chronic MR in a canine model.Seven dogs underwent cardiopulmonary bypass for LV marker placement and creation of MR by disrupting the posterior leaflet. After 7-10 days, three-dimensional marker coordinates were measured with biplane videofluoroscopy to study LV geometry, size and function, plus maximal torsional deformation, time of maximal torsion relative to end-ejection, and early diastolic torsional recoil during the first 5% of filling. After three months, the animals were re-studied.Progression from acute to chronic MR was associated with a significant decrease in maximum LV dP/dt (1,574+/-213 to 1,300+/-252 mmHg/s, p <0.01) and an increase in LVEDP from 11+/-5 to 15+/-5 mmHg (p <0.01). After three months of MR, maximum torsional deformation decreased from 6.3+/-1.9 to 4.7+/-2.0 degrees (p = 0.04), as did early diastolic recoil (-3.8+/-1.0 to -1.5+/-1.7 degrees, p = 0.03).Progression from acute to chronic MR is accompanied by decreased and delayed systolic LV torsional deformation and a decline in early diastolic recoil, which may contribute to LV dysfunction by increasing transmural strain gradients during systole and impairing diastolic filling. As torsional deformation and recoil can be measured non-invasively with MRI in humans, such measurements might prove useful in patients with progressive MR as an adjunct to determine the timing of surgical repair.

  View details for PubMedID 11858164

• Edge-to-edge mitral repair - Tension on the approximating suture and leaflet deformation during acute ischemic mitral regurgitation in the ovine heart CIRCULATION Nielsen, S. L., Timek, T. A., Lai, D. T., Daughters, G. T., Liang, D., Hasenkam, J. M., Ingels, N. B., Miller, D. C. 2001; 104 (12): I29-I35

  Abstract

  Edge-to-edge approximation of the mitral valve leaflets (Alfieri procedure) is a novel surgical treatment for patients with ischemic mitral regurgitation (IMR). Long-term durability may be limited if abnormal mitral leaflet stresses result from this procedure. The aim of the current study was to measure Alfieri stitch tension (F(A)) and to explore its geometric determinants in an ovine model of acute IMR as a reflection of the mitral leaflet stresses imposed by the procedure.Eight sheep were studied immediately after surgical placement of (1) a force transducer interposed between sutures approximating the central leaflet edges and (2) radiopaque markers around the mitral annulus and leaflet edges. Computer-aided analysis of videofluorograms was used to obtained 3D marker coordinates. Simultaneous measurements of F(A), septal-lateral annular dimension (L(S-L)), leaflet edge separation (L(SEP)), anterior (L(AL)) and posterior (L(PL)) leaflet length, and hemodynamic variables were obtained at baseline (CTL) and during acute IMR (circumflex artery occlusion). F(A) was significantly elevated throughout the cardiac cycle during IMR compared with CTL, with maximum F(A) in diastole (0.26+/-0.05 versus 0.46+/-0.08 N, CTL versus IMR; P<0.05). Multivariable analysis revealed L(S-L) as the single independent predictor of maximum F(A) (P<0.001). Positive linear correlations were shown between values of F(A) and L(AL) and L(PL) (dependent variables).These experimental data demonstrate higher F(A) during IMR and cyclic changes in F(A) closely paralleling changes in L(S-L), eg, being greatest in diastole when the annulus is largest. Increased F(A) during IMR is probably indicative of successful therapeutic intent, but higher diastolic leaflet stresses resulting from persistent or progressive mitral annular dilatation may adversely affect repair durability. This indirectly implies that concomitant mitral ring annuloplasty should be added to the Alfieri repair.

  View details for Web of Science ID 000171201500007

  View details for PubMedID 11568026

• Endovascular stent-graft placement for the treatment of acute aortic dissection NEW ENGLAND JOURNAL OF MEDICINE Dake, M. D., Kato, N., Mitchell, R. S., Semba, C. P., Razavi, M. K., Shimono, T., Hirano, T., Takeda, K., Yada, I., Miller, D. C. 1999; 340 (20): 1546-1552

  Abstract

  The standard treatment for acute aortic dissection is either surgical or medical therapy, depending on the morphologic features of the lesion and any associated complications. Irrespective of the form of treatment, the associated mortality and morbidity are considerable.We studied the placement of endovascular stent-grafts across the primary entry tear for the management of acute aortic dissection originating in the descending thoracic aorta. We evaluated the feasibility, safety, and effectiveness of transluminal stent-graft placement over the entry tear in 4 patients with acute type A aortic dissections (which involve the ascending aorta) and 15 patients with acute type B aortic dissections (which are confined to the descending aorta). Dissections involved aortic branches in 14 of the 19 patients (74 percent), and symptomatic compromise of multiple branch vessels was observed in 7 patients (37 percent). The stent-grafts were made of self-expanding stainless-steel covered with woven polyester or polytetrafluoroethylene material.Placement of endovascular stent-grafts across the primary entry tears was technically successful in all 19 patients. Complete thrombosis of the thoracic aortic false lumen was achieved in 15 patients (79 percent), and partial thrombosis was achieved in 4 (21 percent). Revascularization of ischemic branch vessels, with subsequent relief of corresponding symptoms, occurred in 76 percent of the obstructed branches. Three of the 19 patients died within 30 days, for an early mortality rate of 16 percent (95 percent confidence interval, 0 to 32 percent). There were no deaths and no instances of aneurysm or aortic rupture during the subsequent average follow-up period of 13 months.These initial results suggest that stent-graft coverage of the primary entry tear may be a promising new treatment for selected patients with acute aortic dissection. This technique requires further evaluation, however, to assess its therapeutic potential fully.

  View details for PubMedID 10332016

• Replacement of the aortic root in patients with Marfan's syndrome NEW ENGLAND JOURNAL OF MEDICINE Gott, V. L., Greene, P. S., Alejo, D. E., Cameron, D. E., Naftel, D. C., Miller, D. C., Gillinov, A. M., Laschinger, J. C., Pyeritz, R. E. 1999; 340 (17): 1307-1313

  Abstract

  Replacement of the aortic root with a prosthetic graft and valve in patients with Marfan's syndrome may prevent premature death from rupture of an aneurysm or aortic dissection. We reviewed the results of this surgical procedure at 10 experienced surgical centers.A total of 675 patients with Marfan's syndrome underwent replacement of the aortic root. Survival and morbidity-free survival curves were calculated, and risk factors were determined from a multivariable regression analysis.The 30-day mortality rate was 1.5 percent among the 455 patients who underwent elective repair, 2.6 percent among the 117 patients who underwent urgent repair (within 7 days after a surgical consultation), and 11.7 percent among the 103 patients who underwent emergency repair (within 24 hours after a surgical consultation). Of the 675 patients, 202 (30 percent) had aortic dissection involving the ascending aorta. Forty-six percent of the 158 adult patients with aortic dissection and a documented aortic diameter had an aneurysm with a diameter of 6.5 cm or less. There were 114 late deaths (more than 30 days after surgery); dissection or rupture of the residual aorta (22 patients) and arrhythmia (21 patients) were the principal causes of late death. The risk of death was greatest within the first 60 days after surgery, then rapidly decreased to a constant level by the end of the first year.Elective aortic-root replacement has a low operative mortality. In contrast, emergency repair, usually for acute aortic dissection, is associated with a much higher early mortality. Because nearly half the adult patients with aortic dissection had an aortic-root diameter of 6.5 cm or less at the time of operation, it may be prudent to undertake prophylactic repair of aortic aneurysms in patients with Marfan's syndrome when the diameter of the aorta is well below that size.

  View details for Web of Science ID 000080001700002

  View details for PubMedID 10219065

• The "first generation" of endovascular stent-grafts for patients with aneurysms of the descending thoracic aorta 78th Annual Meeting of the American-Association-for-Thoracic-Surgery Dake, M. D., Miller, D. C., Mitchell, R. S., Semba, C. P., Moore, K. A., Sakai, T. MOSBY-ELSEVIER. 1998: 689–703

  Abstract

  Our goal was to determine whether endovascular stent-grafting is feasible and effective for patients with aneurysms of the descending thoracic aorta.Starting in July 1992, we conducted a prospective, uncontrolled clinical trial in 103 patients (mean age 69 years [range 34-89 years]) who underwent endovascular treatment of aneurysms of the descending thoracic aorta using a custom-fabricated, self-expanding stent-graft device. Follow-up was 100% complete and averaged 22 months. Sixty-two patients (60%) were judged not to be reasonable candidates for a conventional "open" surgical procedure.Complete thrombosis of the aneurysm was ultimately achieved in 86 (83%) patients. The early mortality rate was 9% +/- 3% (+/- 70% CL). Multivariable analysis revealed that myocardial infarction or stroke was linked with a higher likelihood of early death (P = .001). Early serious complications included paraplegia in 3% +/- 2% and stroke in 7% +/- 3%. Actuarial survival estimates at 1 year and 2 years were 81% +/- 4% and 73% +/- 5% (+/- 1 SE), respectively; being judged not to be a surgical candidate portended a higher probability of death (P = .003). According to the intent-to-treat principle, "treatment failure" (including all late sudden unexplained deaths) occurred in 38 patients; 53% +/- 10% of patients were free from treatment failure at 3.7 years. Stent-graft related complications occurred commonly and were linked with several anatomic, technical, and patient-related risk factors.This 5-year clinical trial involving use of a "first generation" device indicates that endovascular stent-grafting of descending thoracic aortic aneurysms is feasible with acceptable medium-term results. More refined, commercially developed devices available today offer less traumatic and more precise stent-graft deployment; these major technical advantages, coupled with important lessons we have learned over time and better patient selection, should be associated with more salutary clinical results in the future.

  View details for PubMedID 9806376

• TRANSLUMINAL PLACEMENT OF ENDOVASCULAR STENT-GRAFTS FOR THE TREATMENT OF DESCENDING THORACIC AORTIC-ANEURYSMS NEW ENGLAND JOURNAL OF MEDICINE Dake, M. D., Miller, D. C., Semba, C. P., Mitchell, R. S., Walker, P. J., Liddell, R. P. 1994; 331 (26): 1729-1734

  Abstract

  The usual treatment for thoracic aortic aneurysms is surgical replacement with a prosthetic graft, but the associated morbidity and mortality are considerable. We studied the use of transluminally placed endovascular stent-graft devices as an alternative to surgical repair.We evaluated the feasibility, safety, and effectiveness of transluminally placed stent-graft to treat descending thoracic aortic aneurysms in 13 patients over a 24-month period. Atherosclerotic, anastomotic, and post-traumatic true or false aneurysms and aortic dissections were treated. The mean diameter of the aneurysms was 6.1 cm (range, 5 to 8). The endovascular stent-grafts were custom-designed for each patient and were constructed of self-expanding stainless-steel stents covered with woven Dacron grafts.Endovascular placement of the stent-graft prosthesis was successful in all patients. There was complete thrombosis of the thoracic aortic aneurysm surrounding the stent-graft in 12 patients, and partial thrombosis in 1. Two patients initially had small, residual patent proximal tracts into the aneurysm sac, but both tracts thrombosed within two months after the procedure. In four patients, two prostheses were required to bridge the aneurysm adequately. There have been no deaths or instances of paraplegia, stroke, distal embolization, or infection during an average follow-up of 11.6 months. One patient with an extensive chronic aortic dissection required open surgical graft replacement four months later because of progressive dilatation of the arch.These preliminary results demonstrate that endovascular stent-graft repair is safe in highly selected patients with descending thoracic aortic aneurysms. This new method of treatment will, however, require careful long-term evaluation.

  View details for PubMedID 7984192

• The continuing dilemma concerning medical versus surgical management of patients with acute type B dissections. Seminars in thoracic and cardiovascular surgery Miller, D. C. 1993; 5 (1): 33-46

  View details for PubMedID 8425001

• Global and regional left ventricular systolic performance in the in situ ejecting canine heart. Importance of the mitral apparatus. Circulation Sarris, G. E., Fann, J. I., Niczyporuk, M. A., Derby, G. C., Handen, C. E., Miller, D. C. 1989; 80 (3): I24-42

  Abstract

  The importance of the intact mitral apparatus in left ventricular (LV) systolic performance has been indirectly suggested by clinical studies of chordal-preserving mitral valve replacement (MVR) or reconstruction. The importance of the intact mitral apparatus has been clearly demonstrated in isovolumic experimental preparations but has not been demonstrated unequivocally in ejecting hearts. Therefore, this question was assessed independently of load in an in situ, open-chest ejecting canine heart preparation (n = 9). Three orthogonal LV dimensions were measured by sonomicrometry. During MVR with complete chordal preservation, snares were placed around the anterior and posterior papillary muscles. After the hearts were weaned from cardiopulmonary bypass, LV function was assessed by caval occlusion to alter LV preload abruptly. The slopes of the end-systolic--pressure-volume (end-systolic elastance, Ees) and stroke-work--end-diastolic volume (preload-recruitable stroke work, PRSW) relations were used to measure global LV systolic function; similarly, the slopes of the end-systolic--pressure-dimension (regional end-systolic elastance, rEes) and stroke-work--end-diastolic dimension changes in regional LV systolic performance. All chordae were then divided by pulling the snares. Immediate reassessment revealed deterioration of global LV function: Ees declined by 72% (14.1 +/- 11.2 mm Hg/ml [mean +/- SD] vs. 3.9 +/- 3.5 mm Hg/ml, p less than 0.001), and PRSW declined by 39% (129 +/- 37 vs. 79 +/- 29 mm Hg, p = 0.0001). Regional LV function was also adversely affected but somewhat selectively: rEes decreased significantly in all three LV dimensions (p less than or equal to 0.03), but rPRSW decreased significantly (-21%) only in the anteroposterior minor LV axis (89 +/- 19 vs. 70 +/- 15 mm Hg, p = 0.005) and in the septal-lateral axis (-19%, p = NS). These data demonstrate the importance of the intact mitral apparatus on LV systolic performance in ejecting hearts, particularly in the LV regions subtended by the papillary muscles.

  View details for PubMedID 2766532

• PHYSIOLOGIC ROLE OF THE MITRAL APPARATUS IN LEFT-VENTRICULAR REGIONAL MECHANICS, CONTRACTION SYNERGY, AND GLOBAL SYSTOLIC PERFORMANCE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Hansen, D. E., Sarris, G. E., Niczyporuk, M. A., Derby, G. C., CAHILL, P. D., Miller, D. C. 1989; 97 (4): 521-533

  Abstract

  In animal models, severing the chordae tendineae of the mitral valve reduces the maximum global left ventricular elastance (Emax,g), a load-independent measure of left ventricular systolic performance; moreover, chamber geometry is altered with systolic bulging in the region of the papillary muscle insertions. This suggests that forces transmitted by the mitral apparatus increase the regional volume elastance (Emax,r) of segments subtending the insertions of the papillary muscles, and these regions contribute substantially to overall left ventricular systolic function (Emax,g). To test this hypothesis, we developed a method to evaluate changes in the magnitude and uniformity of Emax,r as quantitated by the slopes (E'max,i) of regional left ventricular isovolumetric pressure-dimension relations. Such measurements were obtained before and after all chordal attachments of the mitral valve were surgically divided in seven open-chest swine preparations. Significant declines in E'max,i were limited to the region of the posteromedial papillary muscle insertion. Although the mean E'max,i of all ventricular regions (E'max,ave) was unchanged, regional left ventricular elastances were less uniform after the mitral chordae tendineae were severed, which indicated a less synergistic contraction, and Emax,g fell by 21% from 7.1 +/- 2.0 to 5.6 +/- 1.2 mm Hg/ml (p less than 0.05). These data demonstrate that the mitral apparatus contributes importantly to the magnitude and uniformity of regional left ventricular elastances and suggest that such alterations in regional mechanics underlie the deterioration in global left ventricular systolic performance (Emax,g) after excision of the mitral apparatus.

  View details for PubMedID 2927157

• Valvular-ventricular interaction: the importance of the mitral chordae tendineae in terms of global left ventricular systolic function. Journal of cardiac surgery Sarris, G. E., Miller, D. C. 1988; 3 (3): 215-234

  Abstract

  While conventional mitral valve replacement (MVR) for patients with chronic mitral regurgitation has been associated with relatively high operative mortality rates and incidence of late postoperative left ventricular (LV) failure and death, chordal-sparing mitral valve operations (valve repair/reconstruction or MVR with preservation of the chordae tendineae) subjectively appear to portend lower operative morbidity and mortality rates, better functional results, and improved long-term survival rates. Such empirical clinical observations have provided the basis for the concept of valvular-ventricular interaction, namely, that the intact mitral chordae are important mediators of more efficient and forceful ventricular contraction that enhances LV performance. This paper reviews the pertinent basic physiology and dynamics of the chordae tendineae and papillary muscles and examines critically the available experimental and clinical data regarding valvular-ventricular interaction. The problems inherent in quantifying LV contractility are central to this discussion and are also examined. While earlier experimental studies have produced conflicting results, more recent experiments utilizing load-independent measures of ventricular performance (particularly in isovolumic preparations) have conclusively demonstrated the importance of chordal integrity for optimal LV systolic function in normal animal hearts. The balance of the clinical evidence is also suggestive (although by no means conclusive) regarding the importance of valvular-ventricular interaction. Recent experimental evidence suggests that the mitral chordae enhance LV systolic function by means of regional afterload reduction. The mechanism(s) responsible for valvular-ventricular interaction, however, remains incompletely characterized at the present time, which underscores the urgent need for further experimental and, most importantly, clinical studies.

  View details for PubMedID 2980020

• RESTORATION OF LEFT-VENTRICULAR SYSTOLIC PERFORMANCE AFTER REATTACHMENT OF THE MITRAL CHORDAE TENDINEAE - THE IMPORTANCE OF VALVULAR-VENTRICULAR INTERACTION JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Sarris, G. E., CAHILL, P. D., Hansen, D. E., Derby, G. C., Miller, D. C. 1988; 95 (6): 969-979

  Abstract

  Clinical studies suggest that chorda-sparing mitral valve replacement techniques are associated with superior postoperative outcome, and several animal experiments have shown that disruption of the mitral subvalvular apparatus is followed by deterioration of left ventricular systolic function. One essential element, however, underlying the importance of chordal integrity for left ventricular function remains unproved: All investigators heretofore have been unable to demonstrate that left ventricular systolic performance can be restored by chordal reattachment after disruption of annular-papillary continuity. Therefore, we studied the effects of chordal detachment and subsequent chordal reattachment on left ventricular systolic performance using an in situ, isovolumic heart preparation in 10 halothane-anesthetized swine. The slope and left ventricular volume intercept of the isovolumic peak pressure-volume relationship were measured to assess global left ventricular systolic performance independent of load. Coronary perfusion pressure was maintained constant (95 +/- 6 mm Hg [+/- standard deviation]), and heart rates were in the physiologic range (133 +/- 26 min-1). Slope changed significantly (repeated measures analysis of variance, p = 0.0002), decreasing by 29% (from 4.74 +/- 0.94 to 3.37 +/- 0.87 mm Hg/ml, p less than 0.001) after chordal detachment and then returning to baseline (6.05 +/- 2.38 mm Hg/ml, p = 0.001) after chordal reattachment. Slope after chordal reattachment was not significantly different from the baseline value (p = 0.074). Volume intercept did not change significantly (p = 0.44) at any time. We conclude that the acute decrease in left ventricular contractility associated with surgical interruption of annular-ventricular continuity can, in fact, be reversed by chordal reattachment in this experimental model (isovolumically contracting normal porcine hearts). These data provide concrete confirmation of the concept of valvular-ventricular interaction; if these findings can be corroborated in the dilated, human left ventricle, such would strongly support efforts to preserve the mitral chordae tendineae during clinical mitral valve replacement to optimize postoperative left ventricular function.

  View details for PubMedID 3374162

• TORSIONAL DEFORMATION OF THE LEFT-VENTRICULAR MIDWALL IN HUMAN HEARTS WITH INTRAMYOCARDIAL MARKERS - REGIONAL HETEROGENEITY AND SENSITIVITY TO THE INOTROPIC EFFECTS OF ABRUPT RATE CHANGES CIRCULATION RESEARCH Hansen, D. E., Daughters, G. T., Alderman, E. L., Ingels, N. B., Miller, D. C. 1988; 62 (5): 941-952

  Abstract

  The spiral orientation of left ventricular (LV) fibers suggests that twisting about the ventricular long axis of the apex with respect to the base, i.e., torsional deformation, may be characteristic of LV contraction. To demonstrate this twisting motion, 10 orthotopic human cardiac allograft recipients were studied with biplane cineradiography of tantalum helices implanted within the LV midwall at 12 specific sites. Counterclockwise twisting about the LV long axis (as reviewed from apex to base) accompanied ventricular ejection in all patients. Torsional deformation angles, measured relative to a reference minor axis at the base, were substantially smaller in the anteroapical wall, as compared with counterparts in the apical third of the inferior and lateral walls (anterior = 13.3 +/- 6.0 degrees, inferior = 18.7 +/- 6.3 degrees, and lateral = 23.4 +/- 10.7 degrees). Torsional angles at the midventricular level were roughly half as much and exhibited similar regional variabilities (anterior = 7.6 +/- 3.3 degrees, inferior = 9.0 +/- 3.3 degrees, lateral = 10.7 +/- 5.2 degrees, and septal = 8.8 +/- 3.8 degrees). Comparison of control beats and the initial beat after abrupt cessation of rapid atrial pacing (126 +/- 10 beats/min) with return to the control heart rate (96 +/- 9 beats/min) permitted the mild positive inotropic effect of tachycardia to be assessed at similar levels of ventricular load. Torsional deformation of the anteroapical and inferoapical sites increased significantly (p less than 0.05) over control values to 15.6 +/- 7.5 degrees and 21.2 +/- 5.5 degrees, respectively. In contrast, torsional deformation of the lateral wall was essentially unchanged. These data provide direct evidence for torsional deformation of the left ventricle in humans, demonstrate that torsion of the LV chamber is nonuniform, and suggest a dependence of LV torsion upon contractile strength that is attenuated in the lateral wall.

  View details for PubMedID 3282715

• Fate of the unoperated ascending thoracic aortic aneurysm-patient selection and the importance of the denominator. European heart journal Solomon, M. D., Liang, D. H., Miller, D. C. 2023

  View details for DOI 10.1093/eurheartj/ehad794

  View details for PubMedID 38087827

• Registry of Aortic Diseases to Model Adverse Events and Progression (ROADMAP) in Uncomplicated Type B Aortic Dissection: Study Design and Rationale. Radiology. Cardiothoracic imaging Mastrodicasa, D., Willemink, M. J., Turner, V. L., Hinostroza, V., Codari, M., Hanneman, K., Ouzounian, M., Ocazionez Trujillo, D., Afifi, R. O., Hedgire, S., Burris, N. S., Yang, B., Lacomis, J. M., Gleason, T. G., Pacini, D., Folesani, G., Lovato, L., Hinzpeter, R., Alkadhi, H., Stillman, A. E., Chen, E. P., van Kuijk, S. M., Schurink, G. W., Sailer, A. M., Bäumler, K., Miller, D. C., Fischbein, M. P., Fleischmann, D. 2022; 4 (6): e220039

  Abstract

  To describe the design and methodological approach of a multicenter, retrospective study to externally validate a clinical and imaging-based model for predicting the risk of late adverse events in patients with initially uncomplicated type B aortic dissection (uTBAD).The Registry of Aortic Diseases to Model Adverse Events and Progression (ROADMAP) is a collaboration between 10 academic aortic centers in North America and Europe. Two centers have previously developed and internally validated a recently developed risk prediction model. Clinical and imaging data from eight ROADMAP centers will be used for external validation. Patients with uTBAD who survived the initial hospitalization between January 1, 2001, and December 31, 2013, with follow-up until 2020, will be retrospectively identified. Clinical and imaging data from the index hospitalization and all follow-up encounters will be collected at each center and transferred to the coordinating center for analysis. Baseline and follow-up CT scans will be evaluated by cardiovascular imaging experts using a standardized technique.The primary end point is the occurrence of late adverse events, defined as aneurysm formation (≥6 cm), rapid expansion of the aorta (≥1 cm/y), fatal or nonfatal aortic rupture, new refractory pain, uncontrollable hypertension, and organ or limb malperfusion. The previously derived multivariable model will be externally validated by using Cox proportional hazards regression modeling.This study will show whether a recent clinical and imaging-based risk prediction model for patients with uTBAD can be generalized to a larger population, which is an important step toward individualized risk stratification and therapy.Keywords: CT Angiography, Vascular, Aorta, Dissection, Outcomes Analysis, Aortic Dissection, MRI, TEVAR© RSNA, 2022See also the commentary by Rajiah in this issue.

  View details for DOI 10.1148/ryct.220039

  View details for PubMedID 36601455

  View details for PubMedCentralID PMC9806732

• Inter-observer variability of expert-derived morphologic risk predictors in aortic dissection. European radiology Willemink, M. J., Mastrodicasa, D., Madani, M. H., Codari, M., Chepelev, L. L., Mistelbauer, G., Hanneman, K., Ouzounian, M., Ocazionez, D., Afifi, R. O., Lacomis, J. M., Lovato, L., Pacini, D., Folesani, G., Hinzpeter, R., Alkadhi, H., Stillman, A. E., Sailer, A. M., Turner, V. L., Hinostroza, V., Baumler, K., Chin, A. S., Burris, N. S., Miller, D. C., Fischbein, M. P., Fleischmann, D. 2022

  Abstract

  OBJECTIVES: Establishing the reproducibility of expert-derived measurements on CTA exams of aortic dissection is clinically important and paramount for ground-truth determination for machine learning.METHODS: Four independent observers retrospectively evaluated CTA exams of 72 patients with uncomplicated Stanford type B aortic dissection and assessed the reproducibility of a recently proposed combination of four morphologic risk predictors (maximum aortic diameter, false lumen circumferential angle, false lumen outflow, and intercostal arteries). For the first inter-observer variability assessment, 47 CTA scans from one aortic center were evaluated by expert-observer 1 in an unconstrained clinical assessment without a standardized workflow and compared to a composite of three expert-observers (observers 2-4) using a standardized workflow. A second inter-observer variability assessment on 30 out of the 47 CTA scans compared observers 3 and 4 with a constrained, standardized workflow. A third inter-observer variability assessment was done after specialized training and tested between observers 3 and 4 in an external population of 25 CTA scans. Inter-observer agreement was assessed with intraclass correlation coefficients (ICCs) and Bland-Altman plots.RESULTS: Pre-training ICCs of the four morphologic features ranged from 0.04 (-0.05 to 0.13) to 0.68 (0.49-0.81) between observer 1 and observers 2-4 and from 0.50 (0.32-0.69) to 0.89 (0.78-0.95) between observers 3 and 4. ICCs improved after training ranging from 0.69 (0.52-0.87) to 0.97 (0.94-0.99), and Bland-Altman analysis showed decreased bias and limits of agreement.CONCLUSIONS: Manual morphologic feature measurements on CTA images can be optimized resulting in improved inter-observer reliability. This is essential for robust ground-truth determination for machine learning models.KEY POINTS: Clinical fashion manual measurements of aortic CTA imaging features showed poor inter-observer reproducibility. A standardized workflow with standardized training resulted in substantial improvements with excellent inter-observer reproducibility. Robust ground truth labels obtained manually with excellent inter-observer reproducibility are key to develop reliable machine learning models.

  View details for DOI 10.1007/s00330-022-09056-z

  View details for PubMedID 36029344

• CTA pulmonary artery enlargement in patients with severe aortic stenosis: Prognostic impact after TAVR. Journal of cardiovascular computed tomography Turner, V. L., Jubran, A., Kim, J. B., Maret, E., Moneghetti, K. J., Haddad, F., Amsallem, M., Codari, M., Hinostroza, V., Mastrodicasa, D., Sailer, A. M., Kobayashi, Y., Nishi, T., Yeung, A. C., Watkins, A. C., Lee, A. M., Miller, D. C., Fischbein, M. P., Fearon, W. F., Willemink, M. J., Fleischmann, D. 2021

  Abstract

  BACKGROUND: Identifying high-risk patients who will not derive substantial survival benefit from TAVR remains challenging. Pulmonary hypertension is a known predictor of poor outcome in patients undergoing TAVR and correlates strongly with pulmonary artery (PA) enlargement on CTA. We sought to evaluate whether PA enlargement, measured on pre-procedural computed tomography angiography (CTA), is associated with 1-year mortality in patients undergoing TAVR.METHODS: We retrospectively included 402 patients undergoing TAVR between July 2012 and March 2016. Clinical parameters, including Society of Thoracic Surgeons (STS) score and right ventricular systolic pressure (RVSP) estimated by transthoracic echocardiography were reviewed. PA dimensions were measured on pre-procedural CTAs. Association between PA enlargement and 1-year mortality was analyzed. Kaplan-Meier and Cox proportional hazards regression analyses were performed.RESULTS: The median follow-up time was 433 (interquartiles 339-797) days. A total of 56/402 (14%) patients died within 1 year after TAVR. Main PA area (area-MPA) was independently associated with 1-year mortality (hazard ratio per standard deviation equal to 2.04 [95%-confidence interval (CI) 1.48-2.76], p​<​0.001). Area under the curve (95%-CI) of the clinical multivariable model including STS-score and RVSP increased slightly from 0.67 (0.59-0.75) to 0.72 (0.72-0.89), p​=​0.346 by adding area-MPA. Although the AUC increased, differences were not significant (p​=​0.346). Kaplan-Meier analysis showed that mortality was significantly higher in patients with a pre-procedural non-indexed area-MPA of ≥7.40​cm2 compared to patients with a smaller area-MPA (mortality 23% vs. 9%; p​<​0.001).CONCLUSIONS: Enlargement of MPA on pre-procedural CTA is independently associated with 1-year mortality after TAVR.

  View details for DOI 10.1016/j.jcct.2021.03.004

  View details for PubMedID 33795188

• Repair of extra-anatomic bypass graft structural degeneration and pseudoaneurysm with endovascular stent-graft relining. JTCVS techniques Stephens, E. H., Fleischmann, D., Starr, A., Miller, D. C. 2020; 3: 259-262

  View details for DOI 10.1016/j.xjtc.2020.04.030

  View details for PubMedID 34317893

  View details for PubMedCentralID PMC8303061

• Outcome of Flow-Gradient Patterns of Aortic Stenosis After Aortic Valve Replacement: An Analysis of the PARTNER 2 Trial and Registry. Circulation. Cardiovascular interventions Salaun, E., Clavel, M., Hahn, R. T., Jaber, W. A., Asch, F. M., Rodriguez, L., Weissman, N. J., Gertz, Z. M., Herrmann, H. C., Dahou, A., Annabi, M., Toubal, O., Bernier, M., Beaudoin, J., Leipsic, J., Blanke, P., Ridard, C., Ong, G., Rodes-Cabau, J., Webb, J. G., Zhang, Y., Alu, M. C., Douglas, P. S., Makkar, R., Miller, D. C., Lindman, B. R., Thourani, V. H., Leon, M. B., Pibarot, P. 2020; 13 (7): e008792

  Abstract

  BACKGROUND: Although aortic valve replacement is associated with a major benefit in high-gradient (HG) severe aortic stenosis (AS), the results in low-gradient (LG, mean gradient <40 mm Hg) AS are conflicting. LG severe AS may be subdivided in classical low-flow (left ventricular ejection fraction <50%) and LG (CLF-LG); paradoxical low-flow (left ventricular ejection fraction ≥50% but stroke volume index <35 mL/m2) and LG; and normal-flow (left ventricular ejection fraction ≥50% and stroke volume index ≥35 mL/m2) and LG. The primary objective is to determine in the PARTNER 2 trial (The Placement of Aortic Transcatheter Valves) and registry the outcomes after aortic valve replacement of the 4 flow-gradient groups.METHODS: A total of 3511 patients from the PARTNER 2 Cohort A randomized trial (n=1910) and SAPIEN 3 registry (n=1601) were included. The flow-gradient pattern was determined at baseline transthoracic echocardiography and classified as follows: (1) HG; (2) CLF-LG; (3) paradoxical low-flow-LG; and (4) normal-flow-LG. The primary end point for this analysis was the composite of (1) death; (2) rehospitalization for heart failure symptoms and valve prosthesis complication; or (3) stroke.RESULTS: The distribution was HG, 2229 patients (63.5%); CLF-LG, 689 patients (19.6%); paradoxical low-flow-LG, 247 patients (7.0%); and normal-flow-LG, 346 patients (9.9%). The 2-year rate of primary end point was higher in CLF-LG (38.8%) versus HG: 31.8% (P=0.002) and normal-flow-LG: 32.1% (P=0.05) but was not statistically different from paradoxical low-flow-LG: 33.6% (P=0.18). There was no significant difference in the 2-year rates of clinical events between transcatheter aortic valve replacement versus surgical aortic valve replacement in the whole cohort and within each flow-gradient group.CONCLUSIONS: The LG AS pattern was highly prevalent (36.5%) in the PARTNER 2 trial and registry. CLF-LG was the most common pattern of LG AS and was associated with higher rates of death, rehospitalization, or stroke at 2 years compared with the HG group. Clinical outcomes were as good in the LG AS groups with preserved left ventricular ejection fraction compared with the HG group.

  View details for DOI 10.1161/CIRCINTERVENTIONS.119.008792

  View details for PubMedID 32674676

• 2018 AATS/ACC/SCAI/STS Expert Consensus Systems of Care Document: Operator and institutional recommendations and requirements for transcatheter aortic valve replacement JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Bavaria, J. E., Tommaso, C. L., Brindis, R. G., Carroll, J. D., Deeb, G., Feldman, T. E., Gleason, T. G., Horlick, E. M., Kavinsky, C. J., Kumbhani, D. J., Miller, D., Seals, A., Shahian, D. M., Shemin, R. J., Sundt, T. M., Thourani, V. H. 2019; 157 (3): E77–E111

  View details for DOI 10.1016/j.jtcvs.2018.07.001

  View details for Web of Science ID 000458822000005

• Observed to expected 30-day mortality as a benchmark for transcatheter aortic valve replacement Henn, M. C., Zajarias, A., Quader, N., Sintek, M., Lasala, J. M., Koogler, K., Damiano, M. S., Kachroo, P., Miller, D., King, C., Melby, S. J., Moon, M. R., Damiano, R. J., Maniar, H. S. MOSBY-ELSEVIER. 2019: 874-+

  View details for DOI 10.1016/j.jtcvs.2018.06.097

  View details for Web of Science ID 000458822000049

• Impact of Short-Term Complications on Mortality and Quality of Life After TranscatheterAortic Valve Replacement. JACC. Cardiovascular interventions Arnold, S. V., Zhang, Y., Baron, S. J., McAndrew, T. C., Alu, M. C., Kodali, S. K., Kapadia, S., Thourani, V. H., Miller, D. C., Mack, M. J., Leon, M. B., Cohen, D. J. 2019; 12 (4): 362–69

  Abstract

  OBJECTIVES: The aim of this study was to examine the independent association of short-term complications of transcatheter aortic valve replacement (TAVR) with survival and quality of life at 1 year.BACKGROUND: Prior studies have examined the mortality and cost implications of various complications of TAVR. However, many of these complications may primarily affect patients' quality of life after TAVR, which has not been previously studied.METHODS: Among patients at intermediate or high surgical risk who underwent TAVR as part of the PARTNER (Placement of Aortic Transcatheter Valve) 2 studies and survived 30 days, the association between complications within the 30 days after TAVR and mortality and quality of life at 1 year was examined. Quality of life was assessed using the Kansas City Cardiomyopathy Questionnaire and the Short-Form 12. Complications assessed included major and minor stroke, life-threatening and major bleeding, vascular injury, stage 3 acute kidney injury, new pacemaker implantation, and mild and moderate or severe paravalvular leak (PVL). Multivariable models that included all complications as well as baseline clinical factors were used to examine the independent association of each complication with outcomes.RESULTS: Among 3,763 TAVR patients, major stroke and stage 3 acute kidney injury were associated with markedly increased risk for 1-year mortality, with adjusted hazard ratios of 5.4 (95% confidence interval [CI]: 3.1 to 9.5) and 4.9 (95% CI: 2.7 to 8.8), respectively, as well as poorer quality of life among survivors (reductions in 1-year Kansas City Cardiomyopathy Questionnaire overall summary score of 15.1 points [95% CI: 24.8 to 5.3 points] and 14.7 points [95% CI: 25.6 to 3.8 points], respectively). Moderate or severe PVL, life-threatening bleeding, and major bleeding were each associated with a more modest increase in mortality and decrement in quality of life, whereas mild PVL was associated with a small decrease in quality of life. After adjusting for baseline characteristics and other complications, need for a new pacemaker, minor stroke, and vascular injury were not independently associated with poor outcomes.CONCLUSIONS: Among patients undergoing TAVR, similar events are associated with increased mortality and impaired quality of life at 1 year. These results suggest that despite considerable progress, efforts to further reduce stroke, acute kidney injury, bleeding, and moderate or severe PVL are likely to yield important clinical benefits and remain key targets for device iteration and procedural improvement.

  View details for PubMedID 30784641

• 2018 AATS/ACC/SCAI/STS Expert Consensus Systems of Care Document: Operator and Institutional Recommendations and Requirements for Transcatheter Aortic Valve Replacement ANNALS OF THORACIC SURGERY Bavaria, J. E., Tommaso, C. L., Brindis, R. G., Carroll, J. D., Deeb, G., Feldman, T. E., Gleason, T. G., Horlick, E. M., Kavinsky, C. J., Kumbhani, D. J., Miller, D., Seals, A., Shahian, D. M., Shemin, R. J., Sundt, T. M., Thourani, V. H., Amer Assoc Thoracic Surgery, Amer Coll Cardiology, Soc Cardiovasc Angiography Interve, Soc Thoracic Surgeons 2019; 107 (2): 650–84

  View details for DOI 10.1016/j.athoracsur.2018.07.001

  View details for Web of Science ID 000456733600073

  View details for PubMedID 30030976

• Do annuloplasty rings designed to treat ischemic/functional mitral regurgitation alter left-ventricular dimensions in the acutely ischemic ovine heart? The Journal of thoracic and cardiovascular surgery Bothe, W., Escobar Kvitting, J., Rausch, M. K., Timek, T. A., Swanson, J. C., Liang, D. H., Walther, M., Kuhl, E., Ingels, N. B., Miller, D. C. 2019

  Abstract

  OBJECTIVE: To quantify the effects of annuloplasty rings designed to treat ischemic/functional mitral regurgitation on left ventricular septal-lateral (S-L) and commissure-commissure (C-C) dimensions.METHODS: Radiopaque markers were placed as opposing pairs on the S-L and C-C aspects of the mitral annulus and the basal, equatorial, and apical level of the left ventricle (LV) in 30 sheep. Ten true-sized Carpentier-Edwards Physio (PHY), Edwards IMR ETlogix (ETL), and GeoForm (GEO; all from Edwards Lifesciences, Irvine, Calif) annuloplasty rings were inserted in a releasable fashion. After 90seconds of left circumflex artery occlusion with the ring implanted (RING), 4-dimensional marker coordinates were obtained using biplane videofluoroscopy. After ring release, another data set was acquired after another 90seconds of left circumflex artery occlusion (NO RING). S-L and C-C diameters were computed as the distances between the respective marker pairs at end-diastole. Percent change in diameters was calculated between RING versus NO RING as 100*(diameter in centimeters [RING]-diameter in centimeters [NO RING])/diameter in centimeters [NO RING]).RESULTS: Compared with NO RING, all ring types (PHY, ETL, and GEO) reduced mitral annular S-L dimensions by -20.7±5.6%, -26.8±3.9%, and -34.5±3.8%, respectively. GEO reduced the S-L dimensions of the LV at the basal level only by -2.3±2.4%, whereas all other S-L dimensions of the LV remained unchanged with all 3 rings implanted. PHY, ETL, and GEO reduced mitral annular C-C dimensions by -17.5±4.8%, -19.6±2.5, and -8.3±4.9%, respectively, but none of the rings altered the C-C dimensions of the LV.CONCLUSIONS: Despite radical reduction of mitral annular size, disease-specific ischemic/functional mitral regurgitation annuloplasty rings do not induce relevantchanges of left ventricular dimensions in the acutely ischemic ovine heart.

  View details for PubMedID 30803776

• Aortic growth and development of partial false lumen thrombosis are associated with late adverse events in type B aortic dissection. The Journal of thoracic and cardiovascular surgery Higashigaito, K. n., Sailer, A. M., van Kuijk, S. M., Willemink, M. J., Hahn, L. D., Hastie, T. J., Miller, D. C., Fischbein, M. P., Fleischmann, D. n. 2019

  Abstract

  Patients with medically treated type B aortic dissection (TBAD) remain at significant risk for late adverse events (LAEs). We hypothesize that not only initial morphological features, but also their change over time at follow-up are associated with LAEs.Baseline and 188 follow-up computed tomography (CT) scans with a median follow-up time of 4 years (range, 10 days to 12.7 years) of 47 patients with acute uncomplicated TBAD were retrospectively reviewed. Morphological features (n = 8) were quantified at baseline and each follow-up. Medical records were reviewed for LAEs, which were defined according to current guidelines. To assess the effects of changes of morphological features over time, the linear mixed effects models were combined with Cox proportional hazards regression for the time-to-event outcome using a joint modeling approach.LAEs occurred in 21 of 47 patients at a median of 6.6 years (95% confidence interval [CI], 5.1-11.2 years). Among the 8 investigated morphological features, the following 3 features showed strong association with LAEs: increase in partial false lumen thrombosis area (hazard ratio [HR], 1.39; 95% CI, 1.18-1.66 per cm2 increase; P < .001), increase of major aortic diameter (HR, 1.24; 95% CI, 1.13-1.37 per mm increase; P < .001), and increase in the circumferential extent of false lumen (HR, 1.05; 95% CI, 1.01-1.10 per degree increase; P < .001).In medically treated TBAD, increases in aortic diameter, new or increased partial false lumen thrombosis area, and increases of circumferential extent of the false lumen are strongly associated with LAEs.

  View details for DOI 10.1016/j.jtcvs.2019.10.074

  View details for PubMedID 31839226

• Incremental Value of Aortomitral Continuity Calcification for Risk Assessment after Transcatheter Aortic Valve Replacement. Radiology. Cardiothoracic imaging Willemink, M. J., Maret, E. n., Moneghetti, K. J., Kim, J. B., Haddad, F. n., Kobayashi, Y. n., Nishi, T. n., Nieman, K. n., Cauwenberghs, N. n., Kuznetsova, T. n., Higashigaito, K. n., Sailer, A. M., Yeung, A. C., Lee, A. M., Miller, D. C., Fischbein, M. n., Fearon, W. F., Fleischmann, D. n. 2019; 1 (5): e190067

  Abstract

  To investigate the association of aortomitral continuity calcification (AMCC) with all-cause mortality, postprocedural paravalvular leak (PVL), and prolonged hospital stay in patients undergoing transcatheter aortic valve replacement (TAVR).The authors retrospectively evaluated 329 patients who underwent TAVR between March 2013 and March 2016. AMCC, aortic valve calcification (AVC), and coronary artery calcification (CAC) were quantified by using preprocedural CT. Pre-procedural Society of Thoracic Surgeons (STS) score was recorded. Associations between baseline AMCC, AVC, and CAC and 1-year mortality, PVL, and hospital stay longer than 7 days were analyzed.The median follow-up was 415 days (interquartiles, 344-727 days). After 1 year, 46 of the 329 patients (14%) died and 52 (16%) were hospitalized for more than 7 days. Of the 326 patients who underwent postprocedural echocardiography, 147 (45%) had postprocedural PVL. The CAC score (hazard ratio: 1.11 per 500 points) and AMCC mass (hazard ratio: 1.13 per 500 mg) were associated with 1-year mortality. AVC mass (odds ratio: 1.93 per 100 mg) was associated with postprocedural PVL. Only the STS score was associated with prolonged hospital stay (odds ratio: 1.19 per point).AMCC is associated with mortality within 1 year after TAVR and substantially improves individual risk classification when added to a model consisting of STS score and AVC mass only.Supplemental material is available for this article.© RSNA, 2019See also the commentary by Brown and Leipsic in this issue.

  View details for DOI 10.1148/ryct.2019190067

  View details for PubMedID 33778530

  View details for PubMedCentralID PMC7977784

• Stroke After Surgical Versus Transfemoral Transcatheter Aortic Valve Replacement in the PARTNER Trial. Journal of the American College of Cardiology Kapadia, S. R., Huded, C. P., Kodali, S. K., Svensson, L. G., Tuzcu, E. M., Baron, S. J., Cohen, D. J., Miller, D. C., Thourani, V. H., Herrmann, H. C., Mack, M. J., Szerlip, M., Makkar, R. R., Webb, J. G., Smith, C. R., Rajeswaran, J., Blackstone, E. H., Leon, M. B., PARTNER Trial Investigators 2018; 72 (20): 2415–26

  Abstract

  BACKGROUND: Transfemoral-transcatheter aortic valve replacement (TF-TAVR) is increasingly used to treat aortic stenosis, but risk of post-procedure stroke is uncertain.OBJECTIVES: The purpose of this study was to assess stroke risk and its association with quality of life after surgical aortic valve replacement (SAVR) versus TF-TAVR.METHODS: The authors performed a propensity-matched study of 1,204 pairs of patients with severe aortic stenosis treated with SAVR versus TF-TAVR in the PARTNER (Placement of AoRTic TraNscathetER Valves) trials from April 2007 to October 2014. Outcomes were: 1) 30-day neurological events; 2) time-varying risk of neurological events early (≤7days) and late (7days to 48months) post-procedure; and 3) association between stroke and quality of life 1 year post-procedure by the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score.RESULTS: Thirty-day stroke (5.1% vs. 3.7%; p=0.09) was similar, but 30-day major stroke (3.9% vs. 2.2%; p=0.018) was lower after TF-TAVR than SAVR. In both groups, risk of stroke peaked in the first post-procedure day, followed by a near-constant low-level risk to 48months. Major stroke was associated with a decline in quality of life at 1 year in both SAVR (KCCQ score median [15th, 85th percentile]: 79 [53, 94] without major stroke vs. 64 [30, 94] with major stroke; p=0.03) and TF-TAVR (78 [49, 96] without major stroke vs. 60 [8, 99] with major stroke; p=0.04).CONCLUSIONS: Despite similar early-peaking (<1 day post-procedure) neurological risk profiles, SAVR is associated with a higher risk of early major stroke than TF-TAVR. Periprocedural strategies are needed to reduce stroke riskafter aortic valve procedures. (Placement of AoRTic TraNscathetER Valve Trial [PARTNER]; NCT00530894).

  View details for PubMedID 30442284

• Stroke After Surgical Versus Transfemoral Transcatheter Aortic Valve Replacement in the PARTNER Trial JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Kapadia, S. R., Huded, C. P., Kodali, S. K., Svensson, L. G., Tuzcu, E., Baron, S. J., Cohen, D. J., Miller, D., Thourani, V. H., Herrmann, H. C., Mack, M. J., Szerlip, M., Makkar, R. R., Webb, J. G., Smith, C. R., Rajeswaran, J., Blackstone, E. H., Leon, M. B., PARTNER Trial Investigators 2018; 72 (20): 2415–26

  View details for DOI 10.1016/j.jacc.2018.08.2172

  View details for Web of Science ID 000450290400001

• Cytokines profile of reverse cardiac remodeling following transcatheter aortic valve replacement INTERNATIONAL JOURNAL OF CARDIOLOGY Kim, J., Kobayashi, Y., Kuznetsova, T., Moneghetti, K. J., Brenner, D. A., O'Malley, R., Dao, C., Wu, J. C., Fischbein, M., Miller, D., Yeung, A. C., Liang, D., Haddad, F., Fearon, W. F. 2018; 270: 83–88

  View details for DOI 10.1016/j.ijcard.2018.05.020

  View details for Web of Science ID 000444609000021

• Outcomes of Transcatheter Aortic Valve Replacement compared to Surgical Aortic Valve Replacement in patients with prior Chest Radiation Chacko, Y., Zhang, X., Jaluba, K., Lee, A., Miller, D., Yeung, A. C., Kim, B., Fearon, W. ELSEVIER SCIENCE INC. 2018: B244–B245

  View details for DOI 10.1016/j.jacc.2018.08.1809

  View details for Web of Science ID 000455137100602

• Outcomes in 937 Intermediate-Risk Patients Undergoing Surgical Aortic Valve Replacement in PARTNER-2A ANNALS OF THORACIC SURGERY Thourani, V. H., Forcillo, J., Szeto, W. Y., Kodali, S. K., Blackstone, E. H., Lowry, A. M., Semple, M., Rajeswaran, J., Makkar, R. R., Williams, M. R., Bavaria, J. E., Herrmann, H. C., Maniar, H. S., Babaliaros, V. C., Smith, C. R., Trento, A., Corso, P. J., Pichard, A. D., Miller, D., Svensson, L. G., Kapadia, S., Ailawadi, G., Suri, R. M., Greason, K. L., Hahn, R. T., Jaber, W. A., Alu, M. C., Leon, M. B., Mack, M. J., PARTNER Trial Investigators 2018; 105 (5): 1322–29

  Abstract

  The Placement of Aortic Transcatheter Valves 2A (PARTNER-2A) randomized trial compared outcomes of transfemoral transcatheter and surgical aortic valve replacement (SAVR) in intermediate-risk patients with severe aortic stenosis. The purpose of the present study was to perform an in-depth analysis of outcomes after SAVR in the PARTNER-2A trial.From January 2012 to January 2014, 937 patients underwent SAVR at 57 centers. Mean age was 82 ± 6.7 years and 55% were men. Less-invasive operations were performed in 140 patients (15%) and concomitant procedures in 198 patients (21%). Major outcomes and echocardiograms were adjudicated by an independent events committee. Follow-up was 94% complete to 2 years.Operative mortality was 4.1% (n = 38, Society of Thoracic Surgeons predicted risk of mortality: 5.2% ± 2.3%), observed to expected ratio (O/E) was 0.8, and in-hospital stroke was 5.4% (n = 51), twice expected. Aortic clamp and bypass times were 75 ± 30 minutes and 104 ± 46 minutes, respectively. Patients having severe prosthesis-patient mismatch (n = 260, 33%) had similar survival to patients without (p > 0.9), as did patients undergoing less-invasive SAVR (p = 0.3). Risk factors for death included cachexia (p = 0.004), tricuspid regurgitation (p = 0.01), coronary artery disease (p = 0.02), preoperative atrial fibrillation (p = 0.001), higher white blood cell count (p < 0.0001), and lower hemoglobin (p = 0.0002).In this adjudicated prospective study, SAVR in intermediate-risk patients had excellent results at 2 years. However, there were more in-hospital strokes than expected, most likely attributable to mandatory neurologic assessment after the procedure. No pronounced structural valve deterioration was found during 2-year follow-up. Continued long-term surveillance remains important.

  View details for PubMedID 29253463

• IMPACT OF AORTIC ROOT REPAIR ON QUALITY OF LIFE IN PATIENTS WITH MARFAN SYNDROME: COMPARISON OF VALVE-SPARING VERSUS VALVE-REPLACEMENT PROCEDURES Helder, M., Schaff, H., Lahr, B., Miller, D., Connolly, H. ELSEVIER SCIENCE INC. 2018: 563

  View details for DOI 10.1016/S0735-1097(18)31104-5

  View details for Web of Science ID 000429659701413

• PREDICTING MORTALITY WITH AORTOMITRAL CALCIFICATIONS IN 317 TAVR PATIENTS Willemink, M., Maret, E., Moneghetti, K., Kim, J., Haddad, F., Kobayashi, Y., Higashigaito, K., Yeung, A., Lee, A., Miller, D., Fischbein, M., Fearon, W., Fleischmann, D. ELSEVIER SCIENCE INC. 2018: 1591

  View details for DOI 10.1016/S0735-1097(18)32132-6

  View details for Web of Science ID 000429659703241

• Transapical Transcatheter Aortic Valve Replacement Is Associated With Increased Cardiac Mortality in Patients With Left Ventricular Dysfunction Insights From the PARTNER I Trial JACC-CARDIOVASCULAR INTERVENTIONS Elmariah, S., Fearon, W. F., Inglessis, I., Vlahakes, G. J., Lindman, B. R., Alu, M. C., Crowley, A., Kodali, S., Leon, M. B., Svensson, L., Pibarot, P., Hahn, R. T., Thourani, V. H., Palacios, I. F., Miller, D., Douglas, P. S., Passeri, J. J., PARTNER Trial Investigators, PARTNER Publications Off 2017; 10 (23): 2414–22

  Abstract

  The authors sought to evaluate the impact of transapical (TA) transcatheter aortic valve replacement (TAVR) on mortality, left ventricular (LV) ejection fraction (LVEF) improvement, and functional recovery in patients with LV dysfunction.LV injury inherent to TA access for structural heart disease interventions may be particularly detrimental to the LV, functional recovery, and survival in patients with LV dysfunction.The study included patients enrolled within the PARTNER I (Placement of Aortic Transcatheter Valves) trial that underwent transfemoral (TF) or TA TAVR. Analyses of clinical outcomes were stratified by the presence of baseline LV dysfunction (LVEF<50%) and adjusted for the propensity of receiving TA TAVR.Of 2,084 subjects, 1,057 underwent TA TAVR. TA access was associated with increased 2-year all-cause mortality in those with (adjusted hazard ratio [HRadjusted]: 1.52; 95% confidence interval [CI]: 1.12 to 2.07; p = 0.008) and without (HRadjusted: 1.38; 95% CI: 1.10 to 1.74; p = 0.006) LV dysfunction. TA TAVR portended increased 2-year cardiac mortality in subjects with LVEF<50% (HRadjusted: 1.92; 95% CI: 1.21 to 3.05; p = 0.006), but not with LVEF≥50% (HRadjusted: 1.29; 95% CI: 0.87 to 1.90; p = 0.21). In those with LVEF<50%, greater improvements in LVEF (TF-TA difference +4.04%, 95% CI: 2.39% to 5.69%; p < 0.0001) and 6-min walk distance (TF-TA difference +45.1 m, 95% CI: 18.4 to 71.9 m; p = 0.001) occurred within 30 days after TF versus TA TAVR.Compared with TF TAVR, TA TAVR is associated with a disproportionate risk of cardiac mortality in patients with LV dysfunction and with delayed and less robust improvement in LV function and overall functional status. Caution is warranted when considering TA access for structural heart disease interventions, particularly in patients with LV dysfunction. (Placement of Aortic Transcatheter Valves [PARTNER]; NCT00530894).

  View details for PubMedID 29217004

• Staging classification of aortic stenosis based on the extent of cardiac damage EUROPEAN HEART JOURNAL Genereux, P., Pibarot, P., Redfors, B., Mack, M. J., Makkar, R. R., Jaber, W. A., Svensson, L. G., Kapadia, S., Tuzcu, E., Thourani, V. H., Babaliaros, V., Herrmann, H. C., Szeto, W. Y., Cohen, D. J., Lindman, B. R., McAndrew, T., Alu, M. C., Douglas, P. S., Hahn, R. T., Kodali, S. K., Smith, C. R., Miller, D., Webb, J. G., Leon, M. B. 2017; 38 (45): 3351-+

  Abstract

  In patients with aortic stenosis (AS), risk stratification for aortic valve replacement (AVR) relies mainly on valve-related factors, symptoms and co-morbidities. We sought to evaluate the prognostic impact of a newly-defined staging classification characterizing the extent of extravalvular (extra-aortic valve) cardiac damage among patients with severe AS undergoing AVR.Patients with severe AS from the PARTNER 2 trials were pooled and classified according to the presence or absence of cardiac damage as detected by echocardiography prior to AVR: no extravalvular cardiac damage (Stage 0), left ventricular damage (Stage 1), left atrial or mitral valve damage (Stage 2), pulmonary vasculature or tricuspid valve damage (Stage 3), or right ventricular damage (Stage 4). One-year outcomes were compared using Kaplan-Meier techniques and multivariable Cox proportional hazards models were used to identify 1-year predictors of mortality. In 1661 patients with sufficient echocardiographic data to allow staging, 47 (2.8%) patients were classified as Stage 0, 212 (12.8%) as Stage 1, 844 (50.8%) as Stage 2, 413 (24.9%) as Stage 3, and 145 (8.7%) as Stage 4. One-year mortality was 4.4% in Stage 0, 9.2% in Stage 1, 14.4% in Stage 2, 21.3% in Stage 3, and 24.5% in Stage 4 (Ptrend < 0.0001). The extent of cardiac damage was independently associated with increased mortality after AVR (HR 1.46 per each increment in stage, 95% confidence interval 1.27-1.67, P < 0.0001).This newly described staging classification objectively characterizes the extent of cardiac damage associated with AS and has important prognostic implications for clinical outcomes after AVR.

  View details for PubMedID 29020232

• Neurologic Events in Patients Treated with Surgical Versus Transfemoral Transcatheter Aortic Valve Replacement: Insights from the PARTNER (Placement of Aortic Transcatheter Valves) Trial Kapadia, S., Huded, C., Kodali, S., Svensson, L., Tuzcu, E., Miller, D., Thourani, V., Herrmann, H., Mack, M., Szerlip, M., Makkar, R., Webb, J., Smith, C., Rajeswaran, J., Blackstone, E. H., Leon, M. ELSEVIER SCIENCE INC. 2017: B143

  View details for Web of Science ID 000413459200346

• Impact of Peri-procedural Complications on Mortality and Quality of Life after TAVR Arnold, S., Zhang, Y., Baron, S., McAndrew, T., Alu, M., Kodali, S., Kapadia, S., Thourani, V., Miller, D., Mack, M., Leon, M., Cohen, D. ELSEVIER SCIENCE INC. 2017: B109–B110

  View details for Web of Science ID 000413459200265

• Impact of Discordant Views in the Management of Descending Thoracic Aortic Aneurysm SEMINARS IN THORACIC AND CARDIOVASCULAR SURGERY Chiu, P., Sailer, A., Baiocchi, M., Goldstone, A. B., Schaffer, J. M., Trojan, J., Fleischmann, D., Mitchell, R., Miller, D., Dake, M. D., Woo, Y., Lee, J. T., Fischbein, M. P. 2017; 29 (3): 283–91

  Abstract

  Thoracic endovascular aortic repair has a lower perceived risk than open surgical repair and has become an increasingly popular alternative. Whether general consensus exists regarding candidacy for either operation among open and endovascular specialists is unknown. A retrospective review of isolated descending thoracic aortic aneurysm at our institution between January 2005 and October 2015 was performed, excluding trauma and dissection. Two cardiac surgeons, 2 cardiovascular surgeons, 1 vascular surgeon, and 1 interventional radiologist gave their preference for open vs endovascular repair. Interobserver agreement was assessed with the kappa coefficient. k-means clustering agnostically grouped various patterns of agreement. The mean rating was predicted using least absolute shrinkage and selection operator regression. Negative binomial regression predicted the discrepancy between our panel of raters and the historical operation. Generalized estimating equation modeling was then used to evaluate the association between the extent of discrepancy and the adverse perioperative outcome. There were 77 patients with preoperative imaging studies. Pairwise interobserver agreement was only fair (median weighted kappa 0.270 [interquartile range 0.211-0.404]). Increasing age and proximal neck length predicted an increasing preference for thoracic endovascular aortic repair in our panel; larger proximal neck diameter predicted a general preference for open surgical repair. Increasing proximal neck diameter predicted a larger discrepancy between our panel and the historical operation. Greater discrepancy was associated with adverse outcome. Substantial disagreement existed among our panel, and an exploratory analysis of the effect of increasing discrepancy demonstrated an association with adverse perioperative outcome. An investigation of the effect of a thoracic aortic team with open and endovascular specialists is warranted.

  View details for PubMedID 29195571

• Dynamic changes in aortic impedance after transcatheter aortic valve replacement and its impact on exploratory outcome. international journal of cardiovascular imaging Kobayashi, Y., Kim, J. B., Moneghetti, K. J., Kobayashi, Y., Zhang, R., Brenner, D. A., O'Malley, R., Schnittger, I., Fischbein, M., Miller, D. C., Yeung, A. C., Liang, D., Haddad, F., Fearon, W. F. 2017

  Abstract

  Valvulo-arterial impedance (Zva) has been shown to predict worse outcome in medically managed aortic stenosis (AS) patients. We aimed to investigate the association between Zva and left ventricular (LV) adaptation and to explore the predictive value of Zva for cardiac functional recovery and outcome after transcatheter aortic valve replacement (TAVR). We prospectively enrolled 128 patients with AS who underwent TAVR. Zva was calculated as: (systolic blood pressure + mean transaortic gradient)/stroke volume index). Echocardiographic assessment occurred at baseline, 1-month and 1-year after TAVR. The primary endpoints were to investigate associations between Zva and global longitudinal strain (GLS) at baseline as well as GLS change after TAVR. The secondary was to compare all-cause mortality after TAVR between patients with pre-defined Zva (=5 mmHg m(2)/ml), stroke volume index (=35 ml/m(2)), and GLS (=-15%) cutoffs. The mean GLS was reduced (-13.0 ± 3.2%). The mean Zva was 5.2 ± 1.6 mmHg*m(2)/ml with 55% of values ≥5.0 mmHg*m(2)/ml, considered to be abnormally high. Higher Zva correlated with worse GLS (r = -0.33, p < 0.001). After TAVR, Zva decreased significantly (5.1 ± 1.6 vs. 4.5 ± 1.6 mmHg*m(2)/ml, p = 0.001). A reduction of Zva at 1-month was associated with GLS improvement at 1-month (r = -0.31, p = 0.001) and at 1-year (r = -0.36 and p = 0.001). By Kaplan-Meier analysis, patients with higher Zva at baseline had higher mortality (Log-rank p = 0.046), while stroke volume index and GLS did not differentiate outcome (Log-rank p = 0.09 and 0.25, respectively). As a conclusion, Zva is correlated with GLS in AS as well as GLS improvement after TAVR. Furthermore, a high baseline Zva may have an additional impact to traditional parameters on predicting worse mortality after TAVR.

  View details for DOI 10.1007/s10554-017-1155-6

  View details for PubMedID 28516313

• Transcatheter Aortic Valve Implantation Within Degenerated Aortic Surgical Bioprostheses PARTNER 2 Valve-in-Valve Registry JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Webb, J. G., Mack, M. J., White, J. M., Dvir, D., Blanke, P., Herrmann, H. C., Leipsic, J., Kodali, S. K., Makkar, R., Miller, D. C., Pibarot, P., Pichard, A., Satler, L. F., Svensson, L., Alu, M. C., Suri, R. M., Leon, M. B. 2017; 69 (18): 2253-2262

  Abstract

  Early experience with transcatheter aortic valve replacement (TAVR) within failed bioprosthetic surgical aortic valves has shown that valve-in-valve (VIV) TAVR is a feasible therapeutic option with acceptable acute procedural results.The authors examined 30-day and 1-year outcomes in a large cohort of high-risk patients undergoing VIV TAVR.Patients with symptomatic degeneration of surgical aortic bioprostheses at high risk (≥50% major morbidity or mortality) for reoperative surgery were prospectively enrolled in the multicenter PARTNER (Placement of Aortic Transcatheter Valves) 2 VIV trial and continued access registries.Valve-in-valve procedures were performed in 365 patients (96 initial registry, 269 continued access patients). Mean age was 78.9 ± 10.2 years, and mean Society of Thoracic Surgeons score was 9.1 ± 4.7%. At 30 days, all-cause mortality was 2.7%, stroke was 2.7%, major vascular complication was 4.1%, conversion to surgery was 0.6%, coronary occlusion was 0.8%, and new pacemaker insertion was 1.9%. One-year all-cause mortality was 12.4%. Mortality fell from the initial registry to the subsequent continued access registry, both at 30 days (8.2% vs. 0.7%, respectively; p = 0.0001) and at 1 year (19.7% vs. 9.8%, respectively; p = 0.006). At 1 year, mean gradient was 17.6 mm Hg, and effective orifice area was 1.16 cm(2), with greater than mild paravalvular regurgitation of 1.9%. Left ventricular ejection fraction increased (50.6% to 54.2%), and mass index decreased (135.7 to 117.6 g/m(2)), with reductions in both mitral (34.9% vs. 12.7%) and tricuspid (31.8% vs. 21.2%) moderate or severe regurgitation (all p < 0.0001). Kansas City Cardiomyopathy Questionnaire score increased (mean: 43.1 to 77.0) and 6-min walk test distance results increased (mean: 163.6 to 252.3 m; both p < 0.0001).In high-risk patients, TAVR for bioprosthetic aortic valve failure is associated with relatively low mortality and complication rates, improved hemodynamics, and excellent functional and quality-of-life outcomes at 1 year. (The PARTNER II Trial: Placement of AoRTic TraNscathetER Valves [PARTNER II]; NCT01314313).

  View details for DOI 10.1016/j.jacc.2017.02.057

  View details for PubMedID 28473128

• Computed Tomography Imaging Features in Acute Uncomplicated Stanford Type-B Aortic Dissection Predict Late Adverse Events CIRCULATION-CARDIOVASCULAR IMAGING Sailer, A. M., Van Kuijk, S. M., Nelemans, P. J., Chin, A. S., Kino, A., Huininga, M., Schmidt, J., Mistelbauer, G., Baeumler, K., Chiu, P., Fischbein, M. P., Dake, M. D., Miller, D. C., Schurink, G. W., Fleischmann, D. 2017; 10 (4)

  Abstract

  Medical treatment of initially uncomplicated acute Stanford type-B aortic dissection is associated with a high rate of late adverse events. Identification of individuals who potentially benefit from preventive endografting is highly desirable.The association of computed tomography imaging features with late adverse events was retrospectively assessed in 83 patients with acute uncomplicated Stanford type-B aortic dissection, followed over a median of 850 (interquartile range 247-1824) days. Adverse events were defined as fatal or nonfatal aortic rupture, rapid aortic growth (>10 mm/y), aneurysm formation (≥6 cm), organ or limb ischemia, or new uncontrollable hypertension or pain. Five significant predictors were identified using multivariable Cox regression analysis: connective tissue disease (hazard ratio [HR] 2.94, 95% confidence interval [CI]: 1.29-6.72; P=0.01), circumferential extent of false lumen in angular degrees (HR 1.03 per degree, 95% CI: 1.01-1.04, P=0.003), maximum aortic diameter (HR 1.10 per mm, 95% CI: 1.02-1.18, P=0.015), false lumen outflow (HR 0.999 per mL/min, 95% CI: 0.998-1.000; P=0.055), and number of intercostal arteries (HR 0.89 per n, 95% CI: 0.80-0.98; P=0.024). A prediction model was constructed to calculate patient specific risk at 1, 2, and 5 years and to stratify patients into high-, intermediate-, and low-risk groups. The model was internally validated by bootstrapping and showed good discriminatory ability with an optimism-corrected C statistic of 70.1%.Computed tomography imaging-based morphological features combined into a prediction model may be able to identify patients at high risk for late adverse events after an initially uncomplicated type-B aortic dissection.

  View details for DOI 10.1161/CIRCIMAGING.116.005709

  View details for PubMedID 28360261

• THE INFLAMMASOME PATHWAY IS ASSOCIATED WITH ADVERSE VENTRICULAR REMODELING FOLLOWING TRANSCATHETER AORTIC VALVE REPLACEMENT Kim, J., Kobayashi, Y., Kouznetsova, T., Moneghetti, K., Brenner, D., O'Malley, R., Dao, C., Schnittger, I., Liang, D., Wu, J., Fischbein, M., Lee, A., Miller, D., Yeung, A., Fearon, W., Haddad, F. ELSEVIER SCIENCE INC. 2017: 1040

  View details for Web of Science ID 000397342301562

• Transcatheter Aortic Valve Replacement for Failed Surgical Bioprostheses: Insights from the PARTNER II Valve-in-Valve Registry on Utilizing Baseline Computed-Tomographic Assessment STRUCTURAL HEART-THE JOURNAL OF THE HEART TEAM Dvir, D., Webb, J. G., Blanke, P., Park, J. K., Mack, M., Pibarot, P., Dewey, T., Herrmann, H. C., Kapadia, S., Kodali, S., Makkar, R., Greason, K., Miller, D., Pichard, A., Satler, L., Smith, C., Suri, R. M., Alu, M., White, J. M., Leon, M. B., Leipsic, J. 2017; 1 (1-2): 34-39

  View details for DOI 10.1080/24748706.2017.1329571

  View details for Web of Science ID 000667257300005

• Prognostic significance of early aortic remodeling in acute uncomplicated type B aortic dissection and intramural hematoma. The Journal of thoracic and cardiovascular surgery Sailer, A. M., Nelemans, P. J., Hastie, T. J., Chin, A. S., Huininga, M. n., Chiu, P. n., Fischbein, M. P., Dake, M. D., Miller, D. C., Schurink, G. W., Fleischmann, D. n. 2017; 154 (4): 1192–1200

  Abstract

  Patients with Stanford type B aortic dissections (ADs) are at risk of long-term disease progression and late complications. The aim of this study was to evaluate the natural course and evolution of acute type B AD and intramural hematomas (IMHs) in patients who presented without complications during their initial hospital admission and who were treated with optimal medical management (MM).Databases from 2 aortic centers in Europe and the United States were used to identify 136 patients with acute type B AD (n = 92) and acute type B IMH (n = 44) who presented without complications during their index admission and were treated with MM. Computed tomography angiography scans were available at onset (≤14 days) and during follow-up for those patients. Relevant data, including evidence of adverse events during follow-up (AE; defined according to current guidelines), were retrieved from medical records and by reviewing computed tomography scan images. Aortic diameters were measured with dedicated 3-dimensional software.The 1-, 2-, and 5-year event-free survival rates of patients with type B AD were 84.3% (95% confidence interval [CI], 74.4-90.6), 75.4% (95% CI, 64.0-83.7), and 62.6% (95% CI, 68.9-73.6), respectively. Corresponding estimates for IMH were 76.5% (95% CI, 57.8-87.8), 76.5% (95% CI, 57.8-87.8), and 68.9% (95% CI, 45.2-83.9), respectively. In patients with type B AD, risk of an AE increased with aortic growth within the first 6 months after onset. A diameter increase of 5 mm in the first half year was associated with a relative risk for AE of 2.29 (95% CI, 1.70-3.09) compared with the median 6 months' growth of 2.4 mm. In approximately 60% of patients with IMH, the abnormality resolved within 12 months and in the patients with nonresolving IMH, risk of an adverse event was greatest in the first year after onset and remained stable thereafter.More than one third of patients with initially uncomplicated type B AD suffer an AE under MM within 5 years of initial diagnosis. In patients with nonresolving IMH, most adverse events are observed in the first year after onset. In patients with type B AD an early aortic growth is associated with a greater risk of AE.

  View details for PubMedID 28668458

• GDF-15 (Growth Differentiation Factor 15) Is Associated With Lack of Ventricular Recovery and Mortality After Transcatheter Aortic Valve Replacement. Circulation. Cardiovascular interventions Kim, J. B., Kobayashi, Y. n., Moneghetti, K. J., Brenner, D. A., O'Malley, R. n., Schnittger, I. n., Wu, J. C., Murtagh, G. n., Beshiri, A. n., Fischbein, M. n., Miller, D. C., Liang, D. n., Yeung, A. C., Haddad, F. n., Fearon, W. F. 2017; 10 (12)

  Abstract

  Recent data suggest that circulating biomarkers may predict outcome in patients undergoing transcatheter aortic valve replacement (TAVR). We examined the association between inflammatory, myocardial, and renal biomarkers and their role in ventricular recovery and outcome after TAVR.A total of 112 subjects undergoing TAVR were included in the prospective registry. Plasma levels of B-type natriuretic peptide, hs-TnI (high-sensitivity troponin I), CRP (C-reactive protein), GDF-15 (growth differentiation factor 15), GAL-3 (galectin-3), and Cys-C (cystatin-C) were assessed before TAVR and in 100 sex-matched healthy controls. Among echocardiographic parameters, we measured global longitudinal strain, indexed left ventricular mass, and indexed left atrial volume. The TAVR group included 59% male, with an average age of 84 years, and 1-year mortality of 18%. Among biomarkers, we found GDF-15 and CRP to be strongly associated with all-cause mortality (P<0.001). Inclusion of GDF-15 and CRP to the Society of Thoracic Surgeons score significantly improved C index (0.65-0.79; P<0.05) and provided a category-free net reclassification improvement of 106% at 2 years (P=0.01). Among survivors, functional recovery in global longitudinal strain (>15% improvement) and indexed left ventricular mass (>20% decrease) at 1 year occurred in 48% and 22%, respectively. On multivariate logistic regression, lower baseline GDF-15 was associated with improved global longitudinal strain at 1 year (hazard ratio=0.29; P<0.001). Furthermore, improvement in global longitudinal strain at 1 month correlated with lower overall mortality (hazard ratio=0.45; P=0.03).Elevated GDF-15 correlates with lack of reverse remodeling and increased mortality after TAVR and improves risk prediction of mortality when added to the Society of Thoracic Surgeons score.

  View details for PubMedID 29222133

• Baseline growth differentiation factor 15 (GDF15) is an independent predictor of reverse left atrial remodeling and mortality at 1-year following Transcatheter Aortic Valve Replacement Kim, J., Kobayashi, Y., Brenner, D., Moneghetti, K., O'Malley, R., Dao, C., Vu, T., Schnittger, I., Liang, D., Wu, J., Fischbein, M., Lee, A., Miller, D., Yeung, A., Haddad, F., Fearon, W. ELSEVIER SCIENCE INC. 2016: B298

  View details for DOI 10.1016/j.jacc.2016.09.150

  View details for Web of Science ID 000398590400257

• Insights Into Timing, Risk Factors, and Outcomes of Stroke and Transient Ischemic Attack After Transcatheter Aortic Valve Replacement in the PARTNER Trial (Placement of Aortic Transcatheter Valves). Circulation. Cardiovascular interventions Kapadia, S., Agarwal, S., Miller, D. C., Webb, J. G., Mack, M., Ellis, S., Herrmann, H. C., Pichard, A. D., Tuzcu, E. M., Svensson, L. G., Smith, C. R., Rajeswaran, J., Ehrlinger, J., Kodali, S., Makkar, R., Thourani, V. H., Blackstone, E. H., Leon, M. B. 2016; 9 (9)

  Abstract

  Prior studies of stroke and transient ischemic attack (TIA) after transcatheter aortic valve replacement (TAVR) are limited by reporting and follow-up variability. This is a comprehensive analysis of time-related incidence, risk factors, and outcomes of these events.From April 2007 to February 2012, 2621 patients, aged 84±7.2 years, underwent transfemoral (TF; 1521) or transapical (TA; 1100) TAVR in the PARTNER trial (Placement of Aortic Transcatheter Valves; as-treated), including the continued access registry. Stroke and TIA were identified by protocol and adjudicated by a Clinical Events Committee. Within 30 days of TAVR, 87 (3.3%) patients experienced a stroke (TF 58 [3.8%]; TA 29 [2.7%]; P=0.09), 85% within 1 week. Instantaneous stroke risk peaked on day 2, then fell to a low prolonged risk of 0.8% by 1 to 2 weeks. Within 30 days, 13 (0.50%) patients experienced a TIA (TF 10 [0.67%]; TA 3 [0.27%]; P>0.17). Stroke and TIA were associated with lower 1-year survival than expected (TF 47% after stroke versus 82%, and 64% after TIA versus 83%; TA 53% after stroke versus 80%, and 64% after TIA versus 83%). Risk factors for early stroke after TA-TAVR included more postdilatations, pure aortic stenosis without regurgitation, and possibly more pacing runs, earlier date of procedure, and no dual antiplatelet therapy; high pre-TAVR aortic peak gradient was a risk factor for stroke early after TF-TAVR.Risk of stroke or TIA is highest early after TAVR and is associated with increased 1-year mortality. Modifications of TAVR, emboli-prevention devices, and better intraprocedural pharmacological protection may mitigate this risk.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894.

  View details for DOI 10.1161/CIRCINTERVENTIONS.115.002981

  View details for PubMedID 27601428

• Evaluation of Flow After Transcatheter Aortic Valve Replacement in Patients With Low-Flow Aortic Stenosis: A Secondary Analysis of the PARTNER Randomized Clinical Trial. JAMA cardiology Anjan, V. Y., Herrmann, H. C., Pibarot, P., Stewart, W. J., Kapadia, S., Tuzcu, E. M., Babaliaros, V., Thourani, V. H., Szeto, W. Y., Bavaria, J. E., Kodali, S., Hahn, R. T., Williams, M., Miller, D. C., Douglas, P. S., Leon, M. B. 2016; 1 (5): 584-592

  Abstract

  Low-flow (LF) severe aortic stenosis (AS) is an independent predictor of mortality in patients undergoing aortic valve replacement (AVR). Little is known about improvement in flow after AVR and its effects on survival.To determine whether higher flow (left-ventricular stroke volume index [LVSVI]) after transcatheter AVR (TAVR) would indicate better clinical outcomes in this at-risk population.A substudy analysis of data from the Placement of Aortic Transcatheter Valves (PARTNER) randomized clinical trial and continued-access registry was conducted. A total of 984 participants with evaluable echocardiograms and baseline LF AS (LVSVI ≤35 mL/m2) were included. The trial was conducted at 26 sites in the United States and Canada. Patients were stratified after TAVR into tertiles by discharge LVSVI status (severe low flow [SLF], moderate low flow [MLF], and normal flow [(NF]). The present study was conducted from May 11, 2007, to January 9, 2012, with data analysis performed from April 25, 2014, to January 21, 2016.The primary end point was all-cause mortality at 1 year.Baseline characteristics of 984 patients with LF AS included mean (SD) age, 84 (7) years; 582 (59.1%) men; mean Society of Thoracic Surgeons (STS) score, 11.4% (4.0%); and mean LVSVI, 27.6 (5.0) mL/m2. The discharge LVSVI values by group were SLF, 23.1 (3.5) mL/m2; MLF, 31.7 (2.2) mL/m2; and NF, 43.1 (7.0). All-cause mortality at 1 year was SLF, 26.5%; MLF, 20.1%; and NF, 19.6% (P = .045). Mean LVSVI normalized by 6 months in the MLF (35.9 [9.3] mL/m2) and NF (38.8 [11.1] mL/m2) groups, but remained low in the SLF group at 6 months and 1 year (31.4 [8.4] and 33.0 [8.3] mL/m2], respectively) (P < .001 for all groups). Reported as multivariate hazard ratio, mortality at 1 year was higher in the SLF group compared with the other groups (1.61; 95% CI, 1.17-2.23; P = .004). In addition to SLF, sex (1.59; 95% CI, 1.18-2.13; P = .002), presence of atrial fibrillation (1.41; 95% CI, 1.06-1.87; P = .02), STS score (1.03; 95% CI, 1.01-1.06; P = .02), presence of moderate or severe mitral regurgitation at discharge (1.65; 95% CI, 1.21-2.26; P = .001), pre-TAVR mean transvalvular gradient (0.98; 95% CI, 0.97-0.99; P = .004), and effective orifice area index (1.87; 95% CI, 1.09-3.19; P = .02) were independent predictors of 1-year mortality.Severe LF at discharge is associated with an increased risk of mortality following TAVR in patients with severe AS and preexisting LF. The identification of remedial causes of persistent LF after TAVR may represent an opportunity to improve the outcome of these patients.clinicaltrials.gov Identifier: NCT00530894.

  View details for DOI 10.1001/jamacardio.2016.0759

  View details for PubMedID 27437665

• Extracellular matrix remodeling in wound healing of critical size defects in the mitral valve leaflet HEART AND VESSELS Stephens, E. H., Nguyen, T. C., Blazejewski, J. G., Vekilov, D. P., Connell, J. P., Itoh, A., Ingels, N. B., Miller, D., Grande-Allen, K. 2016; 31 (7): 1186–95

  Abstract

  The details of valvular leaflet healing following valvuloplasty and leaflet perforation from endocarditis are poorly understood. In this study, the synthesis and turnover of valvular extracellular matrix due to healing of a critical sized wound was investigated. Twenty-nine sheep were randomized to either CTRL (n = 11) or HOLE (n = 18), in which a 2.8-4.8 mm diameter hole was punched in the posterior mitral leaflet. After 12 weeks, posterior leaflets were harvested and histologically stained to localize extracellular matrix components. Immunohistochemistry was also performed to assess matrix components and markers of matrix turnover. A semi-quantitative grading scale was used to quantify differences between HOLE and CTRL. After 12 weeks, the hole diameter was reduced by 71.3 ± 1.4 % (p < 0.001). Areas of remodeling surrounding the hole contained more activated cells, greater expression of proteoglycans, and markers of matrix turnover (prolyl 4-hydroxylase, metalloproteases, and lysyl oxidase, each p ≤ 0.025), along with fibrin accumulation. Two distinct remodeling regions were evident surrounding the hole, one directly bordering the hole rich in versican and hyaluronan and a second adjacent region with abundant collagen and elastic fiber turnover. The remodeling also caused reduced delineation between valve layers (p = 0.002), more diffuse staining of matrix components and markers of matrix turnover (p < 0.001), and disruption of the collagenous fibrosa. In conclusion, acute valve injury elicited distinct, heterogeneous alterations in valvular matrix composition and structure, resulting in partial wound closure. Because these changes could also affect leaflet mechanics and valve function, it will be important to determine their impact on healing wounds.

  View details for PubMedID 26563105

• Salvage Extracorporeal Membrane Oxygenation Prior to "Bridge" Transcatheter Aortic Valve Replacement. Journal of cardiac surgery Chiu, P., Fearon, W. F., Raleigh, L. A., Burdon, G., Rao, V., Boyd, J. H., Yeung, A. C., Miller, D. C., Fischbein, M. P. 2016; 31 (6): 403-405

  Abstract

  We describe a patient who presented in profound cardiogenic shock due to bioprosthetic aortic valve stenosis requiring salvage Extracorporeal Membrane Oxygenation followed by a "bridge" valve-in-valve transcatheter aortic valve replacement. doi: 10.1111/jocs.12750 (J Card Surg 2016;31:403-405).

  View details for DOI 10.1111/jocs.12750

  View details for PubMedID 27109017

• The Outcomes of Transcatheter Aortic Valve Replacement in a Cohort of Patients with End-Stage Renal Disease CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Szerlip, M., Kim, R. J., Adeniyi, T., Thourani, V., Babaliaros, V., Bavaria, J., Herrmann, H. C., Anwaruddin, S., Makkar, R., Chakravarty, T., Rovin, J., Creighton, D., Miller, D., Baio, K., Walsh, E., Katinic, J., Letterer, R., Trautman, L., Herbert, M., Farkas, R., Rudolph, J., Brown, D., Holper, E. M., Mack, M. 2016; 87 (7): 1314–21

  Abstract

  To examine whether transcatheter aortic valve replacement (TAVR) is a safe and effective treatment option for aortic stenosis in patients with end-stage renal disease (ESRD).Patients with ESRD undergoing surgical aortic valve replacement have an operative mortality approaching 20% and a 10-year survival of approximately 12%. We investigated whether TAVR is a more reasonable option.This is a multicenter, retrospective study of all patients with ESRD who underwent TAVR in 8 institutions between 12/2011 and 02/2013. Demographic characteristics, mortality, major, and minor complications were evaluated. Outcomes were stratified by operative approach.Forty-three patients with a mean age 76.2 ± 11.0 years and a mean STS predicted risk of mortality of 15.53 ± 8.70% underwent TAVR. Mean duration of dialysis was 45.2 ± 52.3 months (median 29.5 months). Transfemoral (TF) TAVR was performed in 31/43 (72.1%), transapical in 11/43 (25.6%), and transaortic in 1/43 (2.3%). Operative mortality was 14.0% (6/43) with TF mortality 6.5% (2/31) and 33.3% (4/12) in non-TF patients. Six-month mortality was 11/43 (25.6%: 16.1% TF, 50.0% non-TF). Complications included stroke in 2.3% (1/43) and life-threatening or major bleeding in 14.0% (6/43). Discharge to another healthcare facility was 27.0% (10/37). Readmission within 30 days of procedure for any cause was 18.9% (7/37).Patients with ESRD who undergo TAVR are at high risk for mortality and complications. TAVR outcomes are comparable to but not substantially better than those with SAVR. Transfemoral TAVR seems to be at least as safe and effective as the current standard SAVR in patients undergoing aortic valve replacement. © 2016 Wiley Periodicals, Inc.

  View details for PubMedID 26946240

• Transcatheter aortic valve replacement versus surgical valve replacement in intermediate-risk patients: a propensity score analysis LANCET Thourani, V. H., Kodali, S., Makkar, R. R., Herrmann, H. C., Williams, M., Babaliaros, V., Smalling, R., Lim, S., Malaisrie, S. C., Kapadia, S., Szeto, W. Y., Greason, K. L., Kereiakes, D., Ailawadi, G., Whisenant, B. K., Devireddy, C., Leipsic, J., Hahn, R. T., Pibarot, P., Weissman, N. J., Jaber, W. A., Cohen, D. J., Suri, R., Tuzcu, E. M., Svensson, L. G., Webb, J. G., Moses, J. W., Mack, M. J., Miller, D. C., Smith, C. R., Alu, M. C., Parvataneni, R., D'Agostino, R. B., Leon, M. B. 2016; 387 (10034): 2218-2225

  Abstract

  Transcatheter aortic valve replacement (TAVR) with the SAPIEN 3 valve demonstrates good 30 day clinical outcomes in patients with severe aortic stenosis who are at intermediate risk of surgical mortality. Here we report longer-term data in intermediate-risk patients given SAPIEN 3 TAVR and compare outcomes to those of intermediate-risk patients given surgical aortic valve replacement.In the SAPIEN 3 observational study, 1077 intermediate-risk patients at 51 sites in the USA and Canada were assigned to receive TAVR with the SAPIEN 3 valve [952 [88%] via transfemoral access) between Feb 17, 2014, and Sept 3, 2014. In this population we assessed all-cause mortality and incidence of strokes, re-intervention, and aortic valve regurgitation at 1 year after implantation. Then we compared 1 year outcomes in this population with those for intermediate-risk patients treated with surgical valve replacement in the PARTNER 2A trial between Dec 23, 2011, and Nov 6, 2013, using a prespecified propensity score analysis to account for between-trial differences in baseline characteristics. The clinical events committee and echocardiographic core laboratory methods were the same for both studies. The primary endpoint was the composite of death from any cause, all strokes, and incidence of moderate or severe aortic regurgitation. We did non-inferiority (margin 7·5%) and superiority analyses in propensity score quintiles to calculate pooled weighted proportion differences for outcomes.At 1 year follow-up of the SAPIEN 3 observational study, 79 of 1077 patients who initiated the TAVR procedure had died (all-cause mortality 7·4%; 6·5% in the transfemoral access subgroup), and disabling strokes had occurred in 24 (2%), aortic valve re-intervention in six (1%), and moderate or severe paravalvular regurgitation in 13 (2%). In the propensity-score analysis we included 963 patients treated with SAPIEN 3 TAVR and 747 with surgical valve replacement. For the primary composite endpoint of mortality, strokes, and moderate or severe aortic regurgitation, TAVR was both non-inferior (pooled weighted proportion difference of -9·2%; 90% CI -12·4 to -6; p<0·0001) and superior (-9·2%, 95% CI -13·0 to -5·4; p<0·0001) to surgical valve replacement.TAVR with SAPIEN 3 in intermediate-risk patients with severe aortic stenosis is associated with low mortality, strokes, and regurgitation at 1 year. The propensity score analysis indicates a significant superiority for our composite outcome with TAVR compared with surgery, suggesting that TAVR might be the preferred treatment alternative in intermediate-risk patients.None.

  View details for DOI 10.1016/S0140-6736(16)30073-3

  View details for PubMedID 27053442

• Transcatheter or Surgical Aortic-Valve Replacement in Intermediate-Risk Patients NEW ENGLAND JOURNAL OF MEDICINE Leon, M. B., Smith, C. R., Mack, M. J., Makkar, R. R., Svensson, L. G., Kodali, S. K., Thourani, V. H., Tuzcu, E. M., Miller, D. C., Herrmann, H. C., Doshi, D., Cohen, D. J., Pichard, A. D., Kapadia, S., Dewey, T., Babaliaros, V., Szeto, W. Y., Williams, M. R., Kereiakes, D., Zajarias, A., Greason, K. L., Whisenant, B. K., Hodson, R. W., Moses, J. W., Trento, A., Brown, D. L., Fearon, W. F., Pibarot, P., Hahn, R. T., Jaber, W. A., Anderson, W. N., Alu, M. C., Webb, J. G. 2016; 374 (17): 1609-1620

  Abstract

  Previous trials have shown that among high-risk patients with aortic stenosis, survival rates are similar with transcatheter aortic-valve replacement (TAVR) and surgical aortic-valve replacement. We evaluated the two procedures in a randomized trial involving intermediate-risk patients.We randomly assigned 2032 intermediate-risk patients with severe aortic stenosis, at 57 centers, to undergo either TAVR or surgical replacement. The primary end point was death from any cause or disabling stroke at 2 years. The primary hypothesis was that TAVR would not be inferior to surgical replacement. Before randomization, patients were entered into one of two cohorts on the basis of clinical and imaging findings; 76.3% of the patients were included in the transfemoral-access cohort and 23.7% in the transthoracic-access cohort.The rate of death from any cause or disabling stroke was similar in the TAVR group and the surgery group (P=0.001 for noninferiority). At 2 years, the Kaplan-Meier event rates were 19.3% in the TAVR group and 21.1% in the surgery group (hazard ratio in the TAVR group, 0.89; 95% confidence interval [CI], 0.73 to 1.09; P=0.25). In the transfemoral-access cohort, TAVR resulted in a lower rate of death or disabling stroke than surgery (hazard ratio, 0.79; 95% CI, 0.62 to 1.00; P=0.05), whereas in the transthoracic-access cohort, outcomes were similar in the two groups. TAVR resulted in larger aortic-valve areas than did surgery and also resulted in lower rates of acute kidney injury, severe bleeding, and new-onset atrial fibrillation; surgery resulted in fewer major vascular complications and less paravalvular aortic regurgitation.In intermediate-risk patients, TAVR was similar to surgical aortic-valve replacement with respect to the primary end point of death or disabling stroke. (Funded by Edwards Lifesciences; PARTNER 2 ClinicalTrials.gov number, NCT01314313.).

  View details for DOI 10.1056/NEJMoa1514616

  View details for PubMedID 27040324

• Giant Pulmonary Artery Aneurysm in a Patient With Marfan Syndrome and Pulmonary Hypertension. Circulation Chiu, P., Irons, M., van de Rijn, M., Liang, D. H., Miller, D. C. 2016; 133 (12): 1218-1221

  View details for DOI 10.1161/CIRCULATIONAHA.115.020537

  View details for PubMedID 27002085

• Atrial Fibrillation Is Associated With Increased Mortality in Patients Undergoing Transcatheter Aortic Valve Replacement Insights From the Placement of Aortic Transcatheter Valve (PARTNER) Trial CIRCULATION-CARDIOVASCULAR INTERVENTIONS Biviano, A. B., Nazif, T., Dizon, J., Garan, H., Fleitman, J., Hassan, D., Kapadia, S., Babaliaros, V., Xu, K., Parvataneni, R., Rodes-Cabau, J., Szeto, W. Y., Fearon, W. F., Dvir, D., Dewey, T., Williams, M., Mack, M. J., Webb, J. G., Miller, D. C., Smith, C. R., Leon, M. B., Kodali, S. 2016; 9 (1)

  Abstract

  This study sought to evaluate the impact of atrial fibrillation (AF) on clinical outcomes in patients undergoing transcatheter aortic valve replacement.Data were evaluated in 1879 patients with baseline and discharge ECGs who underwent transcatheter aortic valve replacement in the Placement of AoRTic TraNscathetER Valve (PARTNER) trial. A total of 1262 patients manifested sinus rhythm (SR) at baseline/SR at discharge, 113 SR baseline/AF discharge, and 470 AF baseline/AF discharge. Patients who converted from SR to AF by discharge had the highest rates of all-cause mortality at 30 days (P<0.0001 across all groups; 14.2% SR/AF versus 2.6% SR/SR; adjusted hazard ratio [HR]=3.41; P=0.0002) and over 2-fold difference at 1 year (P<0.0001 across all groups; 35.7% SR/AF versus 15.8% SR/SR; adjusted HR=2.14; P<0.0001). The presence of AF on baseline or discharge ECG was a predictor of 1-year mortality (adjusted HR=2.14 for SR/AF group and HR=1.88 for AF/AF groups; P<0.0001 for both groups versus SR/SR). For patients discharged in AF, those with lower ventricular response (ie, <90 bpm) experienced less 1-year all-cause mortality (HR=0.74; P=0.04).After transcatheter aortic valve replacement, the presence of AF at discharge, and particularly, the conversion to AF by discharge and higher ventricular response are associated with increased mortality. These data underscore the deleterious impact of AF, as well as the need for targeted interventions to improve clinical outcomes, in patients undergoing transcatheter aortic valve replacement.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894.

  View details for DOI 10.1161/CIRCINTERVENTIONS.115.002766

  View details for Web of Science ID 000368611900001

  View details for PubMedCentralID PMC4704130

• Atrial Fibrillation Is Associated With Increased Mortality in Patients Undergoing Transcatheter Aortic Valve Replacement: Insights From the Placement of Aortic Transcatheter Valve (PARTNER) Trial. Circulation. Cardiovascular interventions Biviano, A. B., Nazif, T., Dizon, J., Garan, H., Fleitman, J., Hassan, D., Kapadia, S., Babaliaros, V., Xu, K., Parvataneni, R., Rodes-Cabau, J., Szeto, W. Y., Fearon, W. F., Dvir, D., Dewey, T., Williams, M., Mack, M. J., Webb, J. G., Miller, D. C., Smith, C. R., Leon, M. B., Kodali, S. 2016; 9 (1): e002766

  Abstract

  This study sought to evaluate the impact of atrial fibrillation (AF) on clinical outcomes in patients undergoing transcatheter aortic valve replacement.Data were evaluated in 1879 patients with baseline and discharge ECGs who underwent transcatheter aortic valve replacement in the Placement of AoRTic TraNscathetER Valve (PARTNER) trial. A total of 1262 patients manifested sinus rhythm (SR) at baseline/SR at discharge, 113 SR baseline/AF discharge, and 470 AF baseline/AF discharge. Patients who converted from SR to AF by discharge had the highest rates of all-cause mortality at 30 days (P<0.0001 across all groups; 14.2% SR/AF versus 2.6% SR/SR; adjusted hazard ratio [HR]=3.41; P=0.0002) and over 2-fold difference at 1 year (P<0.0001 across all groups; 35.7% SR/AF versus 15.8% SR/SR; adjusted HR=2.14; P<0.0001). The presence of AF on baseline or discharge ECG was a predictor of 1-year mortality (adjusted HR=2.14 for SR/AF group and HR=1.88 for AF/AF groups; P<0.0001 for both groups versus SR/SR). For patients discharged in AF, those with lower ventricular response (ie, <90 bpm) experienced less 1-year all-cause mortality (HR=0.74; P=0.04).After transcatheter aortic valve replacement, the presence of AF at discharge, and particularly, the conversion to AF by discharge and higher ventricular response are associated with increased mortality. These data underscore the deleterious impact of AF, as well as the need for targeted interventions to improve clinical outcomes, in patients undergoing transcatheter aortic valve replacement.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894.

  View details for DOI 10.1161/CIRCINTERVENTIONS.115.002766

  View details for PubMedID 26733582

  View details for PubMedCentralID PMC4704130

• Descending aortic replacement after Nuss for pectus excavatum in a Marfan patient-Case report INTERNATIONAL JOURNAL OF SURGERY CASE REPORTS Jaroszewski, D., Ewais, M., DeValeria, P., Gotway, M., Miller, D. 2016; 21: 16–19

  Abstract

  The Nuss procedure for pectus excavatum (PE) repair has been successfully performed in Marfan syndrome (MFS) patients however there is concern for future risk of aortic dilation/rupture and need for emergent access with support bars in place.We present a 45 year-old male with MFS that required descending aortic replacement shortly after modified Nuss repair.The majority of MFS patients have severe PE and repair with the Nuss procedure is not uncommon. The risk for life threatening aortic dilation, dissection, or rupture in such patients is a concern when utilizing this technique. Our work has been reported in line with the CARE criteria.Nuss repair should be considered in MFS patients with technique modifications and careful consideration of future risk of aortic dilation and rupture.

  View details for DOI 10.1016/j.ijscr.2016.01.035

  View details for Web of Science ID 000374179300004

  View details for PubMedID 26895112

  View details for PubMedCentralID PMC4802129

• Pre- and Postoperative Imaging of the Aortic Root. Radiographics Hanneman, K., Chan, F. P., Mitchell, R. S., Miller, D. C., Fleischmann, D. 2016; 36 (1): 19-37

  Abstract

  Three-dimensional datasets acquired using computed tomography and magnetic resonance imaging are ideally suited for characterization of the aortic root. These modalities offer different advantages and limitations, which must be weighed according to the clinical context. This article provides an overview of current aortic root imaging, highlighting normal anatomy, pathologic conditions, imaging techniques, measurement thresholds, relevant surgical procedures, postoperative complications and potential imaging pitfalls. Patients with a range of clinical conditions are predisposed to aortic root disease, including Marfan syndrome, bicuspid aortic valve, vascular Ehlers-Danlos syndrome, and Loeys-Dietz syndrome. Various surgical techniques may be used to repair the aortic root, including placement of a composite valve graft, such as the Bentall and Cabrol procedures; placement of an aortic root graft with preservation of the native valve, such as the Yacoub and David techniques; and implantation of a biologic graft, such as a homograft, autograft, or xenograft. Potential imaging pitfalls in the postoperative period include mimickers of pathologic processes such as felt pledgets, graft folds, and nonabsorbable hemostatic agents. Postoperative complications that may be encountered include pseudoaneurysms, infection, and dehiscence. Radiologists should be familiar with normal aortic root anatomy, surgical procedures, and postoperative complications, to accurately interpret pre- and postoperative imaging performed for evaluation of the aortic root. Online supplemental material is available for this article. (©)RSNA, 2015.

  View details for DOI 10.1148/rg.2016150053

  View details for PubMedID 26761529

• A Randomized Evaluation of the SAPIEN XT Transcatheter Heart Valve System in Patients With Aortic Stenosis Who Are Not Candidates for Surgery JACC-CARDIOVASCULAR INTERVENTIONS Webb, J. G., Doshi, D., Mack, M. J., Makkar, R., Smith, C. R., Pichard, A. D., Kodali, S., Kapadia, S., Miller, D. C., Babaliaros, V., Thourani, V., Herrmann, H. C., Bodenhamer, M., Whisenant, B. K., Ramee, S., Maniar, H., Kereiakes, D., Xu, K., Jaber, W. A., Menon, V., Tuzcu, E. M., Wood, D., Svensson, L. G., Leon, M. B. 2015; 8 (14): 1797-1806

  Abstract

  The purpose of this study was to determine the safety and effectiveness of the SAPIEN XT versus SAPIEN systems (Edwards Lifesciences, Irvine, California) in patients with symptomatic, severe aortic stenosis (AS) who were not candidates for surgery.Transcatheter aortic valve replacement (TAVR) has become the standard of care for inoperable patients with severe, symptomatic AS. In the PARTNER (Placement of Aortic Transcatheter Valves) IB trial, a reduction in all-cause mortality was observed in patients undergoing TAVR with the balloon-expandable SAPIEN transcatheter heart valve compared with standard therapy, but the SAPIEN valve was associated with adverse periprocedural complications, including vascular complications, major bleeding, and paravalvular regurgitation. The newer, low-profile SAPIEN XT system was developed to reduce these adverse events.A total of 560 patients were enrolled at 28 sites in the United States from April 2011 to February 2012. Patients were randomized to receive the SAPIEN or SAPIEN XT systems. The primary endpoint was a nonhierarchical composite of all-cause mortality, major stroke, and rehospitalization at 1 year in the intention-to-treat population, assessed by noninferiority testing. Pre-specified secondary endpoints included cardiovascular death, New York Heart Association functional class, myocardial infarction, stroke, acute kidney injury, vascular complications, bleeding, 6-min walk distance, and valve performance (by echocardiography).Both overall and major vascular complications were higher at 30 days in patients undergoing TAVR with SAPIEN compared with SAPIEN XT (overall: 22.1% vs. 15.5%; p = 0.04; major: 15.2% vs. 9.5%; p = 0.04). Bleeding requiring blood transfusions was also more frequent with SAPIEN compared with SAPIEN XT (10.6% vs. 5.3%; p = 0.02). At 1-year follow-up, the nonhierarchical composite of all-cause mortality, major stroke, or rehospitalization was similar (37.7% SAPIEN vs. 37.2% SAPIEN XT; noninferiority p value <0.002); no differences in the other major pre-specified endpoints were found.In inoperable patients with severe, symptomatic AS, the lower-profile SAPIEN XT is noninferior to SAPIEN with fewer vascular complications and a lesser need for blood transfusion. (The PARTNER II Trial: Placement of AoRTic TraNscathetER Valves; NCT01314313).

  View details for DOI 10.1016/j.jcin.2015.08.017

  View details for PubMedID 26718510

• Midterm Outcomes of Open Descending Thoracic Aortic Repair in More Than 5,000 Medicare Patients ANNALS OF THORACIC SURGERY Schaffer, J. M., Lingala, B., Fischbein, M. P., Dake, M. D., Woo, Y. J., Mitchell, R. S., Miller, D. C. 2015; 100 (6): 2087-2094

  Abstract

  Diseases involving the descending thoracic aorta (DTA) represent a heterogeneous substrate with a variety of therapeutic options. Although thoracic endovascular aortic repair has been increasingly applied to DTA disease, open surgical repair is ostensibly more durable.A total of 5,578 patients who underwent open DTA repair (Current Procedural Terminology code 33875) from 1999 to 2010 were identified from the Medicare database; 5,489 patients had complete data. Survival was assessed with Kaplan-Meier analysis. Cox regression determined predictors of death. Hospital and surgeon volume and variability were modeled, and their association with survival assessed.Median survival after open DTA repair was only 4.3 years (95% confidence interval: 4.0 to 4.6). The likelihood of death varied significantly by certain aortic diseases: aortic rupture and acute aortic dissection patients had the highest early mortality. Survival beyond 180 days was best for patients with acute aortic dissection and isolated thoracic aortic aneurysm, and lowest for patients with thoracoabdominal aneurysm and aortic rupture. Hospital and surgeon volume, as well as interhospital and intersurgeon variability, had associations with overall survival.Open DTA repair has treated a spectrum of aortic diseases in Medicare beneficiaries. Overall mortality was high, predominately confined to the initial postoperative hazard phase. Independent hospital and surgeon effects, hospital and surgeon volume, and a more recent date of surgery correlated with improved survival, while increased operative urgency and complexity correlated with worse outcomes. These observations argue for regionalization of DTA treatment for Medicare patients in specialized centers to concentrate expertise, which should translate into better outcomes.

  View details for DOI 10.1016/j.athoracsur.2015.06.068

  View details for PubMedID 26431919

• Risk stratification in patients with pulmonary hypertension undergoing transcatheter aortic valve replacement. Heart Lindman, B. R., Zajarias, A., Maniar, H. S., Miller, D. C., Suri, R. M., Arnold, S. V., Webb, J., Svensson, L. G., Kodali, S., Xu, K., Ayele, G. M., Lin, F., Wong, S., Babaliaros, V., Thourani, V. H., Douglas, P. S., Lim, S., Leon, M. B., Mack, M. J. 2015; 101 (20): 1656-1664

  Abstract

  Pulmonary hypertension (PH) is associated with increased mortality after surgical or transcatheter aortic valve replacement (TAVR) for aortic stenosis (AS), and when the pulmonary artery pressure is particularly elevated, there may be questions about the clinical benefit of TAVR. We aimed to identify clinical and haemodynamic factors associated with increased mortality after TAVR among those with moderate/severe PH.Among patients with symptomatic AS at high or prohibitive surgical risk receiving TAVR in the Placement of Aortic Transcatheter Valves (PARTNER) I randomised trial or registry, 2180 patients with an invasive measurement of mean pulmonary artery pressure (mPAP) recorded were included, and moderate/severe PH was defined as an mPAP ≥35 mm Hg.Increasing severity of PH was associated with progressively worse 1-year all-cause mortality: none (n=785, 18.6%), mild (n=838, 22.7%) and moderate/severe (n=557, 25.0%) (p=0.01). The increased hazard of mortality associated with moderate/severe PH was observed in females, but not males (interaction p=0.03). In adjusted analyses, females with moderate/severe PH had an increased hazard of death at 1 year compared with females without PH (adjusted HR 2.14, 95% CI 1.44 to 3.18), whereas those with mild PH did not. Among males, there was no increased hazard of death associated with any severity of PH. In a multivariable Cox model of patients with moderate/severe PH, oxygen-dependent lung disease, inability to perform a 6 min walk, impaired renal function and lower aortic valve mean gradient were independently associated with increased 1-year mortality (p<0.05 for all), whereas several haemodynamic indices were not. A risk score, including these factors, was able to identify patients with a 15% vs 59% 1-year mortality.The relationship between moderate/severe PH and increased mortality after TAVR is altered by sex, and clinical factors appear to be more influential in stratifying risk than haemodynamic indices. These findings may have implications for the evaluation of and treatment decisions for patients referred for TAVR with significant PH.NCT00530894.

  View details for DOI 10.1136/heartjnl-2015-308001

  View details for PubMedID 26264371

• Poorer Left Ventricular Global Longitudinal Strain and Less Tricuspid Regurgitation Predicts Improvement in Left Ventricular Function Following Transcatheter Aortic Valve Replacement Kim, J. B., Brenner, D., Kobayashi, Y., O'Malley, R., Kobayashi, Y., Dao, C., Thu Vu, Yeung, A., Miller, D., Fischbein, M., Wu, J. C., Haddad, F., Fearon, W. F. ELSEVIER SCIENCE INC. 2015: B263–B264

  View details for DOI 10.1016/j.jacc.2015.08.664

  View details for Web of Science ID 000363329000588

• Appropriate patient selection or health care rationing? Lessons from surgical aortic valve replacement in the Placement of Aortic Transcatheter Valves I trial JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Szeto, W. Y., Svensson, L. G., Rajeswaran, J., Ehrlinger, J., Suri, R. M., Smith, C. R., Mack, M., Miller, D. C., McCarthy, P. M., Bavaria, J. E., Cohn, L. H., Corso, P. J., Guyton, R. A., Thourani, V. H., Lytle, B. W., Williams, M. R., Webb, J. G., Kapadia, S., Tuzcu, E. M., Cohen, D. J., Schaff, H. V., Leon, M. B., Blackstone, E. H. 2015; 150 (3): 557-567

  Abstract

  The study objectives were to (1) compare the safety of high-risk surgical aortic valve replacement in the Placement of Aortic Transcatheter Valves (PARTNER) I trial with Society of Thoracic Surgeons national benchmarks; (2) reference intermediate-term survival to that of the US population; and (3) identify subsets of patients for whom aortic valve replacement may be futile, with no survival benefit compared with therapy without aortic valve replacement.From May 2007 to October 2009, 699 patients with high surgical risk, aged 84 ± 6.3 years, were randomized in PARTNER-IA; 313 patients underwent surgical aortic valve replacement. Median follow-up was 2.8 years. Survival for therapy without aortic valve replacement used 181 PARTNER-IB patients.Operative mortality was 10.5% (expected 9.3%), stroke 2.6% (expected 3.5%), renal failure 5.8% (expected 12%), sternal wound infection 0.64% (expected 0.33%), and prolonged length of stay 26% (expected 18%). However, calibration of observed events in this relatively small sample was poor. Survival at 1, 2, 3, and 4 years was 75%, 68%, 57%, and 44%, respectively, lower than 90%, 81%, 73%, and 65%, respectively, in the US population, but higher than 53%, 32%, 21%, and 14%, respectively, in patients without aortic valve replacement. Risk factors for death included smaller body mass index, lower albumin, history of cancer, and prosthesis-patient mismatch. Within this high-risk aortic valve replacement group, only the 8% of patients with the poorest risk profiles had estimated 1-year survival less than that of similar patients treated without aortic valve replacement.PARTNER selection criteria for surgical aortic valve replacement, with a few caveats, may be more appropriate, realistic indications for surgery than those of the past, reflecting contemporary surgical management of severe aortic stenosis in high-risk patients at experienced sites.

  View details for DOI 10.1016/j.jtcvs.2015.05.073

  View details for PubMedID 26238287

• Aortic Valve Repair SEMINARS IN THORACIC AND CARDIOVASCULAR SURGERY David, T. E., Coselli, J. S., El Khoury, G., Miller, D., Svensson, L. G. 2015; 27 (3): 271–87

  View details for PubMedID 26708368

• Response to Letter Regarding Article, "Long-Term Outcomes of Inoperable Patients With Aortic Stenosis Randomly Assigned to Transcatheter Aortic Valve Replacement or Standard Therapy". Circulation Kapadia, S. R., Tuzcu, E. M., Makkar, R. R., Svensson, L. G., Agarwal, S., Kodali, S., Fontana, G. P., Webb, J. G., Mack, M., Thourani, V. H., Babaliaros, V. C., Herrmann, H. C., Szeto, W. Y., Pichard, A., Williams, M. R., Anderson, W. N., Akin, J. J., Miller, D. C., Smith, C. R., Leon, M. B. 2015; 132 (6): e118-9

  View details for DOI 10.1161/CIRCULATIONAHA.115.015363

  View details for PubMedID 26260504

• SCAI/AATS/ACC/STS operator and institutional requirements for transcatheter valve repair and replacement, Part III: Pulmonic valve CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Hijazi, Z. M., Ruiz, C. E., Zahn, E., Ringel, R., Aldea, G. S., Bacha, E. A., Bavaria, J., Bolman, R. M., Cameron, D. E., Dean, L. S., Feldman, T., Fullerton, D., Horlick, E., Mack, M. J., Miller, D. C., Moon, M. R., Mukherjee, D., Trento, A., Tommaso, C. L. 2015; 86 (1): 85-93

  Abstract

  With the evolution of transcatheter valve replacement, an important opportunity has arisen for cardiologists and surgeons to collaborate in identifying the criteria for performing these procedures. Therefore, The Society for Cardiovascular Angiography and Interventions (SCAI), American Association for Thoracic Surgery (AATS), American College of Cardiology (ACC), and The Society of Thoracic Surgeons (STS) have partnered to provide recommendations for institutions to assess their potential for instituting and/or maintaining a transcatheter valve program. This article concerns transcatheter pulmonic valve replacement (tPVR). tPVR procedures are in their infancy with few reports available on which to base an expert consensus statement. Therefore, many of these recommendations are based on expert consensus and the few reports available. As the procedures evolve, technology advances, experience grows, and more data accumulate, there will certainly be a need to update this consensus statement. The writing committee and participating societies believe that the recommendations in this report serve as appropriate requisites. In some ways, these recommendations apply to institutions more than to individuals. There is a strong consensus that these new valve therapies are best performed using a Heart Team approach; thus, these credentialing criteria should be applied at the institutional level. Partnering societies used the ACC's policy on relationships with industry (RWI) and other entities to author this document (http://www.acc.org/guidelines/about-guidelines-and-clinical-documents). To avoid actual, potential, or perceived conflicts of interest due to industry relationships or personal interests, all members of the writing committee, as well as peer reviewers of the document, were asked to disclose all current healthcare-related relationships including those existing 12 months before the initiation of the writing effort. A committee of interventional cardiologists and surgeons was formed to include a majority of members with no relevant RWI and to be led by an interventional cardiology cochair and a surgical cochair with no relevant RWI. Authors with relevant RWI were not permitted to draft or vote on text or recommendations pertaining to their RWI. RWI were reviewed on all conference calls and updated as changes occurred. Author and peer reviewer RWI pertinent to this document are disclosed in the Appendices. In addition, to ensure complete transparency, authors' comprehensive disclosure information (including RWI not pertinent to this document) is available in Appendix AII. The work of the writing committee was supported exclusively by the partnering societies without commercial support. SCAI, AATS, ACC, and STS believe that adherence to these recommendations will maximize the chances that these therapies will become a successful part of the armamentarium for treating valvular heart disease in the United States. In addition, these recommendations will hopefully facilitate optimum quality during the delivery of this therapy, which will be important to the development and successful implementation of future, less invasive approaches to structural heart disease.

  View details for DOI 10.1002/ccd.25710

  View details for PubMedID 25809590

• Geometric perturbations in multiheaded papillary tip positions associated with acute ovine ischemic mitral regurgitation JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Timek, T. A., Lai, D. T., Bothe, W., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. 2015; 150 (1): 232-237

  Abstract

  Novel surgical approaches are focusing on the "ventricular disease" of ischemic mitral regurgitation (IMR), to correct altered papillary muscle (PM) tip positions (apical displacement) and ameliorate leaflet tethering. Due to the anatomic complexity of the subvalvular apparatus, however, the precise geometric perturbations of the multiheaded PM tips associated with IMR remain uncharacterized.In 6 adult sheep, we implanted 3 markers on each PM. To specifically identify distinct PM tips, 1 marker was placed on the PM origin of the dominant chord to the anterior, posterior, and commissural leaflets. Nine markers were placed on the edge of the posterior mitral leaflet, and 5 on the edge of the anterior mitral leaflet. Eight markers were sewn around the mitral annulus. Animals were studied immediately postoperatively, with biplane videofluoroscopy and transesophageal echocardiography, before and during acute snare occlusion of the proximal left circumflex coronary artery, to induce IMR. Papillary muscle tip and leaflet edge geometry was expressed as the orthogonal distance of each respective marker to the least-squares mitral annulus plane at end-systole. In addition, the distance from each PM tip marker to the mitral annulus "saddle horn" was calculated.Acute left circumflex occlusion significantly increased mitral regurgitation from a baseline of 0.7 ± 0.3 to 2.5 ± 0.5 (P < .05). The IMR was associated with posterior leaflet restriction near the central leaflet edge, with simultaneous prolapse of both leaflets near the posterior commissure. No apical displacement of PM tips was observed during IMR, although the posterior PM moved farther away from the midseptal annulus.During acute ischemia, no apical displacement of any PM tip was observed. Posterior PM movement away from the annular saddle horn, and toward the annulus, was associated with IMR and leaflet prolapse near the posterior commissure, and with restriction near the valve center. These data may help guide development of surgical interventions aimed at PM repositioning.

  View details for DOI 10.1016/j.jtcvs.2015.04.037

  View details for PubMedID 25998465

• Greater asymmetric wall shear stress in Sievers' type 1/LR compared with 0/LAT bicuspid aortic valves after valve-sparing aortic root replacement JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Stephens, E. H., Hope, T. A., Kari, F. A., Kvitting, J. E., Liang, D. H., Herfkens, R. J., Miller, D. C. 2015; 150 (1): 59-68

  Abstract

  To evaluate the role of commissure orientation on downstream blood flow patterns and ascending aortic wall shear stress (WSS) in patients with bicuspid aortic valves (BAV) after valve-sparing aortic root replacement (V-SARR).Nineteen BAV patients after V-SARR (9 Sievers' type 1/LR [type 1 valve with fusion of the left and right cusps] and 10 Sievers' type 0/LAT ["naturally perfect"; type 0 valve without the presence of a raphe, and with the 2 commissures oriented right-anterior-to-left-posterior]) were imaged using time-resolved 3-D phase contrast magnetic resonance imaging. A control group of 5 unoperated tricuspid aortic valve patients were used for comparison purposes. Wall shear stress and eccentricity of flow normalized to aortic diameter were measured in planes placed perpendicular to the axis of the ascending aorta at the level of the sinotubular junction (proximal ascending), main pulmonary artery (mid-ascending), and origin of the brachiocephalic (distal ascending).The ratio of WSS along the outer curvature to that along the inner curvature was greater in Sievers' type 1/LR patients compared with Sievers' type 0/LAT patients in the proximal (3.8 ± 1.6 vs 2.1 ± 0.9, P = .009) and mid- ascending aorta (4.5 ± 2.4 vs 2.4 ± 1.3, P = .027). Relative to control normal tricuspid patients, Sievers' type 1/LR BAV patients had a higher WSS ratio in the mid-ascending aorta (4.5 ± 2.4 vs 1.2 ± 1.2, P = .007). Conversely, WSS in Sievers' type 0/LAT patients was not different than in normal tricuspid patients.After V-SARR, BAV cusp morphology has a major impact on the pattern of blood flow and WSS in the ascending aorta.

  View details for DOI 10.1016/j.jtcvs.2015.04.020

  View details for PubMedID 25956338

• SCAI/AATS/ACC/STS Operator and Institutional Requirements for Transcatheter Valve Repair and Replacement, Part III: Pulmonic Valve JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Hijazi, Z. M., Ruiz, C. E., Zahn, E., Ringel, R., Aldea, G. S., Bacha, E. A., Bavaria, J., Bolman, R. M., Cameron, D. E., Dean, L. S., Feldman, T., Fullerton, D., Horlick, E., Mack, M. J., Miller, D. C., Moon, M. R., Mukherjee, D., Trento, A., Tommaso, C. L. 2015; 65 (23): 2556-2563

  View details for DOI 10.1016/j.jacc.2015.02.031

  View details for PubMedID 25819263

• Propensity-matched comparisons of clinical outcomes after transapical or transfemoral transcatheter aortic valve replacement: a placement of aortic transcatheter valves (PARTNER)-I trial substudy. Circulation Blackstone, E. H., Suri, R. M., Rajeswaran, J., Babaliaros, V., Douglas, P. S., Fearon, W. F., Miller, D. C., Hahn, R. T., Kapadia, S., Kirtane, A. J., Kodali, S. K., Mack, M., Szeto, W. Y., Thourani, V. H., Tuzcu, E. M., Williams, M. R., Akin, J. J., Leon, M. B., Svensson, L. G. 2015; 131 (22): 1989-2000

  Abstract

  The higher risk of adverse outcomes after transapical (TA) versus transfemoral (TF) transcatheter aortic valve replacement (TAVR) could be attributable to TA-TAVR being an open surgical procedure or to clinical differences between TA- and TF-TAVR patients. We compared outcomes after neutralizing patient differences using propensity score matching.From April 2007 to February 2012, 1100 Placement of Aortic Transcatheter Valves (PARTNER)-I patients underwent TA-TAVR and 1521 underwent TF-TAVR with Edwards SAPIEN balloon-expandable bioprostheses. Propensity matching based on 111 preprocedural variables, exclusive of femoral access morphology, identified 501 well-matched patient pairs (46% of possible matches), 95% of whom had peripheral arterial disease. Matched TA-TAVR patients experienced more adverse procedural events, longer length of stay (5 versus 8 days; P<0.0001), and slower recovery (New York Heart Association class I, 31% versus 38% at 30 days, equalizing by 6 months at 51% versus 47%); stroke risk was similar (3.4% versus 3.3% at 30 days and 6.0% versus 6.7% at 3 years); mortality was elevated for the first 6 postprocedural months (19% versus 12%; P=0.01); but aortic regurgitation was less (34% versus 52% mild and 8.9% versus 12% moderate to severe at discharge, P=0.001; 36% versus 50% mild and 10% versus 15% moderate to severe at 6 months, P<0.0001).The likelihood of adverse periprocedural events and prolonged recovery is greater after TA-TAVR than TF-TAVR in vasculopathic patients after accounting for differences in cardiovascular risk factors, although stroke risk is equivalent and aortic regurgitation is less. As smaller delivery systems permit TF-TAVR in many of these patients, we recommend a TF-first access strategy for TAVR when anatomically feasible.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894.

  View details for DOI 10.1161/CIRCULATIONAHA.114.012525

  View details for PubMedID 25832034

• Heterogeneity of Mitral Leaflet Matrix Composition and Turnover Correlates with Regional Leaflet Strain CARDIOVASCULAR ENGINEERING AND TECHNOLOGY Stephens, E. H., Connell, P. S., Fahrenholtz, M. M., Timek, T. A., Daughters, G. T., Kuo, J. J., Patton, A. M., Ingels, N. B., Miller, D., Grande-Allen, K. 2015; 6 (2): 141–50

  Abstract

  To determine how extracellular matrix and contractile valvular cells contribute to the heterogeneous motion and strain across the mitral valve (MV) during the cardiac cycle, regional MV material properties, matrix composition, matrix turnover, and cell phenotype were related to regional leaflet strain. Radiopaque markers were implanted into 14 sheep to delineate the septal (SEPT), lateral (LAT), and anterior and posterior commissural leaflets (ANT-C, POST-C). Videofluoroscopy imaging was used to calculate radial and circumferential strains. Mechanical properties were assessed using uniaxial tensile testing and micropipette aspiration. Matrix composition and cell phenotypes were immunohistochemically evaluated within each leaflet region [basal leaflet (BL), mid-leaflet (ML), and free edge]. SEPT-BL segments were stiffer and stronger than other valve tissues, while LAT segments demonstrated more extensibility and strain. Collagens I and III in SEPT were greater than in LAT, although LAT showed greater collagen turnover [matrix metalloprotease (MMP)-13, lysyl oxidase] and cell activation [smooth muscle alpha-actin (SMaA), and non-muscle myosin (NMM)]. MMP13, NMM, and SMaA were strongly correlated with each other, as well as with radial and circumferential strains in both SEPT and LAT. SMaA and MMP13 in POST-C ML was greater than ANT-C, corresponding to greater radial strains in POST-C. This work directly relates leaflet strain, material properties, and matrix turnover, and suggests a role for myofibroblasts in the heterogeneity of leaflet composition and strain. New approaches to MV repair techniques and ring design should preserve this normal coupling between leaflet composition and motion.

  View details for DOI 10.1007/s13239-015-0214-1

  View details for Web of Science ID 000380356000005

  View details for PubMedID 26213589

  View details for PubMedCentralID PMC4512834

• Cellular and Extracellular Matrix Basis for Heterogeneity in Mitral Annular Contraction CARDIOVASCULAR ENGINEERING AND TECHNOLOGY Stephens, E. H., Fahrenholtz, M. M., Connell, P. S., Timek, T. A., Daughters, G. T., Kuo, J. J., Patton, A. M., Ingels, N. B., Miller, D., Grande-Allen, K. 2015; 6 (2): 151–59

  Abstract

  Regional heterogeneity in mitral annular contraction, which is generally ascribed to the fibrous vs. muscular annular composition, ensures proper leaflet motion and timing of coaptation. It is unknown whether the fibroblast-like cells in the annulus modulate this heterogeneity, even though valvular interstitial cells (VICs) can be mechanically "activated."Fourteen sheep underwent implantation of radiopaque markers around the mitral annulus defining four segments: septal (SEPT), lateral (LAT), and anterior (ANT-C) and posterior (POST-C) commissures. Segmental annular contraction was calculated using biplane videofluoroscopy. Immunohistochemistry of annular cross sections assessed regional matrix content, matrix turnover, and cell phenotype. Micropipette aspiration measured the Young's modulus of the leaflets adjacent to the myocardial border.Whereas SEPT contained more collagen I and III, LAT demonstrated more collagen and elastin turnover as shown by greater decorin, lysyl oxidase, and matrix metalloprotease (MMP)-13 and smooth muscle alpha-actin (SMaA). This greater matrix turnover paralleled greater annular contraction in LAT vs. SEPT (22.5% vs. 4.1%). Similarly, POST-C had more SMaA and MMP13 than ANT-C, consistent with greater annular contraction in POST-C (18.8% vs. 11.1%). Interestingly, POST-C had the greatest effective modulus, significantly higher than LAT.These data suggest that matrix turnover by activated VICs relates to annular motion heterogeneity, maintains steady-state mechanical properties in the annulus, and could be a therapeutic target when annular motion is impaired. Conversely, alterations in this heterogeneous annular contraction, whether through disease or secondary to ring annuloplasty, could disrupt this normal pattern of cell-mediated matrix remodeling and further adversely impact mitral valve function.

  View details for PubMedID 26195991

  View details for PubMedCentralID PMC4505373

• SCAI/AATS/ACC/STS operator and institutional requirements for transcatheter valve repair and replacement, part III: Pulmonic valve JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Hijazi, Z. M., Ruiz, C. E., Zahn, E., Ringel, R., Aldea, G. S., Bacha, E. A., Bavaria, J., Bolman, R. M., Cameron, D. E., Dean, L. S., Feldman, T., Fullerton, D., Horlick, E., Mack, M. J., Miller, D. C., Moon, M. R., Mukherjee, D., Trento, A., Tommaso, C. L. 2015; 149 (5): E71-E78

  View details for DOI 10.1016/j.jtcvs.2015.02.058

  View details for PubMedID 25816957

• SCAI/AATS/ACC/STS Operator and Institutional Requirements for Transcatheter Valve Repair and Replacement, Part III: Pulmonic Valve ANNALS OF THORACIC SURGERY Hijazi, Z. M., Ruiz, C. E., Zahn, E., Ringel, R., Aldea, G. S., Bacha, E. A., Bavaria, J., Bolman, R. M., Cameron, D. E., Dean, L. S., Feldman, T., Fullerton, D., Horlick, E., Mack, M. J., Miller, D. C., Moon, M. R., Mukherjee, D., Trento, A., Tommaso, C. L. 2015; 99 (5): 1857-1864

  View details for DOI 10.1016/j.athoracsur.2014.12.088

  View details for PubMedID 25817888

• Effect of tricuspid regurgitation and the right heart on survival after transcatheter aortic valve replacement: insights from the Placement of Aortic Transcatheter Valves II inoperable cohort. Circulation. Cardiovascular interventions Lindman, B. R., Maniar, H. S., Jaber, W. A., Lerakis, S., Mack, M. J., Suri, R. M., Thourani, V. H., Babaliaros, V., Kereiakes, D. J., Whisenant, B., Miller, D. C., Tuzcu, E. M., Svensson, L. G., Xu, K., Doshi, D., Leon, M. B., Zajarias, A. 2015; 8 (4)

  Abstract

  Tricuspid regurgitation (TR) and right ventricular (RV) dysfunction adversely affect outcomes in patients with heart failure or mitral valve disease, but their impact on outcomes in patients with aortic stenosis treated with transcatheter aortic valve replacement has not been well characterized.Among 542 patients with symptomatic aortic stenosis treated in the Placement of Aortic Transcatheter Valves (PARTNER) II trial (inoperable cohort) with a Sapien or Sapien XT valve via a transfemoral approach, baseline TR severity, right atrial and RV size and RV function were evaluated by echocardiography according to established guidelines. One-year mortality was 16.9%, 17.2%, 32.6%, and 61.1% for patients with no/trace (n=167), mild (n=205), moderate (n=117), and severe (n=18) TR, respectively (P<0.001). Increasing severity of RV dysfunction as well as right atrial and RV enlargement were also associated with increased mortality (P<0.001). After multivariable adjustment, severe TR (hazard ratio, 3.20; 95% confidence interval, 1.50-6.82; P=0.003) and moderate TR (hazard ratio, 1.60; 95% confidence interval, 1.02-2.52; P=0.042) remained associated with increased mortality as did right atrial and RV enlargement, but not RV dysfunction. There was an interaction between TR and mitral regurgitation severity (P=0.04); the increased hazard of death associated with moderate/severe TR only occurred in those with no/trace/mild mitral regurgitation.In inoperable patients treated with transcatheter aortic valve replacement, moderate or severe TR and right heart enlargement are independently associated with increased 1-year mortality; however, the association between moderate or severe TR and an increased hazard of death was only found in those with minimal mitral regurgitation at baseline. These findings may improve our assessment of anticipated benefit from transcatheter aortic valve replacement and support the need for future studies on TR and the right heart, including whether concomitant treatment of TR in operable but high-risk patients with aortic stenosis is warranted.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01314313.

  View details for DOI 10.1161/CIRCINTERVENTIONS.114.002073

  View details for PubMedID 25855679

• Midterm survival after thoracic endovascular aortic repair in more than 10,000 Medicare patients JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Schaffer, J. M., Lingala, B., Miller, C., Woo, J., Mitchell, R. S., Dake, M. D. 2015; 149 (3): 808-820

  Abstract

  Aneurysms and dissections of the descending thoracic aorta represent a complex substrate with a variety of therapeutic options. The introduction of thoracic endovascular aortic repair (TEVAR) has revolutionized the treatment of thoracic aortic disease. However, longitudinal analyses of post-TEVAR outcomes appropriately stratified by aortic disease remain limited.A total of 11,996 patients undergoing TEVAR from 2005-2010 were identified from the Medicare/Centers for Medicare and Medicaid Services database. Patients were stratified by underlying aortic disease and the presence of Current Procedural Terminology (CPT) codes. Survival was assessed using Kaplan-Meier analysis. Cox proportional hazards analysis determined predictors of survival from TEVAR.After TEVAR, patients had a median survival of 57.6 months (95% confidence interval, 54.9-61.3 months). Although patients without CPT codes had significantly fewer recorded comorbidities, TEVAR survival was comparable between patients with and without CPT codes (56.3 vs 59.5 months, P = .54). The early and late incidence of death varied significantly by aortic disease. Patients with aortic rupture, acute aortic dissection, and aortic trauma had the highest early incidence of death, whereas late survival was highest in patients with acute aortic dissection, aortic trauma, and isolated thoracic aortic aneurysm. Although hospital TEVAR volume was not associated with survival, an independent hospital effect (determined by using a mixed-effect Cox model) associated certain hospitals with a hazard for death 50% of what it was at other hospitals.TEVAR has been applied to a multitude of aortic diseases in the Medicare population; early and late post-TEVAR survival varies by aortic disease. The late incidence of death remains high in TEVAR recipients, although certain aortic diagnoses such as acute aortic dissection, aortic trauma, and isolated thoracic aortic aneurysm were associated with improved late survival. An independent hospital effect, but not hospital volume, is correlated with post-TEVAR survival. Future analyses of TEVAR outcomes using the Medicare database should adjust for underlying aortic diagnoses and the presence of CPT codes.

  View details for DOI 10.1016/j.jtcvs.2014.10.036

  View details for Web of Science ID 000351930600052

  View details for PubMedID 25541408

• Outcomes of Inoperable Symptomatic Aortic Stenosis Patients Not Undergoing Aortic Valve Replacement Insight Into the Impact of Balloon Aortic Valvuloplasty From the PARTNER Trial (Placement of AoRtic TraNscathetER Valve Trial) JACC-CARDIOVASCULAR INTERVENTIONS Kapadia, S., Stewart, W. J., Anderson, W. N., Babaliaros, V., Feldman, T., Cohen, D. J., Douglas, P. S., Makkar, R. R., Svensson, L. G., Webb, J. G., Wong, S. C., Brown, D. L., Miller, D. C., Moses, J. W., Smith, C. R., Leon, M. B., Tuzcu, E. M. 2015; 8 (2): 324-333

  Abstract

  The aim of this report is to characterize the impact of balloon aortic valvuloplasty (BAV) in patients not undergoing aortic valve replacement in the PARTNER (Placement of AoRtic TraNscathetER Valves) trial.The PARTNER trial is the only randomized trial with independently adjudicated data of inoperable severe symptomatic aortic stenosis patients, allowing outcome analysis of unoperated-on patients.The design and initial results of the PARTNER trial (Cohort B) were reported previously. After excluding patients with pre-randomization BAV, we compared patients undergoing BAV within 30 days of randomization (BAV group) with those not having BAV within 30 days of randomization (no BAV group) to characterize the use and impact of BAV.In the PARTNER Cohort B study, 179 inoperable patients were randomized to standard treatment including 39 patients (21.8%) who had undergone a BAV before randomization (previous BAV group). Of the 140 patients who did not have BAV before enrollment in the study, 102 patients (73%) had BAV within 30 days of study randomization (BAV group). Survival at 3 months was greater in the BAV group compared with the no BAV group (88.2%; 95% confidence interval [CI]: 82.0% to 94.5% vs. 73.0%; 95% CI: 58.8% to 87.4%). However, survival was similar at 6-month follow-up (74.5%; 95% CI: 66.1% to 83.0% vs. 73.1%; 58.8% to 87.4%). There was improvement in quality of life parameters when paired comparisons were made between baseline and 30 days and 6 months between the BAV and no BAV groups, but this effect was lost at 12-month follow-up.BAV improves functional status and survival in the short term, but these benefits are not sustained. BAV for aortic stenosis patients who cannot undergo aortic valve replacement is a useful palliative therapy. (THE PARTNER TRIAL: Placement of AoRTic TraNscathetER Valve Trial; NCT00530894).

  View details for DOI 10.1016/j.jcin.2014.08.015

  View details for PubMedID 25700756

• Rationale and results of the Stanford modification of the David V reimplantation technique for valve-sparing aortic root replacement (Reprinted from J Thorac Cardiovasc Surg, vol 149, pg 112, 2015) JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Miller, D. 2015; 149 (2): S18–S20

  View details for PubMedID 25726078

• Predictors and Clinical Outcomes of Permanent Pacemaker Implantation After Transcatheter Aortic Valve Replacement The PARTNER (Placement of AoRtic TraNscathetER Valves) Trial and Registry JACC-CARDIOVASCULAR INTERVENTIONS Nazif, T. M., Dizon, J. M., Hahn, R. T., Xu, K., Babaliaros, V., Douglas, P. S., El-Chami, M. F., Herrmann, H. C., Mack, M., Makkar, R. R., Miller, C., Pichard, A., Tuzcu, E. M., Szeto, W. Y., Webb, J. G., Moses, J. W., Smith, C. R., Williams, M. R., Leon, M. B., Kodali, S. K. 2015; 8 (1): 60-69

  Abstract

  The purpose of this study was to identify predictors and clinical implications of permanent pacemaker (PPM) implantation after transcatheter aortic valve replacement (TAVR).Cardiac conduction disturbances requiring PPM are a frequent complication of TAVR. However, limited data is available regarding this complication after TAVR with a balloon-expandable valve.The study included patients without prior pacemaker who underwent TAVR in the PARTNER (Placement of AoRtic TraNscathetER Valves) trial and registry and investigated predictors and clinical effect of new PPM.Of 2,559 TAVR patients, 586 were excluded due to pre-existing PPM. A new PPM was required in 173 of the remaining 1,973 patients (8.8%). By multivariable analysis, predictors of PPM included right bundle branch block (odds ratio [OR]: 7.03, 95% confidence interval [CI]: 4.92 to 10.06, p < 0.001), prosthesis diameter/left ventricular (LV) outflow tract diameter (for each 0.1 increment, OR: 1.29, 95% CI: 1.10 to 1.51, p = 0.002), LV end-diastolic diameter (for each 1 cm, OR: 0.68, 95% CI: 0.53 to 0.87, p = 0.003), and treatment in continued access registry (OR: 1.77, 95% CI: 1.08 to 2.92, p = 0.025). Patients requiring PPM had a longer mean duration of post-procedure hospitalization (7.3 ± 2.7 days vs. 6.2 ± 2.8 days, p = 0.001). At 1 year, new PPM was associated with significantly higher repeat hospitalization (23.9% vs. 18.2%, p = 0.05) and mortality or repeat hospitalization (42.0% vs. 32.6%, p = 0.007). There was no difference between groups in LV ejection fraction at 1 year.PPM was required in 8.8% of patients without prior PPM who underwent TAVR with a balloon-expandable valve in the PARTNER trial and registry. In addition to pre-existing right bundle branch block, the prosthesis to LV outflow tract diameter ratio and the LV end-diastolic diameter were identified as novel predictors of PPM after TAVR. New PPM was associated with a longer duration of hospitalization and higher rates of repeat hospitalization and mortality or repeat hospitalization at 1 year. (THE PARTNER TRIAL: Placement of AoRtic TraNscathetER Valves Trial; NCT00530894).

  View details for DOI 10.1016/j.jcin.2014.07.022

  View details for PubMedID 25616819

• Emergency, automation off: Unstructured transition timing for distracted drivers of automated vehicles Proceedings of the 18th IEEE International Conference on Intelligent Transportation Systems Mok, B., Johns, M., Lee, K., Miller, D., Sirkin, D., Ju, W. 2015

  View details for DOI 10.1109/ITSC.2015.396

• Defining "severe" secondary mitral regurgitation: emphasizing an integrated approach. Journal of the American College of Cardiology Grayburn, P. A., Carabello, B., Hung, J., Gillam, L. D., Liang, D., Mack, M. J., McCarthy, P. M., Miller, D. C., Trento, A., Siegel, R. J. 2014; 64 (25): 2792-2801

  Abstract

  Secondary mitral regurgitation (MR) is associated with poor outcomes, but its correction does not reverse the underlying left ventricular (LV) pathology or improve the prognosis. The recently published American Heart Association/American College of Cardiology guidelines on valvular heart disease generated considerable controversy by revising the definition of severe secondary MR from an effective regurgitant orifice area (EROA) of 0.4 to 0.2 cm(2), and from a regurgitant volume (RVol) of 60 to 30 ml. This paper reviews hydrodynamic determinants of MR severity, showing that EROA and RVol values associated with severe MR depend on LV volume. This explains disparities in the evidence associating a lower EROA threshold with suboptimal survival. Redefining MR severity purely on EROA or RVol may cause significant clinical problems. As the guidelines emphasize, defining severe MR requires careful integration of all echocardiographic and clinical data, as measurement of EROA is imprecise and poorly reproducible.

  View details for DOI 10.1016/j.jacc.2014.10.016

  View details for PubMedID 25541133

• The relative performance characteristics of the logistic European System for Cardiac Operative Risk Evaluation score and the Society of Thoracic Surgeons score in the Placement of Aortic Transcatheter Valves trial. journal of thoracic and cardiovascular surgery Beohar, N., Whisenant, B., Kirtane, A. J., Leon, M. B., Tuzcu, E. M., Makkar, R., Svensson, L. G., Miller, D. C., Smith, C. R., Pichard, A. D., Herrmann, H. C., Thourani, V. H., Szeto, W. Y., Lim, S., Fischbein, M., Fearon, W. F., O'Neill, W., Xu, K., Dewey, T., Mack, M. 2014; 148 (6): 2830-7 e1

  Abstract

  The logistic European System for Cardiac Operative Risk Evaluation (LES) score and the Society of Thoracic Surgeons (STS) score are validated to predict 30-day outcomes following surgical aortic valve replacement (SAVR) with or without coronary artery bypass grafting. Their performance when applied to patients undergoing transcatheter aortic valve replacement (TAVR) is controversial.We compared predicted and observed 30-day/in-hospital and 1-year mortality of patients undergoing TAVR in the first Placement of Aortic Transcatheter Valves trial and continued access registry (N = 2466). The performance of the LES and STS scores (prospectively calculated) was evaluated using standard assessments of discrimination and calibration. Performance of STS and LES scores among 307 patients undergoing SAVR from the high-risk cohort of the randomized trial were also examined.In patients undergoing TAVR, the observed 30-day/in-hospital mortality was 6.5%, whereas the predicted 30-day mortality was higher by both STS score (11.4% ± 3.9%) and LES score (26.6% ± 16.2%). The discrimination for both scores was poor for 30-day/in-hospital and 1-year mortality. Calibration was better for STS score than for LES at 1 year but poor for both at 30 days among TAVR cohort. These results were consistent among the subgroups of patients undergoing transfemoral and transapical access; however, the STS score had better performance among the high-risk patients who underwent SAVR at 30 days but not 1 year.The STS and LES surgical risk scores overestimated 30-day/in-hospital mortality and were poor discriminators of post-TAVR mortality, but the calibration of the STS score was better in these high-risk patients. These data highlight the need for TAVR-specific risk models to optimize patient selection.

  View details for DOI 10.1016/j.jtcvs.2014.04.006

  View details for PubMedID 24820191

• The relative performance characteristics of the logistic European System for Cardiac Operative Risk Evaluation score and the Society of Thoracic Surgeons score in the Placement of Aortic Transcatheter Valves trial JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Beohar, N., Whisenant, B., Kirtane, A. J., Leon, M. B., Tuzcu, E. M., Makkar, R., Svensson, L. G., Miller, D. C., Smith, C. R., Pichard, A. D., Herrmann, H. C., Thourani, V. H., Szeto, W. Y., Lim, S., Fischbein, M., Fearon, W. F., O'Neill, W., Xu, K., Dewey, T., Mack, M. 2014; 148 (6): 2830-U1495

  Abstract

  The logistic European System for Cardiac Operative Risk Evaluation (LES) score and the Society of Thoracic Surgeons (STS) score are validated to predict 30-day outcomes following surgical aortic valve replacement (SAVR) with or without coronary artery bypass grafting. Their performance when applied to patients undergoing transcatheter aortic valve replacement (TAVR) is controversial.We compared predicted and observed 30-day/in-hospital and 1-year mortality of patients undergoing TAVR in the first Placement of Aortic Transcatheter Valves trial and continued access registry (N = 2466). The performance of the LES and STS scores (prospectively calculated) was evaluated using standard assessments of discrimination and calibration. Performance of STS and LES scores among 307 patients undergoing SAVR from the high-risk cohort of the randomized trial were also examined.In patients undergoing TAVR, the observed 30-day/in-hospital mortality was 6.5%, whereas the predicted 30-day mortality was higher by both STS score (11.4% ± 3.9%) and LES score (26.6% ± 16.2%). The discrimination for both scores was poor for 30-day/in-hospital and 1-year mortality. Calibration was better for STS score than for LES at 1 year but poor for both at 30 days among TAVR cohort. These results were consistent among the subgroups of patients undergoing transfemoral and transapical access; however, the STS score had better performance among the high-risk patients who underwent SAVR at 30 days but not 1 year.The STS and LES surgical risk scores overestimated 30-day/in-hospital mortality and were poor discriminators of post-TAVR mortality, but the calibration of the STS score was better in these high-risk patients. These data highlight the need for TAVR-specific risk models to optimize patient selection.

  View details for DOI 10.1016/j.jtcvs.2014.04.006

  View details for Web of Science ID 000345686100086

  View details for PubMedID 24820191

• Long-Term Outcomes of Inoperable Patients With Aortic Stenosis Randomly Assigned to Transcatheter Aortic Valve Replacement or Standard Therapy CIRCULATION Kapadia, S. R., Tuzcu, E. M., Makkar, R. R., Svensson, L. G., Agarwal, S., Kodali, S., Fontana, G. P., Webb, J. G., Mack, M., Thourani, V. H., Babaliaros, V. C., Herrmann, H. C., Szeto, W., Pichard, A. D., Williams, M. R., Anderson, W. N., Akin, J. J., Miller, D. C., Smith, C. R., Leon, M. B. 2014; 130 (17): 1483-U106

  Abstract

  The long-term outcomes of transcatheter aortic valve replacement (TAVR) in inoperable patients with severe aortic stenosis remain unknown.In the Placement of Aortic Transcatheter Valves (PARTNER) study, 358 patients were randomly assigned to TAVR or standard therapy. We report the 3-year outcomes on these patients, and the pooled outcomes for all randomly assigned inoperable patients (n=449) in PARTNER, as well, including the randomized portion of the continued access study (n=91). The 3-year mortality rate in the TAVR and standard therapy groups was 54.1% and 80.9%, respectively (P<0.001; hazard ratio, 0.53; 95% confidence interval, 0.41-0.68; P<0.001). In survivors, there was significant improvement in New York Heart Association functional class sustained at 3 years. The cumulative incidence of strokes at 3-year follow-up was 15.7% in TAVR patients versus 5.5% in patients undergoing standard therapy (hazard ratio, 2.81; 95% confidence interval, 1.26-6.26; P=0.012); however, the composite of death or strokes was significantly lower after TAVR versus standard therapy (57.4% versus 80.9%, P<0.001; hazard ratio, 0.60; 95% confidence interval, 0.46-0.77; P<0.001). Echocardiography showed a sustained increase in aortic valve area and decrease in transvalvular gradient after TAVR. Analysis of the 449 pooled randomly assigned patients (TAVR, n=220; standard therapy, n=229) demonstrated significant improvement in all-cause mortality and functional status during early and 3-year follow-up. The results of the pooled cohort were similar to the results obtained from the pivotal PARTNER trial.TAVR resulted in better survival and functional status in inoperable patients with severe aortic stenosis with durable hemodynamic benefit on long-term follow-up. However, high residual mortality, even in successfully treated TAVR patients, highlights the need for more strategic patient selection.http://www.clinicaltrials.gov. Unique identifier: NCT00530894.

  View details for DOI 10.1161/CIRCULATIONAHA.114.009834

  View details for PubMedID 25205802

• SCAI/AATS/ACC/STS Operator and Institutional Requirements for Transcatheter Valve Repair and Replacement. Part II. Mitral Valve JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Tommaso, C. L., Fullerton, D. A., Feldman, T., Dean, L. S., Hijazi, Z. M., Horlick, E., Weiner, B. H., Zahn, E., Cigarroa, J. E., Ruiz, C. E., Bavaria, J., Mack, M. J., Cameron, D. E., Bolman, R. M., Miller, D. C., Moon, M. R., Mukherjee, D., Trento, A., Aldea, G. S., Bacha, E. A. 2014; 64 (14): 1515-1526

  View details for DOI 10.1016/j.jacc.2014.05.005

  View details for Web of Science ID 000343464800014

• SCAI/AATS/ACC/STS operator and institutional requirements for transcatheter valve repair and replacement. Part II. mitral valve. Journal of the American College of Cardiology Tommaso, C. L., Fullerton, D. A., Feldman, T., Dean, L. S., Hijazi, Z. M., Horlick, E., Weiner, B. H., Zahn, E., Cigarroa, J. E., Ruiz, C. E., Bavaria, J., Mack, M. J., Cameron, D. E., Bolman, R. M., Miller, D. C., Moon, M. R., Mukherjee, D., Trento, A., Aldea, G. S., Bacha, E. A. 2014; 64 (14): 1515-26

  View details for DOI 10.1016/j.jacc.2014.05.005

  View details for PubMedID 24835439

• Temporal Changes in Survival after Cardiac Surgery Are Associated with the Thirty-Day Mortality Benchmark HEALTH SERVICES RESEARCH Maxwell, B. G., Wong, J. K., Miller, D., Lobato, R. L. 2014; 49 (5): 1659–69

  Abstract

  To assess the hypothesis that postoperative survival exhibits heterogeneity associated with the timing of quality metrics.Retrospective observational study using the Nationwide Inpatient Sample from 2005 through 2009.Survival analysis was performed on all admission records with a procedure code for major cardiac surgery (n = 595,089). The day-by-day hazard function for all-cause in-hospital mortality at 1-day intervals was analyzed using joinpoint regression (a data-driven method of testing for changes in hazard).A comprehensive analysis of a publicly available national administrative database was performed.Statistically significant shifts in the pattern of postoperative mortality occurred at day 6 (95 percent CI = day 5-8) and day 30 (95 percent CI = day 20-35).While the shift at day 6 plausibly can be attributed to the separation between routine recovery and a complicated postoperative course, the abrupt increase in mortality at day 30 has no clear organic etiology. This analysis raises the possibility that this observed shift may be related to clinician behavior because of the use of 30-day mortality as a quality metric, but further studies will be required to establish causality.

  View details for DOI 10.1111/1475-6773.12174

  View details for Web of Science ID 000343006400014

  View details for PubMedID 24713085

  View details for PubMedCentralID PMC4213054

• SCAI/AATS/ACC/STS Operator and Institutional Requirements for Transcatheter Valve Repair and Replacement. Part II. Mitral Valve CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Tommaso, C. L., Fullerton, D. A., Feldman, T., Dean, L. S., Hijazi, Z. M., Horlick, E., Weiner, B. H., Zahn, E., Cigarroa, J. E., Ruiz, C. E., Bavaria, J., Mack, M. J., Cameron, D. E., Bolman, R., Miller, D., Moon, M. R., Mukherjee, D., Trento, A., Aldea, G. S., Bacha, E. A. 2014; 84 (4): 567–80

  View details for DOI 10.1002/ccd.25540

  View details for Web of Science ID 000342826900010

  View details for PubMedID 24828236

• Incidence and Sequelae of Prosthesis-Patient Mismatch in Transcatheter Versus Surgical Valve Replacement in High-Risk Patients With Severe Aortic Stenosis A PARTNER Trial Cohort-A Analysis JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Pibarot, P., Weissman, N. J., Stewart, W. J., Hahn, R. T., Lindman, B. R., McAndrew, T., Kodali, S. K., Mack, M. J., Thourani, V. H., Miller, C., Svensson, L. G., Herrmann, H. C., Smith, C. R., Rodes-Cabau, J., Webb, J., Lim, S., Xu, K., Hueter, I., Douglas, P. S., Leon, M. B. 2014; 64 (13): 1323-1334

  Abstract

  Little is known about the incidence of prosthesis-patient mismatch (PPM) and its impact on outcomes after transcatheter aortic valve replacement (TAVR).The objectives of this study were: 1) to compare the incidence of PPM in the TAVR and surgical aortic valve replacement (SAVR) randomized control trial (RCT) arms of the PARTNER (Placement of AoRTic TraNscathetER Valves) I Trial cohort A; and 2) to assess the impact of PPM on regression of left ventricular (LV) hypertrophy and mortality in these 2 arms and in the TAVR nonrandomized continued access (NRCA) registry cohort.The PARTNER Trial cohort A randomized patients 1:1 to TAVR or bioprosthetic SAVR. Postoperative PPM was defined as absent if the indexed effective orifice area (EOA) was >0.85 cm(2)/m(2), moderate if the indexed EOA was ≥0.65 but ≤0.85 cm(2)/m(2), or severe if the indexed EOA was <0.65 cm(2)/m(2). LV mass regression and mortality were analyzed using the SAVR-RCT (n = 270), TAVR-RCT (n = 304), and TAVR-NRCA (n = 1,637) cohorts.The incidence of PPM was 60.0% (severe: 28.1%) in the SAVR-RCT cohort versus 46.4% (severe: 19.7%) in the TAVR-RCT cohort (p < 0.001) and 43.8% (severe: 13.6%) in the TAVR-NRCA cohort. In patients with an aortic annulus diameter <20 mm, severe PPM developed in 33.7% undergoing SAVR compared with 19.0% undergoing TAVR (p = 0.002). PPM was an independent predictor of less LV mass regression at 1 year in the SAVR-RCT (p = 0.017) and TAVR-NRCA (p = 0.012) cohorts but not in the TAVR-RCT cohort (p = 0.35). Severe PPM was an independent predictor of 2-year mortality in the SAVR-RCT cohort (hazard ratio [HR]: 1.78; p = 0.041) but not in the TAVR-RCT cohort (HR: 0.58; p = 0.11). In the TAVR-NRCA cohort, severe PPM was not a predictor of 1-year mortality in all patients (HR: 1.05; p = 0.60) but did independently predict mortality in the subset of patients with no post-procedural aortic regurgitation (HR: 1.88; p = 0.02).In patients with severe aortic stenosis and high surgical risk, PPM is more frequent and more often severe after SAVR than TAVR. Patients with PPM after SAVR have worse survival and less LV mass regression than those without PPM. Severe PPM also has a significant impact on survival after TAVR in the subset of patients with no post-procedural aortic regurgitation. TAVR may be preferable to SAVR in patients with a small aortic annulus who are susceptible to PPM to avoid its adverse impact on LV mass regression and survival. (The PARTNER Trial: Placement of AoRTic TraNscathetER Valve Trial; NCT00530894).

  View details for DOI 10.1016/j.jacc.2014.06.1195

  View details for PubMedID 25257633

• SCAI/AATS/ACC/STS operator and institutional requirements for transcatheter valve repair and replacement. Part II. Mitral valve. journal of thoracic and cardiovascular surgery Tommaso, C. L., Fullerton, D. A., Feldman, T., Dean, L. S., Hijazi, Z. M., Horlick, E., Weiner, B. H., Zahn, E., Cigarroa, J. E., Ruiz, C. E., Bavaria, J., Mack, M. J., Cameron, D. E., Bolman, R. M., Miller, D. C., Moon, M. R., Mukherjee, D., Trento, A., Aldea, G. S., Bacha, E. A. 2014; 148 (2): 387-400

  View details for DOI 10.1016/j.jtcvs.2014.06.014

  View details for PubMedID 24996693

• SCAI/AATS/ACC/STS Operator and Institutional Requirements for Transcatheter Valve Repair and Replacement: Part II. Mitral Valve. Annals of thoracic surgery Tommaso, C. L., Fullerton, D. A., Feldman, T., Dean, L. S., Hijazi, Z. M., Horlick, E., Weiner, B. H., Zahn, E., Cigarroa, J. E., Ruiz, C. E., Bavaria, J., Mack, M. J., Cameron, D. E., Bolman, R. M., Miller, D. C., Moon, M. R., Mukherjee, D., Trento, A., Aldea, G. S., Bacha, E. A. 2014; 98 (2): 765-777

  View details for DOI 10.1016/j.athoracsur.2014.05.002

  View details for PubMedID 24835557

• Comprehensive Analysis of Mortality Among Patients Undergoing TAVR: Results of the PARTNER Trial. Journal of the American College of Cardiology Svensson, L. G., Blackstone, E. H., Rajeswaran, J., Brozzi, N., Leon, M. B., Smith, C. R., Mack, M., Miller, D. C., Moses, J. W., Tuzcu, E. M., Webb, J. G., Kapadia, S., Fontana, G. P., Makkar, R. R., Brown, D. L., Block, P. C., Guyton, R. A., Thourani, V. H., Pichard, A. D., Bavaria, J. E., Herrmann, H. C., Williams, M. R., Babaliaros, V., Généreux, P., Akin, J. J. 2014; 64 (2): 158-168

  Abstract

  Patients with severe aortic stenosis (AS) who were deemed too high risk or inoperable for conventional aortic valve replacement (AVR) in the PARTNER (Placement of Aortic Transcatheter Valves) trial were randomized to transcatheter aortic valve replacement (TAVR) versus AVR (PARTNER-A arm) or standard therapy (PARTNER-B arm).This study compared when and how deaths occurred after TAVR versus surgical AVR or standard therapy.The PARTNER-A arm included 244 transfemoral (TF) and 104 transapical (TA) TAVR patients, and 351 AVR patients; the PARTNER-B arm included 179 TF-TAVR patients and 179 standard therapy patients. Deaths were categorized as cardiovascular, noncardiovascular, or uncategorizable, and were characterized by multiphase hazard modelling.In the PARTNER-A arm, the risk of death peaked after randomization in the TA-TAVR and AVR groups, falling to low levels commensurate with the U.S. population within 3 months. Early risk was less in TF-TAVR patients, resulting in initial superior survival; between 12 and 18 months, risk increased, such that within 2 years, TF-TAVR and AVR patients had similar survival rates. Cardiovascular, noncardiovascular, and uncategorizable deaths for TF-TAVR were 37%, 43%, and 20%, respectively, versus 22%, 41%, and 37%, respectively, for TA-TAVR and 33%, 43%, and 24%, respectively, for AVR. In the PARTNER-B arm, risk with standard therapy was 60% per year; TF-TAVR reduced risk to 20% per year, resulting in 0.5 years of life added within 2.5 years.In inoperable AS patients, TAVR substantially reduced the risk of cardiovascular death. In high-risk patients, TA-TAVR and AVR were associated with elevated peri-procedural risk more than with TF-TAVR, although cardiovascular death was higher after TF-TAVR. Therefore, TF-TAVR should be considered the standard of care for severely symptomatic inoperable patients or those at high risk of noncardiovascular mortality after conventional surgery. (THE PARTNER TRIAL: Placement of AoRTic TraNscathetER Valve Trial; NCT00530894).

  View details for DOI 10.1016/j.jacc.2013.08.1666

  View details for PubMedID 25011720

• Early Regression of Severe Left Ventricular Hypertrophy After Transcatheter Aortic Valve Replacement Is Associated With Decreased Hospitalizations JACC-CARDIOVASCULAR INTERVENTIONS Lindman, B. R., Stewart, W. J., Pibarot, P., Hahn, R. T., Otto, C. M., Xu, K., Devereux, R. B., Weissman, N. J., Enriquez-Sarano, M., Szeto, W. Y., Makkar, R., Miller, D. C., Lerakis, S., Kapadia, S., Bowers, B., Greason, K. L., McAndrew, T. C., Lei, Y., Leon, M. B., Douglas, P. S. 2014; 7 (6): 662-673

  Abstract

  This study sought to examine the relationship between left ventricular mass (LVM) regression and clinical outcomes after transcatheter aortic valve replacement (TAVR).LVM regression after valve replacement for aortic stenosis is assumed to be a favorable effect of LV unloading, but its relationship to improved clinical outcomes is unclear.Of 2,115 patients with symptomatic aortic stenosis at high surgical risk receiving TAVR in the PARTNER (Placement of Aortic Transcatheter Valves) randomized trial or continued access registry, 690 had both severe LV hypertrophy (left ventricular mass index [LVMi] ≥ 149 g/m(2) men, ≥ 122 g/m(2) women) at baseline and an LVMi measurement at 30-day post-TAVR follow-up. Clinical outcomes were compared for patients with greater than versus lesser than median percentage change in LVMi between baseline and 30 days using Cox proportional hazard models to evaluate event rates from 30 to 365 days.Compared with patients with lesser regression, patients with greater LVMi regression had a similar rate of all-cause mortality (14.1% vs. 14.3%, p = 0.99), but a lower rate of rehospitalization (9.5% vs. 18.5%, hazard ratio [HR]: 0.50, 95% confidence interval [CI]: 0.32 to 0.78; p = 0.002) and a lower rate of rehospitalization specifically for heart failure (7.3% vs. 13.6%, p = 0.01). The association with a lower rate of rehospitalization was consistent across subgroups and remained significant after multivariable adjustment (HR: 0.53, 95% CI: 0.34 to 0.84; p = 0.007). Patients with greater LVMi regression had lower B-type natriuretic peptide (p = 0.002) and a trend toward better quality of life (p = 0.06) at 1-year follow-up than did those with lesser regression.In high-risk patients with severe aortic stenosis and severe LV hypertrophy undergoing TAVR, those with greater early LVM regression had one-half the rate of rehospitalization over the subsequent year compared to those with lesser regression.

  View details for DOI 10.1016/j.jcin.2014.02.011

  View details for PubMedID 24947722

• SINGLE-CENTER ACUTE AORTIC SYNDROME REGISTRY: A 10-YEAR EXPERIENCE OF "CLASS 3" LIMITED DISSECTION OF THE AORTA Chin, A. S., Kino, A., Berry, G., Rosenberg, J., Fischbein, M., Miller, D., Fleischmann, D. ELSEVIER SCIENCE INC. 2014: A1000

  View details for DOI 10.1016/S0735-1097(14)61000-7

  View details for Web of Science ID 000359579101658

• Aortic wall thickness: an independent risk factor for aortic dissection? journal of heart valve disease Shiran, H., Odegaard, J., Berry, G., Miller, D. C., Fischbein, M., Liang, D. 2014; 23 (1): 17-24

  Abstract

  Aortic aneurysm size is known to portend a higher likelihood of aortic complications in patients with connective tissue disorders (CTD), but other objective tools are needed to determine which patients are at greatest risk of dissection, especially those which reflect the structural integrity and strength of the aortic wall.The aortic wall pathology was evaluated in CTD patients with and without acute aortic dissection to identify parameters that affect the risk of dissection. A retrospective review was performed of aneurysm pathology from patients with Marfan syndrome (MFS; n = 53) without dissection undergoing prophylactic aortic root surgery, and acute type A aortic dissection patients (AAAoD; n = 16). Patients without a cardiovascular cause of death (n = 19) served as controls. The minimal aortic medial wall thickness was measured, and medial myxoid degeneration (MMD) and the degree of elastin loss and fragmentation were graded.The mean minimal aortic wall thickness was 1,625 +/- 364 microm in controls, and 703 +/- 256 microm and 438 +/- 322 microm for MFS and AAAoD patients, respectively. Aortic root diameters did not correlate with aortic wall thickness. A comparison of aortic medial thickness showed that the media was significantly thinner among acute dissection patients than either elective surgical patients (p = 0.02) or controls (p < 0.001). Aortic size, degree of MMD, and elastin loss did not vary significantly between CTD patients.A diminished aortic wall medial thickness may be linked to aortic dissection. High-resolution imaging techniques in the future may lead to the morphological assessment of aortic medial wall thickness in vivo becoming a reality which, in theory, could provide a more refined risk prognostication for acute aortic dissection.

  View details for PubMedID 24779324

• Impact of Preoperative Moderate/Severe Mitral Regurgitation on 2-Year Outcome After Transcatheter and Surgical Aortic Valve Replacement Insight From the Placement of Aortic Transcatheter Valve (PARTNER) Trial Cohort A CIRCULATION Barbanti, M., Webb, J. G., Hahn, R. T., Feldman, T., Boone, R. H., Smith, C. R., Kodali, S., Zajarias, A., Thompson, C. R., Green, P., Babaliaros, V., Makkar, R. R., Szeto, W. Y., Douglas, P. S., McAndrew, T., Hueter, I., Miller, D. C., Leon, M. B. 2013; 128 (25): 2776-?

  Abstract

  The effect of preoperative mitral regurgitation (MR) on clinical outcomes of patients undergoing transcatheter aortic valve replacement (TAVR) is controversial. This study sought to examine the impact of moderate and severe MR on outcomes after TAVR and surgical aortic valve replacement (SAVR).Data were drawn from the randomized Placement of Aortic Transcatheter Valve (PARTNER) Trial cohort A patients with severe, symptomatic aortic stenosis undergoing either TAVR (n=331) or SAVR (n=299). Both TAVR and SAVR patients were dichotomized according to the degree of preoperative MR (moderate/severe versus none/mild). At baseline, moderate or severe MR was reported in 65 TAVR patients (19.6%) and 63 SAVR patients (21.2%). At 30 days, among survivors who had isolated SAVR/TAVR, moderate/severe MR had improved in 25 SAVR patients (69.4%) and 30 TAVR patients (57.7%), was unchanged in 10 SAVR patients (27.8%) and 19 TAVR patients (36.5%), and worsened in 1 SAVR patient (2.8%) and 4 TAVR patients (5.8%; all P=NS). Mortality at 2 years was higher in SAVR patients with moderate or severe MR than in those with mild or less MR (49.8% versus 28.1%; adjusted hazard ratio, 1.73; 95% confidence interval, 1.01-2.96; P=0.04). In contrast, MR severity at baseline did not affect mortality in TAVR patients (37.0% versus 32.7%, moderate/severe versus none/mild; hazard ratio, 1.14; 95% confidence interval, 0.72-1.78; P=0.58; P for interaction=0.05).Both TAVR and SAVR were associated with a significant early improvement in MR in survivors. However, moderate or severe MR at baseline was associated with increased 2-year mortality after SAVR but not after TAVR. TAVR may be a reasonable option in selected patients with combined aortic and mitral valve disease.http://www.clinicaltrials.gov. Unique identifier: NCT00530894.

  View details for DOI 10.1161/CIRCULATIONAHA.113.003885

  View details for PubMedID 24152861

• Transapical Aortic Valve Replacement for Severe Aortic Stenosis: Results From the Nonrandomized Continued Access Cohort of the PARTNER Trial ANNALS OF THORACIC SURGERY Dewey, T. M., Bowers, B., Thourani, V. H., Babaliaros, V., Smith, C. R., Leon, M. B., Svensson, L. G., Tuzcu, E. M., Miller, D. C., Teirstein, P. S., Tyner, J., Brown, D. L., Fontana, G. P., Makkar, R. R., Williams, M. R., George, I., Kirtane, A. J., Bavaria, J. E., Mack, M. J. 2013; 96 (6): 2083-2089

  Abstract

  Transapical (TA) aortic valve replacement was an integral part of the Placement of Transcatheter Aortic Valves (PARTNER) trial. Enrollment during the randomized trial included 104 transapical (premarket approval TA [PMA-TA]) and 92 surgical aortic valve replacements (SAVR) within the TA cohort. On completion of the trial, enrollment continued in a nonrandomized continued access (NRCA) program. We compared the outcomes of NRCA-TA procedures with those of PMA-TA and SAVR.In 22 centers, 975 patients underwent TA aortic valve replacement as part of the NRCA registry. Inclusion and exclusion criteria were unchanged from the previously reported PARTNER trial. All patients were followed up for at least 1 year.Thirty-day or in-hospital mortality was 8.8% for the NRCA-TA cohort, compared with 10.6% and 12.0% for the PMA-TA and SAVR patients, respectively (p = 0.54). One-year mortality in the NRCA-TA cohort was 22.1%, not significantly lower than the mortality in PMA-TA and SAVR patients at 29.0% and 25.3%, respectively (p = 0.27). Thirty-day or in-hospital stroke was 2.2% among NRCA-TA patients in contrast to the 6.7% stroke rate observed in the PMA-TA group and 5.4% in SAVR patients (p = 0.008). Lower rates of neurologic adverse events in the NRCA-TA group persisted at 1 year compared with the PMA-TA and SAVR patients.Among the 975 patients in the NRCA-TA cohort, rates of major outcomes including death and stroke compared favorably with outcomes of PMA-TA and SAVR patients enrolled in the PARTNER trial. This trend toward improved outcomes may be attributed to improved patient selection, individual centers surmounting the procedural learning curve, and refinements in surgical technique.

  View details for DOI 10.1016/j.athoracsur.2013.05.093

  View details for Web of Science ID 000327794000033

  View details for PubMedID 23968764

• Regression of Severe Left Ventricular Hypertrophy After Transcatheter Valve Replacement for Aortic Stenosis: Impact on Clinical Outcomes in PARTNER Cohort A Lindman, B. R., Stewart, W., Pibarot, P., Hahn, R. T., Weissman, N. J., McAndrew, T. C., Szeto, W. Y., Makkar, R., Miller, D., Babaliaros, V., Kapadia, S., Bowers, B., Greason, K. L., Leon, M. B., Sarano, M., Devereux, R. B., Otto, C. M., Douglas, P. S. LIPPINCOTT WILLIAMS & WILKINS. 2013

  View details for Web of Science ID 000332162907257

• Left Ventricular Ejection Fraction Improves Less after Trans-Apical Transcatheter Aortic Valve Replacement Compared to a Trans-Femoral Approach Fearon, W. F., Elmariah, S., McAndrew, T., Vlahakes, G. J., Fischbein, M., Liang, D., Kodali, S., Leon, M., Svensson, L., Pibarot, P., Douglas, P., Passeri, J. J., Dewey, T., Szeto, W. Y., Babaliaros, V., Thourani, V., Williams, M., Miller, D. ELSEVIER SCIENCE INC. 2013: B36

  View details for DOI 10.1016/j.jacc.2013.08.841

  View details for Web of Science ID 000329845600109

• Mechanics of the mitral valve: a critical review, an in vivo parameter identification, and the effect of prestrain. Biomechanics and modeling in mechanobiology Rausch, M. K., Famaey, N., Shultz, T. O., Bothe, W., Miller, D. C., Kuhl, E. 2013; 12 (5): 1053-1071

  Abstract

  Alterations in mitral valve mechanics are classical indicators of valvular heart disease, such as mitral valve prolapse, mitral regurgitation, and mitral stenosis. Computational modeling is a powerful technique to quantify these alterations, to explore mitral valve physiology and pathology, and to classify the impact of novel treatment strategies. The selection of the appropriate constitutive model and the choice of its material parameters are paramount to the success of these models. However, the in vivo parameters values for these models are unknown. Here, we identify the in vivo material parameters for three common hyperelastic models for mitral valve tissue, an isotropic one and two anisotropic ones, using an inverse finite element approach. We demonstrate that the two anisotropic models provide an excellent fit to the in vivo data, with local displacement errors in the sub-millimeter range. In a complementary sensitivity analysis, we show that the identified parameter values are highly sensitive to prestrain, with some parameters varying up to four orders of magnitude. For the coupled anisotropic model, the stiffness varied from 119,021 kPa at 0 % prestrain via 36 kPa at 30 % prestrain to 9 kPa at 60 % prestrain. These results may, at least in part, explain the discrepancy between previously reported ex vivo and in vivo measurements of mitral leaflet stiffness. We believe that our study provides valuable guidelines for modeling mitral valve mechanics, selecting appropriate constitutive models, and choosing physiologically meaningful parameter values. Future studies will be necessary to experimentally and computationally investigate prestrain, to verify its existence, to quantify its magnitude, and to clarify its role in mitral valve mechanics.

  View details for DOI 10.1007/s10237-012-0462-z

  View details for PubMedID 23263365

  View details for PubMedCentralID PMC3634889

• Mechanics of the mitral valve BIOMECHANICS AND MODELING IN MECHANOBIOLOGY Rausch, M. K., Famaey, N., Shultz, T. O., Bothe, W., Miller, D. C., Kuhl, E. 2013; 12 (5): 1053-1071

  Abstract

  Alterations in mitral valve mechanics are classical indicators of valvular heart disease, such as mitral valve prolapse, mitral regurgitation, and mitral stenosis. Computational modeling is a powerful technique to quantify these alterations, to explore mitral valve physiology and pathology, and to classify the impact of novel treatment strategies. The selection of the appropriate constitutive model and the choice of its material parameters are paramount to the success of these models. However, the in vivo parameters values for these models are unknown. Here, we identify the in vivo material parameters for three common hyperelastic models for mitral valve tissue, an isotropic one and two anisotropic ones, using an inverse finite element approach. We demonstrate that the two anisotropic models provide an excellent fit to the in vivo data, with local displacement errors in the sub-millimeter range. In a complementary sensitivity analysis, we show that the identified parameter values are highly sensitive to prestrain, with some parameters varying up to four orders of magnitude. For the coupled anisotropic model, the stiffness varied from 119,021 kPa at 0 % prestrain via 36 kPa at 30 % prestrain to 9 kPa at 60 % prestrain. These results may, at least in part, explain the discrepancy between previously reported ex vivo and in vivo measurements of mitral leaflet stiffness. We believe that our study provides valuable guidelines for modeling mitral valve mechanics, selecting appropriate constitutive models, and choosing physiologically meaningful parameter values. Future studies will be necessary to experimentally and computationally investigate prestrain, to verify its existence, to quantify its magnitude, and to clarify its role in mitral valve mechanics.

  View details for DOI 10.1007/s10237-012-0462-z

  View details for Web of Science ID 000324378900014

  View details for PubMedCentralID PMC3634889

• Mechanics of the Mitral Annulus in Chronic Ischemic Cardiomyopathy ANNALS OF BIOMEDICAL ENGINEERING Rausch, M. K., Tibayan, F. A., Ingels, N. B., Miller, D. C., Kuhl, E. 2013; 41 (10): 2171-2180

  Abstract

  Approximately one third of all patients undergoing open-heart surgery for repair of ischemic mitral regurgitation present with residual and recurrent mitral valve leakage upon follow up. A fundamental quantitative understanding of mitral valve remodeling following myocardial infarction may hold the key to improved medical devices and better treatment outcomes. Here we quantify mitral annular strains and curvature in nine sheep 5 ± 1 weeks after controlled inferior myocardial infarction of the left ventricle. We complement our marker-based mechanical analysis of the remodeling mitral valve by common clinical measures of annular geometry before and after the infarct. After 5 ± 1 weeks, the mitral annulus dilated in septal-lateral direction by 15.2% (p = 0.003) and in commissure-commissure direction by 14.2% (p < 0.001). The septal annulus dilated by 10.4% (p = 0.013) and the lateral annulus dilated by 18.4% (p < 0.001). Remarkably, in animals with large degree of mitral regurgitation and annular remodeling, the annulus dilated asymmetrically with larger distortions toward the lateral-posterior segment. Strain analysis revealed average tensile strains of 25% over most of the annulus with exception for the lateral-posterior segment, where tensile strains were 50% and higher. Annular dilation and peak strains were closely correlated to the degree of mitral regurgitation. A complementary relative curvature analysis revealed a homogenous curvature decrease associated with significant annular circularization. All curvature profiles displayed distinct points of peak curvature disturbing the overall homogenous pattern. These hinge points may be the mechanistic origin for the asymmetric annular deformation following inferior myocardial infarction. In the future, this new insight into the mechanism of asymmetric annular dilation may support improved device designs and possibly aid surgeons in reconstructing healthy annular geometry during mitral valve repair.

  View details for DOI 10.1007/s10439-013-0813-7

  View details for PubMedID 23636575

• Implementation of Echocardiography Core Laboratory Best Practices: A Case Study of the PARTNER I Trial JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Douglas, P. S., Waugh, R. A., Bloomfield, G., Dunn, G., Davis, L., Hahn, R. T., Pibarot, P., Stewart, W. J., Weissman, N. J., Hueter, I., Siegel, R., Lerakis, S., Miller, D. C., Smith, C. R., Leon, M. B. 2013; 26 (4): 348-?

  Abstract

  Multicenter clinical trials use echocardiographic core laboratories to ensure expertise and consistency in the assessment of imaging eligibility criteria, as well as safety and efficacy end points. The aim of this study was to report the real-world implementation of guidelines for best practices in echocardiographic core laboratories, including their feasibility and quality results, in a large, international multicenter trial.Processes and procedures were developed to optimize the acquisition and analysis of echocardiograms for the Placement of Aortic Transcatheter Valves (PARTNER) I trial of percutaneous aortic valve replacement for aortic stenosis. Comparison of baseline findings in the operative and nonoperative cohorts and reproducibility analyses were performed.Echocardiography was performed in 1,055 patients (mean age, 83 years; 54% men) The average peak and mean aortic valve gradients were 73 ± 24 and 43 ± 15 mm Hg, and the average aortic valve area was 0.64 ± 0.20 cm(2). The average ejection fraction was 52 ± 13% by visual estimation and 53 ± 14% by biplane planimetry. The mean left ventricular mass index was 151 ± 42 g/m(2). The inoperable cohort had lower left ventricular mass and mass indexes and tended to have more severe mitral regurgitation. Core lab reproducibility was excellent, with intraclass correlation coefficients ranging from 0.92 to 0.99 and κ statistics from 0.58 to 0.85 for key variables. The image acquisition quality improvement process brought measurability to >85%, which was maintained for the duration of the study.This real-world echocardiographic core lab experience in the PARTNER I trial demonstrates that a high standard of measurability and reproducibility can result from extensive quality assurance efforts in both image acquisition and analysis. These results and the echocardiographic data reported here provide a reference for future studies of aortic stenosis patients and should encourage the wider use of echocardiography in clinical research.

  View details for DOI 10.1016/j.echo.2013.01.013

  View details for Web of Science ID 000317343600004

  View details for PubMedID 23465887

• Aortic Valve and Ascending Aorta Guidelines for Management and Quality Measures: Executive Summary ANNALS OF THORACIC SURGERY Svensson, L. G., Adams, D. H., Bonow, R. O., Kouchoukos, N. T., Miller, D. C., O'Gara, P. T., Shahian, D. M., Schaff, H. V., Akins, C. W., Bavaria, J., Blackstone, E. H., David, T. E., Desai, N. D., Dewey, T. M., D'Agostino, R. S., Gleason, T. G., Harrington, K. B., Kodali, S., Kapadia, S., Leon, M. B., Lima, B., Lytle, B. W., Mack, M. J., Reece, T. B., Reiss, G. R., Roselli, E., Smith, C. R., Thourani, V. H., Tuzcu, E. M., Webb, J., Williams, M. R. 2013; 95 (4): 1491-1505

  Abstract

  The Society of Thoracic Surgeons Clinical Practice Guidelines are intended to assist physicians and other health care providers in clinical decision making by describing a range of generally acceptable approaches for the diagnosis, management, or prevention of specific diseases or conditions. These guidelines should not be considered inclusive of all proper methods of care or exclusive of other methods of care reasonably directed at obtaining the same results. Moreover, these guidelines are subject to change over time, without notice. The ultimate judgment regarding the care of a particular patient must be made by the physician in light of the individual circumstances presented by the patient.

  View details for DOI 10.1016/j.athoracsur.2012.12.027

  View details for Web of Science ID 000317150600063

  View details for PubMedID 23291103

• Cost-Effectiveness of Transcatheter Aortic Valve Replacement Compared With Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results of the PARTNER (Placement of Aortic Transcatheter Valves) Trial (Cohort A) JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Reynolds, M. R., Magnuson, E. A., Lei, Y., Wang, K., Vilain, K., Li, H., Walczak, J., Pinto, D. S., Thourani, V. H., Svensson, L. G., Mack, M. J., Miller, D. C., Satler, L. E., Bavaria, J., Smith, C. R., Leon, M. B., Cohen, D. J. 2012; 60 (25): 2683-2692

  Abstract

  The aim of this study was to evaluate the cost-effectiveness of transcatheter aortic valve replacement (TAVR) compared with surgical aortic valve replacement (AVR) for patients with severe aortic stenosis and high surgical risk.TAVR is an alternative to AVR for patients with severe aortic stenosis and high surgical risk.We performed a formal economic analysis based on cost, quality of life, and survival data collected in the PARTNER A (Placement of Aortic Transcatheter Valves) trial in which patients with severe aortic stenosis and high surgical risk were randomized to TAVR or AVR. Cumulative 12-month costs (assessed from a U.S. societal perspective) and quality-adjusted life-years (QALYs) were compared separately for the transfemoral (TF) and transapical (TA) cohorts.Although 12-month costs and QALYs were similar for TAVR and AVR in the overall population, there were important differences when results were stratified by access site. In the TF cohort, total 12-month costs were slightly lower with TAVR and QALYs were slightly higher such that TF-TAVR was economically dominant compared with AVR in the base case and economically attractive (incremental cost-effectiveness ratio <$50,000/QALY) in 70.9% of bootstrap replicates. In the TA cohort, 12-month costs remained substantially higher with TAVR, whereas QALYs tended to be lower such that TA-TAVR was economically dominated by AVR in the base case and economically attractive in only 7.1% of replicates.In the PARTNER trial, TAVR was an economically attractive strategy compared with AVR for patients suitable for TF access. Future studies are necessary to determine whether improved experience and outcomes with TA-TAVR can improve its cost-effectiveness relative to AVR.

  View details for DOI 10.1016/j.jacc.2012.09.018

  View details for Web of Science ID 000312527000015

  View details for PubMedID 23122802

• Comparison of Aortic Root Diameter to Left Ventricular Outflow Diameter Versus Body Surface Area in Patients With Marfan Syndrome AMERICAN JOURNAL OF CARDIOLOGY Shiran, H., Haddad, F., Miller, D. C., Liang, D. 2012; 110 (10): 1518-1522

  Abstract

  Aortic root dilation is important in the diagnosis of familial aortic syndromes, such as Marfan syndrome, and an important risk factor for aortic complications, such as dissection or rupture. Transthoracic echocardiography reliably measures the absolute aortic root size; however, the degree of abnormality of the measurement requires correction for the expected normal aortic root size for each patient. The expected normal size is currently predicted according to the body surface area (BSA) and age. However, the correlation between root size and BSA is imperfect, particularly for older patients. A potential exists to improve the diagnosis and treatment of patients with aortic disease, with an improved estimation of normal aortic root size. A reference size derived from within the cardiovascular system has been hypothesized to provide a more direct correlation with the aortic root size. Images from the Stanford echocardiography database were reviewed, and measurements of the aortic root and internal dimensions were performed in a control cohort (n = 150). The measurements were repeated in adult patients with Marfan syndrome (n = 70) on serial echocardiograms (145 total studies reviewed). Of the 150 control patients, excellent correlation was found between the aortic root and left ventricular outflow tract diameters, r(2) = 0.67, and r(2) = 0.34 with BSA (p <0.0001, for both). More importantly, using the left ventricular outflow tract to predict the normal aortic root size, instead of the BSA and age, improved the diagnostic accuracy of aortic root measurements for diagnosing Marfan syndrome. In conclusion, an internal cardiovascular reference, the left ventricular outflow tract diameter, can improve the diagnosis of aortic disease and might provide a better reference for the degree of abnormality.

  View details for DOI 10.1016/j.amjcard.2012.06.062

  View details for Web of Science ID 000311523900021

  View details for PubMedID 22858189

• Iatrogenic Giant Coronary Artery Pseudoaneurysm With "Daughter Aneurysm" Formation Serial Imaging Findings and Natural History JOURNAL OF THORACIC IMAGING Cabarrus, M., Yang, B., Schiller, N., Miller, D. C., Ordovas, K. 2012; 27 (6): W185-W187

  Abstract

  Coronary pseudoaneurysms rarely occur spontaneously; rather, they are more commonly seen as a complication of coronary intervention. We present a case of a giant right coronary artery pseudoaneurysm with partial thrombosis after arterial perforation during percutaneous intervention for acute myocardial infarction and formation of a "daughter aneurysm" due to a contained rupture 12 years later. Right coronary pseudoaneurysm repair and coronary artery bypass grafting were eventually performed 16 years after the acute event. Cardiac magnetic resonance imaging, coronary computed tomography angiography, and autopsy findings are shown.

  View details for DOI 10.1097/RTI.0b013e318255002c

  View details for Web of Science ID 000310432600009

  View details for PubMedID 22688674

• Evidence of adaptive mitral leaflet growth JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS Rausch, M. K., Tibayan, F. A., Miller, D. C., Kuhl, E. 2012; 15: 208-217

  Abstract

  Ischemic mitral regurgitation is mitral insufficiency caused by myocardial infarction. Recent studies suggest that mitral leaflets have the potential to grow and reduce the degree of regurgitation. Leaflet growth has been associated with papillary muscle displacement, but role of annular dilation in leaflet growth is unclear. We tested the hypothesis that chronic leaflet stretch, induced by papillary muscle tethering and annular dilation, triggers chronic leaflet growth. To decipher the mechanisms that drive the growth process, we further quantified regional and directional variations of growth. Five adult sheep underwent coronary snare and marker placement on the left ventricle, papillary muscles, mitral annulus, and mitral leaflet. After eight days, we tightened the snares to create inferior myocardial infarction. We recorded marker coordinates at baseline, acutely (immediately post-infarction), and chronically (five weeks post-infarction). From these coordinates, we calculated acute and chronic changes in ventricular, papillary muscle, and annular geometry along with acute and chronic leaflet strains. Chronic left ventricular dilation of 17.15% (p<0.001) induced chronic posterior papillary muscle displacement of 13.49 mm (p=0.07). Chronic mitral annular area, commissural and septal-lateral distances increased by 32.50% (p=0.010), 14.11% (p=0.007), and 10.84% (p=0.010). Chronic area, circumferential, and radial growth were 15.57%, 5.91%, and 3.58%, with non-significant regional variations (p=0.868). Our study demonstrates that mechanical stretch, induced by annular dilation and papillary muscle tethering, triggers mitral leaflet growth. Understanding the mechanisms of leaflet adaptation may open new avenues to pharmacologically or surgically manipulate mechanotransduction pathways to augment mitral leaflet area and reduce the degree of regurgitation.

  View details for DOI 10.1016/j.jmbbm.2012.07.001

  View details for Web of Science ID 000313598800020

  View details for PubMedID 23159489

  View details for PubMedCentralID PMC3508091

• Contemporary Results for Proximal Aortic Replacement in North America JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Williams, J. B., Peterson, E. D., Zhao, Y., O'Brien, S. M., Andersen, N. D., Miller, D. C., Chen, E. P., Hughes, G. C. 2012; 60 (13): 1156-1162

  Abstract

  The purpose of this study was to characterize operative outcomes for ascending aorta and arch replacement on a national scale and to develop risk models for mortality and major morbidity.Contemporary outcomes for ascending aorta and arch replacement in North America are unknown.We queried the Society of Thoracic Surgeons Database for patients undergoing ascending aorta (with or without root) with or without arch replacement from 2004 to 2009. The database captured 45,894 cases, including 12,702 root, 22,048 supracoronary ascending alone, 6,786 ascending plus arch, and 4,358 root plus arch. Baseline characteristics and clinical outcomes were analyzed. A parsimonious multivariable logistic regression model was constructed to predict risks of mortality and major morbidity.Operative mortality was 3.4% for elective cases and 15.4% for nonelective cases. A risk model for operative mortality (c-index 0.81) revealed a risk-adjusted odds ratio for death after emergent versus elective operation of 5.9 (95% confidence interval: 5.3 to 6.6). Among elective patients, end-stage renal disease and reoperative status were the strongest predictors of mortality (adjusted odds ratios: 4.0 [95% confidence interval: 2.6 to 6.4] and 2.3 (95% confidence interval: 1.9 to 2.7], respectively; p < 0.0001).Current outcomes for ascending aorta and arch replacement in North America are excellent for elective repair; however, results deteriorate for nonelective status, suggesting that increased screening and/or lowering thresholds for elective intervention could potentially improve outcomes. The predictive models presented may serve clinicians in counseling patients.

  View details for DOI 10.1016/j.jacc.2012.06.023

  View details for Web of Science ID 000309112700006

  View details for PubMedID 22958956

  View details for PubMedCentralID PMC3699187

• How Do Annuloplasty Rings Affect Mitral Annular Strains in the Normal Beating Ovine Heart? Meeting of the American-Heart-Association Bothe, W., Rausch, M. K., Kvitting, J. E., Echtner, D. K., Walther, M., Ingels, N. B., Kuhl, E., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2012: S231–S238

  Abstract

  We hypothesized that annuloplasty ring implantation alters mitral annular strains in a normal beating ovine heart preparation.Sheep had 16 radiopaque markers sewn equally spaced around the mitral annulus. Edwards Cosgrove partial flexible band (COS; n=12), St Jude complete rigid saddle-shaped annuloplasty ring (RSA; n=10), Carpentier-Edwards Physio (PHY; n=11), Edwards IMR ETlogix (ETL; n=11), and GeoForm (GEO; n=12) annuloplasty rings were implanted in a releasable fashion. Four-dimensional marker coordinates were obtained using biplane videofluoroscopy with the ring inserted (ring) and after ring release (control). From marker coordinates, a functional spatio-temporal representation of each annulus was generated through a best fit using 16 piecewise cubic Hermitian splines. Absolute total mitral annular ring strains were calculated from the relative change in length of the tangent vector to the annular curve as strains occurring from control to ring state at end-systole. In addition, average Green-Lagrange strains occurring from control to ring state at end-systole along the annulus were calculated. Absolute total mitral annular ring strains were smallest for COS and greatest for ETL. Strains for RSA, PHY, and GEO were similar. Except for COS in the septal mitral annular segment, all rings induced compressive strains along the entire annulus, with greatest values occurring at the lateral mitral annular segment.In healthy, beating ovine hearts, annuloplasty rings (COS, RSA, PHY, ETL, and GEO) induce compressive strains that are predominate in the lateral annular region, smallest for flexible partial bands (COS) and greatest for an asymmetrical rigid ring type with intrinsic septal-lateral downsizing (ETL). However, the ring type with the most drastic intrinsic septal-lateral downsizing (GEO) introduced strains similar to physiologically shaped rings (RSA and PHY), indicating that ring effects on annular strain profiles cannot be estimated from the degree of septal-lateral downsizing.

  View details for DOI 10.1161/CIRCULATIONAHA.111.084046

  View details for PubMedID 22965988

• Bicuspid aortic valve configuration and aortopathy pattern might represent different pathophysiologic substrates JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Kari, F. A., Fazel, S. S., Mitchell, R. S., Fischbein, M. P., Miller, D. C. 2012; 144 (2): 516-517

  View details for DOI 10.1016/j.jtcvs.2012.05.035

  View details for PubMedID 22698560

• Vagal nerve stimulation reduces anterior mitral valve leaflet stiffness in the beating ovine heart JOURNAL OF BIOMECHANICS Swanson, J. C., Krishnamurthy, G., Itoh, A., Kvitting, J. E., Bothe, W., Miller, D. C., Ingels, N. B. 2012; 45 (11): 2007-2013

  Abstract

  The functional significance of the autonomic nerves in the anterior mitral valve leaflet (AML) is unknown. We tested the hypothesis that remote stimulation of the vagus nerve (VNS) reduces AML stiffness in the beating heart.Forty-eight radiopaque-markers were implanted into eleven ovine hearts to delineate left ventricular and mitral anatomy, including an AML array. The anesthetized animals were then taken to the catheterization laboratory and 4-D marker coordinates obtained from biplane videofluoroscopy before and after VNS. Circumferential (E(circ)) and radial (E(rad)) stiffness values for three separate AML regions, Annulus, Belly and Edge, were obtained from inverse finite element analysis of AML displacements in response to trans-leaflet pressure changes during isovolumic contraction (IVC) and isovolumic relaxation (IVR).VNS reduced heart rate: 94±9 vs. 82±10min(-1), (mean±SD, p<0.001). Circumferential AML stiffness was significantly reduced in all three regions during IVC and IVR (all p<0.05). Radial AML stiffness was reduced from control in the annular and belly regions at both IVC and IVR (P<0.05), while the reduction did not reach significance at the AML edge.These observations suggest that one potential functional role for the parasympathetic nerves in the AML is to alter leaflet stiffness. Neural control of the contractile tissue in the AML could be part of a central control system capable of altering valve stiffness to adapt to changing hemodynamic demands.

  View details for DOI 10.1016/j.jbiomech.2012.04.009

  View details for PubMedID 22703898

• Multisociety (AATS, ACCF, SCAI, and STS) expert consensus statement: Operator and institutional requirements for transcatheter valve repair and replacement, part 1: Transcatheter aortic valve replacement CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Tommaso, C. L., Bolman, R. M., Feldman, T., Bavaria, J., Acker, M. A., Aldea, G., Cameron, D. E., Dean, L. S., Fullerton, D., Hijazi, Z. M., Horlick, E., Miller, D. C., Moon, M. R., Ringel, R., Ruiz, C. E., Trento, A., Weiner, B. H., Zahn, E. M. 2012; 80 (1): 1-17

  View details for DOI 10.1002/ccd.24394

  View details for Web of Science ID 000305692100001

  View details for PubMedID 22383383

• Multisociety (AATS, ACCF, SCAI, and STS) Expert Consensus Statement: Operator and Institutional Requirements for Transcatheter Valve Repair and Replacement, Part 1: Transcatheter Aortic Valve Replacement ANNALS OF THORACIC SURGERY Tommaso, C. L., Bolman, R. M., Feldman, T., Bavaria, J., Acker, M. A., Aldea, G., Cameron, D. E., Dean, L. S., Fullerton, D., Hijazi, Z. M., Horlick, E., Miller, D. C., Moon, M. R., Ringel, R., Ruiz, C. E., Trento, A., Weiner, B. H., Zahn, E. M. 2012; 93 (6): 2093-2110

  View details for DOI 10.1016/j.athoracsur.2012.02.063

  View details for Web of Science ID 000304460000072

  View details for PubMedID 22386085

• Multisociety (AATS, ACCF, SCAI, and STS) expert consensus statement: Operator and institutional requirements for transcatheter valve repair and replacement, part 1: Transcatheter aortic valve replacement JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Tommaso, C. L., Bolman, R. M., Feldman, T., Bavaria, J., Acker, M. A., Aldea, G., Cameron, D. E., Dean, L. S., Fullerton, D., Hijazi, Z. M., Horlick, E., Miller, D. C., Moon, M. R., Ringel, R., Ruiz, C. E., Trento, A., Weiner, B. H., Zahn, E. M. 2012; 143 (6): 1254-?

  View details for DOI 10.1016/j.jtcvs.2012.03.002

  View details for Web of Science ID 000304110700004

  View details for PubMedID 22595626

• Multisociety (AATS, ACCF, SCAI, and STS) Expert Consensus Statement: Operator and Institutional Requirements for Transcatheter Valve Repair and Replacement, Part 1: Transcatheter Aortic Valve Replacement JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Tommaso, C. L., Bolman, R. M., Feldman, T., Bavaria, J., Acker, M. A., Aldea, G., Cameron, D. E., Dean, L. S., Fullerton, D., Hijazi, Z. M., Horlick, E., Miller, D. C., Moon, M. R., Ringel, R., Ruiz, C. E., Trento, A., Weiner, B. H., Zahn, E. M. 2012; 59 (22): 2028-2042

  View details for DOI 10.1016/j.jacc.2012.02.016

  View details for Web of Science ID 000304591300016

  View details for PubMedID 22387052

• Two-Year Outcomes after Transcatheter or Surgical Aortic-Valve Replacement NEW ENGLAND JOURNAL OF MEDICINE Kodali, S. K., Williams, M. R., Smith, C. R., Svensson, L. G., Webb, J. G., Makkar, R. R., Fontana, G. P., Dewey, T. M., Thourani, V. H., Pichard, A. D., Fischbein, M., Szeto, W. Y., Lim, S., Greason, K. L., Teirstein, P. S., Malaisrie, S. C., Douglas, P. S., Hahn, R. T., Whisenant, B., Zajarias, A., Wang, D., Akin, J. J., Anderson, W. N., Leon, M. B. 2012; 366 (18): 1686-1695

  Abstract

  The Placement of Aortic Transcatheter Valves (PARTNER) trial showed that among high-risk patients with aortic stenosis, the 1-year survival rates are similar with transcatheter aortic-valve replacement (TAVR) and surgical replacement. However, longer-term follow-up is necessary to determine whether TAVR has prolonged benefits.At 25 centers, we randomly assigned 699 high-risk patients with severe aortic stenosis to undergo either surgical aortic-valve replacement or TAVR. All patients were followed for at least 2 years, with assessment of clinical outcomes and echocardiographic evaluation.The rates of death from any cause were similar in the TAVR and surgery groups (hazard ratio with TAVR, 0.90; 95% confidence interval [CI], 0.71 to 1.15; P=0.41) and at 2 years (Kaplan-Meier analysis) were 33.9% in the TAVR group and 35.0% in the surgery group (P=0.78). The frequency of all strokes during follow-up did not differ significantly between the two groups (hazard ratio, 1.22; 95% CI, 0.67 to 2.23; P=0.52). At 30 days, strokes were more frequent with TAVR than with surgical replacement (4.6% vs. 2.4%, P=0.12); subsequently, there were 8 additional strokes in the TAVR group and 12 in the surgery group. Improvement in valve areas was similar with TAVR and surgical replacement and was maintained for 2 years. Paravalvular regurgitation was more frequent after TAVR (P<0.001), and even mild paravalvular regurgitation was associated with increased late mortality (P<0.001).A 2-year follow-up of patients in the PARTNER trial supports TAVR as an alternative to surgery in high-risk patients. The two treatments were similar with respect to mortality, reduction in symptoms, and improved valve hemodynamics, but paravalvular regurgitation was more frequent after TAVR and was associated with increased late mortality. (Funded by Edwards Lifesciences; ClinicalTrials.gov number, NCT00530894.).

  View details for Web of Science ID 000303434300008

  View details for PubMedID 22443479

• Kinematics of cardiac growth: In vivo characterization of growth tensors and strains JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS Tsamis, A., Cheng, A., Nguyen, T. C., Langer, F., Miller, D. C., Kuhl, E. 2012; 8: 165-177

  Abstract

  Progressive growth and remodeling of the left ventricle are part of the natural history of chronic heart failure and strong clinical indicators for survival. Accompanied by changes in cardiac form and function, they manifest themselves in alterations of cardiac strains, fiber stretches, and muscle volume. Recent attempts to shed light on the mechanistic origin of heart failure utilize continuum theories of growth to predict the maladaptation of the heart in response to pressure or volume overload. However, despite a general consensus on the representation of growth through a second order tensor, the precise format of this growth tensor remains unknown. Here we show that infarct-induced cardiac dilation is associated with a chronic longitudinal growth, accompanied by a chronic thinning of the ventricular wall. In controlled in vivo experiments throughout a period of seven weeks, we found that the lateral left ventricular wall adjacent to the infarct grows longitudinally by more than 10%, thins by more than 25%, lengthens in fiber direction by more than 5%, and decreases its volume by more than 15%. Our results illustrate how a local loss of blood supply induces chronic alterations in structure and function in adjacent regions of the ventricular wall. We anticipate our findings to be the starting point for a series of in vivo studies to calibrate and validate constitutive models for cardiac growth. Ultimately, these models could be useful to guide the design of novel therapies, which allow us to control the progression of heart failure.

  View details for DOI 10.1016/j.jmbbm.2011.12.006

  View details for Web of Science ID 000302586300015

  View details for PubMedID 22402163

  View details for PubMedCentralID PMC3298662

• AORTIC WALL THICKNESS MAY BE AN INDEPENDENT RISK FACTOR FOR AORTIC DISSECTION 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC)/Conference on ACC-i2 with TCT Shiran, H., Odegaard, J., Berry, G., Miller, D. C., Fischbein, M., Liang, D. ELSEVIER SCIENCE INC. 2012: E831–E831

  View details for Web of Science ID 000302326700834

• ACCURACY AND REPRODUCIBILITY OF CONTRAST ENHANCED AND NON-ENHANCED COMPUTED TOMOGRAPHY FOR PREDICTING THE ANGIOGRAPHIC DEPLOYMENT ANGLE IN TRANSCATHETER AORTIC VALVE REPLACEMENT (TAVR) 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC)/Conference on ACC-i2 with TCT Dao, C. N., Blake, T., Liang, D., Fischbein, M. P., Yeung, A., Fearon, W., Miller, D. C., Fleischmann, D. ELSEVIER SCIENCE INC. 2012: E1195–E1195

  View details for Web of Science ID 000302326701306

• COMPUTED TOMOGRAPHY BASED PREDICTION OF ANGIOGRAPHIC DEPLOYMENT ANGLES MAY REDUCE PROCEDURE TIME AND CONTRAST MEDIUM VOLUME FOR TRANSCATHETER AORTIC VALVE REPLACEMENT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC)/Conference on ACC-i2 with TCT Fleischmann, D., Dao, C., Blake, T., Boas, F. E., Liang, D., Yeung, A., Fearon, W., Fischbein, M., Miller, D. C. ELSEVIER SCIENCE INC. 2012: E1199–E1199

  View details for Web of Science ID 000302326701310

• Mitral Valve Annuloplasty A Quantitative Clinical and Mechanical Comparison of Different Annuloplasty Devices ANNALS OF BIOMEDICAL ENGINEERING Rausch, M. K., Bothe, W., Kvitting, J. E., Swanson, J. C., Miller, D. C., Kuhl, E. 2012; 40 (3): 750-761

  Abstract

  Mitral valve annuloplasty is a common surgical technique used in the repair of a leaking valve by implanting an annuloplasty device. To enhance repair durability, these devices are designed to increase leaflet coaptation, while preserving the native annular shape and motion; however, the precise impact of device implantation on annular deformation, strain, and curvature is unknown. In this article, we quantify how three frequently used devices significantly impair native annular dynamics. In controlled in vivo experiments, we surgically implanted 11 flexible-incomplete, 11 semi-rigid-complete, and 12 rigid-complete devices around the mitral annuli of 34 sheep, each tagged with 16 equally spaced tantalum markers. We recorded four-dimensional marker coordinates using biplane videofluoroscopy, first with device and then without, which were used to create mathematical models using piecewise cubic splines. Clinical metrics (characteristic anatomical distances) revealed significant global reduction in annular dynamics upon device implantation. Mechanical metrics (strain and curvature fields) explained this reduction via a local loss of anterior dilation and posterior contraction. Overall, all three devices unfavorably caused reduction in annular dynamics. The flexible-incomplete device, however, preserved native annular dynamics to a larger extent than the complete devices. Heterogeneous strain and curvature profiles suggest the need for heterogeneous support, which may spawn more rational design of annuloplasty devices using design concepts of functionally graded materials.

  View details for DOI 10.1007/s10439-011-0442-y

  View details for PubMedID 22037916

• Contribution of myocardium overlying the anterolateral papillary muscle to left ventricular deformation AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Itoh, A., Stephens, E. H., Ennis, D. B., Carlhall, C., Bothe, W., Nguyen, T. C., Swanson, J. C., Miller, D. C., Ingels, N. B. 2012; 302 (1): H180-H187

  Abstract

  Previous studies of transmural left ventricular (LV) strains suggested that the myocardium overlying the papillary muscle displays decreased deformation relative to the anterior LV free wall or significant regional heterogeneity. These comparisons, however, were made using different hearts. We sought to extend these studies by examining three equatorial LV regions in the same heart during the same heartbeat. Therefore, deformation was analyzed from transmural beadsets placed in the equatorial LV myocardium overlying the anterolateral papillary muscle (PAP), as well as adjacent equatorial LV regions located more anteriorly (ANT) and laterally (LAT). We found that the magnitudes of LAT normal longitudinal and radial strains, as well as major principal strains, were less than ANT, while those of PAP were intermediate. Subepicardial and midwall myofiber angles of LAT, PAP, and ANT were not significantly different, but PAP subendocardial myofiber angles were significantly higher (more longitudinal as opposed to circumferential orientation). Subepicardial and midwall myofiber strains of ANT, PAP, and LAT were not significantly different, but PAP subendocardial myofiber strains were less. Transmural gradients in circumferential and radial normal strains, and major principal strains, were observed in each region. The two main findings of this study were as follows: 1) PAP strains are largely consistent with adjacent LV equatorial free wall regions, and 2) there is a gradient of strains across the anterolateral equatorial left ventricle despite similarities in myofiber angles and strains. These findings point to graduated equatorial LV heterogeneity and suggest that regional differences in myofiber coupling may constitute the basis for such heterogeneity.

  View details for DOI 10.1152/ajpheart.00687.2011

  View details for PubMedID 22037187

• CHRONIC MITRAL VALVE LEAFLET GROWTH FOLLOWING MYOCARDIAL INFARCTION ASME Summer Bioengineering Conference (SBC) Rausch, M. K., Tibayan, F. A., Miller, D. C., Kuhl, E. AMER SOC MECHANICAL ENGINEERS. 2012: 1015–1016

  View details for Web of Science ID 000325036600507

• Intraoperative Conversion after Surgical Failure An Overlooked Complication of Aortic Root Replacement in Marfan Patients? TEXAS HEART INSTITUTE JOURNAL Volguina, I. V., LeMaire, S. A., Palmero, L. C., Miller, D. C., Coselli, J. S. 2011; 38 (6): 684-686

  View details for Web of Science ID 000297963100019

  View details for PubMedID 22199436

  View details for PubMedCentralID PMC3233342

• How do Annuloplasty Rings Affect Mitral Annular Strains in the Beating Ovine Heart? Scientific Sessions of the American-Heart-Association/Resuscitation Science Symposium Bothe, W., Rausch, M. K., Kvitting, J. E., Echtner, D. K., Ingels, N. B., Kuhl, E., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2011

  View details for Web of Science ID 000299738705206

• The Presence of Two Local Myocardial Sheet Populations Confirmed by Diffusion Tensor MRI and Histological Validation JOURNAL OF MAGNETIC RESONANCE IMAGING Kung, G. L., Tom C Nguyen, T. C., Itoh, A., Skare, S., Ingels, N. B., Miller, D. C., Ennis, D. B. 2011; 34 (5): 1080-1091

  Abstract

  To establish the correspondence between the two histologically observable and diffusion tensor MRI (DTMRI) measurements of myolaminae orientation for the first time and show that single myolaminar orientations observed in local histology may result from histological artifact.DTMRI was performed on six sheep left ventricles (LV), then corresponding direct histological transmural measurements were made within the anterobasal and lateral-equatorial LV. Secondary and tertiary eigenvectors of the diffusion tensor were compared with each of the two locally observable sheet orientations from histology. Diffusion tensor invariants were calculated to compare differences in microstructural diffusive properties between histological locations with one observable sheet population and two observable sheet populations.Mean difference ± 1SD between DTMRI and histology measured sheet angles was 8° ± 27°. Diffusion tensor invariants showed no significant differences between histological locations with one observable sheet population and locations with two observable sheet populations.DTMRI measurements of myolaminae orientations derived from the secondary and tertiary eigenvectors correspond to each of the two local myolaminae orientations observed in histology. Two local sheet populations may exist throughout LV myocardium, and one local sheet population observed in histology may be a result of preparation artifact.

  View details for DOI 10.1002/jmri.22725

  View details for Web of Science ID 000296206900011

  View details for PubMedID 21932362

  View details for PubMedCentralID PMC3195899

• Active contraction of cardiac muscle: In vivo characterization of mechanical activation sequences in the beating heart JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS Tsamis, A., Bothe, W., Kvitting, J. E., Swanson, J. C., Miller, D. C., Kuhl, E. 2011; 4 (7): 1167-1176

  Abstract

  Progressive alterations in cardiac wall strains are a classic hallmark of chronic heart failure. Accordingly, the objectives of this study are to establish a baseline characterization of cardiac strains throughout the cardiac cycle, to quantify temporal, regional, and transmural variations of active fiber contraction, and to identify pathways of mechanical activation in the healthy beating heart. To this end, we insert two sets of twelve radiopaque beads into the heart muscle of nine sheep; one in the anterior-basal and one in the lateral-equatorial left ventricular wall. During three consecutive heartbeats, we record the bead coordinates via biplane videofluoroscopy. From the resulting four-dimensional data sets, we calculate the temporally and transmurally varying Green-Lagrange strains in the anterior and lateral wall. To quantify active contraction, we project the strains onto the local muscle fiber directions. We observe that mechanical activation is initiated at the endocardium slightly after end diastole and progresses transmurally outward, reaching the epicardium slightly before end systole. Accordingly, fibers near the outer wall are in contraction for approximately half of the cardiac cycle while fibers near the inner wall are in contraction almost throughout the entire cardiac cycle. In summary, cardiac wall strains display significant temporal, regional, and transmural variations. Quantifying wall strain profiles might be of particular clinical significance when characterizing stages of left ventricular remodeling, but also of engineering relevance when designing new biomaterials of similar structure and function.

  View details for DOI 10.1016/j.jmbbm.2011.03.027

  View details for Web of Science ID 000294187500025

  View details for PubMedID 21783125

  View details for PubMedCentralID PMC3143370

• Another multidisciplinary look at ischemic mitral regurgitation. Seminars in thoracic and cardiovascular surgery Timek, T. A., Miller, D. C. 2011; 23 (3): 220-231

  Abstract

  Ischemic mitral regurgitation (IMR) continues to challenge surgeons and scientists alike. This vexing clinical entity frequently complicates myocardial infarction and carries a poor prognosis both in the setting of coronary disease and idiopathic dilated cardiomyopathy. Ischemic mitral regurgitation encompasses a difficult patient population that is characterized by high operative mortality, poor long term outcomes, and frequent recurrent insufficiency after standard surgical repair. Yet optimal surgical repair and improved clinical outcomes can only be achieved with better knowledge of the pathophysiology of IMR which is still incompletely understood. The causative mechanism of IMR appears to lie in the annular and subvalvular frame of the valve rather than leaflet or chordal structure leading to such labels as "ischemic," "functional," "non-organic," and "cardiomyopathy associated" being applied in the clinical literature. Although ischemic mitral regurgitation is a prevailing clinical entity, it has not been consistently defined in the literature, contributing to considerable confusion and contradictory results of clinical studies. As the mechanisms of pathophysiology have been better elucidated, novel surgical and interventional strategies have been developed recently to provide better treatment for this difficult patient population. In this review, we undertake a multidisciplinary update of the pathophysiology, classification, and surgical and interventional treatment of ischemic mitral regurgitation in today's clinical practice.

  View details for DOI 10.1053/j.semtcvs.2011.07.002

  View details for PubMedID 22172360

• Rigid, Complete Annuloplasty Rings Increase Anterior Mitral Leaflet Strains in the Normal Beating Ovine Heart Annual Meeting of the American-Heart-Association Bothe, W., Kuhl, E., Kvitting, J. E., Rausch, M. K., Goektepe, S., Swanson, J. C., Farahmandnia, S., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2011: S81–S96

  Abstract

  Annuloplasty ring or band implantation during surgical mitral valve repair perturbs mitral annular dimensions, dynamics, and shape, which have been associated with changes in anterior mitral leaflet (AML) strain patterns and suboptimal long-term repair durability. We hypothesized that rigid rings with nonphysiological three-dimensional shapes, but not saddle-shaped rigid rings or flexible bands, increase AML strains.Sheep had 23 radiopaque markers inserted: 7 along the anterior mitral annulus and 16 equally spaced on the AML. True-sized Cosgrove-Edwards flexible, partial band (n=12), rigid, complete St Jude Medical rigid saddle-shaped (n=12), Carpentier-Edwards Physio (n=12), Edwards IMR ETlogix (n=11), and Edwards GeoForm (n=12) annuloplasty rings were implanted in a releasable fashion. Under acute open-chest conditions, 4-dimensional marker coordinates were obtained using biplane videofluoroscopy along with hemodynamic parameters with the ring inserted and after release. Marker coordinates were triangulated, and the largest maximum principal AML strains were determined during isovolumetric relaxation. No relevant changes in hemodynamics occurred. Compared with the respective control state, strains increased significantly with rigid saddle-shaped annuloplasty ring, Carpentier-Edwards Physio, Edwards IMR ETlogix, and Edwards GeoForm (0.14 ± 0.05 versus 0.16 ± 0.05, P=0.024, 0.15 ± 0.03 versus 0.18 ± 0.04, P=0.020, 0.11 ± 0.05 versus 0.14 ± 0.05, P=0.042, and 0.13 ± 0.05 versus 0.16 ± 0.05, P=0.009), but not with Cosgrove-Edwards band (0.15 ± 0.05 versus 0.15 ± 0.04, P=0.973).Regardless of three-dimensional shape, rigid, complete annuloplasty rings, but not a flexible, partial band, increased AML strains in the normal beating ovine heart. Clinical studies are needed to determine whether annuloplasty rings affect AML strains in patients, and, if so, whether ring-induced perturbations in leaflet strain states are linked to repair failure.

  View details for DOI 10.1161/CIRCULATIONAHA.110.011163

  View details for PubMedID 21911823

• Characterization of Mitral Valve Annular Dynamics in the Beating Heart ANNALS OF BIOMEDICAL ENGINEERING Rausch, M. K., Bothe, W., Kvitting, J. E., Swanson, J. C., Ingels, N. B., Miller, D. C., Kuhl, E. 2011; 39 (6): 1690-1702

  Abstract

  The objective of this study is to establish a mathematical characterization of the mitral valve annulus that allows a precise qualitative and quantitative assessment of annular dynamics in the beating heart. We define annular geometry through 16 miniature markers sewn onto the annuli of 55 sheep. Using biplane videofluoroscopy, we record marker coordinates in vivo. By approximating these 16 marker coordinates through piecewise cubic splines, we generate a smooth mathematical representation of the 55 mitral annuli. We time-align these 55 annulus representations with respect to characteristic hemodynamic time points to generate an averaged baseline annulus representation. To characterize annular physiology, we extract classical clinical metrics of annular form and function throughout the cardiac cycle. To characterize annular dynamics, we calculate displacements, strains, and curvature from the discrete mathematical representations. To illustrate potential future applications of this approach, we create rapid prototypes of the averaged mitral annulus at characteristic hemodynamic time points. In summary, this study introduces a novel mathematical model that allows us to identify temporal, regional, and inter-subject variations of clinical and mechanical metrics that characterize mitral annular form and function. Ultimately, this model can serve as a valuable tool to optimize both surgical and interventional approaches that aim at restoring mitral valve competence.

  View details for DOI 10.1007/s10439-011-0272-y

  View details for PubMedID 21336803

• Multiple mitral leaflet contractile systems in the beating heart JOURNAL OF BIOMECHANICS Swanson, J. C., Krishnamurthy, G., Itoh, A., Kvitting, J. E., Bothe, W., Miller, D. C., Ingels, N. B. 2011; 44 (7): 1328-1333

  Abstract

  Mitral valve closure may be aided by contraction of anterior leaflet (AL) cardiac myocytes located in the annular third of the leaflet. This contraction, observed as a stiffening of the annular region of the AL during isovolumic contraction (IVC), is abolished by beta-blockade (βB). Sub-threshold rapid pacing in the region of aorto-mitral continuity (STIM) also causes AL stiffening, although this increases the stiffness of the entire leaflet during both IVC and isovolumic relaxation (IVR). We investigated whether these contractile events share a common pathway or whether multiple AL contractile mechanisms may be present. Ten sheep had radiopaque-markers implanted: 13 silhouetting the LV, 16 on the mitral annulus, an array of 16 on the AL, and one on each papillary muscle tip. 4-D marker coordinates were obtained from biplane videofluoroscopy during control (C), βB (esmolol) and during βB+STIM. Circumferential and radial stiffness values for three AL regions (Annular, Belly, and free-Edge), were obtained from inverse finite element analysis of AL displacements in response to trans-leaflet pressure changes during IVC and IVR. βB+STIM increased stiffness values in all regions at both IVC and IVR by 35 ± 7% relative to βB (p<0.001). Thus, even when AL myocyte contraction was blocked by βB, STIM stiffened all regions of the AL during both IVC and IVR. This demonstrates the presence of at least two contractile systems in the AL; one being the AL annular cardiac muscle, involving a β-dependent pathway, others via a β-independent pathway, likely involving valvular interstitial cells and/or AL smooth muscle cells.

  View details for DOI 10.1016/j.jbiomech.2011.01.006

  View details for Web of Science ID 000291075800015

  View details for PubMedID 21292268

  View details for PubMedCentralID PMC3079073

• In vivo dynamic strains of the ovine anterior mitral valve leaflet JOURNAL OF BIOMECHANICS Rausch, M. K., Bothe, W., Kvitting, J. E., Goektepe, S., Miller, D. C., Kuhl, E. 2011; 44 (6): 1149-1157

  Abstract

  Understanding the mechanics of the mitral valve is crucial in terms of designing and evaluating medical devices and techniques for mitral valve repair. In the current study we characterize the in vivo strains of the anterior mitral valve leaflet. On cardiopulmonary bypass, we sew miniature markers onto the leaflets of 57 sheep. During the cardiac cycle, the coordinates of these markers are recorded via biplane fluoroscopy. From the resulting four-dimensional data sets, we calculate areal, maximum principal, circumferential, and radial leaflet strains and display their profiles on the averaged leaflet geometry. Average peak areal strains are 13.8±6.3%, maximum principal strains are 13.0±4.7%, circumferential strains are 5.0±2.7%, and radial strains are 7.8±4.3%. Maximum principal strains are largest in the belly region, where they are aligned with the circumferential direction during diastole switching into the radial direction during systole. Circumferential strains are concentrated at the distal portion of the belly region close to the free edge of the leaflet, while radial strains are highest in the center of the leaflet, stretching from the posterior to the anterior commissure. In summary, leaflet strains display significant temporal, regional, and directional variations with largest values inside the belly region and toward the free edge. Characterizing strain distribution profiles might be of particular clinical significance when optimizing mitral valve repair techniques in terms of forces on suture lines and on medical devices.

  View details for DOI 10.1016/j.jbiomech.2011.01.020

  View details for PubMedID 21306716

• Electromechanical coupling between the atria and mitral valve AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Swanson, J. C., Krishnamurthy, G., Kvitting, J. E., Miller, D. C., Ingels, N. B. 2011; 300 (4): H1267-H1273

  Abstract

  Anterior leaflet (AL) stiffening during isovolumic contraction (IVC) may aid mitral valve closure. We tested the hypothesis that AL stiffening requires atrial depolarization. Ten sheep had radioopaque-marker arrays implanted in the left ventricle, mitral annulus, AL, and papillary muscle tips. Four-dimensional marker coordinates (x, y, z, and t) were obtained from biplane videofluoroscopy at baseline (control, CTRL) and during basal interventricular-septal pacing (no atrial contraction, NAC; 110-117 beats/min) to generate ventricular depolarization not preceded by atrial depolarization. Circumferential and radial stiffness values, reflecting force generation in three leaflet regions (annular, belly, and free-edge), were obtained from finite-element analysis of AL displacements in response to transleaflet pressure changes during both IVC and isovolumic relaxation (IVR). In CTRL, IVC circumferential and radial stiffness was 46 ± 6% greater than IVR stiffness in all regions (P < 0.001). In NAC, AL annular IVC stiffness decreased by 25% (P = 0.004) in the circumferential and 31% (P = 0.005) in the radial directions relative to CTRL, without affecting edge stiffness. Thus AL annular stiffening during IVC was abolished when atrial depolarization did not precede ventricular systole, in support of the hypothesis. The likely mechanism underlying AL annular stiffening during IVC is contraction of cardiac muscle that extends into the leaflet and requires atrial excitation. The AL edge has no cardiac muscle, and thus IVC AL edge stiffness was not affected by loss of atrial depolarization. These findings suggest one reason why heart block, atrial dysrhythmias, or ventricular pacing may be accompanied by mitral regurgitation or may worsen regurgitation when already present.

  View details for DOI 10.1152/ajpheart.00971.2010

  View details for PubMedID 21278134

• Effects of different annuloplasty ring types on mitral leaflet tenting area during acute myocardial ischemia JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Bothe, W., Kvitting, J. E., Stephens, E. H., Swanson, J. C., Liang, D. H., Ingels, N. B., Miller, D. C. 2011; 141 (2): 345-353

  Abstract

  The study objective was to quantify the effects of different annuloplasty rings on mitral leaflet septal-lateral tenting areas during acute myocardial ischemia.Radiopaque markers were implanted along the central septal-lateral meridian of the mitral valve in 30 sheep: 1 each to the septal and lateral aspects of the mitral annulus and 4 and 2 along the anterior and posterior mitral leaflets, respectively. Ten true-sized Carpentier-Edwards Physio, Edwards IMR ETLogix, and GeoForm annuloplasty rings (Edwards Lifesciences, Irvine, Calif) were inserted in a releasable fashion. Marker coordinates were obtained using biplane videofluoroscopy with ring inserted at baseline (RING_BL) and after 90 seconds of left circumflex artery occlusion (RING_ISCH). After ring release, another dataset was acquired before (No_Ring_BL) and after left circumflex artery occlusion (No_Ring_ISCH). Anterior and posterior mitral leaflet tenting areas were computed at mid-systole from sums of marker triangles with the midpoint between the annular markers being the vertex for all triangles.Compared with No_Ring_BL, mitral regurgitation grades and all tenting areas significantly increased with No_Ring_ISCH. Compared with No_Ring_ISCH, (1) all rings significantly prevented mitral regurgitation and reduced all tenting areas; (2) Edwards IMR ETLogix and GeoForm rings reduced posterior mitral leaflet area, but not anterior mitral leaflet tenting area, to a significantly greater extent than the Carpentier-Edwards Physio ring; and (3) Edwards IMR ETLogix and GeoForm rings affected tenting areas similarly.In response to acute left ventricular ischemia, disease-specific functional/ischemic mitral regurgitation rings (Edwards IMR ETLogix, GeoForm) more effectively reduced posterior mitral leaflet area, but not anterior mitral leaflet tenting area, compared with true-sized physiologic rings (Carpentier-Edwards Physio). Despite its radical 3-dimensional shape and greater amount of mitral annular septal-lateral downsizing, the GeoForm ring did not reduce tenting areas more than the Edwards IMR ETLogix ring, suggesting that further reduction in tenting areas in patients with FMR/IMR may not be effectively achieved on an annular level.

  View details for DOI 10.1016/j.jtcvs.2010.10.015

  View details for PubMedID 21241857

• Standardized Endpoint Definitions for Transcatheter Aortic Valve Implantation Clinical Trials A Consensus Report From the Valve Academic Research Consortium JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Leon, M. B., Piazza, N., Nikolsky, E., Blackstone, E. H., Cutlip, D. E., Kappetein, A. P., Krucoff, M. W., Mack, M., Mehran, R., Miller, C., Morel, M., Petersen, J., Popma, J. J., Takkenberg, J. J., Vahanian, A., van Es, G., Vranckx, P., Webb, J. G., Windecker, S., Serruys, P. W. 2011; 57 (3): 253-269

  Abstract

  To propose standardized consensus definitions for important clinical endpoints in transcatheter aortic valve implantation (TAVI), investigations in an effort to improve the quality of clinical research and to enable meaningful comparisons between clinical trials. To make these consensus definitions accessible to all stakeholders in TAVI clinical research through a peer reviewed publication, on behalf of the public health.Transcatheter aortic valve implantation may provide a worthwhile less invasive treatment in many patients with severe aortic stenosis and since its introduction to the medical community in 2002, there has been an explosive growth in procedures. The integration of TAVI into daily clinical practice should be guided by academic activities, which requires a harmonized and structured process for data collection, interpretation, and reporting during well-conducted clinical trials.The Valve Academic Research Consortium established an independent collaboration between Academic Research organizations and specialty societies (cardiology and cardiac surgery) in the USA and Europe. Two meetings, in San Francisco, California (September 2009) and in Amsterdam, the Netherlands (December 2009), including key physician experts, and representatives from the U.S. Food and Drug Administration (FDA) and device manufacturers, were focused on creating consistent endpoint definitions and consensus recommendations for implementation in TAVI clinical research programs. Important considerations in developing endpoint definitions included: 1) respect for the historical legacy of surgical valve guidelines; 2) identification of pathophysiological mechanisms associated with clinical events; 3) emphasis on clinical relevance. Consensus criteria were developed for the following endpoints: mortality, myocardial infarction, stroke, bleeding, acute kidney injury, vascular complications, and prosthetic valve performance. Composite endpoints for TAVI safety and effectiveness were also recommended.Although consensus criteria will invariably include certain arbitrary features, an organized multidisciplinary process to develop specific definitions for TAVI clinical research should provide consistency across studies that can facilitate the evaluation of this new important catheter-based therapy. The broadly based consensus endpoint definitions described in this document may be useful for regulatory and clinical trial purposes.

  View details for DOI 10.1016/j.jacc.2010.12.005

  View details for Web of Science ID 000286133900003

  View details for PubMedID 21216553

• Standardized endpoint definitions for transcatheter aortic valve implantation clinical trials: a consensus report from the Valve Academic Research Consortium EUROPEAN HEART JOURNAL Leon, M. B., Piazza, N., Nikolsky, E., Blackstone, E. H., Cutlip, D. E., Kappetein, A. P., Krucoff, M. W., Mack, M., Mehran, R., Miller, C., Morel, M., Petersen, J., Popma, J. J., Takkenberg, J. J., Vahanian, A., van Es, G., Vranckx, P., Webb, J. G., Windecker, S., Serruys, P. W. 2011; 32 (2): 205-U144

  Abstract

  To propose standardized consensus definitions for important clinical endpoints in transcatheter aortic valve implantation (TAVI), investigations in an effort to improve the quality of clinical research and to enable meaningful comparisons between clinical trials. To make these consensus definitions accessible to all stakeholders in TAVI clinical research through a peer reviewed publication, on behalf of the public health.Transcatheter aortic valve implantation may provide a worthwhile less invasive treatment in many patients with severe aortic stenosis and since its introduction to the medical community in 2002, there has been an explosive growth in procedures. The integration of TAVI into daily clinical practice should be guided by academic activities, which requires a harmonized and structured process for data collection, interpretation, and reporting during well-conducted clinical trials.The Valve Academic Research Consortium established an independent collaboration between Academic Research organizations and specialty societies (cardiology and cardiac surgery) in the USA and Europe. Two meetings, in San Francisco, California (September 2009) and in Amsterdam, the Netherlands (December 2009), including key physician experts, and representatives from the US Food and Drug Administration (FDA) and device manufacturers, were focused on creating consistent endpoint definitions and consensus recommendations for implementation in TAVI clinical research programs. Important considerations in developing endpoint definitions included (i) respect for the historical legacy of surgical valve guidelines; (ii) identification of pathophysiological mechanisms associated with clinical events; (iii) emphasis on clinical relevance. Consensus criteria were developed for the following endpoints: mortality, myocardial infarction, stroke, bleeding, acute kidney injury, vascular complications, and prosthetic valve performance. Composite endpoints for TAVI safety and effectiveness were also recommended.Although consensus criteria will invariably include certain arbitrary features, an organized multidisciplinary process to develop specific definitions for TAVI clinical research should provide consistency across studies that can facilitate the evaluation of this new important catheter-based therapy. The broadly based consensus endpoint definitions described in this document may be useful for regulatory and clinical trial purposes.

  View details for DOI 10.1093/eurheartj/ehq406

  View details for Web of Science ID 000286215500015

  View details for PubMedID 21216739

  View details for PubMedCentralID PMC3021388

• Functional Coupling of Valvular Interstitial Cells and Collagen Via alpha(2)beta(1) Integrins in the Mitral Leaflet CELLULAR AND MOLECULAR BIOENGINEERING Stephens, E. H., Durst, C. A., Swanson, J. C., Grande-Allen, K. J., Ingels, N. B., Miller, D. C. 2010; 3 (4): 428-437

  View details for DOI 10.1007/s12195-010-0139-6

  View details for Web of Science ID 000285211500011

• FUNCTIONAL COUPLING OF VALVULAR INTERSTITIAL CELLS AND COLLAGEN VIA α2β1 INTEGRINS IN THE MITRAL LEAFLET. Cellular and molecular bioengineering Stephens, E. H., Durst, C. A., Swanson, J. C., Grande-Allen, K. J., Ingels, N. B., Miller, D. C. 2010; 3 (4): 428-437

  Abstract

  Once considered passive flaps, we now understand that mitral leaflets are dynamic structures with their own vasculature and innervation that actively remodel and even generate force in response to their environments. Valvular interstitial cells (VICs) are contractile and could underlie mitral leaflet force generation, but the exact mechanisms for VICs in mitral leaflet force generation are not understood. This study tested the hypothesis that actin-mediated VIC force generation coupled to collagen via alpha2beta1 integrins is necessary for force generation in the mitral leaflet. High magnification fluorescent imaging of freshly excised porcine mitral leaflets revealed VIC cytoplasm tightly conforming to collagen fibers, with actin within VIC cytoplasmic processes appearing to attach to the collagen fibers. Functional studies of isometric force development demonstrated that while control samples developed force in response to KCl, either blocking alpha2beta1 integrins or blocking actin polymerization via cytochalasin abolished KCl-induced force development (p<0.001). These results strongly suggest that VIC-collagen coupling, mediated by alpha2beta1 integrins, is necessary for KCl-induced force generation in the mitral leaflet. This functional coupling between collagen and VICs via alpha2beta1 integrins may play a role for in vivo mitral valve function.

  View details for DOI 10.1007/s12195-010-0139-6

  View details for PubMedID 37829550

  View details for PubMedCentralID PMC10569086

• Rigid, Complete Annuloplasty Rings Increase Anterior Mitral Leaflet Strains in the Normal Beating Ovine Heart Bothe, W., Kuhl, E., Kvitting, J. E., Rausch, M. K., Goektepe, S., Swanson, J. C., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2010

  View details for Web of Science ID 000208231601607

• Health-Related Quality of Life After Transcatheter Aortic Valve Implantation vs. Non-Surgical Therapy Among Inoperable Patients With Severe Aortic Stenosis: Results From the Randomized PARTNER Trial (Cohort B) Cohen, D. J., Reynolds, M. R., Lei, Y., Mahoney, E. M., Svensson, L. G., Tuzcu, E. M., Moses, J. W., Webb, J. G., Mack, M., Miller, D. C., Pichard, A., Makkar, R., Herrmann, H. C., Block, P., Smith, C. R., Leon, M. B. LIPPINCOTT WILLIAMS & WILKINS. 2010: 2223

  View details for Web of Science ID 000284471800046

• Anterior Mitral Leaflet Curvature During the Cardiac Cycle in the Normal Ovine Heart CIRCULATION Kvitting, J. E., Bothe, W., Goektepe, S., Rausch, M. K., Swanson, J. C., Kuhl, E., Ingels, N. B., Miller, D. C. 2010; 122 (17): 1683-1689

  Abstract

  The dynamic changes of anterior mitral leaflet (AML) curvature are of primary importance for optimal left ventricular filling and emptying but are incompletely characterized.Sixteen radiopaque markers were sutured to the AML in 11 sheep, and 4-dimensional marker coordinates were acquired with biplane videofluoroscopy. A surface subdivision algorithm was applied to compute the curvature across the AML at midsystole and at maximal valve opening. Septal-lateral (SL) and commissure-commissure (CC) curvature profiles were calculated along the SL AML meridian (M(SL))and CC AML meridian (M(CC)), respectively, with positive curvature being concave toward the left atrium. At midsystole, the M(SL) was concave near the mitral annulus, turned from concave to convex across the belly, and was convex along the free edge. At maximal valve opening, the M(SL) was flat near the annulus, turned from slightly concave to convex across the belly, and flattened toward the free edge. In contrast, the M(CC) was concave near both commissures and convex at the belly at midsystole but convex near both commissures and concave at the belly at maximal valve opening.While the SL curvature of the AML along the M(SL) is similar across the belly region at midsystole and early diastole, the CC curvature of the AML along the M(CC) flips, with the belly being convex to the left atrium at midsystole and concave at maximal valve opening. These curvature orientations suggest optimal left ventricular inflow and outflow shapes of the AML and should be preserved during catheter or surgical interventions.

  View details for DOI 10.1161/CIRCULATIONAHA.110.961243

  View details for PubMedID 20937973

• "Peninsula- Style" Transverse Aortic Arch Replacement in Patients With Bicuspid Aortic Valve ANNALS OF THORACIC SURGERY Itoh, A., Fischbein, M., Arata, K., Miller, D. C. 2010; 90 (4): 1369-1371

  Abstract

  Although the optimal surgical treatment of the dilated aortic arch is controversial in patients with a bicuspid aortic valve, such exists in more than 70% of bicuspid aortic valve patients. Aortic wall histologic abnormalities are present from the aortic root to the distal arch regardless of aortic size. We describe a simple "peninsula-style" technique of transverse arch replacement used in conjunction with valve-sparing aortic root replacement for patients with a bicuspid aortic valve. This provides resection of the entire dilated thoracic aorta, preserving the arch branches in continuity with the proximal descending aorta.

  View details for DOI 10.1016/j.athoracsur.2009.11.029

  View details for PubMedID 20868855

• How do annuloplasty rings affect mitral leaflet dynamic motion? EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Bothe, W., Kvitting, J. E., Swanson, J. C., Goektepe, S., Vo, K. N., Ingels, N. B., Miller, D. C. 2010; 38 (3): 340-349

  Abstract

  To define the effects of annuloplasty rings (ARs) on the dynamic motion of anterior mitral leaflet (AML) and posterior mitral leaflet (PML).Fifty-eight adult, Dorsett-hybrid, male sheep (49 + or - 5 kg) had radiopaque markers inserted: eight around the mitral annulus, four along the central meridian (from edge to annulus) of the AML (#A(1)-#A(4)) and one on the PML edge (#P(1)). True-sized Edwards Cosgrove (COS, n=12), St Jude RSAR (St. Jude Medical, St. Paul, MN, USA) (n=12), Carpentier-Edwards Physio (PHYSIO, n=12), Edwards IMR ETlogix (ETL, n=10) or Edwards GeoForm (GEO, n=12) ARs were implanted in a releasable fashion. Under acute open-chest conditions, 4D marker coordinates were obtained using biplane videofluoroscopy with the respective AR inserted (COS, RSAR, PHYSIO, ETL and GEO) and after release (COS-Control, RSAR-Control, PHYSIO-Control, ETL-Control and GEO-Control). AML and PML excursions were calculated as the difference between minimum and maximum angles between the central mitral annular septal-lateral chord and the AML edge markers (alpha(1exc)-alpha(4exc)) and PML edge marker (beta(1exc)) during the cardiac cycle.Relative to Control, (1) RSAR, PHYSIO, ETL and GEO increased excursion of the AML annular (alpha(4exc): 13 + or - 6 degrees vs 16 + or - 7 degrees *, 16 + or - 7 degrees vs 23 + or - 10 degrees *, 12 + or - 4 degrees vs 18 + or - 9 degrees *, 15 + or - 1 degrees vs 20 + or - 9 degrees *, respectively) and belly region (alpha(2exc): 41 + or - 10 degrees vs 45 + or - 10 degrees *, 42 + or - 8 degrees vs 45 + or - 6 degrees , n.s., 33 + or - 13 degrees vs 42 + or - 14 degrees *, 39 + or - 6 degrees vs 44 + or - 6 degrees *, respectively, alpha(3exc): 24 + or - 9 degrees vs 29 + or - 11 degrees *, 28 + or - 10 degrees vs 33 + or - 10 degrees *, 16 + or - 9 degrees vs 21 + or - 12 degrees *, 25 + or - 7 degrees vs 29 + or - 9 degrees *, respectively), but not of the AML edge (alpha(1exc): 42 + or - 8 degrees vs 44 + or - 8 degrees , 43 + or - 8 degrees vs 41 + or - 6 degrees , 42 + or - 11 vs 46 + or - 10 degrees , 39 + or - 9 degrees vs 38 + or - 8 degrees , respectively, all n.s.). COS did not affect AML excursion (alpha(1exc): 40 + or - 8 degrees vs 37 + or - 8 degrees , alpha(2exc): 43 + or - 9 degrees vs 41 + or - 9 degrees , alpha(3exc): 27 + or - 11 degrees vs 27 + or - 10 degrees , alpha(4exc): 18 + or - 8 degrees vs 17 + or - 7 degrees , all n.s.). (2) PML excursion (beta(1exc)) was reduced with GEO (53 + or - 5 degrees vs 43 + or - 6 degrees *), but unchanged with COS, RSAR, PHYSIO or ETL (53 + or - 13 degrees vs 52 + or - 15 degrees , 50 + or - 13 degrees vs 49 + or - 10 degrees , 55 + or - 5 degrees vs 55 + or - 7 degrees , 52 + or - 8 degrees vs 58 + or - 6 degrees , respectively, all n.s); *=p<0.05.RSAR, PHYSIO, ETL and GEO rings, but not COS, increase AML excursion of the AML annular and belly region, suggesting higher anterior mitral leaflet bending stresses with rigid rings, which potentially could be deleterious with respect to repair durability. The decreased PML excursion observed with GEO could impair left ventricular filling. Clinical studies are needed to validate these findings in patients.

  View details for DOI 10.1016/j.ejcts.2010.02.011

  View details for PubMedID 20335042

• Early outcomes of deliberate nonoperative management for blunt thoracic aortic injury in trauma JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Caffarelli, A. D., Mallidi, H. R., Maggio, P. M., Spain, D. A., Miller, D. C., Mitchell, R. S. 2010; 140 (3): 598-605

  Abstract

  Traumatic blunt aortic injury has traditionally been viewed as a surgical emergency, whereas nonoperative therapy has been reserved for nonsurgical candidates. This study reviews our experience with deliberate, nonoperative management for blunt thoracic aortic injury.A retrospective chart review with selective longitudinal follow-up was conducted for patients with blunt aortic injury. Surveillance imaging with computed tomography angiography was performed. Nonoperative patients were then reviewed and analyzed for survival, evolution of aortic injury, and treatment failures.During the study period, 53 patients with an average age of 45 years (range, 18-80 years) were identified, with 28% presenting to the Stanford University School of Medicine emergency department and 72% transferred from outside hospitals. Of the 53 patients, 29 underwent planned, nonoperative management. Of the 29 nonoperative patients, in-hospital survival was 93% with no aortic deaths in the remaining patients. Survival was 97% at a median of 1.8 years (range, 0.9-7.2 years). One patient failed nonoperative management and underwent open repair. Serial imaging was performed in all patients (average = 107 days; median, 31 days), with 21 patients having stable aortic injuries without progression and 5 patients having resolved aortic injuries.This experience suggests that deliberate, nonoperative management of carefully selected patients with traumatic blunt aortic injury may be a reasonable alternative in the polytrauma patient; however, serial imaging and long-term follow-up are necessary.

  View details for DOI 10.1016/j.jtcvs.2010.02.056

  View details for PubMedID 20579668

• How much septal-lateral mitral annular reduction do you get with new ischemic/functional mitral regurgitation annuloplasty rings? JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Bothe, W., Swanson, J. C., Ingels, N. B., Miller, D. C. 2010; 140 (1): 117-U142

  Abstract

  Disproportionate reduction of the mitral septal-lateral annular dimension is the goal in the surgical treatment of ischemic or functional mitral regurgitation and avoids the need for ring "downsizing." How much the new annuloplasty rings designed for patients with ischemic/functional mitral regurgitation reduce annular septal-lateral dimension, however, is proprietary information and debated.Outer and inner septal-lateral and commissure-commissure diameters of all available sizes of Edwards GeoForm, Edwards IMR ETlogix (both Edwards Lifesciences, Irvine, Calif), St Jude Medical Rigid Saddle Annuloplasty Ring (St Jude Medical, Inc, St Paul, Minn), and Medtronic Profile 3D (Medtronic, Minneapolis, Minn) annuloplasty rings with and without the fabric covering were measured with electronic calipers. These rings were compared with a Carpentier-Edwards Physio ring (Edwards Lifesciences) to assess the relative amount of septal-lateral and commissure-commissure dimension change. Average fractional changes (% +/-1 standard deviation) versus the Physio ring were calculated.The GeoForm provided the greatest outer septal-lateral reduction relative to Physio ring (-24% +/- 2%), followed by the IMR ETlogix (-9% +/- 2%) and Profile 3D (-8% +/- 5%). The septal-lateral diameter of the Rigid Saddle Annuloplasty Ring was similar to that of the Physio ring (+1% +/- 3%). Although commissure-commissure outer diameters of the IMR ETlogix, Rigid Saddle Annuloplasty Ring, and Profile 3D were similar to that of the Physio ring (0% +/- 2%, +4% +/- 3%, and +3% +/- 4%, respectively), the GeoForm had a larger commissure-commissure dimension (+12% +/- 2%). The inner diameter septal-lateral reductions were even more pronounced.Relative to the Physio ring, the GeoForm has the most outer and inner septal-lateral reduction but larger commissure-commissure dimension; the IMR ETlogix and Profile 3D provide a moderate degree of septal-lateral reduction without affecting commissure-commissure dimension, and Rigid Saddle Annuloplasty Ring septal-lateral and commissure-commissure diameters are similar to those of the Physio ring. Knowing the degree of disproportionate septal-lateral downsizing inherent in each ring type will help guide surgical decision making.

  View details for DOI 10.1016/j.jtcvs.2009.10.033

  View details for PubMedID 20074748

• Determinants of Evolution and Progression of Acute Ovine Ischemic Mitral Regurgitation JOURNAL OF HEART VALVE DISEASE Timek, T. A., Lai, D. T., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. 2010; 19 (4): 420-426

  Abstract

  The optimal treatment of moderate ischemic mitral regurgitation (IMR) remains contested. Thus, radiopaque markers were implanted on valvular structures to investigate the geometric and hemodynamic variables associated with the evolution and progression of acute ovine IMR.Eight adult sheep underwent implantation of five radiopaque markers on the edge of the posterior mitral leaflet (PML), and five on the edge of the anterior mitral leaflet (AML). Eight additional markers were sewn around the mitral annulus (MA). The animals were studied immediately after surgery, using biplane videofluoroscopy and transesophageal echocardiography. Data were acquired at Baseline and at two time points (IMR1 and IMR2) during acute snare occlusion of the proximal left circumflex coronary artery and progressive IMR. The orthogonal distance of each leaflet edge marker to the least-squares annular plane, mitral annular area (MAA), and septal-lateral diameter (SL) were calculated at end-systole. The leaflet tenting area (TA) was calculated at valve center (CENT) and near the anterior (ACOM) and posterior (PCOM) commissures.The degree of MR was 0.6 +/- 0.4, 1.8 +/- 0.7, and 2.8 +/- 0.7 for Baseline, IMR1, and IMR2, respectively (p < 0.005). IMR1 was associated with annular dilatation and leaflet restriction near the valve center, and prolapse near the PCOM versus Baseline. Although both left ventricular pressure (LVP) and left ventricular dP/dt decreased significantly from IMR1 to IMR 2, there were no differences in leaflet or annular geometry.The initiation of moderate IMR was associated with significant alterations in annular and leaflet geometry, but only a small decrease in LV systolic function, was needed for IMR progression. These data suggest that the surgical repair and optimization of LV function may be important in combination to treat moderate IMR, as only small hemodynamic deterioration and perturbations in valvular geometry are necessary for significant IMR progression.

  View details for Web of Science ID 000285280900003

  View details for PubMedID 20845887

• Anterior mitral leaflet curvature in the beating ovine heart: a case study using videofluoroscopic markers and subdivision surfaces. Biomechanics and modeling in mechanobiology Göktepe, S., Bothe, W., Kvitting, J. E., Swanson, J. C., Ingels, N. B., Miller, D. C., Kuhl, E. 2010; 9 (3): 281-293

  Abstract

  The implantation of annuloplasty rings is a common surgical treatment targeted to re-establish mitral valve competence in patients with mitral regurgitation. It is hypothesized that annuloplasty ring implantation influences leaflet curvature, which in turn may considerably impair repair durability. This research is driven by the vision to design repair devices that optimize leaflet curvature to reduce valvular stress. In pursuit of this goal, the objective of this manuscript is to quantify leaflet curvature in ovine models with and without annuloplasty ring using in vivo animal data from videofluoroscopic marker analysis. We represent the surface of the anterior mitral leaflet based on 23 radiopaque markers using subdivision surfaces techniques. Quartic box-spline functions are applied to determine leaflet curvature on overlapping subdivision patches. We illustrate the virtual reconstruction of the leaflet surface for both interpolating and approximating algorithms. Different scalar-valued metrics are introduced to quantify leaflet curvature in the beating heart using the approximating subdivision scheme. To explore the impact of annuloplasty ring implantation, we analyze ring-induced curvature changes at characteristic instances throughout the cardiac cycle. The presented results demonstrate that the fully automated subdivision surface procedure can successfully reconstruct a smooth representation of the anterior mitral valve from a limited number of markers at a high temporal resolution of approximately 60 frames per minute.

  View details for DOI 10.1007/s10237-009-0176-z

  View details for PubMedID 19890668

• The 2008 Scientific Achievement Award recipient: Andrew S. Wechsler, MD JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Cohn, L. H., Miller, D. 2010; 139 (6): 1367–68

  View details for DOI 10.1016/j.jtcvs.2010.02.015

  View details for Web of Science ID 000277937500001

  View details for PubMedID 20392459

• Anterior mitral leaflet curvature in the beating ovine heart: a case study using videofluoroscopic markers and subdivision surfaces BIOMECHANICS AND MODELING IN MECHANOBIOLOGY Goektepe, S., Bothe, W., Kvitting, J. E., Swanson, J. C., Ingels, N. B., Miller, D. C., Kuhl, E. 2010; 9 (3): 281-293

  Abstract

  The implantation of annuloplasty rings is a common surgical treatment targeted to re-establish mitral valve competence in patients with mitral regurgitation. It is hypothesized that annuloplasty ring implantation influences leaflet curvature, which in turn may considerably impair repair durability. This research is driven by the vision to design repair devices that optimize leaflet curvature to reduce valvular stress. In pursuit of this goal, the objective of this manuscript is to quantify leaflet curvature in ovine models with and without annuloplasty ring using in vivo animal data from videofluoroscopic marker analysis. We represent the surface of the anterior mitral leaflet based on 23 radiopaque markers using subdivision surfaces techniques. Quartic box-spline functions are applied to determine leaflet curvature on overlapping subdivision patches. We illustrate the virtual reconstruction of the leaflet surface for both interpolating and approximating algorithms. Different scalar-valued metrics are introduced to quantify leaflet curvature in the beating heart using the approximating subdivision scheme. To explore the impact of annuloplasty ring implantation, we analyze ring-induced curvature changes at characteristic instances throughout the cardiac cycle. The presented results demonstrate that the fully automated subdivision surface procedure can successfully reconstruct a smooth representation of the anterior mitral valve from a limited number of markers at a high temporal resolution of approximately 60 frames per minute.

  View details for DOI 10.1007/s10237-009-0176-z

  View details for Web of Science ID 000277711400003

• Transient stiffening of mitral valve leaflets in the beating heart AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Krishnamurthy, G., Itoh, A., Swanson, J. C., Miller, D. C., Ingels, N. B. 2010; 298 (6): H2221-H2225

  Abstract

  Anterior mitral leaflet stiffness during isovolumic contraction (IVC) is much greater than that during isovolumic relaxation (IVR). We have hypothesized that this stiffening is due to transient early systolic force development in the slip of cardiac myocytes in the annular third of the anterior leaflet. Because the atrium is excited before IVC and leaflet myocytes contract for < or = 250 ms, this hypothesis predicts that IVC leaflet stiffness will drop to near-IVR values in the latter half of ventricular systole. We tested this prediction using radiopaque markers and inverse finite element analysis of 30 beats in 10 ovine hearts. For each beat, circumferential (E(c)) and radial (E(r)) stiffness was determined during IVC (Deltat(1)), end IVC to midsystole (Deltat(2)), midsystole to IVR onset (Deltat(3)), and IVR (Deltat(4)). Group mean stiffness (E(c) + or - SD; E(r) + or - SD; in N/mm(2)) during Deltat(1) (44 + or - 16; 15 + or - 4) was 1.6-1.7 times that during Deltat(4) (28 + or - 11; 9 + or - 3); Deltat(2) stiffness (39 + or - 15; 14 + or - 4) was 1.3-1.5 times that of Deltat(4), but Deltat(3) stiffness (32 + or - 12; 11 + or - 3) was only 1.1-1.2 times that of Deltat(4). The stiffness drop during Deltat(3) supports the hypothesis that anterior leaflet stiffening during IVC arises primarily from transient force development in leaflet cardiac myocytes, with stiffness reduced as this leaflet muscle relaxes in the latter half of ventricular systole.

  View details for DOI 10.1152/ajpheart.00215.2010

  View details for PubMedID 20400687

• Effects of different annuloplasty rings on anterior mitral leaflet dimensions JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Bothe, W., Kvitting, J. E., Swanson, J. C., Hartnett, S., Ingels, N. B., Miller, D. C. 2010; 139 (5): 1114-1122

  Abstract

  To assess the effects of annuloplasty rings on anterior mitral leaflet dimensions.Sixteen radiopaque markers were sutured evenly spaced over the surface of the anterior mitral leaflet in 57 sheep. The following rings were implanted in a releasable fashion: size 28-mm Cosgrove-Edwards band (Edwards Lifesciences, Irvine, Calif) (n = 11), rigid saddle-shaped annuloplasty ring (St Jude Medical Inc, St Paul, Minn) (n = 12), Carpentier-Edwards Physio (Edwards Lifesciences) (n = 12), IMR-ETlogix (Edwards Lifesciences) (n = 10), and GeoForm (Edwards Lifesciences) (n = 12). Under acute open chest conditions, 4-dimensional marker coordinates were measured using biplane videofluoroscopy with the annuloplasty ring inserted and after annuloplasty ring release. Septal-lateral and commissure-commissure dimensions were calculated from opposing marker pairs on the septal-lateral and commissure-commissure aspect of the anterior mitral leaflet at end diastole and end systole. To assess changes in anterior mitral leaflet shape, a "planarity index" was assessed by calculating the root mean square values as distances of the 16 anterior mitral leaflet markers to a best fit anterior mitral leaflet plane at end systole.At end diastole, anterior mitral leaflet septal-lateral and commissure-commissure dimensions did not change with the Cosgrove ring compared with control, whereas the rigid saddle-shaped annuloplasty ring and Physio, IMR-ETlogix, and GeoForm rings reduced anterior mitral leaflet commissure-commissure but not septal-lateral anterior mitral leaflet dimensions. At end systole, the septal-lateral anterior mitral leaflet dimension was smaller with the IMR-ETlogix and GeoForm rings, but did not change with the Cosgrove ring, rigid saddle-shaped annuloplasty ring, and Physio ring. Anterior mitral leaflet shape was unchanged in all 5 groups.With no changes in anterior mitral leaflet planarity, the 4 complete, rigid rings (rigid saddle-shaped annuloplasty ring, Physio, IMR-ETlogix, and GeoForm) reduced the anterior mitral leaflet commissure-commissure dimension at end diastole. The IMR-ETlogix and GeoForm rings decreased the septal-lateral anterior mitral leaflet dimension at end systole, probably as the result of inherent disproportionate downsizing. These changes in anterior mitral leaflet geometry could perturb the stress patterns, which in theory may affect repair durability.

  View details for DOI 10.1016/j.jtcvs.2009.12.014

  View details for PubMedID 20412950

• Electro-Mechanical Coupling between the Atria and Mitral Valve Swanson, J. C., Krishnamurthy, G., Kvitting, J. E., Miller, D. C., Ingels, N. B. KARGER. 2010: 287–88

  View details for Web of Science ID 000276774900092

• Regional stiffening of the mitral valve anterior leaflet in the beating ovine heart JOURNAL OF BIOMECHANICS Krishnamurthy, G., Itoh, A., Swanson, J. C., Bothe, W., Karlsson, M., Kuhl, E., Miller, D. C., Ingels, N. B. 2009; 42 (16): 2697-2701

  Abstract

  Left atrial muscle extends into the proximal third of the mitral valve (MV) anterior leaflet and transient tensing of this muscle has been proposed as a mechanism aiding valve closure. If such tensing occurs, regional stiffness in the proximal anterior mitral leaflet will be greater during isovolumic contraction (IVC) than isovolumic relaxation (IVR) and this regional stiffness difference will be selectively abolished by beta-receptor blockade. We tested this hypothesis in the beating ovine heart. Radiopaque markers were sewn around the MV annulus and on the anterior MV leaflet in 10 sheep hearts. Four-dimensional marker coordinates were obtained from biplane videofluoroscopy before (CRTL) and after administration of esmolol (ESML). Heterogeneous finite element models of each anterior leaflet were developed using marker coordinates over matched pressures during IVC and IVR for CRTL and ESML. Leaflet displacements were simulated using measured left ventricular and atrial pressures and a response function was computed as the difference between simulated and measured displacements. Circumferential and radial elastic moduli for ANNULAR, BELLY and EDGE leaflet regions were iteratively varied until the response function reached a minimum. The stiffness values at this minimum were interpreted as the in vivo regional material properties of the anterior leaflet. For all regions and all CTRL beats IVC stiffness was 40-58% greater than IVR stiffness. ESML reduced ANNULAR IVC stiffness to ANNULAR IVR stiffness values. These results strongly implicate transient tensing of leaflet atrial muscle during IVC as the basis of the ANNULAR IVC-IVR stiffness difference.

  View details for DOI 10.1016/j.jbiomech.2009.08.028

  View details for PubMedID 19766222

• Releasable annuloplasty ring insertion - a novel experimental implantation model EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Bothe, W., Chang, P. A., Swanson, J. C., Itoh, A., Arata, K., Ingels, N. B., Miller, D. C. 2009; 36 (5): 830-832

  Abstract

  Experimental testing of annuloplasty ring (AR) effects requires a control group if the AR is implanted conventionally. Our goal was to develop a reversible AR insertion method that allows for beating heart assessment with and without an AR, providing the ability to evaluate the effects of an AR in the same animal (internal control). We tested the feasibility of this technique in an in vivo ovine model using four-dimensional (4-D) radiopaque marker tracking.Before the operation, a rigid AR (Edwards Geoform, Edwards Lifesciences, Irvine, CA, USA) was prepared by stitching the middle parts of eight double-armed sutures evenly spaced through the ring fabric using a Spring Eye needle. The resulting loops were 'locked' with polypropylene sutures. In addition, two drawstring sutures were attached to the AR. Using cardiopulmonary bypass and cardioplegic arrest, 12 adult sheep had 16 radiopaque markers sewn to the mitral annulus. The AR was implanted by stitching the eight sutures equidistantly in a perpendicular direction through the mitral annulus. The sheep were transferred to the catheterisation laboratory and 4-D marker coordinates were obtained using biplane videofluoroscopy (60 Hz) with the AR inserted (Geo-AR). The locking sutures were then released, the AR was pulled up to the atrial roof using the drawstring sutures and another dataset was acquired (control). Maximum and minimum mitral annular areas (MAA(max), MAA(min)) during the cardiac cycle were derived from implanted markers. Data are provided from one representative animal.AR insertion and release were uneventful in all animals. Whereas the mitral annulus was dynamic in the control state (MAA(max): 9.0 cm(2), MAA(min): 7.8 cm(2)), mitral annular dynamics were abolished in the Geo-AR case (MAA(max): 6.2 cm(2), MAA(min): 6.0 cm(2)).This novel releasable AR implantation method is feasible and permits in vivo assessment of AR effects in the same heart. The new technique should facilitate experimental AR testing and promote the development of ARs based on physical criteria.

  View details for DOI 10.1016/j.ejcts.2009.06.028

  View details for PubMedID 19646892

• Regional Mitral Leaflet Opening During Acute Ischemic Mitral Regurgitation 4th Biennial Meeting of the Society-for-Heart-Valve-Disease Bothe, W., Ennis, D. B., Carlhall, C. J., Nguyen, T. C., Timek, T. A., Lai, D. T., Itoh, A., Ingels, N. B., Miller, D. C. I C R PUBLISHERS. 2009: 586–96

  Abstract

  Diastolic mitral valve (MV) opening characteristics during ischemic mitral regurgitation (IMR) are poorly characterized. The diastolic MV opening dynamics were quantified along the entire valvular coaptation line in an ovine model of acute IMR.Ten radiopaque markers were sutured in pairs on the anterior (A1-E1) and corresponding posterior (A2-E2) leaflet edges from the anterior (A1/A2) to the posterior (E1/E2) commissure in 11 adult sheep. Immediately after surgery, 4-D marker coordinates were obtained before and during occlusion of the proximal left circumflex coronary artery. Distances between marker pairs were calculated throughout the cardiac cycle every 16.7 ms. Leaflet opening was defined as the time after end-systole (ES) when the first derivative of the distance between marker pairs was greater than a threshold value of 3 cm/s. Valve opening velocity was defined as the maximum slope of marker pair tracings.Hemodynamics were consistent with acute ischemia, as reflected by increased MR grade (0.5 +/- 0.3 versus 2.3 +/- 0.7, p < 0.05), decreased contractility (dP/dt(max): 1,948 +/- 598 versus 1,119 +/- 293 mmHg/s, p < 0.05), and slower left ventricular relaxation rate (dP/dt(min): -1,079 +/- 188 versus -538 +/- 147 mmHg/s, p < 0.05). During ischemia, valve opening occurred earlier (A1/A2: 112 +/- 28 versus 83 +/- 43 ms, B1/B2: 105 +/- 32 versus 68 +/- 35 ms, C1/C2: 126 +/- 25 versus 74 +/- 37 ms, D1/D2: 114 +/- 28 versus 71 +/- 34 ms, E1/E2: 125 +/- 29 versus 105 +/- 33 ms; all p < 0.05) and was slower (A1/A2: 16.8 +/- 9.6 versus 14.2 +/- 9.4 cm/s, B1/B2: 40.4 +/- 9.9 versus 32.2 +/- 10.0 cm/s, C1/C2: 59.0 +/- 14.9 versus 50.4 +/- 18.1 cm/s, D1/D2: 34.4 +/- 10.4 versus 25.5 +/- 10.9 cm/s; all p < 0.05), except at the posterior edge (E1/E2: 13.3 +/- 8.7 versus 10.6 +/- 7.2 cm/s). The sequence of regional mitral leaflet separation along the line of coaptation did not change with ischemia.Acute posterolateral left ventricular ischemia causes earlier leaflet opening, probably due to a MR-related elevation in left-atrial pressure; reduces leaflet opening velocity, potentially reflecting an impaired left ventricular relaxation rate; and does not perturb the homogeneous temporal pattern of regional valve opening along the line of coaptation. Future studies will confirm whether these findings are apparent in patients with chronic IMR, and may help to refine the current strategies used to treat IMR.

  View details for PubMedID 20099707

• Mitral annular hinge motion contribution to changes in mitral septal-lateral dimension and annular area 88th Annual Meeting of the American-Association-for-Thoracic-Surgery Itoh, A., Ennis, D. B., Bothe, W., Swanson, J. C., Krishnamurthy, G., Nguyen, T. C., Ingels, N. B., Miller, D. C. MOSBY-ELSEVIER. 2009: 1090–99

  Abstract

  The mitral annulus is a dynamic, saddle-shaped structure consisting of fibrous and muscular regions. Normal physiologic mechanisms of annular motion are incompletely understood, and more complete characterization is needed to provide rational basis for annuloplasty ring design and to enhance clinical outcomes.Seventeen sheep had radiopaque markers implanted; 16 around the annulus and 2 on middle anterior and posterior leaflet edges. Four-dimensional marker coordinates were acquired with biplanar videofluoroscopy at 60 Hz. Hinge angle was quantified between fibrous and muscular annular planes, with 0 degrees defined at end diastole, to characterize its contribution to alterations in mitral septal-lateral dimension and 2-dimensional total annular area throughout the cardiac cycle.During isovolumic contraction (pre-ejection), hinge angle abruptly increased, reaching maximum (steepest saddle shape, change 18 degrees +/- 13 degrees ) at peak left ventricular pressure. During ejection, hinge angle did not change; it then decreased during early filling (change 2 degrees +/- 2 degrees ). Septal-lateral dimension and total area paralleled hinge angle dynamics and leaflet distance (anterior to posterior marker). Pre-ejection septal-lateral reduction was 13% +/- 7% (3.3 +/- 1.5 mm) from 9% muscular dimension fall and 18 degrees +/- 13 degrees hinge angle increase.Pre-ejection increase in hinge angle contributes substantially to septal-lateral and total area reduction, facilitating leaflet coaptation. Semirigid annuloplasty rings or partial bands may preserve hinge motion, but possible recurrent annular dilatation could result in recurrent mitral regurgitation. Long-term clinical studies are required to determine who might benefit most from preserving intrinsic hinge motion without compromising repair durability.

  View details for DOI 10.1016/j.jtcvs.2009.03.067

  View details for PubMedID 19747697

• Significant Changes in Mitral Valve Leaflet Matrix Composition and Turnover With Tachycardia-Induced Cardiomyopathy 81st Annual Scientific Session of the American-Heart-Association Stephens, E. H., Timek, T. A., Daughters, G. T., Kuo, J. J., Patton, A. M., Baggett, L. S., Ingels, N. B., Miller, D. C., Grande-Allen, K. J. LIPPINCOTT WILLIAMS & WILKINS. 2009: S112–S119

  Abstract

  Dilated cardiomyopathy (DCM) involves significant remodeling of the left ventricular-mitral valve (MV) complex, but little is known regarding the remodeling of the mitral leaflets. The aim of this study was to assess changes in matrix composition and turnover in MV leaflets with DCM.Radiopaque markers were implanted in 24 sheep to delineate the MV; 10 sheep underwent tachycardia-induced cardiomyopathy (TIC), whereas 14 sheep remained as controls. Biplane videofluoroscopy was performed before and after TIC. Immunohistochemistry was performed on leaflet cross-sections taken from the septal, lateral, anterior, and posterior commissures attachment segments. Staining intensity was quantified within each attachment segment and leaflet region (basal, mid-leaflet, and free edge). Mitral regurgitation increased from 0.2+/-0.4 before TIC to 2.2+/-0.9 after TIC (P<0.0002). TIC leaflets demonstrated significant remodeling compared to controls, including greater cell density and loss of leaflet layered structure (all P<0.05). Collagen and elastic fiber turnover was greater in TIC, as was the myofibroblast phenotype (all P<0.05). Compositional differences between TIC and control leaflets were heterogeneous by annular segment and leaflet region, and related to regional changes in leaflet segment length with TIC.This study shows that the MV leaflets are significantly remodeled in DCM with changes in leaflet composition, structure, and valve cell phenotype. Understanding how alterations in leaflet mechanics, such as those induced by DCM, drive cell-mediated remodeling of the extracellular matrix will be important in developing future treatment strategies.

  View details for DOI 10.1161/CIRCULATIONAHA.108.844159

  View details for Web of Science ID 000269773000017

  View details for PubMedID 19752355

  View details for PubMedCentralID PMC2863305

• Characterization of Mitral Valve Anterior Leaflet Perfusion Patterns 81st Annual Scientific Session of the American-Heart-Association Swanson, J. C., Davis, L. R., Arata, K., Briones, E. P., Bothe, W., Itoh, A., Ingels, N. B., Miller, D. C. I C R PUBLISHERS. 2009: 488–95

  Abstract

  Although previous histologic studies have demonstrated the presence of blood vessels in the anterior mitral leaflet (AML) and second-order chordae (SC), little is known of the pattern of leaflet perfusion. Hence, the pattern and source of AML perfusion was investigated in an ovine model.Fluorescein angiograms were obtained in 17 ovine hearts immediately after heparinization and cardioplegic arrest, using non-selective left coronary artery (LCA) and selective left anterior descending (LAD), proximal, mid- and distal left circumflex (LCx) perfusion. Serial photographs using a flash/filter system to optimize fluorescence were obtained through a left atriotomy.The proximal half of the AML was seen to be richly vascularized. A loop of vessels was consistently observed in the mitral annulus and AML; these vessels ran along the annulus, extended to the sites of SC insertion, and created anastomoses between these insertions. The SC contributed to the AML perfusion and the anastomotic loop. Selective perfusion of the LAD or proximal LCx artery (ligated before the first obtuse marginal artery) did not perfuse the AML (n = 6). Perfusion of the mid- and distal LCx (n = 7) consistently supplied the AML via SC insertion sites and annular branches.The ovine AML is perfused by vessels that run through the SC and annulus simultaneously, and then create a communicating arcade in the leaflet. These vessels originate from the mid- and distal portions of the LCx. A loss of perfusion as a result of microvascular disease could have adverse implications. Derangements in the extensive vascular component of the mitral valve could be an important contributing factor to valve disease.

  View details for PubMedID 20099688

• Stress-strain behavior of mitral valve leaflets in the beating ovine heart JOURNAL OF BIOMECHANICS Krishnamurthy, G., Itoh, A., Bothe, W., Swanson, J. C., Kuhl, E., Karlsson, M., Miller, D. C., Ingels, N. B. 2009; 42 (12): 1909-1916

  Abstract

  Excised anterior mitral leaflets exhibit anisotropic, non-linear material behavior with pre-transitional stiffness ranging from 0.06 to 0.09 N/mm(2) and post-transitional stiffness from 2 to 9 N/mm(2). We used inverse finite element (FE) analysis to test, for the first time, whether the anterior mitral leaflet (AML), in vivo, exhibits similar non-linear behavior during isovolumic relaxation (IVR). Miniature radiopaque markers were sewn to the mitral annulus, AML, and papillary muscles in 8 sheep. Four-dimensional marker coordinates were obtained using biplane videofluoroscopic imaging during three consecutive cardiac cycles. A FE model of the AML was developed using marker coordinates at the end of isovolumic relaxation (when pressure difference across the valve is approximately zero), as the reference state. AML displacements were simulated during IVR using measured left ventricular and atrial pressures. AML elastic moduli in the radial and circumferential directions were obtained for each heartbeat by inverse FEA, minimizing the difference between simulated and measured displacements. Stress-strain curves for each beat were obtained from the FE model at incrementally increasing transmitral pressure intervals during IVR. Linear regression of 24 individual stress-strain curves (8 hearts, 3 beats each) yielded a mean (+/-SD) linear correlation coefficient (r(2)) of 0.994+/-0.003 for the circumferential direction and 0.995+/-0.003 for the radial direction. Thus, unlike isolated leaflets, the AML, in vivo, operates linearly over a physiologic range of pressures in the closed mitral valve.

  View details for DOI 10.1016/j.jbiomech.2009.05.018

  View details for PubMedID 19535081

• Presystolic mitral annular septal-lateral shortening is independent from left atrial and left ventricular contraction during acute volume depletion 22nd Annual Meeting of the European-Association-for-Cardio-Thoracic-Surgery Bothe, W., Nguyen, T. C., Roberts, M. E., Timek, T. A., Itoh, A., Ingels, N. B., Miller, D. C. ELSEVIER SCIENCE BV. 2009: 236–43

  Abstract

  The mitral annulus (MA) is a dynamic structure that joins the left atrium (LA) and left ventricle (LV), but it is unknown whether MA motion is coupled to the LA or the LV or neither of the two. Since a well orchestrated coordination of LA, MA and LV septal-lateral (S-L) dynamics is essential for efficient valve closure, we assessed their functional coupling in an experimental ovine model. To assess the coupling under a wide range of physiological conditions, data were acquired in normal and acutely volume depleted hearts.In 10 sheep, radiopaque markers were placed in LA, MA and LV base (LVbase). Twelve weeks postoperatively, 4-D marker coordinates were obtained by stereo videofluoroscopy (60 frames/s) before (CTRL) and during acute inferior vena caval occlusion (VCO). Septal-lateral dimensions were calculated as distances between corresponding marker pairs in the LA, MA and LVbase 5 frames before end-diastole (ED-84 ms) and at end-diastole. Dynamics during late diastole are described as changes from ED-84 ms versus end-diastole. To study the functional coupling between LA, MA and LVbase we calculated slopes during late diastole from simple linear regressions on an animal-by-animal basis.During late diastole in CTRL, the LA and MA both shortened along the S-L dimension (32.9 +/- 6.6 mm vs 31.0 +/- 5.5 mm, p = 0.026 and 27.3 +/- 3.7 mm vs 24.6 +/- 4.1 mm, p = 0.005, respectively) whereas the LVbase lengthened (56.2 +/- 9.3 mm vs 57.3 +/- 9.3 mm, p = 0.012). VCO abolished septal-lateral dynamics of LA and LVbase during late diastole (27.8 +/- 4.3 mm vs 27.4 +/- 3.9 mm, p = 0.155 and 49.4 +/- 7.7 mm vs 49.5 +/- 7.5 mm, p = 0.752, respectively) while the MA still shortened (19.0 +/- 2.9 vs 18.0 +/- 2.8, p = 0.042). Under CTRL conditions LA dynamics were linearly dependent from MA dynamics (average coefficient 0.57, p = 0.001), suggesting that LA and MA are functionally coupled. With acute volume depletion, MA dynamics were linearly independent from both, LA and LV (average coefficient 0.28, p = 0.159 and 0.58, p = 0.192, respectively).Whereas MA and LA dynamics are coupled during late diastole in hearts with normal LV volumes, presystolic mitral annular septal-lateral shortening is independent from LA and LV dynamics with acute volume depletion. A better understanding of mitral annular dynamics and their functional coupling may help improve mitral valve repair strategies.

  View details for DOI 10.1016/j.ejcts.2009.03.021

  View details for PubMedID 19394855

• Infolding and collapse of thoracic endoprostheses: Manifestations and treatment options JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Sze, D. Y., Mitchell, R. S., Miller, D. C., Fleischmann, D., Frisoli, J. K., Kee, S. T., Verma, A., Sheehan, M. P., Dake, M. D. 2009; 138 (2): 324-333

  Abstract

  We sought to review the clinical sequelae and imaging manifestations of thoracic aortic endograft collapses and infoldings and to evaluate minimally invasive methods of repairing such collapses.Two hundred twenty-one Gore endografts (Excluder, TAG; W. L. Gore & Associates, Inc, Flagstaff, Ariz) were deployed in 145 patients for treatment of pathologies including aneurysms and pseudoaneurysms, dissections, penetrating ulcers, transections, fistulae, mycotic aneurysms, and neoplastic invasions in 6 different prospective trials at a single institution from 1997 to 2007. Device collapses and infoldings were analyzed retrospectively, including review of anatomic parameters, pathologies treated, device sizing and selection, clinical sequelae, methods of repair, and outcome.Six device collapses and infoldings were identified. Oversized devices placed into small-diameter aortas and imperfect proximal apposition to the lesser curvature were seen in all proximal collapses, affecting patients with transections and pseudoaneurysms. Infoldings in patients undergoing dissection represented incomplete initial expansion rather than delayed collapse. Delayed collapse occurred as many as 6 years after initial successful deployment, apparently as a result of changes in the aortic configuration from aneurysmal shrinkage. Clinical manifestations ranged from life-threatening ischemia to complete lack of symptoms. Collapses requiring therapy were remedied percutaneously by bare stenting or in one case by branch vessel embolization.Use of oversized devices in small aortas carries a risk of device failure by collapse, which can occur immediately or after years of delay. When clinically indicated, percutaneous repair can be effectively performed.

  View details for DOI 10.1016/j.jtcvs.2008.12.007

  View details for PubMedID 19619775

• Multiplanar Reconstruction of Three-Dimensional Transthoracic Echocardiography Improves the Presurgical Assessment of Mitral Prolapse JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Beraud, A., Schnittger, I., Miller, D. C., Liang, D. H. 2009; 22 (8): 907-913

  Abstract

  The aim of this study was to evaluate the value and accuracy of multiplanar reconstruction (MPR) of three-dimensional (3D) transthoracic echocardiographic data sets in assessing mitral valve pathology in patients with surgical mitral valve prolapse (MVP).Sixty-four patients with surgical MVP and preoperative two-dimensional (2D) and 3D transthoracic echocardiography were analyzed. The descriptions obtained by 3D MPR and 2D were compared in the context of the surgical findings.Two-dimensional echocardiography correctly identified the prolapsing leaflets in 32 of 64 patients and 3D MPR in 46 of 64 patients (P=.016). Among the 27 patients with complex pathology (ie, more than isolated middle scallop of the posterior leaflet prolapse), 3D MPR identified 20 correctly, as opposed to 6 with 2D imaging (P<.001).Interpretation of 3D transthoracic echocardiographic images with MPR improved the accuracy of the description of the MVP compared with 2D interpretation. This added value of 3D MPR was most important in extensive and/or commissural prolapse.

  View details for DOI 10.1016/j.echo.2009.05.007

  View details for PubMedID 19553082

• Long-Term Durability of Open Thoracic and Thoracoabdominal Aneurysm Repair SEMINARS IN VASCULAR SURGERY Fischbein, M. P., Miller, D. C. 2009; 22 (2): 74-80

  Abstract

  Results of open surgical repair of descending and thoracoabdominal aortic aneurysms have improved dramatically over the years. Nevertheless, while adjunctive protective strategies, such as spinal cord drainage and distal aortic perfusion, have improved outcomes, clinical challenges remain. In the current era, thoracic aortic surgeons must possess both open and endovascular stent-graft capabilities to offer these complex patients the most optimal and individualized treatment approach. Herein we summarize the contemporary outcomes of open surgical repair of patients with either descending thoracic or thoracoabdominal aortic aneurysms, focusing on the risk of complications and means for preventing their occurrence.

  View details for DOI 10.1053/j.semvascsurg.2009.04.001

  View details for PubMedID 19573745

• Transmural Strains in the Ovine Left Ventricular Lateral Wall During Diastolic Filling JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME Kindberg, K., Carlhall, C., Karlsson, M., Nguyen, T. C., Cheng, A., Langer, F., Rodriguez, F., Daughters, G. T., Miller, D. C., Ingels, N. B. 2009; 131 (6)

  Abstract

  Rapid early diastolic left ventricular (LV) filling requires a highly compliant chamber immediately after systole, allowing inflow at low driving pressures. The transmural LV deformations associated with such filling are not completely understood. We sought to characterize regional transmural LV strains during diastole, with focus on early filling, in ovine hearts at 1 week and 8 weeks after myocardial marker implantation. In seven normal sheep hearts, 13 radiopaque markers were inserted to silhouette the LV chamber and a transmural beadset was implanted into the lateral equatorial LV wall to measure transmural strains. Four-dimensional marker dynamics were obtained 1 week and 8 weeks thereafter with biplane videofluoroscopy in closed-chest, anesthetized animals. LV transmural strains in both cardiac and fiber-sheet coordinates were studied from filling onset to the end of early filling (EOEF, 100 ms after filling onset) and at end diastole. At the 8 week study, subepicardial circumferential strain (ECC) had reached its final value already at EOEF, while longitudinal and radial strains were nearly zero at this time. Subepicardial ECC and fiber relengthening (Eff) at EOEF were reduced to 1 compared with 8 weeks after surgery (ECC:0.02+/-0.01 to 0.08+/-0.02 and Eff:0.00+/-0.01 to 0.03+/-0.01, respectively, both P<0.05). Subepicardial ECC during early LV filling was associated primarily with fiber-normal and sheet-normal shears at the 1 week study, but to all three fiber-sheet shears and fiber relengthening at the 8 week study. These changes in LV subepicardial mechanics provide a possible mechanistic basis for regional myocardial lusitropic function, and may add to our understanding of LV myocardial diastolic dysfunction.

  View details for DOI 10.1115/1.3118774

  View details for Web of Science ID 000266035700004

  View details for PubMedID 19449958

• Valve-sparing and valve-replacing techniques for aortic root replacement in patients with Marfan syndrome: Analysis of early outcome. journal of thoracic and cardiovascular surgery Volguina, I. V., Miller, D. C., LeMaire, S. A., Palmero, L. C., Wang, X. L., Connolly, H. M., Sundt, T. M., Bavaria, J. E., Dietz, H. C., Milewicz, D. M., Coselli, J. S. 2009; 137 (5): 1124-1132

  Abstract

  A prospective, international registry study was initiated to provide contemporary comparative data on short-term clinical outcomes after aortic valve-sparing and aortic valve-replacing root operations in patients with Marfan syndrome. The purpose of this initial report is to describe the study design and to compare early outcomes in the first 151 enrolled patients.We assessed 30-day outcomes in 151 patients who met strict Ghent diagnostic criteria for Marfan syndrome and underwent aortic root replacement with either valve-replacing (n = 46) or valve-sparing techniques (n = 105) at one of 18 participating centers. In the valve replacement group, a mechanical composite valve graft was used in 39 (85%) patients and a bioprosthetic valve in 7 (15%). In the valve-sparing group, David V procedures were performed in 57 (54%) patients, David I in 38 (36%), David IV in 8 (8%), Florida sleeve in 1 (1%), and Yacoub remodeling in 1 (1%).No in-hospital or 30-day deaths occurred. Despite longer crossclamp and cardiopulmonary bypass times in the valve-sparing group, there were no significant between-group differences in postoperative complications. Thirty-day valve-related complications occurred in 2 (4%) patients undergoing valve replacement and in 3 (3%) undergoing valve-sparing procedures (P = .6).The analysis of early outcomes revealed that valve-sparing techniques were the most common approach to root replacement in patients with Marfan syndrome in these centers. The complexity of valve-sparing root replacement did not translate into any demonstrable adverse early outcomes. Subsequent analysis will compare the 3-year durability of these two surgical approaches.

  View details for DOI 10.1016/j.jtcvs.2009.03.023

  View details for PubMedID 19379977

• Factors Portending Endoleak Formation After Thoracic Aortic Stent-Graft Repair of Complicated Aortic Dissection CIRCULATION-CARDIOVASCULAR INTERVENTIONS Sze, D. Y., Van den Bosch, M. A., Dake, M. D., Miller, D. C., Hofmann, L. V., Varghese, R., Malaisrie, S. C., van der Starre, P. J., Rosenberg, J., Mitchell, R. S. 2009; 2 (2): 105-112

  Abstract

  Endoleaks after stent-graft repair of aortic dissections are poorly understood but seem substantially different from those seen after aneurysm repair. We studied anatomic and clinical factors associated with endoleaks in patients who underwent stent-graft repair of complicated type B aortic dissections.From 2000 to 2007, 37 patients underwent stent-graft repair of acute (< or =14 days; n=23), subacute (15 to 90 days; n=10) or chronic (>90 days; n=4) complicated type B aortic dissections using the Gore Thoracic Excluder (n=17) or TAG stent-grafts (n=20) under an investigator-sponsored protocol. Endoleaks were classified as imperfect proximal seal, flow through fenestrations or branches, or complex (both). Variables studied included coverage of the left subclavian artery, aortic curvature, completeness of proximal apposition, dissection chronicity, and device used. Endoleaks were found during follow-up (mean, 22 months) in 59% of patients, and they were associated with coverage of the left subclavian artery (complex, P<0.001), small radius of curvature (type 1 and complex, P=0.05), and greatest length of unapposed proximal stent graft (complex, P<0.0001). During follow-up, 10 endoleaks resolved spontaneously, 6 required reintervention for false lumen dilatation, and 2 were stable without clinical consequences.Endoleaks are common after stent-graft repair of aortic dissection and may lead to false lumen enlargement necessitating reintervention. Anatomic complexities such as acute aortic curvature and covered side branches were associated with endoleaks, illustrating the need for dissection-specific device development.

  View details for DOI 10.1161/CIRCINTERVENTIONS.108.819722

  View details for PubMedID 20031703

• Reduced Systolic Torsion in Chronic "Pure" Mitral Regurgitation CIRCULATION-CARDIOVASCULAR IMAGING Ennis, D. B., Nguyen, T. C., Itoh, A., Bothe, W., Liang, D. H., Ingels, N. B., Miller, D. C. 2009; 2 (2): 85-92

  Abstract

  Global left ventricular (LV) torsion declines with chronic ischemic mitral regurgitation (MR), which may accelerate the LV remodeling spiral toward global cardiomyopathy; however, it has not been definitively established whether this torsional decline is attributable to the infarct, the MR, or their combined effect. We tested the hypothesis that chronic "pure" MR alone reduces global LV torsion.Chronic "pure" MR was created in 13 sheep by surgically punching a 3.5- to 4.8-mm hole (HOLE) in the mitral valve posterior leaflet. Nine control (CNTL) sheep were operated on concurrently. At 1 (WK-01) and 12 weeks (WK-12) postoperatively, the 4D motion of implanted radiopaque markers was used to calculate global LV torsion. MR-grade in HOLE was greater than CNTL at WK-01 and WK-12 (2.5+/-1.1 versus 0.6+/-0.5, P<0.001 at WK-12). HOLE LV mass index was larger at WK-12 compared with CNTL (195+/-14 versus 170+/-17 g/m(2), P<0.01), indicating LV remodeling. Global LV systolic torsion decreased in HOLE from WK-01 to WK-12 (4.1+/-2.8 degrees versus 1.7+/-1.7 degrees , P<0.01), but did not change in CNTL (5.5+/-1.8 degrees versus 4.2+/-2.7 degrees , P=NS). Global LV torsion was lower in HOLE relative to CNTL at WK-12 (P<0.05) but not at WK-01 (P=NS).Twelve weeks of chronic "pure" MR resulting in mild global LV remodeling is associated with significantly increased LV mass index and reduced global LV systolic torsion, but no other significant changes in hemodynamics. MR alone is a major component of torsional deterioration in "pure" MR and may be an important factor in chronic ischemic mitral regurgitation.

  View details for DOI 10.1161/CIRCIMAGING.108.785923

  View details for PubMedID 19808573

• Valve-sparing and valve-replacing techniques for aortic root replacement in patients with Marfan syndrome: Analysis of early outcome Volguina, I. V., Miller, C., LeMaire, S. A., Palmero, L. C., Wang, X., Connolly, H. M., Sundt, T. M., Bavaria, J. E., Dietz, H. C., Milewicz, D. M., Coselli, J. S., Behalf Aortic Valve Operative Outc MOSBY-ELSEVIER. 2009: 641–49

  Abstract

  A prospective, international registry study was initiated to provide contemporary comparative data on short-term clinical outcomes after aortic valve-sparing and aortic valve-replacing root operations in patients with Marfan syndrome. The purpose of this initial report is to describe the study design and to compare early outcomes in the first 151 enrolled patients.We assessed 30-day outcomes in 151 patients who met strict Ghent diagnostic criteria for Marfan syndrome and underwent aortic root replacement with either valve-replacing (n = 46) or valve-sparing techniques (n = 105) at one of 18 participating centers. In the valve replacement group, a mechanical composite valve graft was used in 39 (85%) patients and a bioprosthetic valve in 7 (15%). In the valve-sparing group, David V procedures were performed in 57 (54%) patients, David I in 38 (36%), David IV in 8 (8%), Florida sleeve in 1 (1%), and Yacoub remodeling in 1 (1%).No in-hospital or 30-day deaths occurred. Despite longer crossclamp and cardiopulmonary bypass times in the valve-sparing group, there were no significant between-group differences in postoperative complications. Thirty-day valve-related complications occurred in 2 (4%) patients undergoing valve replacement and in 3 (3%) undergoing valve-sparing procedures (P = .6).The analysis of early outcomes revealed that valve-sparing techniques were the most common approach to root replacement in patients with Marfan syndrome in these centers. The complexity of valve-sparing root replacement did not translate into any demonstrable adverse early outcomes. Subsequent analysis will compare the 3-year durability of these two surgical approaches.

  View details for DOI 10.1016/j.jtcvs.2008.11.030

  View details for Web of Science ID 000263791500021

  View details for PubMedID 19258081

• QUANTIFICATION OF IN VIVO STRESSES IN THE OVINE ANTERIOR MITRAL VALVE LEAFLET ASME Summer Bioengineering Conference Krishnamurthy, G., Ltoh, A., Bothe, W., Ennis, D. B., Swanson, J. C., Kuhl, E., Miller, D. C., Ingels, N. B. AMER SOC MECHANICAL ENGINEERS. 2009: 131–132

  View details for Web of Science ID 000263364700066

• BICUSPID AORTOPATHY OR BICUSPID AORTOPATHIES? THE RISK IN GENERALIZING Reply JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Fazel, S. S., Miller, D. 2008; 136 (6): 1604–6

  View details for DOI 10.1016/j.jtcvs.2008.08.027

  View details for Web of Science ID 000261970100038

• Pre- and Postoperative Imaging of the Aortic Root for Valve-Sparing Aortic Root Repair (V-SARR) SEMINARS IN THORACIC AND CARDIOVASCULAR SURGERY Fleischmann, D., Liang, D. H., Mitchell, R., Miller, D. 2008; 20 (4): 365–73

  View details for DOI 10.1053/j.semtcvs.2008.11.009

  View details for Web of Science ID 000416343300016

• Acute Aortic Syndromes: New Insights from Electrocardiographically Gated Computed Tomography SEMINARS IN THORACIC AND CARDIOVASCULAR SURGERY Fleischmann, D., Mitchell, R., Miller, D. 2008; 20 (4): 340–47

  View details for DOI 10.1053/j.semtcvs.2008.11.011

  View details for Web of Science ID 000416343300013

• Dynamic Characterization of Mitral Valve Anterior Leaflet Perfusion Pattern Swanson, J. C., Davis, L. R., Arata, K., Briones, E. P., Itoh, A., Bothe, W., Chang, P. A., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2008: S1071

  View details for Web of Science ID 000262104504255

• Significant Changes in Mitral Valve Leaflet Matrix Composition and Turnover with Dilated Cardiomyopathy Stephens, E. H., Timek, T., Daughters, G. T., Ingels, N. B., Miller, D. C., Grande-Allen, K. LIPPINCOTT WILLIAMS & WILKINS. 2008: S700

  View details for Web of Science ID 000262104502270

• Alterations in transmural myocardial strain - An early marker of left ventricular dysfunction in mitral regurgitation? 80th Annual Scientific Session of the American-Heart-Association (AHA) Carlhaell, C. J., Nguyen, T. C., Itoh, A., Ennis, D. B., Bothe, W., Liang, D., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2008: S256–S262

  Abstract

  In asymptomatic patients with severe isolated mitral regurgitation (MR), identifying the onset of early left ventricular (LV) dysfunction can guide the timing of surgical intervention. We hypothesized that changes in LV transmural myocardial strain represent an early marker of LV dysfunction in an ovine chronic MR model.Sheep were randomized to control (CTRL, n=8) or experimental (EXP, n=12) groups. In EXP, a 3.5- or 4.8-mm hole was created in the posterior mitral leaflet to generate "pure" MR. Transmural beadsets were inserted into the lateral and anterior LV wall to radiographically measure 3-dimensional transmural strains during systole and diastolic filling, at 1 and 12 weeks postoperatively. MR grade was higher in EXP than CTRL at 1 and 12 weeks (3.0 [2-4] versus 0.5 [0-2]; 3.0 [1-4] versus 0.5 [0-1], respectively, both P<0.001). At 12 weeks, LV mass index was greater in EXP than CTRL (201+/-18 versus 173+/-17 g/m(2); P<0.01). LVEDVI increased in EXP from 1 to 12 weeks (P=0.015). Between the 1 and 12 week values, the change in BNP (-4.5+/-4.4 versus -3.0+/-3.6 pmol/L), PRSW (9+/-13 versus 23+/-18 mm Hg), tau (-3+/-11 versus -4+/-7 ms), and systolic strains was similar between EXP and CTRL. The changes in longitudinal diastolic filling strains between 1 and 12 weeks, however, were greater in EXP versus CTRL in the subendocardium (lateral: -0.08+/-0.05 versus 0.02+/-0.14; anterior: -0.10+/-0.05 versus -0.02+/-0.07, both P<0.01).Twelve weeks of ovine "pure" MR caused LV remodeling with early changes in LV function detected by alterations in transmural myocardial strain, but not by changes in BNP, PRSW, or tau.

  View details for DOI 10.1161/CIRCULATIONAHA.107.753525

  View details for PubMedID 18824764

• The effects of mitral regurgitation alone are sufficient for leaflet remodeling 80th Annual Scientific Session of the American-Heart-Association (AHA) Stephens, E. H., Nguyen, T. C., Itoh, A., Ingels, N. B., Miller, D. C., Grande-Allen, K. J. LIPPINCOTT WILLIAMS & WILKINS. 2008: S243–S249

  Abstract

  Although chronic mitral regurgitation results in adverse left ventricular remodeling, its effect on the mitral valve leaflets per se is unknown. In a chronic ovine model, we tested whether isolated mitral regurgitation alone was sufficient to remodel the anterior mitral leaflet.Twenty-nine sheep were randomized to either control (CTRL, n=11) or experimental (HOLE, n=18) groups. In HOLE, a 2.8- to 4.8-mm diameter hole was punched in the middle scallop of the posterior mitral leaflet to create "pure" mitral regurgitation. At 12 weeks, the anterior mitral leaflet was analyzed immunohistochemically to assess markers of collagen and elastin synthesis as well as matrix metalloproteinases and proteoglycans. A semiquantitative grading scale for characteristics such as intensity and delineation of stain between layers was used to quantify differences between HOLE and CTRL specimens across the heterogeneous leaflet structure. At 12 weeks, mitral regurgitation grade was greater in HOLE versus CTRL (3.0+/-0.8 versus 0.4+/-0.4, P<0.001). In HOLE anterior mitral leaflet, saffron-staining collagen (Movat) decreased, consistent with an increase in matrix metalloproteases throughout the leaflet. Type III collagen expression was increased in the midleaflet and free edge and expression of prolyl-4-hydroxylase (indicating collagen synthesis) was increased in the spongiosa layer. The proteoglycan decorin, also involved in collagen fibrillogenesis, was increased compared with CTRL (all P

  View details for DOI 10.1161/CIRCULATIONAHA.107.757526

  View details for Web of Science ID 000259648600035

  View details for PubMedID 18824762

• Material properties of the ovine mitral valve anterior leaflet in vivo from inverse finite element analysis AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Krishnamurthy, G., Ennis, D. B., Itoh, A., Bothe, W., Swanson, J. C., Karlsson, M., Kuhl, E., Miller, D. C., Ingels, N. B. 2008; 295 (3): H1141-H1149

  Abstract

  We measured leaflet displacements and used inverse finite-element analysis to define, for the first time, the material properties of mitral valve (MV) leaflets in vivo. Sixteen miniature radiopaque markers were sewn to the MV annulus, 16 to the anterior MV leaflet, and 1 on each papillary muscle tip in 17 sheep. Four-dimensional coordinates were obtained from biplane videofluoroscopic marker images (60 frames/s) during three complete cardiac cycles. A finite-element model of the anterior MV leaflet was developed using marker coordinates at the end of isovolumic relaxation (IVR; when the pressure difference across the valve is approximately 0), as the minimum stress reference state. Leaflet displacements were simulated during IVR using measured left ventricular and atrial pressures. The leaflet shear modulus (G(circ-rad)) and elastic moduli in both the commisure-commisure (E(circ)) and radial (E(rad)) directions were obtained using the method of feasible directions to minimize the difference between simulated and measured displacements. Group mean (+/-SD) values (17 animals, 3 heartbeats each, i.e., 51 cardiac cycles) were as follows: G(circ-rad) = 121 +/- 22 N/mm2, E(circ) = 43 +/- 18 N/mm2, and E(rad) = 11 +/- 3 N/mm2 (E(circ) > E(rad), P < 0.01). These values, much greater than those previously reported from in vitro studies, may result from activated neurally controlled contractile tissue within the leaflet that is inactive in excised tissues. This could have important implications, not only to our understanding of mitral valve physiology in the beating heart but for providing additional information to aid the development of more durable tissue-engineered bioprosthetic valves.

  View details for DOI 10.1152/ajpheart.00284.2008

  View details for PubMedID 18621858

• The effect of pure mitral regurgitation on mitral annular geometry and three-dimensional saddle shape 87th Annual Meeting of the American-Association-for-Thoracic-Surgery Nguyen, T. C., Itoh, A., Carlhall, C. J., Bothe, W., Timek, T. A., Ennis, D. B., Oakes, R. A., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. MOSBY-ELSEVIER. 2008: 557–65

  Abstract

  Chronic ischemic mitral regurgitation is associated with mitral annular dilatation in the septal-lateral dimension and flattening of the annular 3-dimensional saddle shape. To examine whether these perturbations are caused by the ischemic insult, mitral regurgitation, or both, we investigated the effects of pure mitral regurgitation (low pressure volume overload) on annular geometry and shape.Eight radiopaque markers were sutured evenly around the mitral annulus in sheep randomized to control (CTRL, n = 8) or experimental (HOLE, n = 12) groups. In HOLE, a 3.5- to 4.8-mm hole was punched in the posterior leaflet to generate pure mitral regurgitation. Four-dimensional marker coordinates were obtained radiographically 1 and 12 weeks postoperatively. Mitral annular area, annular septal-lateral and commissure-commissure dimensions, and annular height were calculated every 16.7 ms.Mitral regurgitation grade was 0.4 +/- 0.4 in CTRL and 3.0 +/- 0.8 in HOLE (P < .001) at 12 weeks. End-diastolic left ventricular volume index was greater in HOLE at both 1 and 12 weeks; end-systolic volume index was larger in HOLE at 12 weeks. Mitral annular area increased in HOLE predominantly in the commissure-commissure dimension, with no difference in annular height between HOLE versus CTRL at 1 or 12 weeks, respectively.In contrast with annular septal-lateral dilatation and flattening of the annular saddle shape observed with chronic ischemic mitral regurgitation, pure mitral regurgitation was associated with commissure-commissure dimension annular dilatation and no change in annular shape. Thus, infarction is a more important determinant of septal-lateral dilatation and annular shape than mitral regurgitation, which reinforces the need for disease-specific designs of annuloplasty rings.

  View details for DOI 10.1016/j.jtcvs.2007.12.087

  View details for PubMedID 18805251

• Complicated acute type B aortic dissection: Midterm results of emergency endovascular stent-grafting 31st Annual Meeting of the Western-Thoracic-Surgical-Association Verhoye, J. P., Miller, D. C., Sze, D., Dake, M. D., Mitchell, R. S. MOSBY-ELSEVIER. 2008: 424–30

  Abstract

  This study assessed midterm results of emergency endovascular stent-grafting for patients with life-threatening complications of acute type B aortic dissection.Between November 1996 and June 2004, 16 patients with complicated acute type B aortic dissections (mean age 57 years, range 16-88 years) underwent endovascular stent-grafting within 48 hours of presentation. Complications included contained rupture, hemothorax, refractory chest pain, and severe visceral or lower limb ischemia. Stent-graft types included custom-made first-generation endografts and second-generation commercial stent-grafts (Gore Excluder or TAG; W. L. Gore & Associates, Inc, Flagstaff, Ariz.). Follow-up was 100% complete, averaged 36 +/- 36 months, and included postprocedural surveillance computed tomographic scans.Early mortality was 25% +/- 11% (70% confidence limit), with no late deaths. No new neurologic complications occurred. According to the latest scan, 4 patients (25%) had complete thrombosis of the false lumen; the lumen was partially thrombosed in 6 patients (38%). Distal aortic diameter was increased in only 1 patient. Actuarial survival at 1 and 5 years was 73% +/- 11%; freedom from treatment failure (including aortic rupture, device fault, reintervention, aortic death, or sudden, unexplained late death) was 67% +/- 14% at 5 years.With follow-up to 9 years, endovascular stent-grafting for patients with complicated acute type B aortic dissection conferred benefit. Consideration of emergency stent-grafting may improve the dismal outlook for these patients; future refinements in stent-graft design and technology and earlier diagnosis and intervention should be associated with improved results.

  View details for DOI 10.1016/j.jtcvs.2008.01.046

  View details for PubMedID 18692652

• Response to letter regarding article, "Effect of chronotropy and inotropy on stitch tension in the edge-to-edge mitral repair" CIRCULATION Timek, T. A., Lai, D. T., Liang, D., Miller, D. C., Nielsen, S. L., Daughters, G. T., Ingels, N. B. 2008; 118 (4): E79-E79

  View details for DOI 10.1161/CIRCULATIONAHA.108.765370

  View details for Web of Science ID 000257797800020

• Effect of local annular interventions on annular and left ventricular geometry 21st Annual Meeting of the European-Association-for-Cardio-Thoracic-Surgery (EACTS) Timek, T. A., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. OXFORD UNIV PRESS INC. 2008: 1049–54

  Abstract

  Etiology-specific annular interventions and annuloplasty rings are now commercially available for the treatment of different types of mitral regurgitation; however, knowledge concerning the effects of local annular alterations on annular and left ventricular (LV) geometry is limited.Seven adult sheep underwent implantation of eight radiopaque markers around the mitral annulus (MA) and eight markers on the LV (four each on two levels: basal and apical), and one on each papillary muscle tip. Trans-annular septal-lateral (SL) sutures were placed between the corresponding markers on the septal and lateral annulus at valve center (CENT) and near anterior (ACOM) and posterior (PCOM) commissures and externalized. Hemodynamic parameters and 4D marker coordinates were measured before and during SL annular cinching ('SLAC'; suture tightening 3-5 mm for 20s) at each suture location. Mitral annular SL diameter, annular area (MAA), and distance from the mid-septal annulus to the LV markers and papillary muscle tips were determined from marker coordinates every 17ms.End-systolic MAA decreased from 5.93+/-1.27 to 5.23+/-1.29(*)cm(2), 5.98+/-1.16 to 5.33+/-1.31(*)cm(2), and 6.30+/-1.65 to 5.61+/-1.37(*)cm(2) for SLAC(ACOM), SLAC(CENT), and SLAC(PCOM), respectively ((*)p<0.05 vs pre-cinching). Each SLAC intervention reduced the SL diameter at all three locations, while both SLAC(ACOM) and SLAC(CENT) affected ventricular geometry, and SLAC(PCOM) only slightly altered valvular-subvalvular distance. Only SLAC(CENT) altered papillary muscle position.Local annular SL reduction influences remote annular SL dimensions and affects LV geometry. The effect of local annular interventions on global annular geometry and LV remodeling should be considered in surgical or interventional approaches to mitral regurgitation and the design of new annular prostheses as well as supra-annular and sub-annular catheter interventions.

  View details for DOI 10.1016/j.ejcts.2008.03.040

  View details for PubMedID 18442919

• Non-uniform transmural remodeling in ovine chronic mitral regurgitation Ennis, D. B., Nguyen, T. C., Itoh, A., Carlhaell, C. J., Oakes, R. A., Bothe, W., Liang, D., Miller, D. C., Ingels, N. B. FEDERATION AMER SOC EXP BIOL. 2008

  View details for Web of Science ID 000208467801528

• Guidelines for reporting mortality and morbidity after cardiac valve interventions ANNALS OF THORACIC SURGERY Akins, C. W., Miller, D. C., Turina, M. I., Kouchoukos, N. T., Blackstone, E. H., Grunkemeier, G. L., Takkenberg, J. J., David, T. E., Butchart, E. G., Adams, D. H., Shahian, D. M., Hagl, S., Mayer, J. E., Lytle, B. W. 2008; 85 (4): 1490-1495

  View details for DOI 10.1016/j.athoracsur.2007.12.082

  View details for Web of Science ID 000254083300070

  View details for PubMedID 18355567

• Guidelines for reporting mortality and morbidity after cardiac valve interventions JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Akins, C. W., Miller, D. C., Turina, M. I., Kouchoukos, N. T., Blackstone, E. H., Grunkemeier, G. L., Takkenberg, J. J., David, T. E., Butchart, E. G., Adams, D. H., Shahian, D. M., Hagl, S., Mayer, J. E., Lytle, B. W. 2008; 135 (4): 732-738

  View details for DOI 10.1016/j.jtcvs.2007.12.002

  View details for Web of Science ID 000254423600003

  View details for PubMedID 18374749

• Effect of semi-rigid or flexible mitral ring annuloplasty on anterior leaflet three-dimensional geometry 4th Biennial Meeting of the Society-for-Heart-Valve-Disease Timek, T. A., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. I C R PUBLISHERS. 2008: 149–54

  Abstract

  A saddle-shaped mitral annulus may optimize anterior leaflet shape and, in theory, reduce leaflet and chordal stress. Although annuloplasty rings alter native annular height and immobilize the posterior mitral leaflet, their effects on anterior leaflet geometry are unknown.Four radiopaque markers were placed on the central meridian of the anterior mitral leaflet (AML), and eight on the mitral annulus, of 20 sheep. Six animals were then implanted with a Carpentier-Edwards Physio ring, and six a Medtronic Duran flexible ring. Eight animals served as controls. All animals were then studied with biplane 60 Hz videofluoroscopy at 7-10 days after surgery. The angle Theta was calculated as the angle between each AML leaflet marker and the annular septal-lateral diameter, while AML marker excursion was expressed as the difference between maximum and minimum angle Theta during the cardiac cycle. The intrinsic AML shape was described by three angles, each between three consecutive leaflet markers from the mid-septal annular marker to the leaflet edge (Phi1-3, from annulus to leaflet edge).Hemodynamic parameters differed only in left ventricular pressure, which was higher in control animals. Anterior leaflet excursion during the cardiac cycle for all four leaflet markers did not change with ring annuloplasty. The intrinsic leaflet angles (Phi1-3) were also unaffected by annular fixation, and thus leaflet shape remained unaltered.Neither semi-rigid nor flexible annuloplasty rings affected anterior leaflet excursion or the intrinsic geometry of the AML at end-systole or end-diastole. These data suggest that, in normal sheep hearts, annuloplasty rings do not alter anterior leaflet shape and hence do not perturb leaflet stress distribution.

  View details for PubMedID 18512484

• Functional uncoupling of the mitral annulus and left ventricle with mitral regurgitation and dopamine 4th Biennial Meeting of the Society-for-Heart-Valve-Disease Nguyen, T. C., Itoh, A., Carlhall, C. J., Oakes, R. A., Liang, D., Ingels, N. B., Miller, D. C. I C R PUBLISHERS. 2008: 168–77

  Abstract

  The mitral annulus and left ventricle are generally thought to be functionally coupled, in the sense that increases in left ventricular (LV) size, as seen in ischemic mitral regurgitation (MR), or decreases in LV size, as seen with inotropic stimulation, are thought to increase or decrease annular dimensions in similar manner. The study aim was to elucidate the functional relationship between the mitral annulus and left ventricle during acute MR and inotrope-induced MR reduction.Radiopaque markers were implanted on the left ventricle and mitral annulus of five adult sheep. A suture was placed on the central scallop of the posterior mitral leaflet and exteriorized through the atrial-ventricular groove. Open-chest animals were studied at baseline (CTRL), at seconds after pulling on the suture to create moderate-severe 'pure' MR (PULL), and after titration of dopamine until the MR grade was maximally reduced (PULL+DOPA). This process was repeated two to three times for each animal.The MR grade was increased with PULL (from 0.5 +/- 0.01 to 3.4 +/- 0.4, p < 0.01) and decreased after PULL+DOPA (from 3.4 +/- 0.4 to 1.5 +/- 0.9, p < 0.001). PULL resulted in an increase in mitral annular (MA) area, predominantly by an increase in the muscular mitral annulus. PULL+DOPA caused a decrease in MA area, but the LV volume and dimensions were not altered with either PULL or PULL+DOPA.The acute geometric response to 'pure' MR and inotrope-induced MR reduction was limited to the mitral annulus. Surprisingly, the LV volume and dimensions did not change with acute MR or with inotrope-induced MR reduction. This suggests that, under these two conditions in an ovine model, the mitral annulus and left ventricle are functionally uncoupled.

  View details for PubMedID 18512487

• Effects of acute ischemic mitral regurgitation on three-dimensional mitral leaflet edge geometry 21st Annual Meeting of the European-Association-for-Cardio-Thoracic-Surgery (EACTS) Bothe, W., Nguyen, T. C., Ennis, D. B., Itoh, A., Carlhall, C. J., Lai, D. T., Ingels, N. B., Miller, D. C. OXFORD UNIV PRESS INC. 2008: 191–97

  Abstract

  Improved quantitative understanding of in vivo leaflet geometry in ischemic mitral regurgitation (IMR) is needed to improve reparative techniques, yet few data are available due to current imaging limitations. Using marker technology we tested the hypotheses that IMR (1) occurs chiefly during early systole; (2) affects primarily the valve region contiguous with the myocardial ischemic insult; and (3) results in systolic leaflet edge restriction.Eleven sheep had radiopaque markers sutured as five opposing pairs along the anterior (A(1)-E(1)) and posterior (A(2)-E(2)) mitral leaflet free edges from the anterior commissure (A(1)-A(2)) to the posterior commissure (E(1)-E(2)). Immediately postoperatively, biplane videofluoroscopy was used to obtain 4D marker coordinates before and during acute proximal left circumflex artery occlusion. Regional mitral orifice area (MOA) was calculated in the anterior (Ant-MOA), middle (Mid-MOA), and posterior (Post-MOA) mitral orifice segments during early systole (EarlyS), mid systole (MidS), and end systole (EndS). MOA was normalized to zero (minimum orifice opening) at baseline EndS. Tenting height was the distance of the midpoint of paired markers to the mitral annular plane at EndS.Acute ischemia increased echocardiographic MR grade (0.5+/-0.3 vs 2.3+/-0.7, p<0.01) and MOA in all regions at EarlyS, MidS, and EndS: Ant-MOA (7+/-10 vs 22+/-19 mm(2), 1+/-2 vs 18+/-16 mm(2), 0 vs 17+/-15 mm(2)); Mid-MOA (9+/-13 vs 25+/-17 mm(2), 3+/-6 vs 21+/-19 mm(2), 0 vs 25+/-17 mm(2)); and Post-MOA (8+/-10 vs 25+/-16, 2+/-4 vs 22+/-13 mm(2), 0 vs 23+/-13 mm(2)), all p<0.05. There was no change in MOA throughout systole (EarlyS vs MidS vs EndS) during baseline conditions or ischemia. Tenting height increased with ischemia near the central and the anterior commissure leaflet edges (B(1)-B(2): 7.1+/-1.8mm vs 7.9+/-1.7 mm, C(1)-C(2): 6.9+/-1.3mm vs 8.0+/-1.5mm, both p<0.05).MOA during ischemia was larger throughout systole, indicating that acute IMR in this setting is a holosystolic phenomenon. Despite discrete postero-lateral myocardial ischemia, Post-MOA was not disproportionately larger. Acute ovine IMR was associated with leaflet restriction near the central and the anterior commissure leaflet edges. This entire constellation of annular, valvular, and subvalvular ischemic alterations should be considered in the approach to mitral repair for IMR.

  View details for DOI 10.1016/j.ejcts.2007.10.024

  View details for PubMedID 18321461

• Reporting "actual freedom" should not be banned JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Grunkemeier, G. L., Takkenberg, J. M., Jamieson, W., Miller, D. 2008; 135 (2): 460–62

  View details for DOI 10.1016/j.jtcvs.2006.03.069

  View details for Web of Science ID 000252830400044

  View details for PubMedID 18242296

• Multiplanar visualization in 3D transthoracic echocardiography for precise delineation of mitral valve pathology ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES Liang, D., Paloma, A., Kuppahally, S. S., Miller, D. C., Schnittger, I. 2008; 25 (1): 84-87

  Abstract

  A novel multiplanar reformatting (MPR) technique in three-dimensional transthoracic echocardiography (3D TTE) was used to precisely localize the prolapsed lateral segment of posterior mitral valve leaflet in a patient symptomatic with mitral valve prolapse (MVP) and moderate mitral regurgitation (MR) before undergoing mitral valve repair surgery. Transesophageal echocardiography was avoided based on the findings of this new technique by 3D TTE. It was noninvasive, quick, reproducible and reliable. Also, it did not need the time-consuming reconstruction of multiple cardiac images. Mitral valve repair surgery was subsequently performed based on the MPR findings and corroborated the findings from the MPR examination.

  View details for DOI 10.1111/j.1540-8175.2007.00566.x

  View details for PubMedID 18186784

• Advances in imaging of cardiovascular diseases: introduction. Seminars in thoracic and cardiovascular surgery Fleischmann, D., Liang, D. H., Miller, D. C. 2008; 20 (4): 332-?

  View details for DOI 10.1053/j.semtcvs.2008.12.002

  View details for PubMedID 19251173

• Pre- and postoperative imaging of the aortic root for valve-sparing aortic root repair (V-SARR). Seminars in thoracic and cardiovascular surgery Fleischmann, D., Liang, D. H., Mitchell, R. S., Miller, D. C. 2008; 20 (4): 365-373

  Abstract

  Valve-sparing aortic root repair (V-SARR) using the David reimplantation method is an increasingly popular alternative to composite valve graft aortic root replacement in patients with aortic root aneurysms or dissections who wish to avoid anticoagulation. Computed tomography (CT) with retrospective electrocardiograph (ECG)-gating has become routine before and following V-SARR at Stanford. CT allows accurate measurement of aortic dimensions and provides unprecedented three-dimensional (3D) images of the sinuses, the aortic valve cusps, and coronary arteries in patients with the Marfan syndrome (MFS), with a bicuspid aortic valve (BAV), or other aortic diseases. This helps the surgeon to conceptualize the size of the aortic grafts required and how much reduction is necessary proximally (aortic annulus) and distally. These maneuvers are used to reduce the aortic annular diameter (when necessary) and replace the sinuses and ascending aorta (T. David-V, Stanford modification V-SARR). Postoperative ECG-gated CT confirms the reconstructed geometry and reliably detects coronary or other anastomotic problems.

  View details for DOI 10.1053/j.semtcvs.2008.11.009

  View details for PubMedID 19251178

• Acute aortic syndromes: new insights from electrocardiographically gated computed tomography. Seminars in thoracic and cardiovascular surgery Fleischmann, D., Mitchell, R. S., Miller, D. C. 2008; 20 (4): 340-347

  Abstract

  The development of retrospective electrocardiographic (ECG)-gating has proved to be a diagnostic and therapeutic boon for computed tomography (CT) imaging of patients with acute thoracic aortic diseases, such as aortic dissection/intramural hematoma (AD/IMH), penetrating atherosclerotic ulcer (APU), and ruptured/leaking aneurysm. The notorious pulsation motion artifacts in the ascending aorta confounding regular CT scanning can be eliminated, and involvement of the sinuses of Valsalva, the valve cusps, the aortic annulus, and the coronary arteries in aortic dissection can be clearly depicted or excluded. Motion-free images also allow reliable identification of the site of the primary intimal tear, the location, and extent of the intimomedial flap, and branch artery involvement. ECG-gated CTA also allows the detection of more subtle lesions and variants of aortic dissection, which may ultimately expand our understanding of these complex, life-threatening disorders.

  View details for DOI 10.1053/j.semtcvs.2008.11.011

  View details for PubMedID 19251175

• Comparison of flow patterns in ascending aortic aneurysms and volunteers using four-dimensional magnetic resonance velocity mapping JOURNAL OF MAGNETIC RESONANCE IMAGING Hope, T. A., Markl, M., Wigstrom, L., Alley, M. T., Miller, D. C., Herfkens, R. J. 2007; 26 (6): 1471-1479

  Abstract

  To determine the difference in flow patterns between healthy volunteers and ascending aortic aneurysm patients using time-resolved three-dimensional (3D) phase contrast magnetic resonance velocity (4D-flow) profiling.4D-flow was performed on 19 healthy volunteers and 13 patients with ascending aortic aneurysms. Vector fields placed on 2D planes were visually graded to analyze helical and retrograde flow patterns along the aortic arch. Quantitative analysis of the pulsatile flow was carried out on manually segmented planes.In volunteers, flow progressed as follows: an initial jet of blood skewed toward the anterior right wall of the ascending aorta is reflected posterolaterally toward the inner curvature creating opposing helices, a right-handed helix along the left wall and a left-handed helix along the right wall; retrograde flow occurred in all volunteers along the inner curvature between the location of the two helices. In the aneurysm patients, the helices were larger; retrograde flow occurred earlier and lasted longer. The average velocity decreased between the ascending aorta and the transverse aorta in volunteers (47.9 mm/second decrease, P = 0.023), while in aneurysm patients the velocity increased (145 mm/second increase, P < 0.001).Dilation of the ascending aorta skews normal flow in the ascending aorta, changing retrograde and helical flow patterns.

  View details for DOI 10.1002/jmri.21082

  View details for PubMedID 17968892

• Andrew S. Wechsler, MD, Editor, The Journal of Thoracic and Cardiovascular Surgery January 2000-December 2007 JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Kron, I. L., Miller, D. 2007; 134 (6): 1391–92

  View details for DOI 10.1016/j.jtcvs.2007.10.001

  View details for Web of Science ID 000251244200001

• Alterations in transmural myocardial strain: An early marker of left ventricular dysfunction in mitral regurgitation? 80th Annual Scientific Session of the American-Heart-Association (AHA) Nguyen, T. C., Carlhall, C. J., Itoh, A., Oakes, R. A., Ennis, D. B., Bothe, W., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2007: 368–68

  View details for Web of Science ID 000250394301667

• Does Preoperative three-dimensional transthoracic Echocardiography with multiplanar reconstruction add value in patients with mitral valve prolapse? Beraud, A., Liang, D. H., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2007: 590

  View details for Web of Science ID 000250394302663

• Mitral leaflet remodeling: Response to isolated mitral regurgitation 80th Annual Scientific Session of the American-Heart-Association (AHA) Stephens, E. H., Nguyen, T. C., Itoh, A., Miller, D. C., Grande-Allen, K. J. LIPPINCOTT WILLIAMS & WILKINS. 2007: 234–34

  View details for Web of Science ID 000250394301085

• Effect of chronotropy and inotropy on stitch tension in the edge-to-edge mitral repair 79th Annual Scientific Session of the American-Heart-Association Timek, T. A., Nielsen, S. L., Lai, D. T., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2007: I276–I281

  Abstract

  Our prior studies suggest that mitral annular septal-lateral (SL) diameter is the chief determinant of "Alfieri stitch" tension, but hemodynamic parameters may also play a role. We approximated the central edge of the mitral leaflets with a miniature force transducer to measure tension (T) at the leaflet approximation point during inotropic and chronotropic stimulation.Eight sheep were studied under open-chest conditions immediately after surgical placement of a miniature force transducer to approximate the leaflets and implantation of radiopaque markers on the LV and mitral annulus (MA). Chronotropic stimulation was induced with atrial pacing at 130 minutes(-1) (n=5) whereas inotropic state was increased with i.v. CaCl2 bolus (n=8). Hemodynamic data, stitch tension, and 3-D marker coordinates were obtained throughout the cardiac cycle before and during each intervention. Peak stitch tension (T(MAX)) under all conditions was observed in diastole and temporally correlated with peak annular SL (SL(MAX)) size. Atrial pacing did not change peak transducer tension or annular size. Calcium infusion also did not alter peak transducer tension (0.29+/-0.11 versus 0.32+/-0.10 N; P=NS) and only slightly reduced SL dimension (29.9+/-3.3 versus 29.3+/-3.5 mm; P<0.05).Isolated increase in heart rate or inotropic state did not alter peak stitch tension whereas enhanced contractile state decreased SL diameter minimally. These data, combined with those from our previous study, suggest that geometric (SL diameter) rather than hemodynamic parameters are the main determinants of "Alfieri stitch" tension. This implies that any interventional or surgical edge-to-edge repair performed without concomitant annular reduction to limit the SL dimension could expose the leaflet junction to forces which could limit repair durability.

  View details for DOI 10.1161/CIRCULATIONAHA.106.680801

  View details for PubMedID 17846317

• Contribution of mitral annular dynamics to LV diastolic filling with alteration in preload and inotropic state AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Carlhall, C., Kindberg, K., Wigstrom, L., Daughters, G. T., Miller, D. C., Karlsson, M., Ingels, N. B. 2007; 293 (3): H1473-H1479

  Abstract

  Mitral annular (MA) excursion during diastole encompasses a volume that is part of total left ventricular (LV) filling volume (LVFV). Altered excursion or area variation of the MA due to changes in preload or inotropic state could affect LV filling. We hypothesized that changes in LV preload and inotropic state would not alter the contribution of MA dynamics to LVFV. Six sheep underwent marker implantation in the LV wall and around the MA. After 7-10 days, biplane fluoroscopy was used to obtain three-dimensional marker dynamics from sedated, closed-chest animals during control conditions, inotropic augmentation with calcium (Ca), preload reduction with nitroprusside (N), and vena caval occlusion (VCO). The contribution of MA dynamics to total LVFV was assessed using volume estimates based on multiple tetrahedra defined by the three-dimensional marker positions. Neither the absolute nor the relative contribution of MA dynamics to LVFV changed with Ca or N, although MA area decreased (Ca, P < 0.01; and N, P < 0.05) and excursion increased (Ca, P < 0.01). During VCO, the absolute contribution of MA dynamics to LVFV decreased (P < 0.001), based on a reduction in both area (P < 0.001) and excursion (P < 0.01), but the relative contribution to LVFV increased from 18 +/- 4 to 45 +/- 13% (P < 0.001). Thus MA dynamics contribute substantially to LV diastolic filling. Although MA excursion and mean area change with moderate preload reduction and inotropic augmentation, the contribution of MA dynamics to total LVFV is constant with sizeable magnitude. With marked preload reduction (VCO), the contribution of MA dynamics to LVFV becomes even more important.

  View details for DOI 10.1152/ajpheart.00208.2007

  View details for PubMedID 17496217

• Alterations in lateral left ventricular wall transmural strains during acute circumflex and anterior descending coronary occlusion 41st Annual Meeting of the Society-of-Thoracic-Surgeons Langer, F., Rodriguez, F., Cheng, A., Ortiz, S., Harrington, K. B., Zasio, M. K., Daughters, G. T., Criscione, J. C., Ingels, N. B., Miller, D. C. ELSEVIER SCIENCE INC. 2007: 51–60

  Abstract

  Increased circumferential-radial shear in the midlateral left ventricle adjacent to ischemic myocardium has been observed during acute midcircumflex ischemia in open-chest animals. Extending this work, we studied transmural strains in closed-chest animals during acute proximal-circumflex (pCX) and proximal-left anterior descending (pLAD) occlusions.Six sheep had radiopaque markers implanted to silhouette the left ventricle and measure regional systolic fractional area shortening; three transmural bead columns were inserted into the midlateral wall for transmural myocardial strain analysis. After 8 weeks, three-dimensional marker coordinates were obtained using biplane videofluoroscopy, both before and during separate 1-minute pLAD and pCX balloon occlusions. Systolic strains were assessed along circumferential, longitudinal, and radial axes, and then transformed into fiber strains using quantitative microstructural measurements.Acute pLAD occlusion and pCX occlusion caused similar hemodynamic insults. Systolic fractional area shortening revealed that the beads were in the ischemic territory during pCX occlusion, but adjacent to the ischemic myocardium during pLAD occlusion. Transmural circumferential strain and fiber shortening fell in the ischemic region during pCX occlusion, but remained normal when adjacent to the ischemic myocardium during pLAD occlusion. Circumferential-radial shear strain increased in the lateral left ventricle during pCX occlusion, but reversed in this same region during pLAD occlusion. Longitudinal-radial shear also decreased during pLAD occlusion.Reversal of lateral wall circumferential-radial shear and decreased longitudinal-radial shear during acute pLAD occlusion reflects altered mechanical interaction between ischemic and nonischemic myocardium. Increased circumferential-radial shear during pCX occlusion also reflects mechanical interaction. The direction of circumferential-radial shear deformation depends on the location of the adjacent ischemic territory.

  View details for DOI 10.1016/j.athoracsur.2007.03.041

  View details for PubMedID 17588382

• Undersized mitral annuloplasty inhibits left ventricular basal wall thickening but does not affect equatorial wall cardiac strains 3rd Biennial Meeting of Society-for-Heart-Valve-Disease Cheng, A., Nguyen, T. C., Malinowski, M., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. I C R PUBLISHERS. 2007: 349–58

  Abstract

  Undersized mitral annuloplasty has been widely employed for patients with ischemic mitral regurgitation. Beyond correction of mitral regurgitation, ring annuloplasty is postulated to normalize global left ventricular (LV) shape, thereby decreasing LV wall stress and promoting reverse LV remodeling. The effect of undersized annuloplasty on regional transmural LV wall thickening and strain patterns, however, has not been examined.In nine sheep, transmural radiopaque beadsets were inserted into the anterobasal and equatorial lateral LV walls, with additional markers silhouetting the left ventricle and mitral annulus. Four-dimensional marker dynamics were studied with biplane videofluoroscopy (open-chest) before and after tightening a Paneth-type mitral annuloplasty suture. LV volumes, mitral dimensions, transmural circumferential, longitudinal, and radial systolic strains, and end-diastolic (ED) and end-systolic (ES) remodeling strains in the two LV regions were computed.In the anterobasal LV wall close to the mitral annulus, annuloplasty increased ED wall thickness and surprisingly reduced systolic radial strain (wall thickening) at all transmural depths. Radial subepicardial, midwall, and subendocardial wall-thickening strains at ES in the anterobasal LV site were 0.25 +/- 0.15, 0.33 +/- 0.16, and 0.47 +/- 0.29, respectively, before tightening the suture annuloplasty, compared to 0.13 +/- 0.12, 0.15 +/- 0.18, and 0.20 +/- 0.26 after tightening. In the equatorial lateral LV wall further away from the annulus, most LV transmural systolic and remodeling strains did not change.Simulated undersized annuloplasty acutely decreased transmural systolic LV wall thickening in the anterobasal region, without substantially affecting transmural deformations in the lateral LV wall. These acute effects of undersized annuloplasty require a better understanding as they may potentially be deleterious, and a direct ventricular approach may be needed as an adjunct to promote reverse LV remodeling.

  View details for PubMedID 17702358

• Rapid aneurysmal degeneration of a Stanford type B aortic dissection in a patient with Loeys-Dietz syndrome JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Lee, R. S., Fazel, S., Schwarze, U., Fleischmann, D., Berry, G. J., Liang, D., Miller, D. C., Mitchell, R. S. 2007; 134 (1): 242-U32

  View details for DOI 10.1016/j.jtcvs.2007.03.004

  View details for PubMedID 17599521

• Fixed anterior leaflet edge 3-D position during end-systole: An important component of mitral regurgitation Experimental Biology 2007 Annual Meeting Nguyen, T. C., Itoh, A., Oakes, R. A., Kameda, Y., Karlsson, M. O., Daughters, G. T., Miller, D. C., Ingels, N. B. FEDERATION AMER SOC EXP BIOL. 2007: A1258–A1258

  View details for Web of Science ID 000245708704239

• Septal-lateral annnular cinching perturbs basal left ventricular transmural strains 20th Annual Meeting of the European-Association-for-Cardio-Thoracic-Surgery/14th Annual Meeting of the European-Society-of-Thoracic-Surgeons Nguyen, T. C., Cheng, A., Tibayan, F. A., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. OXFORD UNIV PRESS INC. 2007: 423–29

  Abstract

  Septal-lateral annular cinching ('SLAC') corrects both acute and chronic ischemic mitral regurgitation in animal experiments, which has led to the development of therapeutic surgical and interventional strategies incorporating this concept (e.g., Edwards GeoForm ring, Myocor Coapsys, Ample Medical PS3). Changes in left ventricular (LV) transmural cardiac and fiber-sheet strains after SLAC, however, remain unknown.Eight normal sheep hearts had two triads of transmural radiopaque bead columns inserted adjacent to (anterobasal) and remote from (midlateral equatorial) the mitral annulus. Under acute, open chest conditions, 4D bead coordinates were obtained using videofluoroscopy before and after SLAC. Transmural systolic strains were calculated from bead displacements relative to local circumferential, longitudinal, and radial cardiac axes. Transmural cardiac strains were transformed into fiber-sheet coordinates (X(f), X(s), X(n)) oriented along the fiber (f), sheet (s), and sheet-normal (n) axes using fiber (alpha) and sheet (beta) angle measurements. Results: SLAC markedly reduced (approximately 60%) septal-lateral annular diameter at both end-diastole (ED) (2.5+/-0.3 to 1.0+/-0.3 cm, p=0.001) and end-systole (ES) (2.4+/-0.4 to 1.0+/-0.3 cm, p=0.001). In the LV wall remote from the mitral annulus, transmural systolic strains did not change. In the anterobasal region adjacent to the mitral annulus, ED wall thickness increased (p=0.01) and systolic wall thickening was less in the epicardial (0.28+/-0.12 vs 0.20+/-0.06, p=0.05) and midwall (0.36+/-0.24 vs 0.19+/-0.11, p=0.04) LV layers. This impaired wall thickening was due to decreased systolic sheet thickening (0.20+/-0.8 to 0.12+/-0.07, p=0.01) and sheet shear (-0.15+/-0.07 to -0.11+/-0.04, p=0.02) in the epicardium and sheet extension (0.21+/-0.11 to 0.10+/-0.04, p=0.03) in the midwall. Transmural systolic and remodeling strains in the lateral midwall (remote from the annulus) were unaffected.Although SLAC is an alluring concept to correct ischemic mitral regurgitation, these data suggest that extreme SLAC adversely effects systolic wall thickening adjacent to the mitral annulus by inhibiting systolic sheet thickening, sheet shear, and sheet extension. Such alterations in LV strains could result in unanticipated deleterious remodeling and warrant further investigation.

  View details for DOI 10.1016/j.ejcts.2006.12.019

  View details for PubMedID 17223567

• Altered myocardial shear strains are associated with chronic ischemic mitral regurgitation 42nd Annual Meeting of the Society-of-Thoracic-Surgeons Nguyen, T. C., Cheng, A., Langer, F., Rodriguez, F., Oakes, R. A., Itoh, A., Ennis, D. B., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. ELSEVIER SCIENCE INC. 2007: 47–54

  Abstract

  Ischemic mitral regurgitation (IMR) limits life expectancy and can lead to postinfarction global left ventricular (LV) dilatation and remodeling, the pathogenesis of which is not completely known. We tested the hypothesis that IMR perturbs adjacent myocardial LV systolic strains.Thirteen sheep had three columns of miniature beads inserted across the lateral LV wall, with additional epicardial markers silhouetting the ventricle. One week later posterolateral infarction was created. Seven weeks thereafter, the animals were divided into two groups according to severity of IMR (< or = 1+, n = 7, IMR[-] vs > or = 2+, n = 6, IMR[+]). Four dimensional marker coordinates and quantitative histology were used to calculate ventricular volumes, transmural myocardial systolic strains, and systolic fiber shortening.Seven weeks after infarction, end-diastolic (ED) volume increased similarly in both groups, end-systolic (ES) E13 (circumferential-radial) shear increased in both groups, but more so in IMR(+) than IMR(-) (+0.12 vs 0.04, p < 0.005), and E12 (circumferential-longitudinal) shear increased in IMR(-) but not IMR(+) (+0.04 vs -0.01, p < 0.005). There were no significant differences in ED or ES remodeling strains or systolic fiber shortening between IMR(-) and IMR(+).An equivalent increase in LV end-diastolic (ED) volume in both groups, coupled with unchanged ED and end-systolic remodeling strains as well as systolic circumferential, longitudinal, and radial strains, argue against a global LV or regional myocardial geometric basis for the cardiomyopathy associated with IMR. Further, similar systolic fiber shortening in both groups militates against an intracellular (cardiomyocyte) mechanism. The differences in subepicardial E12 and E13 shears, however, suggest a causal role of altered interfiber (cytoskeleton and extracellular-matrix) interactions.

  View details for DOI 10.1016/j.athoracsur.2006.08.039

  View details for PubMedID 17184629

• Clinical 3D and 4D imaging of the thoracic aorta 39th International Diagnostic Course Fleischmann, D., Miller, D. C. SPRINGER-VERLAG ITALIA. 2007: 119–130

  View details for Web of Science ID 000246436000020

• Tenting volume: Three-dimensional assessment of geometric perturbations in functional mitral regurgitation and implications for surgical repair 75th Annual Scientific Session of the American-Heart-Association Tibayan, F. A., Wilson, A., Lai, D. T., Timek, T. A., Dagum, P., Rodriguez, F., Zasio, M. K., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. I C R PUBLISHERS. 2007: 1–7

  Abstract

  Functional mitral regurgitation (FMR) often complicates dilated cardiomyopathy (DCM), and portends a poor prognosis. Debate over the optimal treatment continues, underscoring the present incomplete understanding of the patho-anatomic mechanisms of this disease. Studies of mitral tenting volume and tenting area, and echocardiographic measures of abnormal apical systolic leaflet geometry have linked mitral leaflet deformation with subvalvular left ventricular (LV) remodeling in chronic ischemic MR. The relative contributions of annular versus subvalvular remodeling in FMR due to DCM are less clear. Here, the validity of 3-D measurement of mitral deformation, tenting volume, as a correlate of MR in DCM, was tested. The ability of annular and subvalvular remodeling to predict mitral deformation was then determined.Eight sheep underwent placement of radiopaque markers on the mitral annulus and leaflets. Global LV, annular and subvalvular geometry, as well as mitral tenting height, area and volume were calculated before (Control) and after the development of pacing-induced cardiomyopathy and MR (DCM). Multivariable regression determined which measure of mitral deformation was the best predictor of MR. Regression analysis was also used to find geometric predictors of mitral tenting volume.In a multivariable analysis, mitral tenting volume was the only independent predictor of severity of MR (r(2) = 0.79, standard error of estimate (SEE) = 0.58). Increased tenting volume correlated best with increased mitral annular septal-lateral diameter (r(2) = 0.67, SEE = 0.72).The 3-D tenting volume correlates best with severity of FMR. Mitral deformation (increased tenting volume) observed in DCM is predicted by annular dilation, but not by subvalvular LV remodeling. These data support the use of an undersized annuloplasty in DCM complicated by FMR, and may guide the rational design of new therapies for this vexing disease.

  View details for PubMedID 17315376

• Effect of inotropy and chronotropy on stitch tension in the edge-to-edge mitral repair 79th Annual Scientific Session of the American-Heart-Association Timek, T. A., Nielsen, S. L., Liang, D., Lai, D. T., Daughters, G. T., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2006: 564–64

  View details for Web of Science ID 000241792803541

• Early postoperative blunting of rapid diastolic subepicardial fiber lengthening and left ventricular circumferential expansion Kindberg, K., Oom, C., Cheng, A., Langer, F., Rodriguez, F., Daughters, G. T., Miller, D. C., Karlsson, M., Ingels, N. B. LIPPINCOTT WILLIAMS & WILKINS. 2006: 357

  View details for Web of Science ID 000241792802294

• Dobutamine myocardial strain rate response is transmurally inhomogeneous 79th Annual Scientific Session of the American-Heart-Association Itoh, A., Nguyen, T. C., Cheng, A., Oakes, R. A., Ennis, D. B., Kameda, Y., Daughters, G. T., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2006: 570–70

  View details for Web of Science ID 000241792803565

• Isolated giant cell myocarditis in the atrium: An incidental finding? PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Ahmad, I., Miller, D. C., Berry, G. J., Hsia, H. H., Wang, P. J., Al-Ahmad, A. 2006; 29 (10): 1179-1180

  Abstract

  Giant cell myocarditis (GCM) is an uncommon disorder that affects ventricular myocardium causing severe left ventricular dysfunction and ventricular arrhythmias. We report a case of GCM that only affected the atrium sparing the ventricle.

  View details for PubMedID 17038151

• Mitral leaflet remodeling in dilated cardiomyopathy 78th Annual Scientific Session of the American-Heart-Association Timek, T. A., Lai, D. T., Dagum, P., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2006: I518–I523

  Abstract

  Normal mammalian mitral leaflets have regional heterogeneity of biochemical composition, collagen fiber orientation, and geometric deformation. How leaflet shape and regional geometry are affected in dilated cardiomyopathy is unknown.Nine sheep had 8 radio-opaque markers affixed to the mitral annulus (MA), 4 markers sewn on the central meridian of the anterior mitral leaflet (AML) forming 4 distinct segments S1 to S4 and 2 on the posterior leaflet (PML) forming 2 distinct segments S5 and S6. Biplane videofluoroscopy and echocardiography were performed before and after rapid pacing (180 to 230 bpm for 15+/-6 days) sufficient to develop tachycardia-induced cardiomyopathy (TIC) and functional mitral regurgitation (FMR). Leaflet tethering was defined as change of displacement of AML and PML edge markers from the MA plane from baseline values while leaflet length was obtained by summing the segments between respective leaflet markers. With TIC, total AML and PML length increased significantly (2.11+/-0.16 versus 2.43+/-0.23 cm and 1.14+/-0.27 versus 1.33+/-0.25 cm before and after pacing for AML and PML, respectively; P<0.05 for both), but only segments near the edge of each leaflet (S4 lengthened by 23+/-17% and S5 by 24+/-18%; P<0.05 for both) had significant regional remodeling. AML shape did not change and no leaflet tethering was observed.TIC was not associated with leaflet tethering or shape change, but both anterior and posterior leaflets lengthened because of significant remodeling localized near the leaflet edge. Leaflet remodeling accompanies mitral regurgitation in cardiomyopathy and casts doubt on FMR being purely "functional" in etiology.

  View details for PubMedID 16820630

• Passive ventricular constraint prevents transmural shear strain progression in left ventricle remodeling 78th Annual Scientific Session of the American-Heart-Association Cheng, A., Nguyen, T. C., Malinowski, M., Langer, F., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2006: I79–I86

  Abstract

  Passive ventricular constraint provides external cardiac support to reduce left ventricular (LV) wall stress and myocardial stretch, which are primary determinants of LV remodeling. Altered wall strain results in cytokine and reactive oxygen species production, which, in turn, stimulates apoptosis and extracellular matrix disruption and could be an important trigger for adverse global LV dilatation and remodeling. The effects of the Acorn cardiac support device (CSD) on regional transmural LV wall strains, however, remain unknown.Thirty-three sheep had transmural radiopaque beadsets surgically inserted into the anterior basal and lateral equatorial LV walls, with additional markers silhouetting the left ventricle. Eight animals had CSD implanted (myocardial infarction [MI]+CSD). One week thereafter, the MI+CSD group and 10 animals without CSD (MI) underwent posterior LV infarction by snaring obtuse marginal coronary arteries. Fifteen animals (Sham) had no infarction or CSD. 4D marker dynamics were measured with biplane videofluoroscopy 1 and 8 weeks postoperatively. LV volumes, sphericity index, and transmural circumferential, longitudinal, and radial systolic strains were analyzed. Compared with Sham, infarction (MI) dilated the heart, reduced sphericity index (LV length/width), and increased longitudinal-radial shear strains in the inner half of both the anterior and lateral LV walls. CSD prevented this shear strain perturbation, minimized LV end diastolic volume increase, and augmented the LV sphericity index.Prophylactic CSD prevented infarct-induced shear strain progression not only in myocardium adjacent to, but also remote from, the infarct. CSD also prevented LV dilatation and sphericalization. By attenuating shear strain abnormalities, CSD could prevent the heart from entering into a positive feedback loop of further LV dilatation and exaggeration of LV wall stress and may reduce biochemical triggers portending adverse LV remodeling.

  View details for PubMedID 16820650

• Effects of undersized mitral annuloplasty on regional transmural left ventricular wall strains and wall thickening mechanisms 78th Annual Scientific Session of the American-Heart-Association Cheng, A., Nguyen, T. C., Malinowski, M., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2006: I600–I609

  Abstract

  Undersized mitral annuloplasty, widely used for ischemic and functional mitral regurgitation (MR), has been proposed as an "annular solution to a ventricular problem." Beyond relief of MR, it is thought to improve global left ventricular (LV) shape, hence potentially reducing myocardial stress and promoting beneficial reverse LV remodeling. We previously observed that undersized annuloplasty inhibited systolic wall thickening at the LV base near the mitral annulus. In this study, we measured the effects of undersized annuloplasty on regional transmural LV wall fiber and sheet strains and wall thickening mechanisms.Nine sheep had transmural radiopaque beadsets surgically inserted into anterobasal and lateral equatorial LV regions, with additional markers silhouetting the LV and mitral annulus. 4-Dimensional marker dynamics were studied with biplane videofluoroscopy before and after tightening an adjustable Paneth-type mitral annuloplasty suture. Transmural circumferential, longitudinal, and radial systolic and remodeling strains in the subepicardium (20% depth), midwall (50%), and subendocardium (80%) in both regions were computed. Fiber and sheet angles from quantitative regional histology allowed transformation of these strains into local fiber (f), sheet (s), and sheet-normal (n) coordinates. Further analysis calculated the transmural contributions of sheet extension (E(ssc)), sheet thickening (E(nnc)), and sheet shear (E(snc)) to systolic wall thickening (E(33)). In the anterobasal region, undersized annuloplasty reduced systolic wall thickening (E33) by &50% at all transmural depths by inhibiting: (1) subendocardial systolic fiber shortening (-0.10+/-0.05 versus -0.04+/-0.05; P<0.05); (2) subepicardial (0.16+/-0.15 versus 0.09+/-0.08; P<0.05) and subendocardial (0.45+/-0.40 versus 0.19+/-0.18; P<0.05) systolic sheet thickening; (3) midwall sheet extension (0.22+/-0.12 versus 0.11+/-0.06; P<0.05); and (4) transmural sheet shear (subepicardium, -0.14+/-0.07 versus -0.08+/-0.07; midwall, 0.21+/-0.12 versus 0.10+/-0.11; subendocardium, -0.19+/-0.23 versus -0.11+/-0.16; P<0.05). In the remote lateral equatorial region, fiber-sheet strains and E33 were unchanged.In this acute animal study, undersized annuloplasty inhibited systolic wall thickening in the anterobasal region by reducing subendocardial systolic fiber shortening and laminar sheet wall thickening, but had no effects in a more distant LV region. This suggests that undersized mitral annuloplasty may have potentially deleterious effects on local myocardial mechanics.

  View details for PubMedID 16820645

• Left ventricular volume shifts and aortic root expansion during isovolumic contraction 52nd Annual Scientific Session of the American-College-of-Cardiology Rodriguez, F., Green, G. R., Dagum, P., Nistal, J. F., Harrington, K. B., Daughters, G. T., Ingels, N. B., Miller, D. C. I C R PUBLISHERS. 2006: 465–73

  Abstract

  Aortic valve opening involves conformational changes of the aortic root, including the ventricular-aortic junction (VAJ), sinotubular junction (STJ), and cusps. Moreover, the aortic root is contiguous with the left ventricular outflow tract (LVOT), which changes diameter throughout the cardiac cycle. Aortic root expansion prior to valve opening facilitates outward displacement of aortic cusp attachments, which helps flatten the cusps, thereby reducing cusp stress and fatigue, ultimately enhancing functional valve durability. The mechanisms underlying aortic root expansion prior to valve opening, however, remain incompletely characterized. The study aim was to establish a link between such aortic root expansion and intraventricular volume shifts into the LVOT during isovolumic contraction (IVC).Miniature radiopaque markers were implanted on the left ventricle, VAJ, STJ, and aortic cusps of six sheep. After one week, 3-D marker coordinates were obtained using biplane videofluoroscopy (60 Hz). Triangular areas at the VAJ and STJ were calculated; LV main chamber (non-LVOT) and LVOT volumes were calculated using multiple tetrahedra. End-diastole was defined as the peak of the electrocardiogram R-wave, and end-IVC when aortic cusp separation began.During IVC, blood within the left ventricle was redistributed to the LVOT: mean LVOT volume was increased (+0.2 +/- 0.1 ml, p = 0.009) as non-LVOT volume fell (-0.8 +/- 0.4 ml, p = 0.006). Concomitantly, the aortic root expanded as both VAJ and STJ areas increased (+0.23 +/- 0.12 cm2 (p = 0.005) and +0.25 +/- 0.14 cm2 (p = 0.007), respectively) prior to aortic cusp separation.Aortic root expansion prior to valve opening is closely related to intraventricular volume shifts into the LVOT during IVC. Such volume shifts may 'prime' the aortic valve for ejection. These findings expand our understanding of cardiac dynamics by showing that blood acts as a coupling link between various cardiac units. Preservation of these normal aortic root dynamics may enhance the efficacy and durability of aortic surgical interventions.

  View details for PubMedID 16901037

• Plasma cefazolin levels during cardiovascular surgery: Effects of cardiopulmonary bypass and profound hypothermic circulatory arrest JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Caffarelli, A. D., Holden, J. P., Baron, E. J., Lemmens, H. J., D'Souza, H., Yau, V., Olcott, C., Reitz, B. A., Miller, D. C., van der Starre, P. J. 2006; 131 (6): 1338-1343

  Abstract

  We sought to assess the effects of cardiopulmonary bypass and profound hypothermic circulatory arrest on plasma cefazolin levels administered for antimicrobial prophylaxis in cardiovascular surgery.Four groups (10 patients per group) were prospectively studied: vascular surgery without cardiopulmonary bypass (group A), cardiac surgery with a cardiopulmonary bypass time of less than 120 minutes (group B), cardiac surgery with a cardiopulmonary bypass time of greater than 120 minutes (group C), and cardiac surgery with cardiopulmonary bypass and profound hypothermic circulatory arrest (group D). Subjects received cefazolin at induction and a second dose before wound closure. Arterial blood samples were obtained preceding cefazolin administration, at skin incision, hourly during the operation, and before redosing. Cefazolin plasma concentrations were determined by using a radial diffusion assay, with Staphylococcus aureus as the indicator microorganism. Cefazolin plasma concentrations were considered noninhibitory at 8 microg/mL or less, intermediate at 16 mug/mL, and inhibitory at 32 microg/mL or greater.In group A cefazolin plasma concentrations remained greater than 16 microg/mL during the complete surgical procedure. In group B cefazolin plasma concentrations diminished to 16 microg/mL or less in 30% of the patients but remained greater than 8 microg/mL. In group C cefazolin plasma concentrations decreased to less than 16 microg/mL in 60% of patients and were less than 8 microg/mL in 50% of patients. In group D cefazolin plasma concentrations reached 16 microg/mL in 66% of the patients but decreased to 8 microg/mL in only 1 patient.For patients undergoing cardiac surgery with a cardiopulmonary bypass time of greater than 120 minutes, a single dose of cefazolin before skin incision with redosing at wound closure does not provide targeted antimicrobial cefazolin plasma levels during the entire surgical procedure. Patients undergoing profound hypothermic circulatory arrest are better protected, but the described protocol of prophylaxis is not optimal.

  View details for DOI 10.1016/j.jtcvs.2005.11.047

  View details for PubMedID 16733167

• Posterior mitral leaflet extension: An adjunctive repair option for ischemic mitral regurgitation? JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Langer, F., Rodriguez, F., Cheng, A., Ortiz, S., Nguyen, T. C., Zasio, M. K., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. 2006; 131 (4): 868-875

  Abstract

  Residual or recurrent mitral regurgitation frequently occurs after mitral valve repair for ischemic mitral regurgitation with an annuloplasty ring. Because annuloplasty primarily addresses annular dilatation, we studied an adjunctive technique that might correct restricted leaflet (Carpentier type IIIb) systolic closing motion, which often accompanies annular dilatation in patients with ischemic mitral regurgitation.Six sheep had radiopaque markers placed on the left ventricle, mitral leaflets and annulus, and mitral subvalvular apparatus. A pericardial patch was sutured into the middle scallop of the posterior mitral valve leaflet and furled in with a reefing stitch placed in the radial axis. Posterolateral left ventricular myocardial ischemia was created by using proximal circumflex occlusion to induce acute ischemic mitral regurgitation. Under open-chest conditions, 3-dimensional marker coordinates were measured by using biplane videofluoroscopy at baseline and during acute ischemia both before and after release of the reefing stitch (leaflet extension); transesophageal echocardiography was used to grade ischemic mitral regurgitation.Leaflet apical systolic tethering was not improved by leaflet extension, but ischemic mitral regurgitation decreased (control, 0.9 +/- 0.3*; ischemia, 2.4 +/- 0.3; leaflet extension, 1.5 +/- 0.3; *P < 0.002). Posterior mitral valve leaflet midline length (control, 1.45 +/- 0.09*; ischemia, 1.53 +/- 0.10; leaflet extension, 1.83 +/- 0.13*; *P < 0.001) and posterior mitral valve leaflet middle scallop area (control, 1.66 +/- 0.20 cm2*; ischemia, 1.91 +/- 0.22 cm2; leaflet extension, 2.36 +/- 0.22 cm2*; *P < 0.006) increased with leaflet extension because of patch unfurling (mean +/- 1 standard error of the mean; repeated-measures analysis of variance, Dunnet post-hoc test vs ischemia).Posterior mitral valve leaflet extension ameliorated acute ischemic mitral regurgitation but did not correct the abnormal apically restricted systolic posterior mitral valve leaflet closing motion. This technique might be a useful adjunct repair in combination with ring annuloplasty for ischemic mitral regurgitation, but the clinical role of this adjunct remains to be defined in patients.

  View details for DOI 10.1016/j.jtcvs.2005.11.027

  View details for PubMedID 16580446

• The visible heart - Analysis of myocardial fiber structure using three-dimensional histology Experimental Biology 2006 Annual Meeting Wigstrom, L., Ennis, D. B., Nguyen, T. C., Miller, D. C., Ingels, N. B. FEDERATION AMER SOC EXP BIOL. 2006: A1198–A1198

  View details for Web of Science ID 000236326203229

• Regional contribution of mitral annular dynamics to LV filling Carlhall, C., Kindberg, K., Karlsson, M., Daughters, G. T., Miller, D. C., Ingeis, N. B. FEDERATION AMER SOC EXP BIOL. 2006: A1194

  View details for Web of Science ID 000236326203215

• Spatial and temporal inhomogeneity of transmural LV myocardial strains during diastole Kindberg, K., Cheng, A., Langer, F., Rodriguez, F., Criscione, J. C., Daughters, G. T., Miller, D. C., Karlsson, M., Ingels, N. B. FEDERATION AMER SOC EXP BIOL. 2006: A1410

  View details for Web of Science ID 000236326205207

• Transmural left ventricular shear strain alterations adjacent to and remote from infarcted myocardium JOURNAL OF HEART VALVE DISEASE Cheng, A., Langer, F., Nguyen, T. C., Malinowski, M., Ennis, D. B., Daughters, G. T., Ingels, N. B., Miller, D. C. 2006; 15 (2): 209-218

  Abstract

  In some patients, dysfunction in a localized infarct region spreads throughout the left ventricle to aggravate mitral regurgitation and produce deleterious global left ventricular (LV) remodeling. Alterations in transmural strains could be a trigger for this process, as these changes can produce apoptosis and extracellular matrix disruption. The hypothesis was tested that localized infarction perturbs transmural strain patterns not only in adjacent regions but also at remote sites.Transmural radiopaque beadsets were inserted surgically into the anterior basal and lateral equatorial LV walls of 25 sheep; additional markers were used to silhouette the left ventricle. One week thereafter, 10 sheep had posterior wall infarction from (obtuse marginal occlusion, INFARCT) and 15 had no infarction (SHAM). Four-dimensional marker dynamics were studied with biplane videofluoroscopy eight weeks later. Fractional area shrinkage, LV volumes and transmural circumferential, longitudinal and radial systolic strains were analyzed.Compared to SHAM, INFARCT greatly increased longitudinal-radial shear (mid-wall: 0.07 +/- 0.07 versus 0.14 +/- 0.06; subendocardium: 0.03 +/- 0.07 versus 0.20 +/- 0.08) in the inner half of the lateral LV wall and increased circumferential-radial shear (mid-wall: 0.03 +/- 0.05 versus 0.10 +/- 0.04; subepicardium: 0.02 +/- 0.05 versus 0.12 +/- 0.10) increased in the outer half of the LATERAL wall. In the ANTERIOR wall, INFARCT also increased longitudinal-radial shear (midwall: 0.01 +/- 0.05 versus 0.12 +/- 0.04; subendocardium: 0.04 +/- 0.09 versus 0.25 +/- 0.20) in the inner layers.Increased transmural shear strains were found not only in an adjacent region, but also at a site remote from a localized infarction. This perturbation could trigger remodeling processes that promote the progression of ischemic cardiomyopathy. A better understanding of this process is important for the future development of surgical therapies to reverse destructive LV remodeling.

  View details for PubMedID 16607903

• In response to: Bodnar E, Blackstone EH. Editorial: An 'actual' problem: another issue of apples and oranges. J Heart Valve Dis 2005; 14:706-708. journal of heart valve disease Grunkemeier, G. L., Takkenberg, J. J., Jamieson, W. R., Miller, D. C. 2006; 15 (2): 305-306

  View details for PubMedID 16607916

• Abnormal myocardial transmural shear strains persist during evolution from acute ischemia to infarction 55th Annual Scientific Session of the American-College-of-Cardiology Nguyen, T. C., Langer, F., Chang, A., Rodriguez, F., Daughters, G. T., Ingels, N. B., Miller, D. C. ELSEVIER SCIENCE INC. 2006: 181A–181A

  View details for Web of Science ID 000235530401096

• Photonic crystals: Straightening out light Nature Materials Miller, D., A. B. 2006; 5: 83–84

  View details for DOI 10.1038/nmat1566

• Mitral leaflet remodeling in heart failure 78th Annual Scientific Session of the American-Heart-Association Timek, T., Lai, D., Dagum, P., Liang, D., Daughters, G. T., Ingels, N. B., Alto, P., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2005: U392–U393

  View details for Web of Science ID 000232956402260

• Passive ventricular constraint prevents transmural shear strain progression in left ventricle remodeling Cheng, A., Malinowski, M., Nguyen, T. C., Langer, F., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2005: U461

  View details for Web of Science ID 000232956402540

• Heterogeneity of left ventricular wall thickening mechanisms 78th Annual Scientific Session of the American-Heart-Association Cheng, A., Nguyen, T. C., Malinowski, M., Daughters, G. T., Miller, D. C., Ingels, N. B. LIPPINCOTT WILLIAMS & WILKINS. 2005: U680–U681

  View details for Web of Science ID 000232956404226

• Effects of preload reduction on transmural end-diastolic fiber length and systolic fiber shortening 78th Annual Scientific Session of the American-Heart-Association Nguyen, T. C., Langer, F., Cheng, A., Rodriguez, F., Criscione, J. C., Daughters, G. T., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2005: U619–U619

  View details for Web of Science ID 000232956403564

• Effects of undersized mitral annuloplasty on regional transmural LV wall strains and wall thickening mechanisms 78th Annual Scientific Session of the American-Heart-Association Cheng, A., Nguyen, T. C., Malinowski, M., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2005: U555–U555

  View details for Web of Science ID 000232956403296

• Transmural sheet strains in the lateral wall of the ovine left ventricle AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Cheng, A., Langer, F., Rodriguez, F., Criscione, J. C., Daughters, G. T., Miller, D. C., Ingels, N. B. 2005; 289 (3): H1234-H1241

  Abstract

  In an attempt to provide a better understanding of our finding that regions with contracting left ventricular myofibers need not develop a significant transmural systolic wall thickening gradient, the analytic approach of Costa et al. was applied to the four-dimensional dynamic data obtained 1 and 8 wk after surgical implantation of transmural radiopaque beads in the lateral equatorial left ventricular wall in seven ovine hearts. Quantitative histology of tissue blocks demonstrated that fiber angles varied linearly across the wall in this region from -37 degrees in the subepicardium to +18 degrees in the subendocardium. Sheet angles exhibited a pleated-sheet behavior, alternating sign from subepicardium to subendocardium. From end diastole (reference configuration) to end systole (deformed configuration), fiber strain was uniformly negative, sheet extension and sheet thickening were uniformly positive, and sheet-normal shear contributed to wall thickening at all wall depths. Subepicardial radial wall thickening increased significantly from week 1 to week 8, with significant increases in the contributions from subepicardial sheet extension and sheet-normal shear. At 1 and 8 wk, the contribution of sheet-normal shear to wall thickening was substantial at all transmural depths; the contribution of sheet extension to wall thickening was greatest in the subepicardium and least in the subendocardium, and the contribution of sheet thickening to wall thickening was greatest in the subendocardium and least in the subepicardium. A mechanistic model is proposed that provides a working hypothesis that a selective decrease in subepicardial intercellular matrix stiffness is responsible for elimination of the transmural wall thickening gradient 1-8 wk after marker implantation surgery.

  View details for DOI 10.1152/ajpheart.00119.2005

  View details for PubMedID 15879489

• Effect of cutting second-order chordae on in-vivo anterior mitral leaflet compound curvature 3rd Biennial Meeting of Society-for-Heart-Valve-Disease Rodriguez, F., Langer, F., Harrington, K. B., Tibayan, F. A., Zasio, M. K., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. I C R PUBLISHERS. 2005: 592–601

  Abstract

  Leaflet curvature determines leaflet stress. In order to assess the influence of second-order chordae (2 degrees CT) on anterior mitral valve leaflet (AMVL) geometry, AMVL curvature was measured before (Baseline) and after (CUT) cutting the 2 degrees CT.Miniature radiopaque markers were sutured onto the AMVL in eight sheep: four along the central-meridian from mid-septal annulus to the free-margin; and one each at the 2 degrees CT insertion. Biplane videofluoroscopic data were acquired (open-chest) before and after CUT. Marker-triplet 3-D coordinates were used to calculate radii-of-curvature at LVPmax along the central-meridian (ROCm) and across the AMVL belly (commissure-commissure axis, ROCc-c).CUT did not change LVPmax (111 +/- 12 versus 106 +/- 11 mmHg; p = 0.19). At baseline, the AMVL central-meridian had compound curvature: Convex to the left ventricle near the annulus (-ROCm) and concave near the free-margin (+ROCm). After CUT, the AMVL flattened: ROCm increased near the annulus (from -1.37 +/- 0.52 to -12.58 +/- 29.04 cm; p = 0.02), but did not change near the edge. In the commissure-commissure axis, ROCc-c was concave to the left ventricle at baseline and increased after CUT in all eight animals. In five sheep, ROCc-c was increased (from 1.93 +/- 1.01 to 2.80 +/- 1.36 cm; p = 0.03), but in three sheep ROCc-c was increased and inverted (from 3.65 +/- 2.17 to -1.72 +/- 0.53 cm; p = 0.03), becoming convex to the left ventricle.Compound curvature along the AMVL central-meridian appears to be an intrinsic leaflet property that persists even without support from second-order chordae, whereas concave curvature in the commissure-commissure axis is more dependent on intact second-order chordae. Leaflet compound curvature must be incorporated into future finite element models to characterize leaflet stresses accurately. The importance of second-order chordae in maintaining leaflet shape must be considered during mitral repair. A larger ROC increases leaflet stresses, while reversal of ROC changes tensile stress to compressive stress; this might trigger deleterious leaflet remodeling after chordal cutting.

  View details for PubMedID 16245497

• Subvalvular repair - The key to repairing ischemic mitral regurgitation? 77th Scientific Meeting of the American-Heart-Association Langer, F., Rodriguez, F., Ortiz, S., Cheng, A., Nguyen, T. C., Zasio, M. K., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2005: I383–I389

  Abstract

  Residual or recurrent mitral regurgitation frequently occurs after mitral ring annuloplasty repair for ischemic mitral regurgitation (IMR), because annuloplasty primarily addresses annular dilatation. We describe a subvalvular repair technique addressing posterior papillary muscle (PPM) displacement.Ten sheep had radiopaque markers placed on the left ventricle (LV) and mitral apparatus. A suture was anchored at the right fibrous trigone, passed through the PPM tip and LV wall, and exteriorized through a tourniquet (STRING-1). A second suture was anchored transmurally in the high septum (anterobasal LV wall) and passed through the PPM and LV wall (STRING-2). Reversible posterolateral ischemia was induced by temporarily occluding the proximal circumflex artery. Under open chest conditions, 3D marker coordinates were obtained with biplane videofluoroscopy at baseline and during acute ischemia before and after tightening of each STRING using transesophageal echocardiography to grade IMR. IMR decreased (mean+/-SEM, 2.0+/-0.1 to 1.2+/-0.1; P<0.05) when STRING-1 was tightened, did not change after tightening STRING-2 (2.3+/-0.1 to 2.3+/-0.1), and decreased after tightening both sutures (STRING-1+2, 2.3+/-0.2 to 1.3+/-0.2; P<0.05). STRING-1 and STRING-1+2 (STRING-1, 1.7+/-0.4 mm; STRING-2, 0.7+/-0.5 mm; STRING-1+2, 1.5+/-0.3 mm; P<0.05) resulted in significant PPM basal repositioning. Tightening of any STRING sutures did not affect anterior mitral leaflet excursion.Basal repositioning of the PPM with STRING-1 reduced acute IMR without concomitant annular reduction. This technique may be a useful adjunct if residual IMR is likely after undersized ring annuloplasty.

  View details for DOI 10.1161/CIRCULATIONAHA.104.523464

  View details for PubMedID 16159851

• Annular height-to-commissural width ratio of annulolasty rings in vivo 77th Scientific Meeting of the American-Heart-Association Timek, T. A., Glasson, J. R., Lai, D. T., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2005: I423–I428

  Abstract

  A "saddle-shaped" mitral annulus with an optimal ratio between annular height and commissural diameter may reduce leaflet and chordal stress and is purported to be conserved across mammalian species. Whether annuloplasty rings maintain this relationship is unknown.Twenty-three adult sheep underwent implantation of radiopaque markers on the left ventricle and mitral annulus. Eight animals underwent implantation of a Carpentier-Edwards Physio ring, 7 underwent a Medtronic Duran flexible ring, and 8 served as controls. Animals were studied with biplane videofluoroscopy 7 to 10 days postoperatively. Annular height and commissural width (CW) were determined from 3D marker coordinates, and annular height:CW ratio (AHWCR) was calculated. Annular height was similar in Control and Duran animals but significantly lower in the Physio group at end diastole (8.4+/-3.8, 6.7+/-2.3, and 3.4+/-0.6 mm, respectively, for Control, Duran, and Physio; ANOVA=0.005) and at end systole (14.5+/-6.2, 10.5+/-5.5, and 5.8+/-2.5 mm, respectively, for Control, Duran, and Physio; ANOVA=0.004). Both ring groups reduced CW significantly relative to Control. AHCWR did not differ between Control and Duran but was lower in Physio (23+/-11%, 24+/-7%, and 12+/-2% at end diastole and 42+/-17%, 37+/-17%, and 21+/-10% at end systole, respectively, for Control, Duran, and Physio, respectively; ANOVA <0.05 for both).Mitral annular height and AHWCR of the native valve were unchanged by a Duran ring, whereas the Physio ring led to a lower AHWCR. Theoretically, such a flexible annuloplasty ring may provide better leaflet stress distribution by maintaining normal AHWCR.

  View details for DOI 10.1161/CIRCULATIONAHA.104.525485

  View details for PubMedID 16159857

• Time-resolved three-dimensional magnetic resonance velocity mapping of aortic flow in healthy volunteers and patients after valve-sparing aortic root replacement 30th Annual Meeting of the Western-Thoracic-Surgical-Association Markl, M., Draney, M. T., Miller, D. C., Levin, J. M., Williamson, E. E., Pelc, N. J., Liang, D. H., Herfkens, R. J. MOSBY-ELSEVIER. 2005: 456–63

  Abstract

  To provide more complete characterization of ascending aortic blood flow, including vortex formation behind the valve cusps, in healthy subjects and patients after valve-sparing aortic root replacement (David reimplantation).Time-resolved 3-dimensional magnetic resonance imaging velocity mapping was performed to analyze pulsatile blood flow by using encoded 3-directional vector fields in the thoracic aortas of 10 volunteers and 12 patients after David reimplantation using a cylindrical tube graft (T. David I) and two versions of neosinus recreation (T. David-V and T. David-V-S mod ). Aortic flow was evaluated by using 3-dimensional time-resolved particle traces and velocity vector fields reformatted onto 2-dimensional planes. Semiquantitative data were derived by using a blinded grading system (0-3: 0, none; 1, minimal; 2, medium; 3, prominent) to analyze the systolic vortex formation behind the cusps, as well as retrograde and helical flow in the ascending aorta.Systolic vortices were seen in both coronary sinuses of all volunteers (greater in the left sinus [2.5 +/- 0.5] than the right [1.8 +/- 0.8]) but in only 4 of 10 noncoronary sinuses (0.7 +/- 0.9). Comparable coronary vortices were detected in all operated patients. Vorticity was minimal in the noncoronary cusp in T. David-I repairs (0.7 +/- 0.7) but was prominent in T. David-V noncoronary graft pseudosinuses (1.5 +/- 0.6; P = .035). Retrograde flow (P = .001) and helicity (P = .028) were found in all patients but were not distinguishable from normal values in the T. David-V-S mod patients.Coronary cusp vorticity was preserved after David reimplantation, regardless of neosinus creation. Increased retrograde flow and helicity were more prominent in T. David-V patients. These novel magnetic resonance imaging methods can assess the clinical implications of altered aortic flow dynamics in patients undergoing various types of valve-sparing aortic root replacement.

  View details for DOI 10.1016/j.jtcvs.2004.08.056

  View details for PubMedID 16077413

• The myocardial band: simplicity can be a weakness EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Criscione, J. C., Rodriguez, F., Miller, D. C. 2005; 28 (2): 363–64

  View details for DOI 10.1016/j.ejcts.2005.04.015

  View details for Web of Science ID 000231351800059

  View details for PubMedID 15939612

• Annular or subvalvular approach to chronic ischemic mitral regurgitation? 30th Annual Meeting of the Western-Thoracic-Surgical-Association Tibayan, F. A., Rodriguez, F., Langer, F., Zasio, M. K., Bailey, L., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. MOSBY-ELSEVIER. 2005: 1266–75

  Abstract

  We sought to investigate whether annular or subvalvular interventions corrected chronic ischemic mitral regurgitation differently.Sheep underwent placement of markers on the left ventricle, mitral annulus, papillary muscles (anterior and posterior), and both leaflet edges. A transannular suture (septal-lateral annular cinching) was anchored to the midseptal mitral annulus and externalized through the midlateral mitral annulus. Another suture (papillary muscle repositioning) from the posterior papillary muscle was passed through the mitral annulus near the posterior commissure and externalized. After 7 days, 3-dimensional marker data were obtained before inducing posterolateral myocardial infarction. After 7 weeks, animals in whom chronic ischemic mitral regurgitation developed (n = 10) were restudied before and after pulling septal-lateral annular cinching or papillary muscle repositioning sutures. End-systolic septal-lateral annular diameter and 3-dimensional displacement of the papillary muscles and leaflet edges were computed.Infarction increased mitral regurgitation (0.6 +/- 0.5 to 2.3 +/- 1.1); mitral annular septal-lateral dilation (4 +/- 1 mm); posterior papillary muscle displacement laterally (4 +/- 2 mm), posteriorly (9 +/- 3 mm), and toward the annulus (2 +/- 1 mm); posterior mitral leaflet apical tethering (3 +/- 1 mm); and interleaflet separation (+3 +/- 1 mm, P < .05 baseline vs chronic ischemic mitral regurgitation). Septal-lateral annular cinching reduced septal-lateral dimension (-9 +/- 3 mm), corrected lateral posterior papillary muscle displacement (4 +/- 1 mm) and septal-lateral interleaflet separation (-4 +/- 2 mm), and decreased mitral regurgitation (0.6 +/- 0.6, P < .05 septal-lateral annular cinching vs chronic ischemic mitral regurgitation) without affecting posterior leaflet restriction. Papillary muscle repositioning reduced septal-lateral diameter (-4 +/- 1 mm), moved the anterior papillary muscle closer to the annulus (2 +/- 1 mm), and relieved posterior leaflet apical restriction (2 +/- 1 mm, P < .05 papillary muscle repositioning vs chronic ischemic mitral regurgitation) but did not change lateral posterior papillary muscle displacement or decrease mitral regurgitation (1.9 +/- 1.2).Septal-lateral annular cinching moved the lateral annulus and the posterior papillary muscle closer to the septum and reduced mitral regurgitation unlike posterior papillary muscle repositioning, and thus the key mitral subvalvular repair component must correct posterior papillary muscle lateral displacement.

  View details for DOI 10.1016/j.jtcvs.2005.01.021

  View details for PubMedID 15942566

• Altered mitral valve kinematics with atrioventricular and ventricular pacing 2nd Biennial Meeting of the Society-for-Heart-Valve-Disease Langer, F., Tibayan, F. A., Rodriguez, F., Timek, T., Zasio, M. K., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. I C R PUBLISHERS. 2005: 286–94

  Abstract

  Pacing-induced mitral regurgitation contributes to the 'pacemaker syndrome', which usually is observed with ventricular (V) pacing, but has also been reported with atrioventricular (AV) sequential pacing. Effects of different pacing modes on 3-D kinematics of the mitral apparatus are incompletely understood.Radio-opaque markers were placed on the left ventricular (LV) and mitral apparatus including the annulus, leaflets and papillary muscles of eight sheep. Hemodynamic and 3-D dynamic marker geometry were obtained one week later with biplane videofluoroscopy (60 Hz) during atrial (pacing site = left atrium), AV-sequential (140 ms interval) and (anterolateral LV epicardial) ventricular pacing.Compared with A-pacing (*p <0.05): 1) The regurgitant fraction increased with both AV- and V-pacing (A: 6 +/- 3%, AV: 13 +/- 3%*, V: 15 +/- 2%*); 2) AV and V-pacing delayed closure at the leaflet center (A: 21 +/- 10 ms, AV: 52 + 5 ms*, V: 92 +/- 6 ms*) and posterior commissure (A: 17 +/- 10 ms, AV: 46 +/- 8 ms*, V: 94 +/- 6 ms*). V-pacing delayed valve closure at the anterior commissure (A: 27 +/- 9 ms, V: 94 +/- 6 ms*); 3) The end-diastolic leaflet opening angle was greater with AV- and V-pacing (anterior mitral leaflet (AML): A: 32 +/- 2 degrees, AV: 41 +/- 4 degrees*, V: 46 +/- 4 degrees*; posterior mitral leaflet (PML): A: 56 +/- 4 degrees, AV: 62 +/- 3 degrees*, V: 68 +/- 3 degrees*); 4) 'Effective' end-diastolic PML midline length was reduced with AV- and V-pacing (A: 11.2 +/- 0.7 mm, AV: 10.0 +/- 0.4 mm*, V: 10.2 +/- 0.3 mm*), as was the distance from each papillary muscle (PM) tip to the AML edge ('effective' chordal length) close to the commissures (anterior PM-AML: A: 31.5 +/-1.8 mm, AV: 30.5 +/- 1.9 mm*, V: 29.7 +/- 1.8 mm*; posterior PM-AML: A: 33.7 +/- 1.8 mm, AV: 33.1 +/- 1.9 mm*, V: 32.8 +/- 1.9 mm*).Both ventricular and AV-sequential-pacing resulted in a more widely opened valve at end-diastole and leaflet dyssynchrony with delayed mitral valve closure and early systolic mitral regurgitation. These alterations which result in pacing-induced mitral regurgitation may be clinically important in patients with impaired LV function.

  View details for PubMedID 15974520

• Transmural cardiac strains in the lateral wall of the ovine left ventricle AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Cheng, A., Langer, F., Rodriguez, F., Criscione, J. C., Daughters, G. T., Miller, D. C., Ingels, N. B. 2005; 288 (4): H1546-H1556

  Abstract

  The constant-volume property of contracting cardiac muscle has been invoked in models of heart wall mechanics that predict that systolic subendocardial left ventricular (LV) wall thickening must significantly exceed subepicardial thickening. To examine this prediction, we implanted arrays of radiopaque markers to measure lateral equatorial wall transmural strains and global and regional LV geometry in seven sheep and studied the four-dimensional dynamics of these arrays using biplane videofluoroscopy (60 Hz) in anesthetized intact animals 1 and 8 wk after surgery. A transmural gradient of systolic lateral wall thickening was observed at 1 wk (P = 0.009; linear regression) but was no longer present at 8 wk (P = 0.243). Referenced to end diastole, group mean (+/-SD) end-systolic radial subepicardial, midwall, and subendocardial wall thickening strains were, respectively, 0.08 +/- 0.08, 0.14 +/- 0.08, and 0.22 +/- 0.12 at 1 wk and 0.19 +/- 0.07 (P = 0.02; 1 vs. 8 wk), 0.20 +/- 0.04, and 0.23 +/- 0.07 at 8 wk. With the exception of an 8-ml (7%) increase in end-diastolic volume (P = 0.04) from 1 to 8 wk, LV shape and hemodynamics were otherwise unchanged. We conclude that equivalent hemodynamics can be generated by the left ventricle with or without a transmural gradient of systolic wall thickening in this region; thus such a gradient is unlikely to be a fundamental property of the contracting LV myocardium. We discuss some implications of these findings regarding mechanisms involved in systolic wall thickening.

  View details for DOI 10.1152/ajpheart.00716.2004

  View details for PubMedID 15591101

• Alterations in transmural strains adjacent to ischemic myocardium during acute midcircumflex occlusion 84th Annual Meeting of the American-Association-for-Thoracic-Surgery Rodriguez, F., Langer, F., Harrington, K. B., Cheng, A., Daughters, G. T., Criscione, J. C., Ingels, N. B., Miller, D. C. MOSBY-ELSEVIER. 2005: 791–802

  Abstract

  Helically oriented left ventricular fibers assemble into transmural sheets, which are important for wall-thickening mechanics: 15% fiber shortening results in 40% cross-fiber left ventricular wall thickening and a 60% ejection fraction through sheet extension, thickening, and shear. Normal cardiac microstructure and strains are optimized; deviations could result in apoptosis and deleterious matrix remodeling, which degenerates into global cardiomyopathy. We studied alterations in transmural strains adjacent to ischemic myocardium during acute midcircumflex occlusion.Nine sheep had radiopaque markers implanted to measure left ventricular systolic fractional area shortening; 3 transmural bead columns were inserted into the midlateral wall for strain analysis. Three-dimensional marker coordinates were obtained with biplane videofluoroscopy before and during 70 seconds of ischemia. Systolic strains were quantified along circumferential, longitudinal, and radial axes (n = 9) and were transformed into fiber-sheet coordinates by using quantitative microstructural measurements (n = 5).A functional border was defined in the midlateral left ventricle; ischemia decreased posterolateral fractional area shortening, and anterolateral fractional area shortening increased. In this demarcation junction, subepicardial end-systolic radial wall thickening decreased (0.16 +/- 0.08 vs 0.11 +/- 0.06) and sheet-normal shear was abolished (0.08 +/- 0.04 vs -0.01 +/- 0.03). Longitudinal shortening decreased in the subepicardium and midwall (-0.05 +/- 0.04 vs +/- -0.01 +/- 0.06), but circumferential-radial shear increased at these depths (0.04 +/- 0.04 vs 0.11 +/- 0.05). Subendocardial fiber stretch occurred during early systole (-0.01 +/- 0.03 vs 0.02 +/- 0.03), and end-systolic fiber-sheet shear increased (0.07 +/- 0.01 vs 0.11 +/- 0.04, all P < .05).Increased circumferential-radial shear and altered fiber-sheet strains reflect mechanical interactions between ischemic and nonischemic myocardium, which might be important in triggering remodeling processes that evolve into global ischemic cardiomyopathy.

  View details for DOI 10.1016/j.jtcvs.2004.11.011

  View details for PubMedID 15821645

• Treatment of aortic disease in patients with Marfan syndrome CIRCULATION Milewicz, D. M., Dietz, H. C., Miller, C. 2005; 111 (11): E150–E157

  View details for DOI 10.1161/01.CIR.0000155243.70456.F4

  View details for Web of Science ID 000227805700015

  View details for PubMedID 15781745

• A transmural gradient of systolic wall thickening is not a fundamental property of the contracting LV myocardium Cheng, A., Langer, F., Rodriguez, F., Criscione, J. C., Daughters, G. T., Miller, D. C., Ingels, N. B. FEDERATION AMER SOC EXP BIOL. 2005: A1317

  View details for Web of Science ID 000227610902269

• A transmural gradient of systolic wall thickening is not a fundamental property of the contracting LV myocardium Cheng, A., Langer, F., Rodriguez, F., Criscione, J. C., Daughters, G. T., Miller, D. C., Ingels, N. B. FEDERATION AMER SOC EXP BIOL. 2005: A554

  View details for Web of Science ID 000227610704028

• Computed tomography angiographic demonstration of a ventricular septal defect EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Verhoye, J. P., Levin, J. M., Ihnken, K., Miller, D. C. 2004; 26 (5): 1037-1037

  View details for DOI 10.1016/j.ejcts.2004.06.024

  View details for PubMedID 15519200

• Aorto-mitral angle and flexion are altered by acute ischemic mitral regurgitation and undersized annuloplasty 77th Scientific Meeting of the American-Heart-Association Tibayan, F., Rodriguez, F., Langer, F., Liang, D., Daughters, G., Ingels, N., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2004: 423–23

  View details for Web of Science ID 000224783502307

• Heterogeneous calcium effects on myofiber-sheet mechanics and systolic wall thickening across the left ventricular myocardium Cheng, A., Langer, F., Rodriguez, F., Daughters, G. T., Criscione, J. C., Miller, D. C., Ingels, N. B. LIPPINCOTT WILLIAMS & WILKINS. 2004: 599

  View details for Web of Science ID 000224783503236

• Subvalvular repair: The key to ischemic mitral regurgitation? 77th Scientific Meeting of the American-Heart-Association Langer, F., Rodriguez, F., Ortiz, S., Cheng, A., Zasio, M. K., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2004: 397–97

  View details for Web of Science ID 000224783502202

• In vivo annular height to commissural width ratio of mitral annuloplasty rings 77th Scientific Meeting of the American-Heart-Association Timek, T. A., Lai, D., Glasson, J., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2004: 588–88

  View details for Web of Science ID 000224783503188

• Left ventricular remodeling in chronic ischemic mitral regurgitation (CIMR) 77th Scientific Meeting of the American-Heart-Association Tibayan, F., Rodriguez, F., Langer, F., Zasio, M., Bailey, L., Liang, D., Daughters, G., Ingels, N., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2004: 631–31

  View details for Web of Science ID 000224783503385

• Cutting second-order chords does not prevent acute ischemic mitral regurgitation 76th Annual Scientific Session of the American-Heart-Association Rodriguez, F., Langer, F., Harrington, K. B., Tibayan, F. A., Zasio, M. K., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2004: II91–II97

  Abstract

  Cutting anterior mitral leaflet second-order chordae has been proposed for repair in ischemic mitral regurgitation (IMR). We examined the efficacy of such chordal cutting in preventing acute IMR.Six sheep underwent radiopaque marker placement (left ventricle, mitral annulus, papillary muscles [PMs], and leaflets). The largest second-order chord from each PM was encircled with exteriorized wire snares. Three-dimensional marker coordinates were obtained with biplane videofluoroscopy before and during acute ischemia (80 seconds of mid-circumflex occlusion). Color Doppler transesophageal echocardiography was used to grade MR on a 0 to 4+ scale. Data were acquired immediately before and after dividing second-order chordae. Slope of the end-diastolic volume-stroke work relationship (PRSW) was calculated to assess systolic function. Chordal cutting increased anterior leaflet inflection angle (155+/-12 versus 162+/-9 degrees; P=0.03), resulting in a flatter leaflet, but did not increase effective leaflet length (1.97+/-0.24 versus 2.08+/-0.23 cm; P=0.15); PRSW decreased (63+/-15 versus 56+/-12 mm Hg; P=0.008). Both before and after chordal cutting, ischemia caused: Septal-lateral annular dilation (P=0.005), posterior PM displacement away from the mid-septal annulus (P=0.06), increased leaflet tenting area (P=0.001), and increased leaflet tenting volume (P=0.002). Before chordal cutting, MR increased significantly during ischemia (0.5+/-0.3 versus 1.7+/-0.4; P<0.001), and IMR increased similarly even after the second-order chords were cut (0.7+/-0.4 versus 1.9+/-0.9; P<0.001).Cutting second-order chordae resulted in LV systolic dysfunction and neither prevented nor decreased the severity of acute IMR, septal-lateral annular dilation, leaflet tenting area, or leaflet tenting volume.

  View details for DOI 10.1161/01.CIR.0000138396.24335.6a

  View details for PubMedID 15364845

• Importance of mitral valve second-order chordae for left ventricular geometry, wall thickening mechanics, and global systolic function 40th Annual Meeting of the Society-of-Thoracic-Surgeons Rodriguez, F., Langer, F., Harrington, K. B., Tibayan, F. A., Zasio, M. K., Cheng, A., Liang, D., Daughters, G. T., Covell, J. W., Criscione, J. C., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2004: II115–II122

  Abstract

  Mitral valvular-ventricular continuity is important for left ventricular (LV) systolic function, but the specific contributions of the anterior leaflet second-order "strut" chordae are unknown.Eight sheep had radiopaque markers implanted to silhouette the LV, annulus, and papillary muscles (PMs); 3 transmural bead columns were inserted into the mid-lateral wall between the PMs. The strut chordae were encircled with exteriorized wire snares. Three-dimensional marker images and hemodynamic data were acquired before and after chordal cutting. Preload recruitable stroke work (PRSW) and end-systolic elastance (E(es)) were calculated to assess global LV systolic function (n=7). Transmural strains were measured from bead displacements (n=4). Chordal cutting caused global LV dysfunction: E(es) (1.48+/-1.12 versus 0.98+/-1.30 mm Hg/mL, P=0.04) and PRSW (69+/-16 versus 60+/-15 mm Hg, P=0.03) decreased. Although heart rate and time from ED to ES were unchanged, time of mid-ejection was delayed (125+/-18 versus 136+/-19 ms, P=0.01). Globally, the LV apex and posterior PM tip were displaced away from the fibrous annulus and LV base-apex length increased at end-diastole and end-systole (all +1 mm, P<0.05). Locally, subendocardial end-diastolic strains occurred: Longitudinal strain (E22) 0.030+/-0.013 and radial thickening (E33) 0.081+/-0.041 (both P<0.05 versus zero). Subendocardial systolic shear strains were also perturbed: Circumferential-longitudinal "micro-torsion" (E12) (0.099+/-0.035 versus 0.075+/-0.025) and circumferential radial shear (E13) (0.084+/-0.023 versus 0.039+/-0.008, both P<0.05).Cutting second-order chords altered LV geometry, remodeled the myocardium between the PMs, perturbed local systolic strain patterns affecting micro-torsion and wall-thickening, and caused global systolic dysfunction, demonstrating the importance of these chordae for LV structure and function.

  View details for DOI 10.1161/01.CIR.0000138580.57971.b4

  View details for PubMedID 15364849

• Effects of paracommissural septal-lateral annular cinching on acute ischemic mitral regurgitation 76th Annual Scientific Session of the American-Heart-Association Timek, T. A., Liang, D., Tibayan, F., Langer, F., Rodriguez, F., Daughters, G. T., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2004: II79–II84

  Abstract

  Previous experimental studies demonstrated that central septal-lateral (SL) annular cinching (SLAC) abolishes acute ischemic mitral regurgitation (IMR), but whether localized cinching near the anterior (ACOM) or posterior (PCOM) commissure is equally effective is unknown.Six adult sheep underwent implantation of 9 radiopaque markers on the left ventricle, 8 around the mitral annulus (MA) and 1 on each papillary muscle (PM) tip. Transannular SL sutures were placed at the valve center (CENT) and near ACOM and PCOM and externalized. Acute IMR was induced by proximal circumflex coronary snare occlusion. Biplane videofluoroscopy and transesophageal echocardiography were performed before and continuously during 3 episodes of myocardial ischemia including 20 seconds of SLAC at each different location. End-systolic MA SL dimension at each suture location and distances between the anterior and posterior PM tips and mid-septal annulus ("saddle horn") were calculated from the 3-dimensional (3D) marker coordinates.SLAC interventions in all 3 locations reduced the degree of IMR, but cinching at the center, SLAC(CENT), had a significantly greater effect on reducing the magnitude of IMR than SLAC(PCOM) or SLAC(ACOM) (mean grade of IMR reduction=1.0+/-0.5, 1.8+/-0.5, and 0.9+/-0.2 for SLAC(ACOM), SLAC(CENT), and SLAC(PCOM), respectively; P=0.044). Although ACOM and PCOM cinching reduced SL(CENT) somewhat, only SLAC(CENT) simultaneously reduced both SL(ACOM) and SL(PCOM) and also repositioned both PM tips closer to the annular saddle horn.SLAC in all 3 positions reduced acute IMR, but central SLAC cinching was most effective, reduced all mitral annular SL dimensions, and relocated both PM tips closer to the mid-septal annulus. Central SLAC is most capable of correcting the annular and subvalvular perturbations accompanying acute left ventricular ischemia that lead to IMR.

  View details for DOI 10.1161/01.CIR.0000138975.05902.a5

  View details for PubMedID 15364843

• Alterations in left ventricular torsion and diastolic recoil after myocardial infarction with and without chronic ischemic mitral regurgitation CIRCULATION Tibayan, F. A., Rodriguez, F., Langer, F., Zasio, M. K., Bailey, L., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. 2004; 110 (11): II109-II114

  Abstract

  Chronic ischemic mitral regurgitation (CIMR) is associated with heart failure that continues unabated whether the valve is repaired, replaced, or ignored. Altered left ventricular (LV) torsion dynamics, with deleterious effects on transmural gradients of oxygen consumption and diastolic filling, may play a role in the cycle of the failing myocardium. We hypothesized that LV dilatation and perturbations in torsion would be greater in animals in which CIMR developed after inferior myocardial infarction (MI) than in those that it did not.8+/-2 days after marker placement in sheep, 3-dimensional fluoroscopic marker data (baseline) were obtained before creating inferior MI by snare occlusion. After 7+/-1 weeks, the animals were restudied (chronic). Inferior MI resulted in CIMR in 11 animals but not in 9 (non-CIMR). End-diastolic septal-lateral and anterior-posterior LV diameters, maximal torsional deformation (phi(max), rotation of the LV apex with respect to the base), and torsional recoil in early diastole (phi(5%), first 5% of filling) for each LV free wall region (anterior, lateral, posterior) were measured.Both CIMR and non-CIMR animals demonstrated derangement of LV torsion after inferior MI. In contrast to non-CIMR, CIMR animals exhibited greater LV dilation and significant reductions in posterior maximal torsion (6.1+/-4.3 degrees to 3.9+/-1.9 degrees * versus 4.4+/-2.5 degrees to 2.8+/-2.0 degrees; mean+/-SD, baseline to chronic, *P<0.05) and anterior torsional recoil (-1.4+/-1.1 degrees to -0.2+/-1.0 degrees versus -1.2+/-1.0 degrees to -1.3+/-1.6 degrees ).MI associated with CIMR resulted in greater perturbations in torsion and recoil than inferior MI without CIMR. These perturbations may be linked to more LV dilation in CIMR, which possibly reduced the effectiveness of fiber shortening on torsion generation. Altered torsion and recoil may contribute to the "ventricular disease" component of CIMR, with increased gradients of myocardial oxygen consumption and impaired diastolic filling. These abnormalities in regional torsion and recoil may, in part, underlie the "ventricular disease" of CIMR, which may persist despite restoration of mitral competence.

  View details for DOI 10.1161/01.CIR.0000138385.05471.41

  View details for PubMedID 15364848

• Undersized mitral annuloplasty alters left ventricular shape during acute ischemic mitral regurgitation CIRCULATION Tibayan, F. A., Rodriguez, F., Langer, F., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. 2004; 110 (11): II98-II102

  Abstract

  Underlying left ventricular (LV) dysfunction contributes to poor survival after operation to correct ischemic mitral regurgitation (IMR). Many surgeons do not appreciate that a key component of the Bolling undersized mitral ring annuloplasty concept is to decrease LV wall stress by altering LV shape, but precise 3-dimensional (3-D) geometric data do not exist substantiating this effect. We tested the hypothesis that annular reduction decreases regional circumferential LV radius of curvature (ROC) in a model of acute IMR.Eight adult sheep underwent insertion of an adjustable Paneth-type annuloplasty suture and radiopaque markers on the LV and mitral annulus. The animals were studied with biplane videofluoroscopy during baseline conditions, then before and after tightening the annuloplasty suture during proximal left circumflex occlusion. End-systolic circumferential regional LV ROC and mitral annular area were computed.Acute IMR was eliminated (MR grade 2.1+/-0.4 to 0.4+/-0.4, mean+/-SD, P<0.05) by tightening the Paneth annuloplasty suture. Paneth suture tightening during circumflex occlusion also decreased end-systolic regional circumferential radii of curvature at the basal (anterior, 3.40+/-0.16 to 3.34+/-0.14 cm; posterior, 3.31+/-0.23 to 3.24+/-0.26 cm; P<0.05) and equatorial levels (anterior, 2.99+/-0.21 to 2.89+/-0.29 cm; posterior, 2.86+/-0.38 to 2.81+/-0.41 cm; P<0.05).Acute proximal circumflex occlusion caused IMR and increased end-systolic LV radii of curvature in this experimental preparation. Annular reduction sufficient to abolish IMR also decreased end-systolic anterior and posterior LV ROC, which would be expected to reduce LV wall stress and oxygen consumption in these regions, both potentially beneficial effects. The long-term effects of undersized annuloplasty on LV remodeling and function, however, will require further study in chronic animal preparations or patients with chronic IMR.

  View details for DOI 10.1161/01.CIR.0000128395.45145.45

  View details for PubMedID 15364846

• Increases in mitral leaflet radii of curvature with chronic ischemic mitral regurgitation 2nd Biennial Meeting of the Society-for-Heart-Valve-Disease Tibayan, F. A., Rodriguez, F., Langer, F., Zasio, M. K., Bailey, L., Liang, D., Daughters, G. T., Karlsson, M., Ingels, N. B., Miller, D. C. I C R PUBLISHERS. 2004: 772–78

  Abstract

  Leaflet curvature is a primary determinant of leaflet stress, but no quantitative in-vivo leaflet curvature data exist. Chronic ischemic mitral regurgitation (CIMR) is associated with remodeling of the valvular-ventricular complex. It was hypothesized that leaflet radii of curvature (ROC) would change with such remodeling.Twelve sheep had placement of radiopaque markers on the anterior (APM) and posterior (PPM) papillary muscles, mitral annulus, and anterior (AL) and posterior leaflet (PL) midlines. After 8 +/- 2 days, videofluoroscopy provided baseline 3-D marker data prior to creating inferior myocardial infarction (MI) by snare occlusion of the obtuse marginal coronary arteries. After 7 +/- 1 weeks, the animals were re-studied; 3-D marker coordinates were used to determine end-systolic leaflet ROC, leaflet length, annular septal-lateral diameter, and the distance of each papillary muscle to the mid-septal annulus and each commissure.Before and after CIMR, the AL had compound curvature, and CIMR increased ROC of both curves (proximal ROC 1.27 +/- 0.59 to 1.38 +/- 0.60 cm (p <0.05); distal ROC 1.41 +/- 0.61 to 2.60 +/- 1.52 cm (p < 0.05)). The PL ROC also increased with CIMR (from 2.01 +/- 1.40 to 3.46 +/- 3.93) (p <0.05). Multiple regression analysis determined that annular septal-lateral diameter (proximal AL and distal AL), distance from the APM to anterior commissure (distal AL), and PPM to mid-septal annulus (PL) were independent predictors of leaflet ROC.CIMR increased ROC of both the AL and PL. Leaflet extension may be a compensatory mechanism to minimize the regurgitant orifice, but the attendant increase in ROC will tend to augment leaflet stress. Annular and subvalvular geometry both affect leaflet curvature, and should be considered during mitral repair. These novel quantitative in-vivo data are now available for modification of finite element models, and for comparison to finite element model output.

  View details for PubMedID 15473478

• Mitral suture annuloplasty corrects both annular and subvalvular geometry in acute ischemic mitral regurgitation JOURNAL OF HEART VALVE DISEASE Tibayan, F. A., Rodriguez, F., Langer, F., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. 2004; 13 (3): 414-420

  Abstract

  Papillary muscle displacement is an important element in the pathogenesis of ischemic mitral regurgitation (IMR). The effects of standard ring annuloplasty on subvalvular geometry are incompletely understood. The hypothesis was tested that annular reduction with a Panethtype suture annuloplasty would correct both annular and papillary muscle geometric abnormalities during acute left ventricular (LV) ischemia.Eight adult sheep underwent insertion of an adjustable, double-suture Paneth-type mitral annuloplasty and radiopaque markers on the left ventricle, mitral annulus, leaflet edges, and anterior (APM) and posterior (PPM) papillary muscle tips. Immediately after surgey, 3-D marker coordinates were determined during Control conditions and during proximal left circumflex occlusion before and after tightening the annuloplasty suture.Acute IMR (MR grade 0.3 +/- 0.3 to 2.1 +/- 0.4, Control versus Ischemia) was associated with end-systolic LV dilatation (+27 +/- 16 ml, change relative to Control), greater septal-lateral (+4.6 +/- 3.1 cm) and commissure-commissure (+3.3 +/- 1.6 cm) mitral annular diameters, longer anterior (+1.5 +/- 0.9 cm) and posterior (+0.6 +/- 0.9 cm) papillary muscle tethering distances, greater distance from the APM to the anterior commissure (+0.9 +/- 0.8 cm), and shorter distance from the PPM to the poslerior commissure (-1.3 +/- 1.5 cm). Suture annuloplasty corrected the annular and subvalvular changes, and IMR returned to Control levels (0.5 +/- 0.5); only LV end-systolic volume (ESV) was different from Control (+25 +/- 18 ml) (mean +/- SD, p < 0.05 versus Control by RMANOVA and Dunnett's test).Suture annuloplasty corrected ischemia-induced end-systolic distortions of the entire valvular-ventricular complex (i.e. inter-leaflet separation, mitral annular dilatation in both axes, and papillary muscle displacements), and abolished acute IMR, independent of any change in ESV. A better understanding of the effects of annular reduction on papillary muscle geometry may lead to improved subvalvular mitral repair techniques.

  View details for PubMedID 15222288

• Mitral valve dynamics with different pacing sites 53rd Annual Scientific Session of the American-College-of-Cardiology Langer, F., Tibayan, F. A., Rodriguez, F., Timek, T., Zasio, M. K., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. ELSEVIER SCIENCE INC. 2004: 112A–112A

  View details for Web of Science ID 000189388500466

• Effects of inotropic stimulation on left ventricular torsional deformation in tachycardia-induced dilated cardiomyopathy Rodriguez, F., Harrington, K. B., Tibayan, F. A., Dagum, P., Langer, F., Daughters, G. T., Ingels, N. B., Miller, D. C. ELSEVIER SCIENCE INC. 2004: 218A–219A

  View details for DOI 10.1016/S0735-1097(04)90926-6

  View details for Web of Science ID 000189388500928

• Torsional deformation in ischemic and remote left ventricular regions during acute circumflex and anterior descending coronary occlusion 53rd Annual Scientific Session of the American-College-of-Cardiology Rodriguez, E., Timek, T. A., Langer, F., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. ELSEVIER SCIENCE INC. 2004: 427A–427A

  View details for Web of Science ID 000189388501800

• Computer-generated three-dimensional animation of the mitral valve 28th Annual Meeting of the Western-Thoracic-Surgical-Association Dayan, J. H., Oliker, A., Sharony, R., Baumann, F. G., Galloway, A., Colvin, S. B., Miller, D. C., Grossi, E. A. MOSBY-ELSEVIER. 2004: 763–69

  Abstract

  Three-dimensional motion-capture data offer insight into the mechanical differences of mitral valve function in pathologic states. Although this technique is precise, the resulting time-varying data sets can be both difficult to interpret and visualize. We used a new technique to transform these 3-dimensional ovine numeric analyses into an animated human model of the mitral apparatus that can be deformed into various pathologic states.In vivo, high-speed, biplane cinefluoroscopic images of tagged ovine mitral apparatus were previously analyzed under normal and pathologic conditions. These studies produced serial 3-dimensional coordinates. By using commercial animation and custom software, animated 3-dimensional models were constructed of the mitral annulus, leaflets, and subvalvular apparatus. The motion data were overlaid onto a detailed model of the human heart, resulting in a dynamic reconstruction.Numeric motion-capture data were successfully converted into animated 3-dimensional models of the mitral valve. Structures of interest can be isolated by eliminating adjacent anatomy. The normal and pathophysiologic dynamics of the mitral valve complex can be viewed from any perspective.This technique provides easy and understandable visualization of the complex and time-varying motion of the mitral apparatus. This technology creates a valuable research and teaching tool for the conceptualization of mitral valve dysfunction and the principles of repair.

  View details for DOI 10.1016/S0022-5223(03)00959-0

  View details for Web of Science ID 000220115400024

  View details for PubMedID 15001905

• Mitral annular size predicts Alfieri stitch tension in mitral edge-to-edge repalir JOURNAL OF HEART VALVE DISEASE Timek, T. A., Nielsen, S. L., Lai, D. T., Tibayan, F., Liang, D., Daughters, G. T., Beineke, P., Hastie, T., Ingels, N. B., Miller, D. C. 2004; 13 (2): 165-173

  Abstract

  Whilst increased 'Alfieri stitch' tension may reduce the durability of 'edge-to-edge' mitral repair, the factors affecting suture tension are unknown. In order to study hemodynamics and left ventricular (LV) and annular dynamics that determine suture tension, the central edge of the mitral leaflets was approximated with a miniature force transducer to measure leaflet tension (T) at the leaflet approximation point.Eight sheep were studied under open-chest conditions immediately after surgical placement of a force transducer and implantation of radiopaque markers on the left ventricle and mitral annulus (MA). Hemodynamic variables were altered by two caval occlusion steps (deltaV1 and deltaV2) and dobutamine infusion. Three-dimensional marker coordinates were obtained by simultaneous biplane videofluoroscopy to measure LV volume, MA area (MAA) and septal-lateral (SL) annular dimension throughout the cardiac cycle.At baseline, peak Alfieri stitch tension (0.30 +/- 0.18 N) was observed 96 +/- 61 ms prior to end-diastole coincident with peak annular SL diameter (98 +/- 58 ms before end-diastole). Dobutamine infusion decreased suture tension (from 0.30 +/- 0.18 N to 0.20 +/- 0.12 N, p = 0.01), although peak systolic pressure increased significantly (138 +/- 19 versus 115 +/- 14 mmHg; p = 0.03). A regression model was fitted with the goal of interpreting the hemodynamic and geometric predictors of tension as their influence varied with time: Tt (N) = 0.1916 + 0.2115 x SL (cm) - 0.1996 x MAA/SL (cm2/cm) + ft x LVP (mmHg), where Tt is tension at any time during the cardiac cycle and ft is the time-varying coefficient of LVP.Tension on the leaflets in the edge-to-edge repair is determined primarily by MA SL size, and paradoxically is lower when the contractile state is enhanced. This indicates that annular and/or LV dilatation increase stitch tension and may adversely affect durability of the repair if concomitant ring annuloplasty is not performed.

  View details for PubMedID 15086253

• Can the principles of evidence-based medicine be applied to the treatment of aortic dissections? EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Myrmel, T., Lai, D. T., Miller, D. C. 2004; 25 (2): 236-242

  Abstract

  Surgical treatment of patients with acute type A aortic dissections has improved early survival from 10-20 to approximately 80%. Data supporting several other treatment recommendations in patients with aortic dissection, however, are less convincing. We hypothesized that applying strict principles of evidence-based medicine would invalidate most of the recommendations in these published papers. We conducted a literature search asking three questions: (1) Is the use of routine circulatory arrest and an 'open distal' anastomosis technique better than traditional aortic cross clamping? (2) Does a persistent false lumen in the distal aorta wall have an adverse influence on long-term event-free survival? and (3) Is primary surgical or medical treatment of patients with Stanford acute type B dissections preferable in terms of long-term event-free survival? We searched Entrez Pubmed (National Library of Medicine) for all papers on these topics from 1980 to January 2003. Screening 3164 papers identified using the search terms 'aortic dissection' and 'treatment' yielded 15 papers fulfilling a set of a priori inclusion criteria. No study had a design that allowed unequivocal conclusions; moreover, the heterogeneity in study design and patient populations precluded formal meta-analysis. The difficulties inherent in conducting stringent clinical studies addressing various treatment strategies for patients with aortic dissection hamper their quality and weaken their recommendations for different treatment options. Specifically, no conclusive evidence exists favoring use of an open distal anastomosis in patients with acute type A dissections or complete elimination of flow in the distal aortic false lumen; similarly, medical therapy of patients with acute type B aortic dissections has no proven advantage over surgical treatment.

  View details for DOI 10.1016/j.ejcts.2003.11.022

  View details for PubMedID 14747119

• Fixed-apex mitral annular descent correlates better with left ventricular systolic function than does free-apex left ventricular long-axis shortening 75th Annual Scientific Session of the American-Heart-Association Rodriguez, F., Tibayan, F. A., Glasson, J. R., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. MOSBY-ELSEVIER. 2004: 101–7

  Abstract

  Echocardiographic measures of mitral annular descent (MAD) assume a fixed left ventricular (LV) apex throughout the cardiac cycle, ignoring the apical component of LV long-axis shortening (LAS). We tested whether apical motion contributes significantly to LAS, making LAS a better surrogate of LV systolic function than MAD. Three-dimensional LV systolic MAD, LAS, and apical motion were measured in sheep using implanted radiopaque markers and biplane videofluoroscopy. End-diastolic volume-stroke work relationship (preload recruitable stroke work) was computed as a load-independent index of LV systolic function. Apical motion was 1.4 +/- 0.8 mm, representing 22% of LAS (P <.05). Linear regression demonstrated that MAD correlated slightly better with preload recruitable stroke work (r = 0.808) than LAS (r = 0.792, both P <.001). Receiver operating characteristic curves demonstrated MAD was more accurate in predicting depressed LV function than LAS (93% vs 84%, respectively). Although LV apical motion contributed significantly to LAS, MAD measured with a fixed-apex assumption, as currently done echocardiographically, correlated more closely with LV preload recruitable stroke work.

  View details for DOI 10.1067/j.echo.2003.11.007

  View details for PubMedID 14752482

• Stent-graft repair of penetrating atherosclerotic ulcers in the descending thoracic aorta: Mid-term results ANNALS OF THORACIC SURGERY Demers, P., Miller, D. C., Mitchell, R. S., Kee, S. T., Chagonjian, L., Dake, M. D. 2004; 77 (1): 81-86

  Abstract

  Localized aortic pathoanatomic abnormalities are good targets for endovascular stent-grafting but only short-term results have been reported. Our objective was to determine the effectiveness of endovascular stent-graft treatment of patients with descending thoracic atherosclerotic penetrating atherosclerotic ulcers (PAU) and to identify risk factors for treatment failure.Between 1993 and 2000 endovascular repair of PAU with first-generation (custom-fabricated) and second-generation (commercial) stent-grafts was performed in 26 patients (mean age, 70 years), 6 (23%) of whom had rupture. Fourteen patients (54%) were not candidates for open surgical repair. Follow-up was 100% complete (average, 51 months; maximum, 114 months). Outcome variables considered in the multivariable analysis included death and treatment failure (composite end-point comprising early death, endoleak, stent-graft mechanical fault, late aortic event, reintervention, and aortic-related or sudden death).Three patients (12% +/- 7% [+/-70% confidence limits]) died within 30 days and 2 had an early type I endoleak. Primary success rate was 92%. Actuarial survival estimates at 1, 3, and 5 years were 85% +/- 8%, 76% +/- 8% and 70% +/- 10% respectively and actuarial freedom from treatment failure was 81% +/- 8%, 71% +/- 9% and 65% +/- 10%. Multivariable analyses identified previous cerebrovascular accident (hazard ratio [HR] 17.1, p = 0.02) and female sex (HR 7.4, p = 0.08) as independent risk factors for death. For treatment failure the predictors were increasing aortic diameter (HR 1.1 [per mm above the mean value], p = 0.01) and female sex (HR 5.5, p = 0.09).Endovascular stent-graft repair is effective but not curative treatment for selected, high surgical risk, elderly patients with a descending aortic PAU over the medium term. Assiduous serial follow-up imaging after stent-grafting is mandatory to detect late complications especially in those with a large aorta.

  View details for DOI 10.1016/S0003-4975(03)00816-6

  View details for PubMedID 14726040

• Aorto-mitral annular dynamics 39th Annual Meeting of the Society-of-Thoracic-Surgeons Timek, T. A., Green, G. R., Tibayan, F. A., Lai, D. T., Rodriguez, F., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. ELSEVIER SCIENCE INC. 2003: 1944–50

  Abstract

  The aortic and mitral valves are coupled through fibrous aorto-mitral continuity, but their synchronous dynamic physiology has not been completely characterized.Seven sheep underwent implantation of five radiopaque markers on the left ventricle, 10 on the mitral annulus, and 3 on the aortic annulus. One of the mitral annulus markers was placed at the center of aorto-mitral continuity (mitral annulus "saddle horn"). Animals were studied with bi-plane videofluoroscopy 7 to 10 days postoperatively. Total circumference and lengths of mitral fibrous annulus, mitral muscular annulus, aortic fibrous annulus, and aortic muscular annulus were calculated throughout the cardiac cycle from three dimensional marker coordinates as was mitral annular area and aortic annular area. Aorto-mitral angle was determined as the angle between the centroid of the aortic annulus markers, the saddle horn, and the centroid of the mitral annulus markers. Aortic annulus and mitral annulus flexion was expressed as the difference between maximum and minimum values of the aortic and mitral annulus angles during the cardiac cycle.Mitral and aortic annular areas changed in roughly a reciprocal fashion during late diastole and early systole with an overall 32 +/- 8% change in aortic annular area and a 13 +/- 13% change in mitral annular area. Aortic fibrous annulus changed much less than aortic muscular annulus (6 +/- 2% vs 18 +/- 4%; p = 0.0003) as did mitral fibrous annulus relative to mitral muscular annulus (4 +/- 1% vs 8 +/- 2%; p = 0.004). Aortic annulus and mitral annulus flexion was 8 +/- 2 degrees and increased to 11 +/- 2 degrees (p = 0.009) with inotropic stimulation.Dynamic aortic and mitral annular area changes were not mediated through the anatomic fibrous continuity. Aorto-mitral flexion, which increased with enhanced contractility, may facilitate left ventricle ejection. The effect of valvular surgical interventions on aorto-mitral flexion needs further investigation.

  View details for DOI 10.1016/S0003-4975(03)01078-6

  View details for Web of Science ID 000186986500037

  View details for PubMedID 14667619

• Annular remodeling in chronic ischemic mitral regurgitation: Ring selection implications 39th Annual Meeting of the Society-of-Thoracic-Surgeons Tibayan, F. A., Rodriguez, F., Langer, F., Zasio, M. K., Bailey, L., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. ELSEVIER SCIENCE INC. 2003: 1549–54

  Abstract

  More precise understanding of annular remodeling in the evolution of chronic ischemic mitral regurgitation is needed to provide a more rational basis for optimal annuloplasty ring sizing and selection as well as the design of new reparative techniques. Three-dimensional in vivo data describing these geometric perturbations however are lacking. Using an ovine model of chronic myocardial infarction we determined the three-dimensional distortions of the mitral annulus associated with the development of chronic ischemic mitral regurgitation.Ten sheep underwent placement of radiopaque markers on the left ventricle and mitral annulus as well as placement of snares around the second and third obtuse marginal coronary arteries. After 8 days biplane cinefluoroscopy provided three-dimensional marker data and snare occlusion created an inferior infarction. After 7 more weeks the animals were studied again.Severity of mitral regurgitation increased (0.6 +/- 0.5 to 2.5 +/- 0.7). Septal-lateral (2.99 +/- 0.20 cm to 3.64 +/- 0.35 cm, maximum dimension) and commissure-commissure (3.71 +/- 0.32 cm to 4.40 +/- 0.30 cm) mitral annular diameters and the lengths of the muscular (7.77 +/- 0.39 cm to 9.51 +/- 0.72 cm) and fibrous annular perimeters (3.36 +/- 0.37 cm to 3.85 +/- 0.39 cm, p < 0.0001 for all) increased while the height of the annular "saddle horn" above a best-fit plane fell (0.73 +/- 0.52 cm to 0.57 +/- 0.42 cm, minimum dimension, p = 0.01).These three-dimensional in vivo data reflect annular remodeling in chronic ischemic mitral regurgitation and suggest that mitral repair in this context should be aimed at preventing further lengthening of the intertrigonal distance, reducing the septal-lateral annular diameter to reestablish adequate leaflet coaptation, and restoring the saddle shape of the annulus.

  View details for DOI 10.1016/S0003-4975(03)00880-4

  View details for PubMedID 14602284

• Importance of the anterior mitral valve leaflet second-order chordae tendineae for left ventricular structure and function 76th Annual Scientific Session of the American-Heart-Association Rodriguez, F., Harrington, K. B., Langer, F., Tibayan, F. A., Zasio, M. K., Liang, D., Daughters, G. T., Criscione, J. C., Covell, J. W., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2003: 366–67

  View details for Web of Science ID 000186360601768

• Does cutting the second-order chordae tendineae prevent acute ischemic mitral regurgitation? 76th Annual Scientific Session of the American-Heart-Association Rodriguez, F., Langer, F., Harrington, K. B., Tibayan, F. A., Zasio, M. K., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2003: 327–28

  View details for Web of Science ID 000186360601598

• Importance of the anterior mitral valve leaflet second-order chordae tendineae for left ventricular structure and function 76th Annual Scientific Session of the American-Heart-Association Rodriguez, F., Harrington, K. B., Langer, F., Tibayan, F. A., Zasio, M. K., Liang, D., Daughters, G. T., Criscione, J. C., Covell, J. W., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2003: Q-Q

  View details for Web of Science ID 000186360600042

• Simultaneous "Tirone David-V" valve-sparing aortic root replacement and radical mitral valve repair for the Marfan syndrome with Barlow syndrome CIRCULATION Demers, P., Liang, D., Miller, D. C. 2003; 108 (16): E116-E117

  View details for DOI 10.1161/01.CIR.0000092236.67713.04

  View details for Web of Science ID 000186055600021

• Ablation of mitral annular and leaflet muscle: effects on annular and leaflet dynamics AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Timek, T. A., Lai, D. T., Dagum, P., Tibayan, F., Daughters, G. T., Liang, D., Berry, G. J., Miller, D. C., Ingels, N. B. 2003; 285 (4): H1668-H1674

  Abstract

  Mitral annular (MA) and leaflet three-dimensional (3-D) dynamics were examined after circumferential phenol ablation of the MA and anterior mitral leaflet (AML) muscle. Radiopaque markers were sutured to the left ventricle, MA, and both mitral leaflets in 18 sheep. In 10 sheep, phenol was applied circumferentially to the atrial surface of the mitral annulus and the hinge region of the AML, whereas 8 sheep served as controls. Animals were studied with biplane video fluoroscopy for computation of 3-D mitral annular area (MAA) and leaflet shape. MAA contraction (MAACont) was determined from maximum to minimum value. Presystolic MAA (PS-MAACont) reduction was calculated as the percentage of total reduction occurring before end diastole. Phenol ablation decreased PS-MAACont (72 +/- 6 vs. 47 +/- 31%, P = 0.04) and delayed valve closure (31 +/- 11 vs. 57 +/- 25 ms, P = 0.017). In control, the AML had a compound sigmoid shape; after phenol, this shape was entirely concave to the atrium during valve closure. These data indicate that myocardial fibers on the atrial side of the valve influence the 3-D dynamic geometry and shape of the MA and AML.

  View details for DOI 10.1152/ajpheart.00179.2003

  View details for PubMedID 12969884

• Edge-to-edge mitral valve repair without ring annuloplasty for acute ischemic mitral regurgitation. Circulation Timek, T. A., Nielsen, S. L., Lai, D. T., Tibayan, F. A., Liang, D., Rodriguez, F., Daughters, G. T., Ingels, N. B., Miller, D. C. 2003; 108: II122-7

  Abstract

  Alfieri edge-to-edge mitral repair has been used clinically with ring annuloplasty to correct ischemic mitral regurgitation (IMR), but its efficacy without concomitant ring annuloplasty has not been described in this setting.Seventeen sheep underwent implantation of 9 radiopaque markers on the left ventricle, 8 on the mitral annulus (MA), 1 on each papillary muscle (PM) tip, and 1 on the anterior and posterior leaflet edges near the anterior and posterior commissures. Alfieri repair was performed in 7 animals, and 10 were controls. Biplane videofluoroscopy and transesophageal echocardiography (TEE) were performed (open chest) before and continuously during left circumflex coronary artery occlusion to induce acute IMR. MA area (MAA), anterior (APM), and posterior (PPM) papillary muscle tip distances to midseptal MA ("saddle horn"), and distance of each leaflet marker to the mitral annular plane were calculated from 3-dimensional marker coordinates at end-systole (ES).Severity of IMR was not different between groups (+1.9+/-0.7 versus +1.4+/-0.5 for Control and Alfieri, respectively; P=not significant [NS]). Mitral annular area (MAA; 21+/-15 versus 19+/-9%; P =NS) and septal-lateral (SL) annular diameter (12+/-6 versus 12+/-11%; P =NS) increased similarly during ischemia. While PPM-saddle horn distance increased in both groups (1.5+/-1.3 and 1.6+/-1.4 mm for Control and Alfieri, respectively; P<0.05 versus preischemia), APM-saddle horn distance increased in Control (1.0+/-1.2 mm; P=0.03) but not in the Alfieri animals (0.8+/-08 mm; P=0.07). Leaflet edge displacements from the annular plane during ischemia were similar in both groups.Alfieri repair did not prevent acute IMR nor alter ischemic valvular or subvalvular geometric perturbations. Adjunct surgical procedures, such as ring annuloplasty, are also necessary.

  View details for PubMedID 12970220

• Edge-to-edge mitral valve repair without ring annuloplasty for acute ischemic mitral regurgitation CIRCULATION Timek, T. A., Nielsen, S. L., Lai, D. T., Tibayan, F. A., Liang, D., Rodriguez, F., Daughters, G. T., Ingels, N. B., Miller, D. C. 2003; 108 (10): 122-127

  View details for DOI 10.1161/01.cir.0000087943.76135.fd

  View details for Web of Science ID 000185265000022

• Geometric distortions of the mitral valvular-ventricular complex in chronic ischemic mitral regurgitation CIRCULATION Tibayan, F. A., Rodriguez, F., Zasio, M. K., Bailey, L., Liang, D., Daughters, G. T., Langer, F., Ingels, N. B., Miller, D. C. 2003; 108 (10): 116-121

  View details for DOI 10.1161/01.cir.0000087940.17524.8a

  View details for Web of Science ID 000185265000021

• Paneth suture annuloplasty abolishes acute ischemic mitral regurgitation but preserves annular and leaflet dynamics CIRCULATION Tibayan, F. A., Rodriguez, F., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. 2003; 108 (10): 128-133

  View details for DOI 10.1161/01.cir.0000087942.09226.b2

  View details for Web of Science ID 000185265000023

• Paneth suture annuloplasty abolishes acute ischemic mitral regurgitation but preserves annular and leaflet dynamics. Circulation Tibayan, F. A., Rodriguez, F., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. 2003; 108: II128-33

  Abstract

  Ring annuloplasty, the standard treatment for ischemic mitral regurgitation (IMR), abolishes normal annular dynamics and freezes the posterior leaflet. We examined the impact of Paneth suture annuloplasty during acute IMR on motion of the mitral annulus and leaflets in an ovine model.Eight sheep had radiopaque markers placed on the left ventricle, anterior mitral leaflet, posterior mitral leaflet, and mitral annulus. A Paneth suture annuloplasty that could be reversibly tightened was anchored to each fibrous trigone and externalized through the mid-lateral mitral annulus. Acute IMR was induced by proximal circumflex artery occlusion. Transesophageal echocardiography assessed the degree of IMR, and biplane cinefluoroscopy measured 3-dimensional marker coordinates before and during circumflex ischemia, and tightening of the Paneth suture. Paneth suture annuloplasty eliminated acute IMR, and reduced septal-lateral and commissure-commissure mitral annular dimensions. Tightening of the annuloplasty sutures, even beyond the degree necessary to eliminate mitral regurgitation (MR), did not reduce septal-lateral or commissure-commissure annular shortening, shortening of the muscular annular perimeter, annular flexion, or angular excursion of the anterior or posterior leaflets relative to ischemic conditions.In contrast to ring annuloplasty, annular reduction sufficient to restore mitral competence during acute IMR can be achieved with a Paneth suture annuloplasty while simultaneously maintaining normal annular and leaflet dynamic motion. These findings should prompt additional investigation and design of repair methods that preserve the mobility of the mitral apparatus.

  View details for PubMedID 12970221

• Prosthesis size and long-term survival after aortic valve replacement 80th Annual Meeting of the American-Association-for-Thoracic-Surgery Blackstone, E. H., Cosgrove, D. M., Jamieson, W. R., Birkmeyer, N. J., Lemmer, J. H., Miller, D. C., Butchart, E. G., Rizzoli, G., Yacoub, M., Chai, A. K. MOSBY-ELSEVIER. 2003: 783–96

  Abstract

  This study was undertaken to quantify the relationship between prosthesis size adjusted for patient size (prosthesis-patient size) and long-term survival after aortic valve replacement.Data from nine representative sources on 13,258 aortic valve replacements provided 69,780 patient-years of follow-up (mean 5.3 +/- 4.7 years), with reliable survival estimates to 15 years. Prostheses included 5757 stented porcine xenografts, 3198 stented bovine pericardial xenografts, 3583 mechanical valves, and 720 allografts. Manufacturers' labeled prosthesis size was 19 mm or smaller in 1109 patients. Expressions of prosthesis-patient size assessed were indexed internal prosthesis orifice area (in centimeters squared per square meter of body surface area) and standardized internal prosthesis orifice size (Z, the number of SDs from mean normal native aortic valve size). Multivariable hazard domain analysis with balancing score and risk factor adjustment quantified the association of prosthesis-patient size with survival.Prosthesis-patient size down to at least 1.1 cm(2)/m(2) or -3 Z did not adversely affect intermediate- or long-term survival (P >.2). However, 30-day mortality increased 1% to 2% when indexed orifice area fell below 1.2 cm(2)/m(2) (P =.002) or standardized orifice size fell below -2.5 Z (P =.0003). The increased early risk affected fewer than 1% of patients receiving bioprostheses but about 25% of those receiving mechanical devices.Aortic prosthesis-patient size down to 1.1 cm(2)/m(2) or -3 Z did not reduce intermediate- or long-term survival after aortic valve replacement. However, patient-prosthesis size under 1.2 cm(2)/m(2) or -2.5 Z was associated with a 1% to 2% increase in 30-day mortality. Prosthesis-patient sizes this small or smaller were rarely implanted in patients receiving bioprostheses.

  View details for DOI 10.1016/S0022-5223(03)00591-9

  View details for Web of Science ID 000185417200030

  View details for PubMedID 14502155

• Alterations in left ventricular curvature and principal strains in dilated cardiomyopathy with functional mitral regurgitation ACC Annual Scientific Meeting Tibayan, F. A., Lai, D. T., Timek, T. A., Dagum, P., Liang, D., Zasio, M. K., Daughters, G. T., Miller, D. C., Ingels, N. B. I C R PUBLISHERS. 2003: 292–99

  Abstract

  Functional mitral regurgitation (FMR) is increasingly recognized as a left ventricular (LV) disease. Dilated cardiomyopathy (DCM) is commonly accompanied by FMR and reduction of LV torsion. Therapeutic targets for DCM include LV size reduction, altered LV shape, elimination of MR, and increasing LV torsion. It was hypothesized that, in addition to increasing LV size, DCM with FMR would alter normal LV shape and reduce and alter the direction of principal strains across the LV wall. This hypothesis was tested by measuring changes in epicardial and endocardial 2-D principal strains and regional radii of curvature accompanying tachycardia-induced cardiomyopathy in ovine hearts.Radio-opaque marker arrays were implanted into the left ventricle of eight sheep, including one subepicardial triangle and one subendocardial triangle in the anterior wall of the left ventricle. At one week postoperatively, biplane videofluoroscopy was used to determine marker dynamics. Rapid ventricular pacing was then instituted until FMR and signs of heart failure developed, and fluoroscopy was repeated. Circumferential LV radii of curvature were determined from marker triplets.DCM changed the normal epicardial oval LV cross-section to a more circular configuration. The endocardium maintained its normal circular shape as the left ventricle dilated. Deformations of the triangles from end-diastole to end-systole were determined, and the magnitude and direction of 2-D principal strains calculated. DCM was associated with decreased magnitude of both epicardial (-0.095 +/- 0.055 versus -0.040 +/- 0.032, p = 0.006) and endocardial (-0.117 +/- 0.047 versus -0.073 +/- 0.037, p = 0.023) principal strains. DCM reduced the angle of epicardial but not endocardial principal strain.DCM with FMR is associated with LV dilation, circularization of the normally oval equatorial circumferential LV epicardium, transmural reduction in principal strain, and decrease in angle of principal epicardial strain. These changes contribute to a reduction in the net torsional moment and may guide the development of reverse remodeling procedures for the dilated, failing ventricle with FMR.

  View details for PubMedID 12803327

• Left ventricular volume shifts during isovolumic contraction contribute to dynamic opening of the aortic valve Rodriguez, F., Green, G. R., Dagum, P., Nistal, F. J., Tibayan, F. A., Langer, F., Daughters, G. T., Ingels, N. B., Miller, D. C. ELSEVIER SCIENCE INC. 2003: 513A

  View details for Web of Science ID 000181669502222

• Ischemia in three left ventricular regions: Insights into the pathogenesis of acute ischemic mitral regurgitation 82nd Annual Meeting of the American-Association-for-Thoracic-Surgery Timek, T. A., Lai, D. T., Tibayan, F., Liang, D., Daughters, G. T., Dagum, P., Zasio, M. K., Lo, S., Hastie, T., Ingels, N. B., Miller, D. C. MOSBY-ELSEVIER. 2003: 559–69

  Abstract

  Acute posterolateral left ventricular ischemia in sheep results in ischemic mitral regurgitation, but the effects of ischemia in other left ventricular regions on ischemic mitral regurgitation is unknown.Six adult sheep had radiopaque markers placed on the left ventricle, mitral annulus, and anterior and posterior mitral leaflets at the valve center and near the anterior and posterior commissures. After 6 to 8 days, animals were studied with biplane videofluoroscopy and transesophageal echocardiography before and during sequential balloon occlusion of the left anterior descending, distal left circumflex, and proximal left circumflex coronary arteries. Time of valve closure was defined as the time when the distance between leaflet edge markers reached its minimum plateau, and systolic leaflet edge separation distance was calculated on the basis of left ventricular ejection.Only proximal left circumflex coronary artery occlusion resulted in ischemic mitral regurgitation, which was central and holosystolic. Delayed valve closure (anterior commissure, 58 +/- 29 vs 92 +/- 24 ms; valve center, 52 +/- 26 vs 92 +/- 23 ms; posterior commissure, 60 +/- 30 vs 94 +/- 14 ms; all P <.05) and increased leaflet edge separation distance during ejection (mean increase, 2.2 +/- 1.5 mm, 2.1 +/- 1.9 mm, and 2.1 +/- 1.5 mm at the anterior commissure, valve center, and posterior commissure, respectively; P <.05 for all) was seen during proximal left circumflex coronary artery occlusion but not during left anterior descending or distal left circumflex coronary artery occlusion. Ischemic mitral regurgitation was associated with a 19% +/- 10% increase in mitral annular area, and displacement of both papillary muscle tips away from the septal annulus at end systole.Acute ischemic mitral regurgitation in sheep occurred only after proximal left circumflex coronary artery occlusion along with delayed valve closure in early systole and increased leaflet edge separation throughout ejection in all 3 leaflet coaptation sites. The degree of left ventricular systolic dysfunction induced did not correlate with ischemic mitral regurgitation, but both altered valvular and subvalvular 3-dimensional geometry were necessary to produce ischemic mitral regurgitation during acute left ventricular ischemia.

  View details for DOI 10.1067/mtc.2003.43

  View details for PubMedID 12658198

• Tachycardia-induced cardiomyopathy in the ovine heart: Mitral annular dynamic three-dimensional geometry JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Timek, T. A., Dagum, P., Lai, D. T., Liang, D., Daughters, G. T., Tibayan, F., Ingels, N. B., Miller, D. C. 2003; 125 (2): 315-324

  Abstract

  Ring annuloplasty has been used to correct annular dilatation and mitral regurgitation in dilated cardiomyopathy, but little is known about the dynamic precise 3-dimensional geometry of the mitral annulus in this condition.Nine sheep had radiopaque markers sewn to the mitral annulus, creating 8 distinct segments beginning at the posterior commissure (segments 1-4, septal mitral annulus; segments 5-8, lateral mitral annulus). Biplane videofluoroscopy and transesophageal echocardiography were performed before and after rapid pacing (180-230 min(-1) for 15 +/- 6 days) sufficient to develop tachycardia-induced cardiomyopathy and mitral regurgitation. Mitral annular segment contraction was defined as the percentage difference between maximum and minimum lengths. Mitral annular area and mitral annular septal-lateral and commissure-commissure diameters and 3-dimensional shape were determined from marker coordinates.With tachycardia-induced cardiomyopathy, end-diastolic mitral annular area, septal-lateral diameter, and commissure-commissure diameter increased by 36% +/- 14%, 25% +/- 12%, and 9% +/- 5%, respectively (P <.01), whereas mitral regurgitation increased from 0.3 +/- 0.2 to 2.2 +/- 0.9 (P <.0001). All annular segments dilated at end-diastole with tachycardia-induced cardiomyopathy, except the segment between the midseptal annulus and the left fibrous trigone. Annular segment contraction was significantly decreased with tachycardia-induced cardiomyopathy in the lateral, but not in the septal, regions. Three-dimensional reconstruction of annular shape revealed a saddle shape of the annulus at baseline; this shape was also measured with tachycardia-induced cardiomyopathy, but there was some flattening of the septal annulus.With tachycardia-induced cardiomyopathy, the mitral annulus dilated substantially, being more in the septal-lateral than in the commissure-commissure dimension. Greater annular segmental dilatation and decreased contraction occurred in the lateral annulus. The saddle shape of the annulus was retained but flattened.

  View details for DOI 10.1067/mtc.2003.80

  View details for PubMedID 12579100

• Atrial contraction and mitral annular dynamics during acute left atrial and ventricular ischemia in sheep AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Timek, T. A., Lai, D. T., Tibayan, F., Daughters, G. T., Liang, D., Dagum, P., Lo, S., Miller, D. C., Ingels, N. B. 2002; 283 (5): H1929-H1935

  Abstract

  In six sheep, radiopaque markers were placed on the left ventricle (LV), the mitral annulus, the left atrium (LA), and the central edge of both mitral leaflets to investigate the effects of acute LV ischemia on atrial contraction, mitral annular area (MAA), and mitral regurgitation (MR). Animals were studied with biplane videofluoroscopy and transesophageal echocardiography before and during balloon occlusion of the left anterior descending (LAD), distal circumflex (dLCX), and proximal circumflex (pLCX) coronary arteries. MAA and LA area were calculated from the corresponding markers. LAD occlusion did not alter LA area reduction or presystolic MAA reduction, whereas dLCX occlusion resulted in a mild decrease in the former with no change in the latter. Neither occlusion resulted in MR. pLCX occlusion, however, significantly decreased LA area and presystolic MAA reduction and resulted in increased end-diastolic MAA, delayed valve closure from end diastole, and MR. Decreased atrial contractile function, as observed during acute posterolateral ischemia, is linked to diminished presystolic mitral annular reduction, a larger mitral annular size at end diastole, and MR.

  View details for DOI 10.1152/ajpheart.00149.2002

  View details for PubMedID 12384471

• Ischemia-induced malcoaptation of scallops within the posterior mitral leaflet JOURNAL OF HEART VALVE DISEASE Myrmel, T., Lai, D. T., Lo, S., Timek, T. A., Liang, D., Miller, D. C., Ingels, N. B., Daughters, G. T. 2002; 11 (6): 823-829

  Abstract

  The posterior mitral leaflet is divided into a variable number of scallops, and little is known about the role of scallopmalcoaptation in ischemic mitral regurgitation. The study aim was to assess whether acute ischemia in the posterolateral wall of the left ventricle would induce scallop separation that would contribute to mitral regurgitation.Radio-opaque markers were surgically placed in the left ventricle, around the mitral annulus, and at three sites along the posterior mitral leaflet edge in eight sheep. Three-dimensional marker coordinates were obtained by biplane videofluoroscopy at 60 Hz and 0.1 mm resolution before and during echocardiographically verified acute ischemic mitral regurgitation produced by balloon occlusion of the circumflex coronary artery.During systole, the mean (+/-SD) distance between the central and anterolateral markers, both placed on the central scallop of the posterior mitral leaflet, was unaffected by ischemia (7.4+/-2.4 versus 7.4+/-2.5 mm; n = 8; p = NS). In contrast, the systolic distance between the central scallop marker and the posteromedial marker increased by 2.3+/-0.2 mm (p = 0.008) in three hearts with the posteromedial marker on the posteromedial scallop, compared with no separation (0.2+/-0.5 mm; p = NS) in five hearts with both the central and posteromedial markers on the central scallop itself. This result shows systolic separation of the central and posteromedial scallops during acute ischemic mitral regurgitation.During acute left ventricular ischemia, the central and posteromedial scallops of the posterior mitral leaflet can fail to coapt during systole, potentially contributing to the mitral regurgitation observed.

  View details for PubMedID 12479283

• What is the best treatment for patients with acute type B aortic dissections - Medical, surgical, or endovascular stent-grafting? Aortic Surgery Symposium VIII Umana, J. P., Miller, D. C., Mitchell, R. S. ELSEVIER SCIENCE INC. 2002: S1840–S1843

  Abstract

  Controversy continues regarding treatment for patients with acute type B aortic dissection.One hundred eighty-nine patients with acute type B aortic dissection managed over a 36-year period were analyzed retrospectively for three outcome endpoints: survival; freedom from reoperation, and freedom from late aortic-related complications or late death. Risk factors for death were identified using a multivariable Cox proportional hazards model. Then to account for patient selection bias, heterogeneity of the population, and continuous evolution in techniques, propensity score analysis was used to identify risk-matched cohorts (quintiles I and II) in which the results of medical (n = 111) or surgical (n = 31) therapy were compared more comprehensively.The two main determinants of death were shock (hazard ratio [HR] = 14.5, 95% confidence level [CL] 4.7, 44.5; p < 0.001) and visceral ischemia (HR = 10.9, 95% CL 3.9, 30.3; p < 0.001). Arch involvement, rupture, stroke, previous sternotomy, and coronary or lung disease roughly doubled the hazard. Female sex was also a significant but weaker independent predictor of death. Actuarial survival estimates for all patients were 71%, 60%, 35%, and 17% at 1, 5, 10, and 15 years, respectively, and were similar for the medical and surgical patients. The Marfan syndrome predicted reoperation and late aortic complications or late death. In a separate analysis of the 142 patients in quintiles I and II, survival, freedom from reoperation, as well as freedom from late aortic complications or death were almost identical in the medical and surgical subsets.The poor long-term prognosis of patients with acute type B aortic dissection is determined primarily by dissection-related and patient-specific risk factors, which are not readily modifiable. Whether the outlook in the future will be improved using stent-grafts remains to be determined.

  View details for PubMedID 12440677

• The effects of mitral annuloplasty rings on mitral valve complex 3-D geometry during acute left ventricular ischemia 37th Annual Meeting of the Society-of-Thoracic-Surgeons Lai, D. T., Timek, T. A., Tibayan, F. A., Green, G. R., Daughters, G. T., Liang, D., Ingels, N. B., Miller, D. C. ELSEVIER SCIENCE BV. 2002: 808–16

  Abstract

  Annuloplasty rings are used to treat ischemic mitral regurgitation (IMR), but their exact effects on 3-D geometry of the overall mitral valve complex during acute left ventricular (LV) ischemia remain unknown.Radiopaque markers were sutured to the mitral leaflet edges, annulus, papillary muscle tips, and ventricle in three groups of sheep. One group served as control (n = 5), and the others underwent Duran (n = 6) or Physio (n = 5) ring annuloplasty. One week later, 3-D marker coordinates at end-systole were obtained before and during balloon occlusion of the circumflex artery.In all control animals, acute LV ischemia was associated with: (i) septal-lateral separation of the leaflet edges, which was predicted by lateral displacement of the lateral annulus during septal-lateral mitral annular dilatation; (ii) apical restriction of the posterior leaflet edge, which was predicted by displacement of the lateral annulus away from the non-ischemic anterior papillary muscle; (iii) displacement of the posterior papillary muscle, which was not predictive of either septal-lateral leaflet separation or leaflet restriction; and (iv) mitral regurgitation. In the Duran group during ischemia, the posterior leaflet edge shifted posteriorly due to posterior movement of the lateral annulus, but no IMR occurred. In the Physio group during ischemia, neither the posterior leaflet edge nor the lateral annulus changed positions, and there was no IMR. In both the Duran and Physio groups, displacement of the posterior papillary muscle did not lead to IMR.Either annuloplasty ring prevented the perturbations of mitral leaflet and annular--but not papillary muscle tip--3-D geometry during acute LV ischemia. By fixing the septal-lateral annular dimension and preventing lateral displacement of the lateral annulus, annuloplasty rings prevented systolic septal-lateral leaflet separation and posterior leaflet restriction, and no acute IMR occurred. The flexible ring allowed posterior displacement of the posterior leaflet edge and the lateral annulus, which was not observed with a semi-rigid ring.

  View details for PubMedID 12414050

• Stentless bioprosthetic aortic valve replacement after valve-sparing aortic root replacement JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Ikonomidis, J. S., Miller, D. C. 2002; 124 (4): 848-851

  View details for DOI 10.1067/mtc.2002.124396

  View details for PubMedID 12324750

• Will a partial posterior annuloplasty ring prevent acute ischemic mitral regurgitation? Circulation Timek, T. A., Dagum, P., Lai, D. T., Tibayan, F., Liang, D., Daughters, G. T., Hayase, M., Ingels, N. B., Miller, D. C. 2002; 106 (12): I33-I39

  Abstract

  Acute posterolateral ischemia in sheep results in ischemic mitral regurgitation (IMR). While complete ring annuloplasty prevents acute IMR, partial annuloplasty rings may offer a more physiologic repair, but are untested in animal models of IMR.Radiopaque markers were placed on the LV, mitral annulus (MA), and leaflets in 13 sheep. Seven sheep served as controls, and 6 had a St. Jude Tailor partial flexible ring implanted (29 mm in 5, 31 mm in 1). After 8+/-1 day, the animals were studied with biplane videofluoroscopy and echocardiography before and during acute posterolateral LV ischemia (balloon occlusion of circumflex artery). Mitral annular area (MAA), septal-lateral annular diameter (SL), annular perimeters, and leaflet edge separation were calculated from 3-D marker coordinates.The average degree of mitral regurgitation increased from 0.0+/-0.0 to 2.1+/-0.7 (P=0.0006) in the control group during acute ischemia but remained unchanged in the Tailor group (0.1+/-0.2 for both conditions). The change in MAA throughout the cardiac cycle before ischemia was 17+/-4% in control animals, but only 5+/-2% (P=0.0002) in the Tailor ring group. Unlike the control animals, there was no increase in MAA (5.4+/-0.8 and 5.5+/-0.7 cm(2), respectively; p=NS) nor dilatation of the muscular annulus (6.2+/-0.3 and 6.2+/-0.4, respectively; p=NS) during ischemia with the Tailor ring. Mitral SL dimension increased slightly with ischemia (2.3+/-0.2 versus 2.2+/-0.2 cm, P=0.03). Although posterior leaflet motion was limited, as observed with complete rings, normal annular flexion was maintained with the Tailor ring before and during acute ischemia.The Tailor partial annuloplasty ring prevented acute IMR probably by limiting SL diameter dilatation during acute ischemia. In this animal model of acute IMR, a partial, flexible posterior annuloplasty ring is as effective as a complete ring.

  View details for PubMedID 12354706

• Mechanistic insights into posterior mitral leaflet inter-scallop malcoaptation during acute ischemic mitral regurgitation CIRCULATION Lai, D. T., Tibayan, F. A., Myrmel, T., Timek, T. A., Dagum, P., Daughters, G. T., Liang, D., Ingels, N. B., Miller, C. 2002; 106 (13): I40-I45

  Abstract

  Three-dimensional dynamics of the 3 individual scallops within the posterior mitral leaflet during acute ischemic mitral regurgitations have not been previously measured.Radiopaque markers were sutured to the mitral annulus, papillary muscle tips, and leaflet edges in 13 sheep. Immediately postoperatively, under open-chest conditions, 3-D marker coordinates were obtained using high-speed biplane videofluoroscopy before and during echocardiographically verified acute ischemic mitral regurgitation produced by occlusion of the left circumflex coronary artery.During acute ischemic mitral regurgitation, at end systole, the anterolateral edge of the central scallop was displaced 0.8+/-0.9 mm laterally and 0.9+/-0.6 mm apically away from the anterolateral scallop; such displacement correlated with lateral displacement of the lateral annulus (R(2)=0.7, SEE=0.7 mm, P<0.001) and movement of the right lateral annulus away from the nonischemic anterior papillary tip (R(2)=0.6, SEE=0.8 mm, P=0.002), respectively. End-systolic displacement of the posteromedial edge of the central scallop was 1.4+/-0.9 mm anteriorly and 0.9+/-0.6 mm laterally away from the posteromedial scallop, corresponding to anterior displacement of the mid-lateral annulus (R(2)=0.5, SEE=1.0 mm, P<0.001).Malcoaptation of the scallops within the posterior leaflet during acute left ventricular ischemia is a novel observation. The primary geometric mechanism underlying scallop malcoaptation in acute ischemic mitral regurgitation was annular dilatation, which hindered leaflet coaptation by drawing the individual scallops apart. These findings support the use of annular reduction in the repair of ischemic mitral regurgitation and also suture closure of prominent subcommissures between posterior leaflet scallops.

  View details for DOI 10.1161/01.cir.0000032874.55215.82

  View details for Web of Science ID 000178318900009

• Will a partial posterior annuloplasty ring prevent acute ischemic mitral regurgitation? 74th Annual Scientific Sessions of the American-Heart-Association Timek, T. A., Dagum, P., Lai, D. T., Tibayan, F., Liang, D., Daughters, G. T., Hayase, M., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2002: I33–I39

  Abstract

  Acute posterolateral ischemia in sheep results in ischemic mitral regurgitation (IMR). While complete ring annuloplasty prevents acute IMR, partial annuloplasty rings may offer a more physiologic repair, but are untested in animal models of IMR.Radiopaque markers were placed on the LV, mitral annulus (MA), and leaflets in 13 sheep. Seven sheep served as controls, and 6 had a St. Jude Tailor partial flexible ring implanted (29 mm in 5, 31 mm in 1). After 8+/-1 day, the animals were studied with biplane videofluoroscopy and echocardiography before and during acute posterolateral LV ischemia (balloon occlusion of circumflex artery). Mitral annular area (MAA), septal-lateral annular diameter (SL), annular perimeters, and leaflet edge separation were calculated from 3-D marker coordinates.The average degree of mitral regurgitation increased from 0.0+/-0.0 to 2.1+/-0.7 (P=0.0006) in the control group during acute ischemia but remained unchanged in the Tailor group (0.1+/-0.2 for both conditions). The change in MAA throughout the cardiac cycle before ischemia was 17+/-4% in control animals, but only 5+/-2% (P=0.0002) in the Tailor ring group. Unlike the control animals, there was no increase in MAA (5.4+/-0.8 and 5.5+/-0.7 cm(2), respectively; p=NS) nor dilatation of the muscular annulus (6.2+/-0.3 and 6.2+/-0.4, respectively; p=NS) during ischemia with the Tailor ring. Mitral SL dimension increased slightly with ischemia (2.3+/-0.2 versus 2.2+/-0.2 cm, P=0.03). Although posterior leaflet motion was limited, as observed with complete rings, normal annular flexion was maintained with the Tailor ring before and during acute ischemia.The Tailor partial annuloplasty ring prevented acute IMR probably by limiting SL diameter dilatation during acute ischemia. In this animal model of acute IMR, a partial, flexible posterior annuloplasty ring is as effective as a complete ring.

  View details for DOI 10.1161/01.cir.0000032873.55215.4c

  View details for Web of Science ID 000178318900008

• Does profound hypothermic circulatory arrest improve survival in patients with acute type a aortic dissection? CIRCULATION Lai, D. T., Robbins, R. C., Mitchell, R. S., Moore, K. A., Oyer, P. E., Shumway, N. E., Reitz, B. A., Miller, D. C. 2002; 106 (13): I218-I228

  Abstract

  No evidence exists that profound hypothermic circulatory arrest (PHCA) improves survival or reduces the likelihood of distal aortic reoperation in patients with acute type A aortic dissection.Records of 307 patients with acute type A aortic dissection from 1967 to 1999 were retrospectively reviewed. The influence of repair using PHCA (n=121) versus without PHCA (n=186) on death and freedom from distal aortic reoperation was analyzed using multivariable Cox regression models. Propensity score analysis identified a subset of 152 comparable patients in 3 quintiles (QIII-V) in which the effects of PHCA (n=113) versus no PHCA (n=39) were further compared.For all patients, 30-day, 1-year, and 5-year survival estimates were 81+/-2%, 74+/-3%, and 63+/-3% (+/-1 SE). Survival rates and actual freedom from distal aortic reoperation was not significantly different between treatment methods in the entire patient cohort nor in the matched patients in quintiles III-V. Treatment method was not associated with differences in early major complications, late survival, or distal aortic reoperation rates in the entire patient sample or in quintiles III-V.Aortic repair with or without circulatory arrest was associated with comparable early complications, survival, and distal aortic reoperation rates in patients with acute type A aortic dissection. Despite the lack of concrete evidence favoring the use of PHCA, it does no harm, and most of our group uses PHCA regularly because of its practical technical advantages and theoretical potential merit.

  View details for DOI 10.1161/01.cir.000032890.55215.27

  View details for Web of Science ID 000178318900039

• Mechanistic insights into posterior mitral leaflet inter-scallop malcoaptation during acute ischemic mitral regurgitation. Circulation Lai, D. T., Tibayan, F. A., Myrmel, T., Timek, T. A., Dagum, P., Daughters, G. T., Liang, D., Ingels, N. B., Miller, D. C. 2002; 106 (12): I40-I45

  Abstract

  Three-dimensional dynamics of the 3 individual scallops within the posterior mitral leaflet during acute ischemic mitral regurgitations have not been previously measured.Radiopaque markers were sutured to the mitral annulus, papillary muscle tips, and leaflet edges in 13 sheep. Immediately postoperatively, under open-chest conditions, 3-D marker coordinates were obtained using high-speed biplane videofluoroscopy before and during echocardiographically verified acute ischemic mitral regurgitation produced by occlusion of the left circumflex coronary artery.During acute ischemic mitral regurgitation, at end systole, the anterolateral edge of the central scallop was displaced 0.8+/-0.9 mm laterally and 0.9+/-0.6 mm apically away from the anterolateral scallop; such displacement correlated with lateral displacement of the lateral annulus (R(2)=0.7, SEE=0.7 mm, P<0.001) and movement of the right lateral annulus away from the nonischemic anterior papillary tip (R(2)=0.6, SEE=0.8 mm, P=0.002), respectively. End-systolic displacement of the posteromedial edge of the central scallop was 1.4+/-0.9 mm anteriorly and 0.9+/-0.6 mm laterally away from the posteromedial scallop, corresponding to anterior displacement of the mid-lateral annulus (R(2)=0.5, SEE=1.0 mm, P<0.001).Malcoaptation of the scallops within the posterior leaflet during acute left ventricular ischemia is a novel observation. The primary geometric mechanism underlying scallop malcoaptation in acute ischemic mitral regurgitation was annular dilatation, which hindered leaflet coaptation by drawing the individual scallops apart. These findings support the use of annular reduction in the repair of ischemic mitral regurgitation and also suture closure of prominent subcommissures between posterior leaflet scallops.

  View details for PubMedID 12354707

• Hemodynamic performance of an unstented xenograft mitral valve substitute JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Timek, T. A., Lai, D. T., Tibayan, F. A., Dagum, P., Daughters, T., Liang, D., Ingels, N. B., Miller, D. C. 2002; 124 (3): 541-552

  Abstract

  Stentless mitral xenografts offer potential clinical benefits because they mimic the normal bileaflet mitral valve. How best to implant them and their hemodynamic performance and durability, however, remain unknown.A stentless porcine mitral xenograft valve (Medtronic physiologic mitral valve) was implanted in 7 sheep with papillary muscle sewing tubes attached with transmural left ventricular sutures. Radiopaque markers were inserted on the leaflets, annular cuff, papillary tips, and left ventricle. After 10 +/- 5 days, the animals were studied with biplane videofluoroscopy to determine 3-dimensional marker coordinates at baseline and during dobutamine infusion. Transesophageal echocardiography assessed mitral regurgitation and valvular gradients. Mitral annular area was calculated from the annular markers. Physiologic mitral valve leaflet and annular dynamics were compared with 8 native sheep valves.Average mitral regurgitation grade at baseline was 1.2 +/- 1.0 (range, 0-4), and the mean transvalvular pressure gradients were 3.6 +/- 1.3 and 6.2 +/- 2.2 mm Hg during baseline and dobutamine infusion, respectively. Xenograft mitral annular area contraction throughout the cardiac cycle was reduced (6% +/- 6% vs 13% +/- 4% for physiologic mitral valve and control valve, respectively; P =.03). Physiologic mitral valve leaflet geometry during closure differed from the native valve, with the anterior leaflet being convex to the atrium and with little motion of the posterior leaflet. Three animals survived more than 3 months; good healing of the annular cuff and papillary muscle tubes was demonstrated.This stentless xenograft mitral valve substitute had low gradients at baseline and during stress conditions early postoperatively, with mild mitral regurgitation. Preliminary analysis of healing characteristics appeared favorable at 3 months. Additional studies are needed to determine long-term xenograft mitral valve performance and resistance to calcification.

  View details for DOI 10.1067/mtc.2002.124390

  View details for PubMedID 12202871

• Alterations in left ventricular torsion in tachycardia-induced dilated cardiomyopathy JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Tibayan, F. A., Lai, D. T., Timek, T. A., Dagum, P., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. 2002; 124 (1): 43-49

  Abstract

  Left ventricular torsion reduces transmural systolic gradients of fiber strain, and torsional recoil in early diastole is thought to enhance left ventricular filling. Left ventricular remodeling in dilated cardiomyopathy may result in changes in torsion dynamics, but these effects are not yet characterized. Tachycardia-induced cardiomyopathy is accompanied by systolic and diastolic heart failure and left ventricular remodeling. We hypothesized that cardiomyopathy would alter systolic and diastolic left ventricular torsion mechanics, and this hypothesis was tested by studying sheep before and after the development of tachycardia-induced cardiomyopathy.Implanted miniature radiopaque markers were used in 8 sheep to measure left ventricular geometry and function, maximal torsional deformation, and early diastolic recoil before and after rapid ventricular pacing was used to create tachycardia-induced cardiomyopathy.All animals had significant heart failure with ventricular dilatation and remodeling. With tachycardia-induced cardiomyopathy, maximum torsion relative to control conditions decreased (1.69 degrees +/- 0.61 degrees vs 4.25 degrees +/- 2.33 degrees ), and early diastolic recoil was completely abolished (0.53 degrees +/- 1.19 degrees vs -1.17 degrees +/- 0.94 degrees ).Cardiomyopathy is accompanied by decreased and delayed systolic left ventricular torsional deformation and loss of early diastolic recoil, which may contribute to left ventricular dysfunction by increasing systolic transmural strain gradients and impairing diastolic filling. Analysis of left ventricular torsion with radiofrequency-tagging magnetic resonance imaging should be explored to elucidate the role of torsion in patients with cardiomyopathy.

  View details for DOI 10.1067/mtc.2002.121299

  View details for PubMedID 12091807

• A simple trick for repairing coronary pseudoaneurysm complicating a Bentall operation ANNALS OF THORACIC SURGERY Schmoker, J. D., Miller, D. C. 2002; 74 (1): 268–70

  Abstract

  Coronary pseudoaneurysms are a known complication of the Bentall wrap-inclusion method of composite valve grafting. We describe two cases to illustrate a straightforward technique for repair and prevention of coronary pseudoaneurysm formation.

  View details for DOI 10.1016/S0003-4975(02)03543-9

  View details for Web of Science ID 000176622500074

  View details for PubMedID 12118785

• Randomized trial comparing partial versus complete chordal-sparing mitral valve replacement: Effects on left ventricular volume and function 27th Annual Meeting of the Western-Thoracic-Surgical-Association Yun, K. L., Sintek, C. F., Miller, D. C., Pfeffer, T. A., Kochamba, G. S., Khonsari, S., Zile, M. R. MOSBY-ELSEVIER. 2002: 707–14

  Abstract

  The merits of retaining the subvalvular apparatus during mitral valve replacement for chronic mitral regurgitation have been demonstrated in numerous retrospective clinical investigations but not in a randomized study. In this report we analyzed the early and late effects of complete versus partial chordal preservation on left ventricular mechanics.Forty-seven patients undergoing isolated surgical correction of mitral insufficiency were prospectively randomized to either total or partial chordal-sparing mitral valve replacement. Complete data from 36 patients were available for analysis. Of these individuals, 15 had preservation of the posterior leaflet only (P-MVR group), and 21 had complete preservation of all chordal structures (C-MVR group). Echocardiography was performed preoperatively, at the time of discharge, and after 1 year to determine dimensions, wall stress, left ventricular mass, and ejection function.End-diastolic volume decreased in both groups initially but continued to decline only in the C-MVR cohort. Similarly, although end-systolic volume decreased over time with total chordal preservation, no notable changes were observed in the P-MVR group. In the C-MVR group, end-systolic stress decreased initially but rose slightly by 1 year. In contrast, end-systolic stress remained unchanged at discharge in the P-MVR group and increased at 1 year. In terms of systolic performance, ejection fraction declined after surgical intervention with partial chordal-sparing techniques and did not improve by 1 year. Ejection fraction returned to the preoperative level after an initial decrease in the C-MVR group. Finally, left ventricular mass was reduced in the C-MVR cohort versus no change in the P-MVR group.Complete retention of the mitral subvalvular apparatus during mitral valve replacement confers a significant early advantage by reducing left ventricular chamber size and systolic afterload compared with partial chordal preservation. Furthermore, left ventricular ejection performance continues to improve over time, probably because of more favorable left ventricular remodeling.

  View details for DOI 10.1067/mtc.2002.121048

  View details for Web of Science ID 000175400100015

  View details for PubMedID 11986599

• Mitral annular dynamics and LV diastolic filling Tibayan, F. A., Karlsson, M., Rodriguez, F., Glasson, J., Daughters, G., Miller, D. C., Ingels, N. B. FEDERATION AMER SOC EXP BIOL. 2002: A1127

  View details for Web of Science ID 000174593902222

• Septal-lateral annular cinching ('SLAC') reduces mitral annular size without perturbing normal annular dynamics 1st Biennial Meeting of the Society-for-Heart-Valve-Disease Timek, T. A., Lai, D. T., Tibayan, F. A., Daughters, G. T., Liang, D., Dagum, P., Ingels, N. B., Miller, D. C. I C R PUBLISHERS. 2002: 2–9

  Abstract

  Septal-lateral (S-L) mitral annular diameter reduction is thought to be central to the efficacy of ring annuloplasty in correcting functional mitral regurgitation (MR), but rings perturb mitral annulus (MA) dynamic motion and limit posterior leaflet excursion. The effects of S-L annular cinching ('SLAC'), a novel method for mitral annular reduction, were investigated.Eight adult sheep had multiple radioopaque markers placed on the left ventricle, leaflet edges, and around the MA. The S-L trans-annular suture was anchored to the mid-septal MA and externalized through the mid-lateral MA and left ventricular wall. Animals were studied immediately postoperatively with biplane videofluoroscopy before and after suture cinching to reduce annular size. MA area (MAA) and S-L dimension were calculated throughout the cardiac cycle from the annular marker coordinates. MAA contraction (AMAA) was expressed as percentage decrease from maximum to minimum MAA. Anterior (AML) and posterior (PML) leaflet angular excursion were calculated as the change in angle between each leaflet edge marker and the S-L annular dimension during the cardiac cycle. MA folding was calculated as the change in distance during systole of the mid-septal annular marker from a plane fitted to the lateral MA markers.SLAC reduced end-diastolic (ED) S-L diameter (21.6+/-2.8 versus 17.1+/-2.6 mm; p = 0.0005) and ED MAA (618+/-126 versus 525+/-114 mm2; p = 0.0004), but did not perturb normal AMAA (15.8+/-4.1 versus 15.1+/-4.8%; p = 0.4), annular flexion (2.0+/-0.7 versus 1.8+/-0.7 mm; p = 0.3) or AML excursion (55+/-7 versus 53+/-7 degrees; p = 0.1). PML excursion was decreased only slightly (52+/-11 versus 44+/-12 degrees; p = 0.002).SLAC substantially reduced S-L annular size, but without perturbing normal MA contraction dynamics, MA flexion, or anterior leaflet excursion. This novel surgical method might represent an alternative to mitral annuloplasty for patients with certain types of mitral pathology.

  View details for PubMedID 11843501

• Ischemic mitral regurgitation redux - To repair or to replace? JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Miller, D. C. 2001; 122 (6): 1059–62

  View details for DOI 10.1067/mtc.2001.120341

  View details for Web of Science ID 000172724600001

  View details for PubMedID 11726880

• Three-dimensional in-vivo dimensions of 'He's triangle' during acute left ventricular ischemia 1st Biennial Meeting of the Society-for-Heart-Valve-Disease Lai, D. T., Tibayan, F. A., Timek, T. A., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. I C R PUBLISHERS. 2001: 767–73

  Abstract

  Changes in the dimensions of 'He's triangle' (formed by mitral leaflet segments subtending two associated chordae tendineae) derived from data obtained in in-vitro mitral valve models have been proposed to provide a mechanistic explanation for mitral leaflet malcoaptation. The in-vivo dynamics of He's triangle, however, have not been hitherto determined.Radio-opaque markers were placed in 13 sheep to delineate the mitral annulus and four (of an infinite number of possible) He's triangles formed by: (i) the anterior mitral leaflet (AML), first- (CT1) and second-order (CT2) chordae tendineae emanating from the anterior papillary tip (APT1) as well as from the posterior papillary tip (PPT1), respectively; and (ii) the posterior mitral leaflet (PML), CT1 and CT2 emanating from other loci on the anterior as well as the posterior papillary tips (APT2 and PPT2), respectively. Immediately postoperatively (anesthetized, open-chest), three-dimensional end-systolic marker positions were measured before and during circumflex coronary artery occlusion sufficient to produce mitral regurgitation, as verified by echocardiography.During ischemia, three leaflet segments constituting one side of three He's triangles elongated: The AML attached to APT1 and to PPT1 by 1.5+/-1.2 mm (p <0.001) and 1.3+/-0.8 mm (p <0.001), respectively, and the posterior leaflet attached to APT2 by 1.4+/-1.9 mm (p = 0.02). Apart from a 0.9+/-1.1 mm (p = 0.02) increase in the length of CT2 attached to APT2, the length of the seven other CT1 and CT2 remained relatively unchanged during acute left ventricular ischemia.With acute posterolateral ischemia, the lengths of CT1 and CT2 remained relatively constant, but the AML and PML lengths were not constant as the AML and PML 'unfurled' during acute left ventricular ischemia. These geometric changes may provide further insight into the mechanisms of acute ischemic mitral regurgitation, though it is not clear how they will be clinically helpful.

  View details for PubMedID 11767184

• Does hypothermic circulatory arrest (PHCA) improve survival in patients with acute type A aortic dissection? Lai, D. T., Robbins, R. C., Mitchell, R. S., Moore, K. A., Oyer, P. E., Shumway, N. E., Reitz, B. A., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2001: 524–24

  View details for Web of Science ID 000171895002459

• Three-dimensional geometric comparison of partial and complete flexible mitral annuloplasty rings JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Dagum, P., Timek, T., Green, G. R., Daughters, G. T., Liang, D., Ingels, N. B., Miller, D. C. 2001; 122 (4): 665-673

  Abstract

  It has previously been shown in sheep that mitral annular physiologic dynamics during the cardiac cycle are abolished by complete ring annuloplasty, but recent clinical studies suggest that flexible partial ring annuloplasty preserves normal mitral annular dynamics.Eight radiopaque markers were sutured equidistantly around the mitral anulus in 3 groups of sheep: no-ring control animals (n = 16); animals with a flexible Tailor partial ring annuloplasty (n = 6; St Jude Medical, Inc, St Paul, Minn); and animals with a flexible Duran ring annuloplasty (n = 7; Medtronic, Inc, Minneapolis, Minn). After 7 to 10 days' recovery, 3-dimensional marker coordinates were measured by biplane cinefluoroscopy. Mitral annular area and folding (defined as displacement of the mitral anulus from a least-squares plane) and mitral annular septal-lateral and commissure-commissure dimensions were calculated from the 3-dimensional marker coordinates throughout the cardiac cycle every 17 ms.In the no-ring control group mitral annular area varied from 8.0 +/- 0.2 to 7.2 +/- 0.2 cm(2) (10% +/- 2%), and the septal-lateral and commissure-commissure dimensions varied from 27.7 +/- 0.4 to 25.9 +/- 0.4 mm (7% +/- 1%) and from 38.2 +/- 0.8 to 36.4 +/- 0.8 mm (5% +/- 1%), respectively (mean +/- standard error of the mean, P <.001 for all comparisons). In the Duran ring annuloplasty and Tailor partial ring annuloplasty groups, the anulus was fixed in size throughout the cardiac cycle (area = 4.8 +/- 0.1 and 5.3 +/- 0.3 cm(2), septal-lateral = 21.8 +/- 0.7 and 22.0 +/- 0.8 mm, and commissure-commissure = 27.7 +/- 0.7 and 31.2 +/- 1.7 mm). Mitral annular folding did not differ significantly between the control and Tailor partial ring annuloplasty groups but was dampened in the Duran ring annuloplasty group.Partial Tailor flexible ring annuloplasty fixed mitral annular area and dimensions throughout the cardiac cycle in sheep; however, it preserved physiologic mitral annular folding dynamics, which might be important in terms of long-term valve function and prevention of left ventricular outflow tract obstruction.

  View details for PubMedID 11581596

• Aprotinin, blood loss, and renal dysfunction in deep hypothermic circulatory arrest CIRCULATION Mangano, C. T., Neville, M. J., Hsu, P. H., Mignea, I., KING, J., Miller, D. C. 2001; 104 (12): I276-I281

  Abstract

  The technique of deep hypothermic circulatory arrest (DHCA) for cardiothoracic surgery is associated with increased risk for perioperative blood loss and renal dysfunction. Although aprotinin, a serine protease inhibitor, reduces blood loss in patients undergoing cardiopulmonary bypass, its use has been limited in the setting of DHCA because of concerns regarding aprotinin-induced renal dysfunction. Therefore, we assessed the affect of aprotinin on both blood transfusion requirements and renal function in patients undergoing cardiovascular surgery and DHCA.We reviewed the records of 853 patients who underwent aortic or thoracoabdominal surgery at Stanford University Medical Center between January 1992 and March 2000. Two hundred three of these patients were treated with DHCA, and 90% (183) survived for more than 24 hours. Preoperative patient characteristics and intraoperative and postoperative clinical and surgical variables were recorded, and creatinine clearance (CRCl) was calculated for the preoperative and postoperative periods; renal dysfunction was prospectively defined as a 25% reduction in CRCl. The association between perioperative variables, including aprotinin use, and renal dysfunction was assessed by ANOVA techniques. Total urine output was 1294+/-1024 mL and 3492+/-1613 mL during and after surgery, respectively. CRCl decreased significantly after DHCA from 86+/-8 mL/min (before surgery) to 67+/-4 mL/min (in the intensive care unit) (P<0.01). Thirty-eight percent of patients (70 of 183) had postoperative renal dysfunction. Multivariate regression analyses identified 5 factors independently associated with a >25% reduction in CRCl: requirement for >/=5 U of packed red blood cells(P=0.0002; OR=2.1),

  View details for PubMedID 11568069

• Pathogenesis of mitral regurgitation in tachycardia-induced cardiomyopathy CIRCULATION Timek, T. A., Dagum, P., Lai, D. T., Liang, D., Daughters, G. T., Ingels, N. B., Miller, D. C. 2001; 104 (12): I47-I53

  Abstract

  Dilated cardiomyopathy is often associated with mitral regurgitation (MR), or so-called functional MR, the mechanism of which continues to be debated. We studied the valvular and ventricular 3D geometric perturbations associated with MR in an ovine model of tachycardia-induced cardiomyopathy (TIC).Nine sheep underwent myocardial marker implantation in the left ventricle (LV), mitral annulus, and mitral leaflets. After 5 to 8 days, the animals were studied with biplane videofluoroscopy (baseline), and mitral competence was assessed by transesophageal echocardiography. Rapid ventricular pacing (180 to 230 bpm) was subsequently initiated for 15+/-6 days until the development of TIC and MR, whereupon biplane videofluoroscopy and transesophageal echocardiography studies were repeated. LV volume was calculated from the epicardial marker array. Valve closure time was defined as the time after end diastole when the distance between leaflet edge markers reached its minimal plateau. TIC resulted in increased LV end-diastolic volume (P=0.001) and LV end-systolic volume (P=0.0001) and greater LV sphericity (P=0.02). MR increased significantly (grade 0.2+/-0.3 versus 2.2+/-0.9, P=0.0001), as did mitral annulus area (817+/-146 versus 1100+/-161 mm(2), P=0.0001) and mitral annulus septal-lateral diameter (28.2+/-3.5 versus 35.1+/-2.6 mm, P=0.0001). Time of valve closure (70+/-18 versus 87+/-14 ms, P=0.23) and angular displacement of both the anterior (29+/-5 degrees versus 27+/-3 degrees, P=0.3) and posterior (55+/-15 degrees versus 44+/-11 degrees, P=0.13) leaflet edges relative to the mitral annulus after valve closure did not change, but leaflet edge separation after closure increased (5.2+/-0.9 versus 6.8+/-1.2 mm, P=0.019).MR in TIC resulted from decreased leaflet coaptation secondary to annular dilatation in the septal-lateral direction. These data support the use of annular reduction procedures, such as rigid, complete ring annuloplasty, to address functional MR in patients with dilated cardiomyopathy.

  View details for PubMedID 11568029

• Experimental and clinical assessment of mitral annular area and dynamics: What are we actually measuring? ANNALS OF THORACIC SURGERY Timek, T. A., Miller, D. C. 2001; 72 (3): 966-974

  Abstract

  The mitral annulus is an essential, dynamic, and tightly coupled component of the mitral valve/left atrial/left ventricular complex that aids in effective and efficient valve closure and unimpeded left ventricular filling. Although the dynamic nature of mitral annular motion has been studied carefully for more than 30 years, accurate measurement of mitral annular area and motion continues to be a challenge for physiologists and clinicians alike. Roentgenographic ciné imaging of radiopaque markers, sonomicrometry, magnetic resonance imaging, and two-dimensional echocardiography have all been used to evaluate mitral annular area and dynamics, yet widely disparate measurements abound. Paradoxically, newer three-dimensional transesophageal echocardiographic findings may have added to this miasma. To explore the variability of these measurements, we reviewed our experimental data as well as clinical and experimental observations reported in the literature to clarify what we are actually measuring and perhaps explain the reported disagreement. The objective was to shed some light on the possible reasons for these discordant findings.

  View details for PubMedID 11565706

• Resection of ascending aortic aneurysm without use of an interposition aortic graft JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Ikonomidis, J. S., DeAnda, A., Miller, D. C. 2001; 122 (2): 395-397

  View details for PubMedID 11479521

• Influence of anterior mitral leaflet second-order chordae on leaflet dynamics and valve competence ANNALS OF THORACIC SURGERY Timek, T. A., Nielsen, S. L., Green, G. R., Dagum, P., Bolger, A. F., Daughters, G. T., Hasenkam, J. M., Ingels, N. B., Miller, D. C. 2001; 72 (2): 535-540

  Abstract

  Chordal transposition is used in mitral valve repair, yet the effects of second-order chord transection on valve function have not been extensively studied. We evaluated leaflet coaptation, three-dimensional anterior mitral valve leaflet shape, and valve competence after cutting anterior second-order chordae.In 8 sheep radiopaque markers were affixed to the left ventricle, mitral annulus, and leaflets. Animals were studied immediately with biplane videofluoroscopy and echocardiography before (Control) and after (Cut2) severing two anterior second-order "strut" chordae. Leaflet coaptation was assessed as separation between leaflet edge markers in the midleaflet and near each commissure (anterior commissure, posterior commissure). Anterior leaflet geometry was determined 100 milliseconds after end-diastole from three-dimensional coordinates of 13 markers.Anterior leaflet geometry changed only slightly after chordal transection without inducing mitral regurgitation. Leaflet coaptation times were 79+/-17 and 87+/-22 milliseconds at the anterior commissure; 72+/-21, 72+/-19 milliseconds at midleaflet, and 71+/-12 and 75+/-8 milliseconds at the posterior commissure (p = NS) for Control and Cut2, respectively.Cutting anterior second-order chordae did not cause delayed leaflet coaptation, alter leaflet shape, or create mitral regurgitation. These data indicate that transposition of second-order anterior chordae ("strut" chordae) is not deleterious to anterior leaflet motion per se.

  View details for PubMedID 11515894

• The role of atrial contraction in mitral valve closure JOURNAL OF HEART VALVE DISEASE Timek, T., Dagum, P., Lai, D. T., Green, G. R., Glasson, J. R., Daughters, G. T., Ingels, N. B., Miller, D. C. 2001; 10 (3): 312-319

  Abstract

  Ovine mitral valve closure is associated with presystolic mitral annular reduction coincident with atrial contraction, which is abolished with ventricular pacing. Whether lack of properly timed atrial contraction influences mitral valve closure or competence, however, is not known.Eight sheep underwent myocardial marker implantation on the left ventricle, mitral annulus (MA), and mitral leaflets. After 7-10 days, the animals were studied with biplane videofluoroscopy at baseline and during ventricular or atrioventricular (AV) sequential pacing. Valve closure was timed from end-diastole (ED) and defined as minimum distance between two leaflet edge markers. ED was defined as peak of ECG R wave, end-systole as peak negative left ventricular (LV) dP/dt, and end-isovolumic contraction (EIVC) as 83.5 ms after ED. Septal-lateral (S-L) annular diameter was defined as distance between two markers at the middle of the anterior and posterior annulus. Regurgitant volume (RV) was calculated as relative volume change between ED and EIVC.V-pacing was associated with delayed leaflet closure (65 +/- 5 versus 29 +/- 10 ms, p = 0.008); moreover, RV (4.1 +/- 0.5 versus 1.4 +/- 0.5 ml, p = 0.02), end-diastolic S-L diameter (2.87 +/- 0.10 versus 2.67 +/- 0.09 cm, p = 0.0005), and MA area (8.12 +/- 0.37 versus 7.26 +/- 0.31 cm2, p = 0.009) all increased. RV and leaflet and annular dynamics during AV-pacing were similar to baseline.V-pacing increased S-L MA diameter by only 8 +/- 1%, but this change was associated with delayed leaflet coaptation and a 16 +/- 1% regurgitant fraction. These findings provide direct evidence that a properly timed atrial contraction is functionally important for effective mitral leaflet closure.

  View details for PubMedID 11380093

• Edge-to-edge mitral repair: gradients and three-dimensional annular dynamics in vivo during inotropic stimulation 14th Annual Meeting of the European-Association-for-Cardio-Thoracic-Surgery Timek, T. A., Nielsen, S. L., Liang, D., Lai, D. T., Dagum, P., Daughters, G. T., Ingels, N. B., Miller, D. C. ELSEVIER SCIENCE BV. 2001: 431–37

  Abstract

  The edge-to-edge (Alfieri) mitral repair technique appears to be clinically promising, but the potential for functional mitral stenosis, especially with exercise, remains a concern. We used the myocardial marker method combined with Doppler echocardiography to evaluate mitral annular (MA) three-dimensional (3-D) dynamics and transvalvular gradients after leaflet approximation before and during dobutamine infusion.Eight adult sheep underwent implantation of eight myocardial markers around the MA and nine in the left ventricle. Mitral leaflet edges were approximated at the valve center and micromanometers were placed in the left ventricle and atrium. The animals were studied with biplane videofluoroscopy to determine 3-D marker coordinates for computation of precise 3-D MA area and left ventricular (LV) volume. Epicardial Doppler echocardiography measured peak and mean diastolic mitral valve gradients at baseline and during dobutamine infusion (10 microg/kg per min).During dobutamine stimulation, left ventricular dP/dt increased from 1776+/-712 to 3390+/-618 mmHg/s (P=0.002), and cardiac output (CO) increased from 2.7+/-1.1 to 5.1+/-1.2 l/min (P=0.009). Mitral annular area (MAA) at end-diastole (ED) fell from 8.6+/-1.4 to 7.0+/-1.8 cm(2) (P=0.001) with inotropic stimulation, but only a modest increase was observed in mean (1.4+/-0.4 vs. 2.4+/-1.0 mmHg, P=0.046) and peak (2.7+/-0.8 vs. 4.9+/-2.5 mmHg, P=0.03) diastolic mitral valve gradients. MAA changed dynamically throughout the cardiac cycle, reflecting normal physiology, but the magnitude of MAA change was augmented during inotropic stimulation (18+/-5% and 27+/-4% for control and dobutamine, respectively; P=0.004).Dobutamine increased CO by 89% and decreased ED annular area by 19% after edge-to-edge repair, yet only a small increase in valve gradient occurred. Marker analysis showed enhanced dynamic motion of the mitral annulus. Thus, the edge-to-edge mitral valve repair was not associated with substantial transvalvular obstruction during high flow conditions and did not perturb normal MA 3-D dynamics in normal ovine hearts.

  View details for PubMedID 11306308

• Treatment of endocarditis with valve replacement: The question of tissue versus mechanical prosthesis ANNALS OF THORACIC SURGERY Moon, M. R., Miller, D. C., Moore, K. A., Oyer, P. E., Mitchell, R. S., Robbins, R. C., Stinson, E. B., Shumway, N. E., Reitz, B. A. 2001; 71 (4): 1164-1171

  Abstract

  It remains unknown whether there is any important clinical advantage to the use of either a bioprosthetic or mechanical valve for patients with native or prosthetic valve endocarditis.Between 1964 and 1995, 306 patients underwent valve replacement for left-sided native (209 patients) or prosthetic (97 patients) valve endocarditis. Mechanical valves were implanted in 65 patients, bioprostheses in 221 patients, and homografts in 20 patients.Operative mortality was 18+/-2% and was independent of replacement valve type (p > 0.74). Long-term survival was superior for patients with native valve endocarditis (44+/-5% at 20 years) compared with those with prosthetic valve endocarditis (16+/-7% at 20 years) (p < 0.003). Survival was independent of valve type (p > 0.27). The long-term freedom from reoperation for patients who received a biologic valve who were younger than 60 years of age was low (51+/-5% at 10 years, 19+/-6% at 15 years). For patients older than 60 years, however, freedom from reoperation with a biological valve (84+/-7% at 15 years) was similar to that for all patients with mechanical valves (74+/-9% at 15 years) (p > 0.64).Mechanical valves are most suitable for younger patients with native valve endocarditis; however, tissue valves are acceptable for patients greater than 60 years of age with native or prosthetic valve infections and for selected younger patients with prosthetic valve infections because of their limited life expectancy.

  View details for PubMedID 11308154

• Cardiocyte cytoskeleton in patients with left ventricular pressure overload hypertrophy JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Zile, M. R., Green, G. R., Schuyler, G. T., Aurigemma, G. P., Miller, D. C., Cooper, G. 2001; 37 (4): 1080-1084

  Abstract

  We sought to determine whether the cardiocyte microtubule network densification characteristic of animal models of severe pressure overload cardiac hypertrophy occurs in human patients.In animal models of clinical entities causative of severe right and left ventricular (LV) pressure overload hypertrophy, increased density of the cellular microtubule network, through viscous loading of active myofilaments, causes contractile dysfunction that is normalized by microtubule depolymerization. These linked contractile and cytoskeletal abnormalities, based on augmented tubulin synthesis and microtubule stability, progress during the transition to heart failure.Thirteen patients with symptomatic aortic stenosis (AS) (aortic valve area = 0.6 +/- 0.1 cm2) and two control patients without AS were studied. No patient had aortic insufficiency, significant coronary artery disease or abnormal segmental LV wall motion. Left ventricular function was assessed by echocardiography and cardiac catheterization before aortic valve replacement. Left ventricular biopsies obtained at surgery before cardioplegia were separated into free and polymerized tubulin fractions before analysis. Midwall LV fractional shortening versus mean LV wall stress in the AS patients was compared with that in 84 normal patients.Four AS patients had normal LV function and microtubule protein concentration; six had decreased LV function and increased microtubule protein concentration, and three had borderline LV function and microtubule protein concentration, such that there was an inverse relationship of midwall LV fractional shortening to microtubule protein.In patients, as in animal models of severe LV pressure overload hypertrophy, myocardial dysfunction is associated with increased microtubules, suggesting that this may be one mechanism contributing to the development of congestive heart failure in patients with AS.

  View details for Web of Science ID 000167515700018

  View details for PubMedID 11263612

• Ablation of mitral myocardial muscle effect on annular and leaflet dynamics in the context of mitral repair Timek, T. A., Lai, D. T., Liang, D., Berry, G., Tibayan, F. A., Dagum, P., Daughters, G. T., Ingels, N. B., Miller, D. C. ELSEVIER SCIENCE INC. 2001: 480A

  View details for Web of Science ID 000166914402182

• Coordinate-free analysis of mitral valve dynamics in normal and ischemic hearts. Circulation Dagum, P., Timek, T. A., Green, G. R., Lai, D., Daughters, G. T., Liang, D. H., Hayase, M., Ingels, N. B., Miller, D. C. 2000; 102 (19): III62-9

  Abstract

  The purpose of this investigation was to study mitral valve 3D geometry and dynamics by using a coordinate-free system in normal and ischemic hearts to gain mechanistic insight into normal valve function, valve dysfunction during ischemic mitral regurgitation (IMR), and the treatment effects of ring annuloplasty.Radiopaque markers were implanted in sheep: 9 in the ventricle, 1 on each papillary tip, 8 around the mitral annulus, and 1 on each leaflet edge midpoint. One group served as a control (n=7); all others underwent flexible Tailor partial (n=5) or Duran complete (n=6) ring annuloplasty. After an 8+/-2-day recovery, 3D marker coordinates were measured with biplane videofluoroscopy before and during posterolateral left ventricular ischemia, and MR was assessed by color Doppler echocardiography. Papillary to annular distances remained constant throughout the cardiac cycle in normal hearts, during ischemia, and after ring annuloplasty with either type of ring. Papillary to leaflet edge distances similarly remained constant throughout ejection. During ischemia, however, the absolute distances from the papillary tips to the annulus changed in a manner consistent with leaflet tethering, and IMR was observed. In contrast, during ischemia in either ring group, those distances did not change from preischemia, and no IMR was observed.This analysis uncovered a simple pattern of relatively constant intracardiac distances that describes the 3D geometry and dynamics of the papillary tips and leaflet edges from the dynamic mitral annulus. Ischemia perturbed the papillary-annular distances, and IMR occurred. Either type of ring annuloplasty prevented such changes, preserved papillary-annular distances, and prevented IMR.

  View details for PubMedID 11082364

• Coordinate-free analysis of mitral valve dynamics in normal and ischemic hearts CIRCULATION Dagum, P., Timek, T. A., Green, G. R., Lai, D., Daughters, G. T., Liang, D. H., Hayase, M., Ingels, N. B., Miller, D. C. 2000; 102 (19): 62-69

  View details for Web of Science ID 000165177300012

• The effects of ring annuloplasty on mitral leaflet geometry during acute left ventricular ischemia 80th Annual Meeting of the American-Association-for-Thoracic-Surgery Lai, D. T., Timek, T. A., Dagum, P., Green, G. R., Glasson, J. R., Daughters, G. T., Liang, D., Ingels, N. B., Miller, D. C. MOSBY-ELSEVIER. 2000: 966–75

  Abstract

  The perturbed mitral leaflet geometry that leads to acute ischemic mitral regurgitation during acute left ventricular ischemia has not been quantified, nor is it known whether annuloplasty rings affect these detrimental changes in leaflet geometry.Radiopaque markers were implanted on both mitral leaflets and around the anulus in 3 groups of sheep: one group without rings served as the control group (n = 7); the others underwent Duran (n = 6; Medtronic Heart Valve Division, Minneapolis, Minn) or Carpentier-Edwards Physio (n = 5; Baxter Cardiovascular Division, Santa Ana, Calif) ring annuloplasty. After recovery, 3-dimensional marker coordinates were obtained by means of biplane videofluoroscopy before and during acute posterolateral left ventricular ischemia. Leaflet geometry was defined by measuring distances between annular and leaflet markers and perpendicular distances to the leaflet markers from a best-fit annular plane.In all control animals, left ventricular ischemia was associated with acute ischemic mitral regurgitation and apical displacement (away from the annular plane) of the posterior leaflet edge and base markers by 0.6 +/- 0.4 mm (P =.01) and 0.7 +/- 0.2 mm (P <.001), respectively. The distance between the posterior leaflet markers and the mid-posterior anulus did not change significantly during ischemia. The anterior leaflet edge marker extended 1.0 +/- 0. 5 mm (P =.01) away from the mid-anterior anulus during ischemia, but compared with its nonischemic position, the anterior leaflet was not displaced apically away from the annular plane. In all animals in the Duran and Physio groups, leaflet geometry was unchanged during ischemia, and acute ischemic mitral regurgitation was not detected.Acute ischemic mitral regurgitation was associated with restricted motion of the posterior leaflet and extension of the anterior leaflet. Annuloplasty rings prevented these geometric perturbations of the mitral leaflets during acute left ventricular ischemia and preserved valvular competence.

  View details for PubMedID 11044323

• Timing and location of acute ischemic mitral regurgitation in sheep Timek, T. A., Lai, D. T., Liang, D. H., Lo, S. T., Daughters, G. T., Ingels, N. B., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2000: 530–31

  View details for Web of Science ID 000090072302574

• Endovascular repair of abdominal aortic aneurysms: Eligibility rate and impact on the rate of open repair JOURNAL OF VASCULAR SURGERY Wolf, Y. G., Fogarty, T. J., Olcott, C., Hill, B. B., Harris, E. J., Mitchell, R. S., Miller, D. C., Dalman, R. L., Zarins, C. K. 2000; 32 (3): 519-523

  Abstract

  The purpose of this study was to determine the rate of eligibility among patients with abdominal aortic aneurysms (AAAs) considered for endovascular repair and to examine the effect of an endovascular program on the institutional pattern of AAA repair.All patients evaluated for endovascular AAA repair since the inception of an endovascular program were reviewed for determination of eligibility rates and eventual treatment. Open AAA repairs were categorized as simple (uncomplicated infrarenal), complex (juxtarenal, suprarenal, thoracoabdominal, infected), or ruptured, and their rates before and after initiation of an endovascular program were compared.Over 3 years, 324 patients were considered for endovascular AAA repair; 176 (54%) were candidates, 138 (43%) were not candidates, and 10 (3%) did not complete the evaluation. The rate of eligibility increased significantly from 45% (66/148 patients) during the first half of this period to 63% (110/176 patients) during the second half (P <. 001). Candidates were significantly younger (74.4 +/- 7.6 years) than noncandidates (78.3 +/- 6.7 years) (P <.01), and their aneurysm diameter tended to be smaller (57.6 +/- 9.2 mm compared with 60.8 +/- 12.3 mm; P =.06). The most common reason for ineligibility was an inadequate proximal aortic neck. Of 176 candidates, 78% underwent endovascular repair, and 6% underwent open repair. Of 138 noncandidates, 56% underwent surgical repair. Over a period of 6 years, 542 patients with AAAs (429 simple, 86 complex, 27 ruptured) underwent open repair. The total number and ratio of simple to complex open repairs for nonruptured aneurysms during the 3 years before the initiation of the endovascular program (213 simple, 44 complex) were not significantly different from the repairs over the subsequent 3-year period (216 simple, 42 complex). Similarly, no difference in the total number and the ratio of simple to complex open repairs was found between the first and the second 18-month periods since the initiation of the endovascular program.The rate of eligibility of patients with AAA for endovascular repair appears to be higher than previously reported. The presence of an active endovascular program has not decreased the number or shifted the distribution of open AAA repair.

  View details for PubMedID 10957658

• Mitral annular dynamics during rapid atrial pacing 61st Annual Meeting of the Society-of-University-Surgeons Timek, T. A., Lai, D. T., Dagum, P., Green, G. R., Glasson, J. R., Daughters, G. T., Ingels, N. B., Miller, D. C. MOSBY-ELSEVIER. 2000: 361–67

  Abstract

  Ovine mitral annular area (MAA) reduction predominantly occurs before ventricular systole. We used the myocardial marker methods to investigate left atrial and MAA dynamics during rapid atrial pacing.Seven sheep underwent implantation of 21 myocardial markers around the mitral annulus, the left ventricle and left atrium. After 7 to 10 days, animals were studied with biplane videofluoroscopy to determine 3-dimensional marker coordinates unpaced and during rapid atrial pacing at 140 minutes(-1). Left ventricle volume, left atrial volume (LAV), and MAA were calculated from marker coordinates. End diastole (ED) was defined at peak of the electrocardiogram R wave; times of minimum MAA and minimum LAV were expressed relative to ED (t = 0). Percent reduction in MAA and LAV were calculated from maximum and minimum values between diastole and early systole.The time of minimum MAA occurred earlier relative to ED during rapid pacing compared with control (-48 +/- 21 vs 19 +/- 14 msec; P <.001), as did the time of minimum LAV (-47 +/- 18 vs 4 +/- 16 msec; P <.001). Minimum MAA and LAV were significantly smaller with rapid pacing (6. 8 +/- 0.6 vs 6.5 +/- 0.5 cm(2); P <.05, respectively; and 15.4 +/- 2. 4 vs 16.5 +/- 2.3 mL; P <.01, respectively), and a relatively greater fractional reduction in MAA and LAV was observed during presystole.Rapid atrial pacing resulted in greater MAA and LAV reduction, both of which occurred entirely during diastole. This study supports the notion that MAA reduction is closely linked to LA dynamics.

  View details for PubMedID 10923017

• Ring annuloplasty prevents delayed leaflet coaptation and mitral regurgitation during acute left ventricular ischemia 71st Scientific Session of the American-Heart-Association Timek, T., Glasson, J. R., Dagum, P., Green, G. R., Nistal, J. F., Komeda, M., Daughters, G. T., Bolger, A. F., Foppiano, L. E., Ingels, N. B., Miller, D. C. MOSBY-ELSEVIER. 2000: 774–83

  Abstract

  Incomplete mitral leaflet coaptation during acute left ventricular ischemia is associated with end-diastolic mitral annular dilatation and ischemic mitral regurgitation. Annular rings were implanted in sheep to investigate whether annular reduction alone is sufficient to prevent mitral regurgitation during acute posterolateral left ventricular ischemia.Radiopaque markers were inserted around the mitral anulus, on papillary muscle tips, and on the central meridian of both mitral leaflets in three groups of sheep: control (n = 5), Physio ring (n = 5) (Baxter Cardiovascular Div, Santa Ana, Calif), and Duran ring (n = 6) (Medtronic Heart Valve Div, Minneapolis, Minn). After 8 +/- 1 days, animals were studied with biplane videofluoroscopy before and during left ventricular ischemia. Annular area was calculated from 3-dimensional marker coordinates and coaptation defined as minimal distance between leaflet edge markers.Before ischemia, leaflet coaptation occurred just after end-diastole in all groups (control 17 +/- 41, Duran 33 +/- 30, Physio 33 +/- 24 ms, mean +/- SD, P >.2 by analysis of variance). During ischemia, regurgitation was detected in all control animals, and leaflet coaptation was delayed to 88 +/- 8 ms after end-diastole (P =.02 vs preischemia). This was associated with increased end-diastolic annular area (8.0 +/- 0.9 vs 6.7 +/- 0.6 cm(2), P =.004) and septal-lateral annular diameter (2.9 +/- 0.1 vs 2.5 +/- 0.1 cm, P =.02). Mitral regurgitation did not develop in Duran or Physio sheep, time to coaptation was unchanged (Duran 25 +/- 25 ms, Physio 30 +/- 48 ms [both P >.2 vs preischemia]), and annular area remained fixed.Mitral annular area reduction and fixation with an annuloplasty ring eliminated delayed leaflet coaptation and prevented mitral regurgitation during acute left ventricular ischemia after ring implantation.

  View details for PubMedID 10733769

• Cinefluoroscopic assessment of human mitral anulus after mitral valvuloplasty. The Journal of thoracic and cardiovascular surgery Miller, D. C. 1999; 118 (6): 1155-1156

  View details for PubMedID 10596002

• Restricted posterior leaflet motion after mitral ring annuloplasty 35th Annual Meeting of the Society-of-Thoracic-Surgeons Green, G. R., Dagum, P., Glasson, J. R., Nistal, J. F., Daughters, G. T., Ingels, N. B., Miller, D. C. ELSEVIER SCIENCE INC. 1999: 2100–2106

  Abstract

  The effects of ring annuloplasty on mitral leaflet motion are incompletely known. The three-dimensional dynamics of the mitral valve in vivo were examined to determine how two types of annuloplasty rings affect leaflet motion during valve closure.Miniature radiopaque markers on the mitral leaflets, annulus, and left ventricle were implanted in three groups of sheep. One group served as control (n = 7); other sheep were randomly assigned to receive either a flexible Duran (n = 6) or a semirigid Carpentier-Edwards Physio ring (n = 6). After recovery, three-dimensional marker coordinates were computed from simultaneous (60 Hz) biplane videofluoroscopic marker images.Both types of rings immobilized the middle scallop of the posterior leaflet without affecting anterior leaflet motion. The excursion of the anterior leaflet edge from maximally open to fully closed was not different between the groups (control, 13+/-2 mm; Duran 13+/-1 mm; Physio ring, 14+/-1 mm; p > 0.05), but posterior leaflet edge excursion was restricted (control, 7.4+/-0.4 mm; 2.3+/-0.3 mm [p < 0.001]; Physio, 2.7+/-0.2 mm [p < 0.001]) by both rings.Mitral annuloplasty with either ring type markedly reduced the mobility of the central posterior leaflet in normal ovine hearts such that valve closure became essentially a single (anterior) leaflet process with the frozen posterior leaflet serving only as a buttress for closing.

  View details for PubMedID 10616984

• Deformational dynamics of the aortic root: modes and physiologic determinants. Circulation Dagum, P., Green, G. R., Nistal, F. J., Daughters, G. T., Timek, T. A., Foppiano, L. E., Bolger, A. F., Ingels, N. B., Miller, D. C. 1999; 100 (19): II54-62

  Abstract

  Current surgical methods for treating aortic valve and aortic root pathology vary widely, and the basis for selecting one repair or replacement alternative over another continues to evolve. More precise knowledge of the interaction between normal aortic root dynamics and aortic valve mechanics may clarify the implications of various surgical procedures on long-term valve function and durability.To investigate the role of aortic root dynamics on valve function, we studied the deformation modes of the left, right, and noncoronary aortic root regions during isovolumic contraction, ejection, isovolumic relaxation, and diastole. Radiopaque markers were implanted at the top of the 3 commissures (sinotubular ridge) and at the annular base of the 3 sinuses in 6 adult sheep. After a 1-week recovery, ECG and left ventricular and aortic pressures were recorded in conscious, sedated animals, and the 3D marker coordinates were computed from biplane videofluorograms (60 Hz). Left ventricular preload, contractility, and afterload were independently manipulated to assess the effects of changing hemodynamics on aortic root 3D dynamic deformation. The ovine aortic root undergoes complex, asymmetric deformations during the various phases of the cardiac cycle, including aortoventricular and sinotubular junction strain and aortic root elongation, compression, shear, and torsional deformation. These deformations were not homogeneous among the left, right, and noncoronary regions. Furthermore, changes in left ventricular volume, pressure, and contractility affected the degree of deformation in a nonuniform manner in the 3 regions studied, and these effects varied during isovolumic contraction, ejection, isovolumic relaxation, and diastole.These complex 3D aortic root deformations probably minimize aortic cusp stresses by creating optimal cusp loading conditions and minimizing transvalvular turbulence. Aortic valve repair techniques or methods of replacement using unstented autograft, allograft, or xenograft tissue valves that best preserve this normal pattern of aortic root dynamics should translate into a lower risk of long-term cusp deterioration.

  View details for PubMedID 10567279

• Randomized trial of partial versus complete chordal preservation methods of mitral valve replacement: A preliminary report. Circulation Yun, K. L., Sintek, C. F., Miller, D. C., Schuyler, G. T., Fletcher, A. D., Pfeffer, T. A., Kochamba, G. S., Khonsari, S., Zile, M. R. 1999; 100 (19): II90-4

  Abstract

  The merits of retaining the subvalvular apparatus during mitral valve replacement for chronic mitral regurgitation have been demonstrated in numerous clinical and laboratory investigations. In this preliminary report, we analyzed the early effects of complete versus partial chordal preservation on left ventricular mechanics.Fifty patients undergoing isolated surgical correction of mitral insufficiency were prospectively randomized to either total or partial chordal-sparing mitral valve replacement. Of the first 19 patients studied, 8 had preservation of the posterior leaflet only, and 11 had complete preservation of all chordal structures. A comparison group consisted of 6 patients who had primary mitral valve repair. Echocardiography was performed preoperatively and at discharge from the hospital to determine dimensions, wall stress, and ejection fraction. Preservation of the posterior leaflet only resulted in a reduction in end-diastolic volume, an increase in end-systolic volume (P=0.058), a rising trend in end-systolic stress, a decrease in long-axis fractional shortening, and a fall in ejection fraction from 0.68+/-0.16 to 0. 46+/-0.19 (P=0.001). Although patients who had preservation of all chordal structures also had decreased end-diastolic volume, long-axis fractional shortening, and ejection fraction (0.60+/-0.13 to 0.52+/-0.07, P=0.01), end-systolic stress fell and end-systolic volume decreased instead of increased. Compared with the posterior leaflet preservation group, those in the group with completely preserved chordal structures had a larger decline in end-diastolic volume and smaller decreases in long-axis fractional shortening and ejection fraction. Changes in end-systolic volume and stress were also statistically different between the 2 cohorts. No differences were detected between the group with total preserved chordal structures and the mitral repair group in any of the measured parameters.Compared with posterior chordal preservation only, complete retention of the subvalvular apparatus during mitral valve replacement resulted in improved ejection performance and smaller chamber volumes due to reduced systolic wall stress. These hemodynamic advantages are comparable to those observed with primary mitral reconstruction.

  View details for PubMedID 10567284

• Mitral annular dilatation and papillary muscle dislocation without mitral regurgitation in sheep CIRCULATION Green, G. R., Dagum, P., Glasson, J. R., Daughters, G. T., Bolger, A. F., Foppiano, L. E., Berry, G. J., Ingels, N. B., Miller, D. C. 1999; 100 (19): 95-102

  View details for Web of Science ID 000083605200016

• Deformational dynamics of the aortic root - Modes and physiologic determinants CIRCULATION Dagum, P., Green, G. R., Nistal, F. J., Daughters, G. T., Timek, T. A., Foppiano, L. E., Bolger, A. F., Ingels, N. B., Miller, D. C. 1999; 100 (19): 54-62

  Abstract

  Current surgical methods for treating aortic valve and aortic root pathology vary widely, and the basis for selecting one repair or replacement alternative over another continues to evolve. More precise knowledge of the interaction between normal aortic root dynamics and aortic valve mechanics may clarify the implications of various surgical procedures on long-term valve function and durability.To investigate the role of aortic root dynamics on valve function, we studied the deformation modes of the left, right, and noncoronary aortic root regions during isovolumic contraction, ejection, isovolumic relaxation, and diastole. Radiopaque markers were implanted at the top of the 3 commissures (sinotubular ridge) and at the annular base of the 3 sinuses in 6 adult sheep. After a 1-week recovery, ECG and left ventricular and aortic pressures were recorded in conscious, sedated animals, and the 3D marker coordinates were computed from biplane videofluorograms (60 Hz). Left ventricular preload, contractility, and afterload were independently manipulated to assess the effects of changing hemodynamics on aortic root 3D dynamic deformation. The ovine aortic root undergoes complex, asymmetric deformations during the various phases of the cardiac cycle, including aortoventricular and sinotubular junction strain and aortic root elongation, compression, shear, and torsional deformation. These deformations were not homogeneous among the left, right, and noncoronary regions. Furthermore, changes in left ventricular volume, pressure, and contractility affected the degree of deformation in a nonuniform manner in the 3 regions studied, and these effects varied during isovolumic contraction, ejection, isovolumic relaxation, and diastole.These complex 3D aortic root deformations probably minimize aortic cusp stresses by creating optimal cusp loading conditions and minimizing transvalvular turbulence. Aortic valve repair techniques or methods of replacement using unstented autograft, allograft, or xenograft tissue valves that best preserve this normal pattern of aortic root dynamics should translate into a lower risk of long-term cusp deterioration.

  View details for Web of Science ID 000083605200010

• Functional evaluation of the medtronic stentless porcine xenograft mitral valve in sheep CIRCULATION Dagum, P., Green, G. R., Timek, T. A., Daughters, G. T., Foppiano, L. E., Tye, T. L., Bolger, A. F., Ingels, N. B., Miller, D. C. 1999; 100 (19): 70-77

  View details for Web of Science ID 000083605200012

• Randomized trial of partial versus complete chordal preservation methods of mitral valve replacement - A preliminary report CIRCULATION Yun, K. L., Sintek, C. F., Miller, D. C., Schuyler, G. T., Fletcher, A. D., Pfeffer, T. A., Kochamba, G. S., Khonsari, S., Zile, M. R. 1999; 100 (19): 90-94

  Abstract

  The merits of retaining the subvalvular apparatus during mitral valve replacement for chronic mitral regurgitation have been demonstrated in numerous clinical and laboratory investigations. In this preliminary report, we analyzed the early effects of complete versus partial chordal preservation on left ventricular mechanics.Fifty patients undergoing isolated surgical correction of mitral insufficiency were prospectively randomized to either total or partial chordal-sparing mitral valve replacement. Of the first 19 patients studied, 8 had preservation of the posterior leaflet only, and 11 had complete preservation of all chordal structures. A comparison group consisted of 6 patients who had primary mitral valve repair. Echocardiography was performed preoperatively and at discharge from the hospital to determine dimensions, wall stress, and ejection fraction. Preservation of the posterior leaflet only resulted in a reduction in end-diastolic volume, an increase in end-systolic volume (P=0.058), a rising trend in end-systolic stress, a decrease in long-axis fractional shortening, and a fall in ejection fraction from 0.68+/-0.16 to 0. 46+/-0.19 (P=0.001). Although patients who had preservation of all chordal structures also had decreased end-diastolic volume, long-axis fractional shortening, and ejection fraction (0.60+/-0.13 to 0.52+/-0.07, P=0.01), end-systolic stress fell and end-systolic volume decreased instead of increased. Compared with the posterior leaflet preservation group, those in the group with completely preserved chordal structures had a larger decline in end-diastolic volume and smaller decreases in long-axis fractional shortening and ejection fraction. Changes in end-systolic volume and stress were also statistically different between the 2 cohorts. No differences were detected between the group with total preserved chordal structures and the mitral repair group in any of the measured parameters.Compared with posterior chordal preservation only, complete retention of the subvalvular apparatus during mitral valve replacement resulted in improved ejection performance and smaller chamber volumes due to reduced systolic wall stress. These hemodynamic advantages are comparable to those observed with primary mitral reconstruction.

  View details for Web of Science ID 000083605200015

• Mitral annular dilatation and papillary muscle dislocation without mitral regurgitation in sheep. Circulation Green, G. R., Dagum, P., Glasson, J. R., Daughters, G. T., Bolger, A. F., Foppiano, L. E., Berry, G. J., Ingels, N. B., Miller, D. C. 1999; 100 (19): II95-102

  Abstract

  Asymmetrical mitral annular (MA) dilatation and papillary muscle dislocation are implicated in the pathogenesis of functional mitral regurgitation (MR).To determine the mechanism by which annular and papillary muscle geometric alterations result in MR, we implanted radiopaque markers in the left ventricle, mitral annulus, anterior and posterior mitral leaflets, and papillary muscle tips and bases in 2 groups of sheep. One group served as controls (CTL, n=7); an experimental group (EXP, n=9) underwent topical phenol application to obliterate anterior annular and leaflet muscle (confirmed histologically ex vivo). After 1 week of recovery, markers were imaged with biplane videofluoroscopy, and hemodynamic data were recorded. MA area (computed from 3-dimensional marker coordinates) was 11% to 13% larger in the EXP group than in the CTL group (P<0.05 by ANOVA). This area increase resulted exclusively from intercommissural axis increase except in 1 heart with large (>1 cm) increases in both the intercommissural and septolateral annular axes. The anterior papillary muscle tip in EXP was displaced from CTL by 2.9+/-0.23 mm toward the anterolateral left ventricle and 2.5+/-0.12 mm toward the mitral annulus at end systole; the posterior papillary muscle geometry was unchanged. Transthoracic echocardiography revealed MR only in the heart exhibiting biaxial annular enlargement.MA dilatation in the intercommissural dimension with anterior papillary muscle tip displacement toward the annulus is insufficient to produce MR in sheep. Functional MR may require MA dilatation in the septolateral axis, as observed with proximal circumflex coronary occlusion.

  View details for PubMedID 10567285

• Functional evaluation of the medtronic stentless porcine xenograft mitral valve in sheep. Circulation Dagum, P., Green, G. R., Timek, T. A., Daughters, G. T., Foppiano, L. E., Tye, T. L., Bolger, A. F., Ingels, N. B., Miller, D. C. 1999; 100 (19): II70-7

  Abstract

  Recently, renewed interest in allograft and stentless "freehand" bileaflet xenograft mitral valve replacement has arisen. The variability of human papillary tip anatomy and scarcity of donors limit allograft availability, making xenograft mitral valves an attractive alternative; however, these valves require new surgical implantation techniques, and assessment of their hemodynamics and functional geometry is lacking.Seven sheep underwent implantation of a new stentless, glutaraldehyde-preserved porcine mitral valve (Physiological Mitral Valve [PMV], Medtronic) and were studied acutely under open-chest conditions. A new method of retrograde cardioplegia was developed. Hemodynamic valve function was assessed by epicardial Doppler echocardiography. 3D motion of miniature radiopaque markers sutured to the valve leaflets, annulus, and papillary tips was measured. Six other sheep with implanted markers served as controls.Both papillary muscle tips avulsed in the first animal, leaving 6 other animals. Mitral regurgitation was not observed in any xenograft valve. The peak and mean transvalvular gradients were 4.6+/-1.8 mm Hg and 2.6+/-1.5 mm Hg, respectively. The average mitral valve area was 5.7+/-1.6 cm(2). Valve closure in the xenograft group occurred later (30+/-11 ms, P<0. 015) and at higher left-ventricular pressure (61+/-9 mm Hg, P<0.001) than in the control group; furthermore, leaflet coaptation was displaced more apically (5.6+/-2.2 mm, P<0.001) and septally (5. 8+/-1.5 mm, P<0.001), and the anterolateral papillary tip underwent greater septal-lateral displacement (2.7+/-1.5 mm, P<0.001). Annular contraction during the cardiac cycle was similar in the 2 groups (xenograft 9.2+/-4.5% versus control 10.6+/-4.5% [mean+/-SD; 2-factor ANOVA model]).Successful freehand stentless porcine mitral valve implantation is feasible in sheep and was associated with excellent early postoperative hemodynamics. Physiological mitral valve annular contraction and functional leaflet closure mechanics were preserved. Long-term valve durability, calcification, and hemodynamic performance remain to be determined in models.

  View details for PubMedID 10567281

• Effects of mitral valve replacement on regional left ventricular systolic strain ANNALS OF THORACIC SURGERY Moon, M. R., DeAnda, A., Daughters, G. T., Ingels, N. B., Miller, C. D. 1999; 68 (3): 894-902

  Abstract

  Mitral valve replacement (MVR) with chordal excision impairs left ventricular (LV) systolic function, but the responsible mechanisms remain incompletely characterized. Loss of normal annular-papillary continuity also adversely affects LV torsional deformation, possibly due to changes in myocardial fiber contraction pattern.Twenty-seven dogs underwent insertion of LV myocardial markers and a sham procedure (cardiopulmonary bypass, no MVR, n = 6), conventional MVR with chordae tendineae excision (n = 7), or chordal-sparing MVR with reattachment of the anterior leaflet chordae to the anterior annulus (n = 7) or to the posterior annulus (n = 7). In the anterior, lateral, posterior, and septal LV regions, linear chords were constructed from each region's central marker to its surrounding markers. Percent systolic shortening (regional LV strain) was calculated for each chord, and the chords were assigned to one of four angular groups: I, left-handed oblique (subepicardial fiber direction); II, circumferential (midwall); III, right-handed oblique (subendocardial); or IV, longitudinal. Regional LV strain data were compared before and after MVR.Sham and anterior chordal-sparing MVR had minimal effects on regional LV strain. With posterior chordal-sparing MVR: anteriorly, left-oblique (I) strain fell (31%, p<0.05), as did circumferential (II) and right-oblique (III) strains (by 49% and 51%, respectively; p<0.01). Laterally, left-oblique (I) strain fell by 36% (p<0.05), as did longitudinal (IV) strain (54% decline, p<0.01). Conventional MVR with chordal excision disrupted regional fiber shortening diffusely, affecting oblique fibers (I and III) in the anterior and septal regions and impairing longitudinal (IV) strain in all regions (45% to 68% fall, p<0.05).Sham and anterior chordal-sparing MVR did not substantially alter regional LV strain; however, loss of normal anatomic valvular-ventricular integrity (conventional MVR) or posterior chordal-sparing MVR resulted in pronounced alterations in LV strain, most notably in the longitudinal and oblique fiber directions. These findings demonstrate that the deleterious effects of chordal excision are associated with perturbed internal myocardial systolic deformation, which suggests that chordal disruption distorts myofiber architecture or regional systolic loading.

  View details for PubMedID 10509980

• Percutaneous balloon fenestration and stenting for life-threatening ischemic complications in patients with acute aortic dissection 24th Annual Meeting of the Western-Thoracic-Surgical-Association Slonim, S. M., Miller, D. C., Mitchell, R. S., Semba, C. P., Razavi, M. K., Dake, M. D. MOSBY-ELSEVIER. 1999: 1118–26

  Abstract

  Acute aortic dissection frequently causes life-threatening ischemia of end-organs, historically associated with mortality exceeding 60%. Reperfusion with the use of interventional radiologic methods has evolved as a promising treatment. We report results of our initial 6 years of experience with percutaneous balloon fenestration of the intimal flap and endovascular stenting.Forty patients (32 male and 8 female) with a median age of 53 years (range 16-86 years) underwent percutaneous treatment for peripheral ischemic complications of 10 type A and 30 type B acute aortic dissections since 1991. Twenty patients had ischemia of multiple organ systems. Thirty patients had renal, 22 had leg, 18 had mesenteric, and 1 had arm ischemia.Fourteen patients were treated with stenting of either the true or false lumen combined with balloon fenestration of the intimal flap, 24 with stenting alone, and 2 with fenestration alone. Successful revascularization was achieved in 93% +/- 4% (+/-70% confidence levels) of patients (37/40). Nine patients had procedure-related complications. The 30-day mortality rate was 25% +/- 7% (10/40), often related to irreversible ischemia of intra-abdominal organs that was present before the procedure. Of the remaining 30 patients, 5 have died and the remaining 25 continue to have relief of ischemic symptoms at a mean follow-up of 29 months.Percutaneous balloon fenestration of the intimal flap and endovascular stenting is an effective treatment for life-threatening ischemic complications of acute aortic dissection.

  View details for PubMedID 10343260

• Endovascular treatment of descending thoracic aortic aneurysms and dissections SURGICAL CLINICS OF NORTH AMERICA Fann, J. I., Miller, D. C. 1999; 79 (3): 551-?

  Abstract

  Various endovascular techniques have become viable therapeutic alternatives in the treatment of patients with many types of descending thoracic aortic pathology and aortic dissections. Descending thoracic aortic aneurysms can be successfully treated using stent grafts. This technique is less invasive and is associated with acceptable morbidity and mortality rates. Patients who are particularly likely to benefit include the very elderly population; those with markedly compromised cardiac, pulmonary, or renal status; and individuals who have previously undergone complex operations on the thoracic aorta. Other endovascular methods, such as aortic flap fenestration, stent, or covering of the primary intimal tear in the descending thoracic aorta with a stent graft, have also been effectively employed in the treatment of peripheral arterial complications of aortic dissection. Despite the reported early success of these endovascular percutaneous methods, true assessment of the effectiveness of these various techniques awaits long-term follow-up evaluation in large patient populations.

  View details for PubMedID 10410687

• Thoracic aortic aneurysm repair with an endovascular stent graft: The "first generation" Aortic Surgery Symposium VI Mitchell, R. S., Miller, D. C., Dake, M. D., Semba, C. P., Moore, K. A., Sakai, T. ELSEVIER SCIENCE INC. 1999: 1971–74

  Abstract

  The feasibility and efficacy trial of an endovascular stent-grafting system for the treatment of aneurysms of the descending thoracic aorta was investigated.After Institutional Review Board approval, 103 patients (mean age 69 years) underwent stent graft repair of a descending thoracic aortic aneurysm between July 1992 and November 1997. The stent graft was fabricated using self-expanding "Z" stents covered by a woven Dacron tube graft. Follow-up, which averaged 22 months, was 100% complete. Simultaneous open abdominal aortic aneurysm repair was performed in 19 patients.Complete aneurysm thrombosis was achieved in 86 patients (83%). Early mortality, defined as a death during the same hospitalization or in less than 30 days, was 9 +/- 3%, and was significantly associated with preoperative cerebrovascular accident (CVA) or myocardial infarction. Major perioperative morbidity occurred in 31 patients, and included paraplegia in 3, CVA in 7, and respiratory insufficiency in 12 patients each. Actuarial survival was 81 +/- 4% at 1 year, and 73 +/- 5% at 2 years. Treatment failure (including all late, sudden, unexplained deaths) occurred in 38 patients, and only 53 +/- 10% of patients were free of treatment failure at 3.7 years. Five patients required late operative therapy for endoleaks associated with aneurysm enlargement.Satisfactory results were achieved using this "first-generation" homemade stent graft device. Mortality and morbidity occurred frequently, but may have been associated with the high-risk character of this patient population. Medium-term results were acceptable, but continued aortic enlargement, with the late development of endoleaks, is a significant concern. Second-generation devices with commercial development, coupled with this initial experience, should allow improved clinical results in the future. Longer term follow-up is still necessary to fully define the efficacy of this endovascular approach.

  View details for PubMedID 10391350

• Endografts for the treatment of descending thoracic aortic aneurysm: Results of the first 150 procedures Dake, M., Semba, C., Kee, S., Razavi, M., Slonim, S., Samuels, S., Sze, D., Mitchell, R., Miller, D. INT SOC ENDOVASCULAR SPECIALIST. 1999: 189–89

  View details for Web of Science ID 000083522600024

• Potential mechanism of left ventricular outflow tract obstruction after mitral ring annuloplasty 24th Annual Meeting of the Western-Thoracic-Surgical-Association Dagum, P., Green, G. R., Glasson, J. R., Daughters, G. T., Bolger, A. F., Foppiano, L. E., Ingels, N. B., Miller, D. C. MOSBY-ELSEVIER. 1999: 472–80

  Abstract

  The purpose of this study was to explore whether geometric changes that predispose to left ventricular outflow tract obstruction after mitral ring annuloplasty are coupled to subvalvular apparatus disturbances.Radiopaque markers were implanted in sheep: 9 in the ventricle, 1 in the high interventricular septum, 1 on each papillary muscle tip, 8 around the mitral anulus, 4 on the anterior mitral leaflet, and 2 on the posterior leaflet. One group served as control (n = 5); the others were randomized to undergo annuloplasty with the Duran ring (n = 6; Medtronic, Inc, Minneapolis, Minn) or Carpentier-Edwards Physio ring (n = 6; Baxter Healthcare Corp, Irvine, Calif). After a 7- to 10-day recovery period, 3-dimensional marker coordinates were measured with biplane videofluoroscopy.At the beginning of ejection, (1) the anterior leaflet was displaced toward the left ventricular outflow tract; (2) the normal atrially flexed anterior anulus was flattened into the left ventricular outflow tract; (3) the posterior anulus was displaced toward the left ventricular outflow tract; (4) the anterior papillary muscle was displaced septally; and (5) the posterior papillary muscle was dislocated inwardly toward the anterior papillary muscle in the Physio ring group compared with the control group. During ejection, all these structures moved septally, encroaching further on the left ventricular outflow tract. In the Duran ring group, only the posterior anulus was displaced toward the left ventricular outflow tract; the anterior leaflet was not displaced toward the left ventricular outflow tract, and it did not move septally during ejection.The semirigid Physio ring was associated with perturbations in annular dynamics that caused changes in papillary muscle geometry. We propose an integrated valvular-subvalvular mechanism to explain displacement of the anterior leaflet into the left ventricular outflow tract after mitral ring annuloplasty.

  View details for Web of Science ID 000078921100007

  View details for PubMedID 10047649

• Mitral annular size and shape in sheep with annuloplasty rings Meeting of the American-Heart-Association Glasson, J. R., Green, G. R., Nistal, J. F., Dagum, P., Komeda, M., Daughters, G. T., Bolger, A. F., Foppiano, L. E., Ingels, N. B., Miller, D. C. MOSBY-ELSEVIER. 1999: 302–9

  Abstract

  Mitral annuloplasty is an important element of most mitral repairs, yet the effects of various types of annuloplasty rings on mitral annular dynamics are still debated. Recent studies suggest that flexible rings preserve physiologic mitral annular area change during the cardiac cycle, while rigid rings do not.To clarify the effects of mitral ring annuloplasty on mitral annular dynamic geometry, we sutured 8 radiopaque markers equidistantly around the mitral anulus in 3 groups of sheep (n = 7 each: no ring, Carpentier-Edwards semi-rigid Physio-Ring [Baxter Healthcare Corp, Edwards Division, Santa Ana, Calif], and Duran flexible ring [Medtronic, Inc, Minneapolis, Minn]). Ring sizes were selected according to anterior leaflet area and inter-trigonal distance (Physio-Ring 28 mm, n = 7; Duran ring 31 mm, n = 5, and 29 mm, n = 2). After 8 +/- 1 days of recovery, the sheep were sedated and studied by means of biplane videofluoroscopy. Mitral annular area was calculated from 3-dimensional marker coordinates without assuming circular or planar geometry.In the no ring group, mitral annular area varied during the cardiac cycle by 11% +/- 2% (mean +/- SEM; maximum = 7.6 +/- 0.2, minimum = 6.8 +/- 0.2 cm2; P

  View details for PubMedID 9918972

• Semirigid or flexible mitral annuloplasty rings do not affect global or basal regional left ventricular systolic function CIRCULATION Green, G. R., Dagum, P., Glasson, J. R., Daughters, G. T., Bolger, A. F., Foppiano, L. E., Ingels, N. B., Miller, D. C. 1998; 98 (19): II128-II135

  Abstract

  Previous studies have revealed that rigid mitral annuloplasty rings may be associated with left ventricular (LV) systolic dysfunction, but whether ring type affects regional systolic function at the base of the LV, in the region near the mitral annulus, is unclear. We tested the hypothesis that rigid fixation of the mitral annulus results in significant regional systolic dysfunction at the base of the LV.Twenty-six adult male sheep underwent placement of 13 miniature tantalum markers into the LV epicardium and around the mitral annulus to allow calculation of LV volume and regional epicardial area. Group I (n = 7) sheep served as controls; animals randomized to groups II (n = 11) and III (n = 8) underwent mitral annuloplasty with either a semirigid or flexible ring, respectively. After a 7- to 10-day recovery period, animals were studied in a closed-chest, sedated, autonomically blocked state. Global LV systolic function (end-systolic elastance and preload recruitable stroke work) were not significantly different among the 3 groups (P = 1.0, ANOVA). Regional systolic function at the base of the LV (fractional area shrinkage [FAS] of 4 epicardial areas) at comparable LV preload and afterload was similar in the 4 basal areas (P = 0.223, MANOVA). With the use of load-insensitive indexes (slope and area intercept of the end-systolic pressure-regional area relationship and regional stroke work-end-diastolic area relationship), regional systolic function also was not different between groups at baseline or with inotropic stimulation in any basal region (P > 0.05, MANOVA). Furthermore, neither annuloplasty ring perturbed the regional pattern of basal LV systolic function.Postoperative LV systolic function, both globally and in the region of the base of the LV (near the mitral annulus), was not altered with either semirigid or flexible ring fixation of the mitral annulus.

  View details for PubMedID 9852894

• Estimation of regional left ventricular wall stresses in intact canine hearts 45th Annual Scientific Session of the American-College-of-Cardiology DeAnda, A., Komeda, M., Moon, M. R., Green, G. R., Bolger, A. F., Nikolic, S. D., Daughters, G. T., Miller, D. C. AMER PHYSIOLOGICAL SOC. 1998: H1879–H1885

  Abstract

  Left ventricular (LV) wall stress is an important element in the assessment of LV systolic function; however, a reproducible technique to determine instantaneous local or regional wall stress has not been developed. Fourteen dogs underwent placement of twenty-six myocardial markers into the ventricle and septum. One week later, marker images were obtained using high-speed biplane videofluoroscopy under awake, sedated, atrially paced baseline conditions and after inotropic stimulation (calcium). With a model taking into account LV pressure, regional wall thickness, and meridional and circumferential regional radii of curvature, we computed average midwall stress for each of nine LV sites. Regional end-systolic and maximal LV wall stress were heterogeneous and dependent on latitude (increasing from apex to base, P < 0.001) and specific wall (anterior > lateral and posterior wall stresses; P = 0. 002). Multivariate ANOVA demonstrated only a trend (P = 0.056) toward increased LV stress after calcium infusion; subsequent univariate analysis isolated significant increases in end-systolic LV wall stress with increased inotropic state at all sites except the equatorial regions. The model used in this analysis incorporates local geometric factors and provides a reasonable estimate of regional LV wall stress compared with previous studies. LV wall stress is heterogeneous and dependent on the particular LV site of interest. Variation in wall stress may be caused by anatomic differences and/or extrinsic interactions between LV sites, i.e., influences of the papillary muscles and the interventricular septum.

  View details for Web of Science ID 000076935700044

  View details for PubMedID 9815097

• Estimation of regional left ventricular wall stresses in intact canine hearts. American journal of physiology. Heart and circulatory physiology DeAnda, A. J., Komeda, M., Moon, M. R., Green, G. R., Bolger, A. F., Nikolic, S. D., Daughters, G. T., Miller, D. C. 1998; 275 (5): H1879–H1885

  Abstract

  Left ventricular (LV) wall stress is an important element in the assessment of LV systolic function; however, a reproducible technique to determine instantaneous local or regional wall stress has not been developed. Fourteen dogs underwent placement of twenty-six myocardial markers into the ventricle and septum. One week later, marker images were obtained using high-speed biplane videofluoroscopy under awake, sedated, atrially paced baseline conditions and after inotropic stimulation (calcium). With a model taking into account LV pressure, regional wall thickness, and meridional and circumferential regional radii of curvature, we computed average midwall stress for each of nine LV sites. Regional end-systolic and maximal LV wall stress were heterogeneous and dependent on latitude (increasing from apex to base, P < 0.001) and specific wall (anterior > lateral and posterior wall stresses; P = 0.002). Multivariate ANOVA demonstrated only a trend ( P = 0.056) toward increased LV stress after calcium infusion; subsequent univariate analysis isolated significant increases in end-systolic LV wall stress with increased inotropic state at all sites except the equatorial regions. The model used in this analysis incorporates local geometric factors and provides a reasonable estimate of regional LV wall stress compared with previous studies. LV wall stress is heterogeneous and dependent on the particular LV site of interest. Variation in wall stress may be caused by anatomic differences and/or extrinsic interactions between LV sites, i.e., influences of the papillary muscles and the interventricular septum.

  View details for DOI 10.1152/ajpheart.1998.275.5.H1879

  View details for PubMedID 29592229

• Endovascular stent-graft placement to obliterate the entry tear: A new treatment for acute aortic dissection Dake, M. D., Kato, N., Slonim, S. M., Razavi, M. K., Semba, C. P., Kee, S. T., Sze, D. Y., Samuels, S. L., Mitchell, R. S., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 1998: 67–67

  View details for Web of Science ID 000076594400382

• Mitral valve replacement with partial vs complete chordal preservation: Functional outcome compared to primary repair Sintek, C. F., Schuyler, G. T., Fletcher, A. D., Miller, D. C., Pheffer, T. A., Permanente, K., Zile, M. R., Khonsari, S. LIPPINCOTT WILLIAMS & WILKINS. 1998: 59–59

  View details for Web of Science ID 000076594400344

• Effects of partial left ventriculectomy on left ventricular geometry and wall stress in excised porcine hearts JOURNAL OF HEART VALVE DISEASE Green, G. R., Moon, M. R., DeAnda, A., Daughters, G. T., Glasson, J. R., Miller, D. C. 1998; 7 (5): 474-483

  Abstract

  Partial left ventriculectomy (PLV, the "Batista procedure") has received recent attention as a surgical treatment for patients with dilated cardiomyopathy and end-stage congestive heart failure; however, the mechanisms responsible for the purported short-term improvement in left ventricular (LV) function are poorly characterized. This study examined the effects of PLV on three-dimensional (3-D) LV geometry, wall stress and passive LV mechanics in excised porcine hearts.Thirty-three radio-opaque tantalum markers were placed into the LV wall of nine freshly excised, porcine hearts (arrested with cold crystalloid cardioplegia) to measure three dimensional LV geometry and volume. Simultaneous biplane video-fluoroscopic marker images and LV pressure (LVP) were obtained over a wide range of LV volumes generated with an intracavitary LV balloon. Measurements were repeated after excision of a diamond-shaped wedge of the lateral LV wall between the papillary muscles (mean: 8 x 3 x 2 cm; 10 +/- 2% of LV mass).Following PLV, the ventricle assumed a more elliptical shape (LV eccentricity rose from 0.71 +/- 0.15 to 0.81 +/- 0.09, p < 0.01). Circumferential radius of curvature fell in the anterior, lateral and posterior regions at the equatorial level (p < 0.01), while the posterior wall longitudinal radius of curvature increased at the basal, equatorial and apical levels (p < 0.01). No change in the longitudinal radius of curvature was observed in the other walls. These changes were associated with a fall in average equatorial LV wall stress from 176 +/- 34 to 159 +/- 30 kdyne/cm2 (p < 0.02). Myocardial stiffness (slope of the LV stress-strain relation) fell from 12.4 +/- 4.0 to 10.0 +/- 3.4 (p < 0.004), indicating lower global LV wall stress at any given LV size.In flaccid porcine hearts, the left ventricle became more elliptical and chamber size decreased after PLV, which resulted in lower regional LV wall stress and myocardial stiffness. LV ellipticalization may improve systolic LV performance by decreasing regional LV afterload (e.g., systolic wall stress), which would thereby lower myocardial oxygen consumption and improve LV pump efficiency.

  View details for PubMedID 9793842

• Early systolic mitral leaflet "loitering" during acute ischemic mitral regurgitation JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Glasson, J. R., Komeda, M., Daughters, G. T., Bolger, A. F., Karlsson, M. O., Foppiano, L. E., Hayase, M., Oesterle, S. N., Ingels, N. B., Miller, D. C. 1998; 116 (2): 193-204

  Abstract

  The mechanism by which incomplete mitral leaflet coaptation develops during ischemic mitral regurgitation is debated, with recent studies suggesting that incomplete mitral leaflet coaptation may be due to apically displaced papillary muscle tips. Yet quantitative in vivo three-dimensional mitral leaflet motion during ischemic mitral regurgitation has never been described.Radiopaque markers (sutured around the mitral anulus, to the central free mitral leaflet edges, and to both papillary muscle tips and bases) were imaged with the use of biplane videofluoroscopy in six closed-chest, sedated sheep before (control) and during induction of acute ischemic mitral regurgitation. Leaflet coaptation was defined as the minimum distance measured between edge markers during control conditions.During control, leaflet coaptation occurred 23 +/- 7 msec (mean +/- standard error of the mean) after end-diastole, when left ventricular pressure was 27 +/- 6 mm Hg. During ischemic mitral regurgitation, coaptation was delayed to 115 +/- 19 msec after end-diastole (p < or = 0.01 vs control [n = 4]) when left ventricular pressure was 88 +/- 4 mm Hg. At end-diastole during ischemic mitral regurgitation, the mitral anulus area was 14% +/- 2% larger than control (7.4 +/- 0.3 cm2 vs 6.5 +/- 0.2 cm2, p < or = 0.005) as the result of the lengthening of muscular annular regions (76.0 +/- 2.5 mm vs 70.5 +/- 1.4 mm, p < or = 0.01). Mitral anulus shape (ratio of two diameters) at end-diastole was more circular during ischemic mitral regurgitation (0.79 +/- 0.01 vs 0.71 +/- 0.02, p < 0.01). At end-diastole during ischemic mitral regurgitation, the posterior papillary muscle tip was displaced 1.5 +/- 0.5 mm laterally and 2.0 +/- 0.6 mm posteriorly (p < or = 0.02 vs control), but there was no apical displacement of either papillary muscle tip.Incomplete mitral leaflet coaptation during acute ischemic mitral regurgitation occurred early in systole, not at end-systole, and was due to "loitering" of the leaflets associated with posterior mitral anulus enlargement and circularization, as well as some posterolateral, but not apical, posterior papillary muscle tip displacement. These data suggest that early systolic mitral anulus dilatation and shape change and altered posterior papillary muscle motion are the primary mechanisms by which incomplete mitral leaflet coaptation occurs during acute ischemic mitral regurgitation.

  View details for PubMedID 9699570

• Mitral valve opening in the ovine heart AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Karlsson, M. O., Glasson, J. R., Bolger, A. F., Daughters, G. T., Komeda, M., Foppiano, L. E., Miller, D. C., Ingels, N. B. 1998; 274 (2): H552-H563

  Abstract

  To study the three-dimensional size, shape, and motion of the mitral leaflets and annulus, we surgically attached radiopaque markers to sites on the mitral annulus and leaflets in seven sheep. After 8 days of recovery, the animals were sedated, and three-dimensional marker positions were measured by computer analysis of biplane videofluorograms (60/s). We found that the oval mitral annulus became most elliptical in middiastole. Both leaflets began to descend into the left ventricle (LV) during the rapid fall of LV pressure (LVP), before leaflet edge separation. The anterior leaflet exhibited a compound curvature in systole and maintained this shape during opening. The central cusp of the posterior leaflet was curved slightly concave to the LV during opening. Markers at the border of the "rough zone" were separated by 10 mm during systole. We conclude that coaptation occurs very near the leaflet edges, that the annulus and leaflets move toward their open positions during the rapid fall of LVP, and that leaflet edge separation, the last event in the opening sequence, occurs near the time of minimum LVP.

  View details for Web of Science ID 000071868500023

  View details for PubMedID 9486259

• Diastolic function in the progression from acute to chronic MR Dagum, P., Green, G. R., Daughters, G. T., Ingels, N. B., Yun, K. L., Miller, D. C. ELSEVIER SCIENCE INC. 1998: 205A–206A

  View details for DOI 10.1016/S0735-1097(97)84598-6

  View details for Web of Science ID 000071920600862

• Chordal preservation does not influence left ventricular diastolic function immediately following mitral valve replacement Green, G. R., Dagum, P., Daughters, G. T., Ingels, N. B., Yun, K. L., Miller, D. C. ELSEVIER SCIENCE INC. 1998: 151A

  View details for DOI 10.1016/S0735-1097(97)84362-8

  View details for Web of Science ID 000071920600631

• Mitral valve opening in the ovine heart. American journal of physiology. Heart and circulatory physiology Karlsson, M. O., Glasson, J. R., Bolger, A. F., Daughters, G. T., Komeda, M., Foppiano, L. E., Miller, D. C., Ingels, N. B., (With the Technical Assistance of Carol W. Mead, M. K. 1998; 274 (2): H552–H563

  Abstract

  To study the three-dimensional size, shape, and motion of the mitral leaflets and annulus, we surgically attached radiopaque markers to sites on the mitral annulus and leaflets in seven sheep. After 8 days of recovery, the animals were sedated, and three-dimensional marker positions were measured by computer analysis of biplane videofluorograms (60/s). We found that the oval mitral annulus became most elliptical in middiastole. Both leaflets began to descend into the left ventricle (LV) during the rapid fall of LV pressure (LVP), before leaflet edge separation. The anterior leaflet exhibited a compound curvature in systole and maintained this shape during opening. The central cusp of the posterior leaflet was curved slightly concave to the LV during opening. Markers at the border of the "rough zone" were separated by 10 mm during systole. We conclude that coaptation occurs very near the leaflet edges, that the annulus and leaflets move toward their open positions during the rapid fall of LVP, and that leaflet edge separation, the last event in the opening sequence, occurs near the time of minimum LVP.

  View details for DOI 10.1152/ajpheart.1998.274.2.H552

  View details for PubMedID 29586096

• Treatment of aortoiliac aneurysms with use of single-piece tapered stent-grafts JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Kato, N., Dake, M. D., Semba, C. P., Razavi, M. K., Kee, S. T., Slonim, S. M., Samuels, S. L., Terasaki, K. K., Zarins, C. K., Mitchell, R. S., Miller, D. C. 1998; 9 (1): 41-49

  Abstract

  The authors describe their experience with the use of single-piece, tapered stent-grafts for the treatment of abdominal aortic or aortoiliac aneurysms.Single-piece, tapered stent-grafts were placed in 15 patients for the treatment of abdominal aortic aneurysms with small distal necks (n = 13), and aortoiliac aneurysms (n = 2). There were 13 men and two women who ranged in age from 59 to 83 years (mean, 71 years). Usual open surgery was considered high risk in all patients because of comorbid medical conditions. The stent-grafts were made of Z stents covered with polytetrafluoroethylene (PTFE). Additional stent-grafts needed to treat perigraft leaks were made of Z stents covered with woven polyester (n = 5), Wallstents covered with PTFE (n = 2), Z stents covered with PTFE (n = 1), and a PTFE-covered Palmaz stent (n = 1). After stent-graft placement, the contralateral iliac artery was occluded by a blocking device composed of either a PTFE-covered Palmaz (n = 1) or Z stent (n = 13), and a femoral-femoral bypass was created.After placement of the stent-grafts, immediate perigraft leaks were observed in eight patients (53%). These were at the proximal (n = 5) or the distal end (n = 3). All, except one, were treated successfully with additional stent-grafts. The one failure was in a patient who developed aortic rupture after balloon dilation, requiring open surgical repair. Second procedures were required in four patients (27%), including three leaks treated successfully with coil embolization and/or a back-up stent-graft, and one stent-graft migration and thrombosis treated by thrombolysis and placement of an additional stent-graft. One patient died of respiratory failure 23 days after placement of the stent-graft. The mean follow-up was 12 months (range, 4-26 months). On the last follow-up, the aneurysms in the 13 living patients remained thrombosed.Treatment of aortoiliac aneurysms with use of single-piece, tapered stent-grafts is feasible in selected patients. The morbidity and mortality rates compare favorably with those of the open surgical procedures in a high-risk population. Further improvements in the technique and longer follow-up data are needed before this procedure can be recommended for the treatment of all aortoiliac aneurysms.

  View details for PubMedID 9468394

• Mycotic aneurysms of the thoracic aorta: Repair with use of endovascular stent-grafts JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Semba, C. P., Sakai, T., Slonim, S. M., Razavi, M. K., Kee, S. T., Jorgensen, M. J., Hagberg, R. C., Lee, G. K., Mitchell, R. S., Miller, D. C., Dake, M. D. 1998; 9 (1): 33-40

  Abstract

  Standard therapy of mycotic aneurysms in the descending aorta consists of thoracotomy and in situ graft placement or extraanatomic bypass. The alternative use of endovascular stent-grafts was evaluated for management of infected aneurysms of the thoracic aorta.In a retrospective analysis during a 5-year period, 112 patients underwent stent-graft placement for thoracic aortic aneurysms. Three patients (mean age, 68.6; range, 64-70 years) had mycotic thoracic aneurysms. Stent-grafts were constructed from Z stents covered with polyester fabric and were delivered remotely through a catheter under fluoroscopic guidance.Complete thrombosis of the mycotic aneurysms was achieved in all patients. One patient required a second separate stent-graft placement procedure because of migration of the initial device; the second patient underwent surgical repair of a ruptured mycotic abdominal aortic aneurysm followed immediately by stent-graft placement for a chronic mycotic thoracic aneurysm; a third patient underwent repair of two infected false aneurysms secondary to complete rupture of a surgical interposition graft. There were no complications of persistent bacteremia despite placement of the stent-graft device at the site of primary infection, reinfection, delayed rupture, paraplegia, distal emboli, or surgical conversion. One patient died of cardiac arrest at 25 months; there were no perioperative deaths (< or = 30 days). The remaining two patients were alive and well at median follow-up of 24 months (range, 4-25 months).Endovascular stent-grafts combined with antibiotic therapy may be an alternative to conventional thoracotomy in managing mycotic aneurysms of the descending thoracic aorta.

  View details for PubMedID 9468393

• Traumatic thoracic aortic aneurysm: Treatment with endovascular stent-grafts RADIOLOGY Kato, N., Dake, M. D., Miller, D. C., Semba, C. P., Mitchell, R. S., Razavi, M. K., Kee, S. T. 1997; 205 (3): 657-662

  Abstract

  To demonstrate the feasibility and safety of endovascular stent-graft placement for treatment of traumatic aortic aneurysm.Ten patients with traumatic aortic aneurysm were treated with endovascular stent-grafts. Three patients had an acute traumatic aneurysm; seven had a chronic aneurysm. Stent-grafts were constructed from modified Z-stents covered with woven polyester or expanded polytetrafluoroethylene graft material and were deployed through a 20-24-F delivery sheath in an exposed artery located remotely from the lesion.Stent-graft placement and thrombosis of the aneurysmal sac were successful in all patients. Major complications were encountered in three patients after endovascular treatment. One patient had a peri-graft leak; complete thrombosis of the aneurysmal sac was achieved after coil embolization of the leak. Transposition of the left subclavian artery was necessary to relieve left arm ischemia in another patient. In the third patient, stent placement in the left main stem bronchus was needed to relieve left lung atelectasis. All patients were alive and without complications during the follow-up period (mean, 15 months).Transluminal placement of endovascular stent-grafts is a technically feasible method for treatment of traumatic thoracic aortic aneurysm and may be an effective alternative to open-chest surgery.

  View details for PubMedID 9393517

• Stent-graft repair of thoracic aortic aneurysms. Seminars in vascular surgery Mitchell, R. S., Miller, D. C., Dake, M. D. 1997; 10 (4): 257-271

  Abstract

  Aneurysmal disease of the thoracic aorta continues to be a very challenging management problem for physicians because of the many comorbidities harbored by these patients, as well as the morbidity of the conventional open repair via left thoracotomy. In a combined effort between interventional radiology and cardiovascular surgery, an endovascular stent graft repair has been devised for these patients in an effort to reduce morbidity. This report documents the results in the first 108 patients so treated. The graft itself, custom-made for each individual, is composed of interlocked, self-expanding "Z" stents covered with a woven Dacron graft. Compressed in a loading capsule, the graft can then be advanced through a 27-French (outside diameter; OD) sheath, which is positioned within the aneurysm under fluoroscopic guidance. Relatively normal 2- to 3-cm segments of proximal and distal aorta allow an adequate friction seal to prevent stent graft dislodgement and also provide a hemostatic seal to obliterate aneurysm filling. Complete aneurysm thrombosis was achieved primarily in 103 patients. There were 10 deaths (9.25%) within the first 30 days, four of which were directly attributable to the stent graft procedure. Perioperative strokes occurred in four patients, and there were four instances of paraplegia. There have been two documented stent graft failures in a mean follow-up of 21.8 months (range, 1 to 57 months). Although the long-term durability of this procedure remains unknown, we believe this less invasive endovascular approach will prove to be an effective and less morbid treatment for aneurysmal disease of the descending thoracic aorta.

  View details for PubMedID 9431597

• Most ovine mitral annular three-dimensional size reduction occurs before ventricular systole and is abolished with ventricular pacing. Circulation Glasson, J. R., Komeda, M., Daughters, G. T., Foppiano, L. E., Bolger, A. F., Tye, T. L., Ingels, N. B., Miller, D. C. 1997; 96 (9): II-115 22

  Abstract

  Conventional surgical thinking indicates that mitral annular (MA) size reduction plays a key role in mitral valve closure, and most MA size and shape changes are thought to occur during left ventricular (LV) systole. The influences of left atrial (LA) and LV systole on MA size and shape, however, remain debated.Eight radiopaque markers were placed equidistantly around the MA and imaged using high-speed simultaneous biplane videofluoroscopy in seven closed-chest, sedated sheep before and during asynchronous LV pacing. Marker images were used to compute the three-dimensional coordinates of each marker every 16.7 ms throughout the cardiac cycle, allowing calculation of three-dimensional MA area, septal-lateral (SL) dimension, and commissure-commissure (CC) dimension under control and LV pacing conditions. Maximum MA area occurred in early diastole, and minimum MA area near end-diastole; maximum area reduction was 12+/-1% (P< or =.001). Interestingly, 89+/-3% of area reduction occurred before LV systole. During this "presystolic" period, SL decreased by 8+/-1% and CC by 2+/-1%; the SL/CC ratio fell from 0.73+/-0.02 to 0.69+/-0.01 (P< or =.005), indicating a less circular shape at end-diastole. With LV pacing, total MA area reduction was similar (13+/-2 versus 12+/-1%, P=NS versus control); however, all MA area reduction occurred during LV systole with minimum MA area occurring at end-systole. Presystolic shortening in both SL and CC dimensions was lost, and presystolic ellipticalization disappeared.Changes in MA size and shape coincident with LA systole included area reduction and shape change prior to the onset of LV contraction. These presystolic changes vanished when LA systole was absent (LV pacing). Thus, LA systole plays a pivotal role in MA size reduction and shape alteration. The unexpected timing of these MA dynamics should be taken into account during mitral valve reparative procedures.

  View details for PubMedID 9386085

• Time-related analysis of nonfatal heart valve complications - Cumulative incidence (actual) versus Kaplan-Meier (actuarial) Grunkemeier, G. L., Anderson, R. P., Miller, C., Starr, A. AMER HEART ASSOC. 1997: 70-74

  View details for Web of Science ID A1997YG41000017

• Time-related analysis of nonfatal heart valve complications: cumulative incidence (actual) versus Kaplan-Meier (actuarial). Circulation Grunkemeier, G. L., Anderson, R. P., Miller, D. C., Starr, A. 1997; 96 (9): II-70 4

  Abstract

  The cumulative incidence of a postoperative event is the percentage of patients who experience the event by postoperative time T. Its complete determination requires all patients to be followed until T. In ongoing series, the Kaplan-Meier method is employed because not all patients have been observed until T. When applied to nonfatal events, however, the Kaplan-Meier estimates probabilities as if the patients who die before they sustain an event continue to be at risk thereafter. It thus estimates risk in the unrealistic situation where death does not occur.Cumulative incidence can be estimated directly, to provide the probability of actually experiencing an event before death, that is, when death properly eliminates patients from further risk of the event. We compare cumulative incidence and Kaplan-Meier estimates in two series of mitral valve replacement patients: thromboembolism in a completed series of ball valves implanted in relatively young patients and valve explant in an ongoing series of porcine valves in older patients. Kaplan-Meier estimated a higher event percentage than the cumulative incidence, and the difference was greater in the older patients, who had a higher death rate.Cumulative incidence, unlike Kaplan-Meier, provides estimates of the percentage of patients who will actually sustain an event. Cumulative incidence is more meaningful for individual patient counseling and more useful for estimating resource utilization in a managed population.

  View details for PubMedID 9386078

• Composite valve graft versus separate aortic valve and ascending aortic replacement - Is there still a role for the separate procedure? 69th Annual Scientific Session of the American-Heart-Association Yun, K. L., Miller, D. C., Fann, J. I., Mitchell, S., Robbins, R. C., Moore, K. A., Oyer, P. E., Stinson, E. B., Shumway, N. E., Reitz, B. A. LIPPINCOTT WILLIAMS & WILKINS. 1997: 368–75

  View details for Web of Science ID A1997YG41000081

• Most ovine mitral annular three-dimensional size reduction occurs before ventricular systole and is abolished with ventricular pacing CIRCULATION Glasson, J. R., Komeda, M., Daughters, G. T., Foppiano, L. E., Bolger, A. F., Tye, T. L., Ingels, N. B., Miller, C. 1997; 96 (9): 115-122

  View details for Web of Science ID A1997YG41000029

• Composite valve graft versus separate aortic valve and ascending aortic replacement: is there still a role for the separate procedure? Circulation Yun, K. L., Miller, D. C., Fann, J. I., Mitchell, R. S., Robbins, R. C., Moore, K. A., Oyer, P. E., Stinson, E. B., Shumway, N. E., Reitz, B. A. 1997; 96 (9): II-368 75

  Abstract

  To ascertain if operative technique has any bearing on outcome, the surgical results after aortic root replacement using either a composite valve graft (CVG) or a separate graft and valve (GV) were analyzed.Three hundred and ninety consecutive, nonrandomized patients treated for aortic valve disease and ascending aortic aneurysm (n=278) or type A dissection (n=112 [45 acute]) between 1965 and 1995 were analyzed retrospectively. One hundred and thirty-five patients received a CVG, and 255 had separate GV replacement. Mean age was 52+/-16 years (+/-1 SD). Eighty-two patients (44% of the CVG group) had the Marfan syndrome (MFS). Follow-up (96% complete) totaled 2247 patient-years and extended to 27 years. The operative mortality rate was 10+/-3% (+/-70% confidence limits) for patients receiving a CVG and 15+/-2% for GV replacement (P=NS). The 15-year actuarial survival estimate was higher for the CVG group (53+/-14% [+/-SEM] versus 36+/-4%, P=.037). Seven patients in the CVG group required reoperation on the aortic valve or ascending aorta, as did 49 in the GV group. The probabilities of freedom from reoperation on the aortic rootwere 82+/-9% and 75+/-4% at 10 years for the CVG and GV group (P=NS). Thirty variables were analyzed in a multivariate model: pulmonary disease, higher New York Heart Association functional class, and longer cardiopulmonary bypass time were linked with higher operative mortality risk; older age, emergency operation, coronary artery disease, and liver dysfunction were independent determinants of late death. Younger age and use of a bioprosthesis were predictors of late reoperation. Type of procedure (GV versus CVG) was not a significant predictor of any outcome variable.The long-term results after CVG or GV were similar, which reflects proper patient selection. Use of a composite valve graft theoretically confers more protection against recurrent aortic root aneurysm, and, unless one opts for a valve-sparing aortic root replacement procedure, is most appropriate for younger patients, those with the MFS (including acute dissections), and others with marked pathological involvement of the sinuses. On the other hand, use of a separate GV should not be abandoned; in carefully selected patients (and if properly performed, eg, excision of the sinuses), GV also provides satisfactory results.

  View details for PubMedID 9386126

• Geometric determinants of ischemic mitral regurgitation. Circulation Komeda, M., Glasson, J. R., Bolger, A. F., Daughters, G. T., MacIsaac, A., Oesterle, S. N., Ingels, N. B., Miller, D. C. 1997; 96 (9): II-128 33

  Abstract

  The precise geometric determinants of ischemic mitral regurgitation (MR) are incompletely understood, although such knowledge is important to improve mitral valve reparative techniques.The three-dimensional geometry of the mitral apparatus was studied using radiopaque markers in eight closed-chest dogs with acute posterior left ventricular wall ischemia either with (MR) or without (no-MR) MR as assessed by using color Doppler. Using a cylindrical coordinate system (origin at the midpoint between the mitral annulus commissures [anterolateral and posteromedial] and z-axis directed toward the left ventricular apex), we measured the distance to the midpoint (z, in millimeters), radial distance from the z-axis (r, in millimeters), and angle from the intercommissural line (theta) of each marker. A multivariate analysis of variance showed the following differences (P < .005) between the MR and the no-MR groups: 1) markedly increased r of the posterior papillary muscle tip (10.3 versus 6.4 mm, MR versus no-MR, at end-systole) and increased r of the anterior papillary muscle tip; 2) dilation (in the septal-lateral direction) of the midpart of the mitral annulus and near the anterolateral region; 3) increased posterior mitral leaflet r near both commissures (eg, 8.3 versus 6.2 mm on the posteromedial side) and increased z (ie, shifted toward the left ventricular apex) of the posterior leaflet on the anterolateral side (eg, 7.0 versus 6.2 mm), which is analogous to restricted (or type III) leaflet motion.These findings indicate that the geometric determinants of ischemic MR in dogs are complex and involve many parts of the mitral valve apparatus. This complexity suggests that surgical attention to the entire annulus and excursion of the posterior leaflet may be helpful when annuloplasty alone is inadequate.

  View details for PubMedID 9386087

• Complete unloading alone may not adequately protect the left ventricle 33rd Annual Meeting of the Society-of-Thoracic-Surgeons Komeda, M., DeAnda, A., Glasson, J. R., Bolger, A. F., Daughters, G. T., Ingels, N. B., Miller, D. C. ELSEVIER SCIENCE INC. 1997: 1250–55

  Abstract

  The benefit of left ventricular (LV) unloading for preserving LV function is commonly accepted, but its efficacy remains incompletely defined.We studied the influence of complete LV unloading on LV systolic and diastolic mechanics using an in situ isovolumic preparation with two different coronary perfusion pressures (CPPs) in 12 dogs during prolonged normothermic cardiopulmonary bypass.Multivariate analysis of covariance with time as a covariate revealed that a high CPP (143 +/- 36 mm Hg; n = 6) was associated with better preservation of systolic LV function over time as assessed by LV end-systolic elastance (p < 0.001) and the end-systolic pressure-volume relation physiologic intercept (p < 0.001) compared with a moderate CPP (107 +/- 18 mm Hg; p < 0.005 versus a high CPP by t-test; n = 6). Dobutamine (2 micrograms.kg-1.min-1) improved LV end-systolic elastance (p < 0.005) and LV physiologic intercept (p < 0.01) only in the high-CPP group. Conversely, impaired LV diastolic function (as measured by LV stiffness) was observed (p < 0.001) with a high CPP, but did not change with a moderate CPP.These observations in canine hearts suggest that complete LV unloading may not preserve LV systolic function adequately over time when CPP is maintained in the accepted clinical range. A higher CPP is required to prevent deterioration over prolonged cardiopulmonary bypass times, but diastolic dysfunction still occurs.

  View details for PubMedID 9386687

• Continuing dilemmas concerning aortic valve replacement in patients with advanced left ventricular systolic dysfunction JOURNAL OF HEART VALVE DISEASE Green, G. R., Miller, D. C. 1997; 6 (6): 562-579

  Abstract

  Aortic valve replacement in patients with aortic stenosis or aortic regurgitation who have severe left ventricular (LV) systolic dysfunction continues to be associated with a high mortality risk despite surgical, cardiological and anesthetic improvements over time. As a result of earlier surgical referral, however, fewer patients with aortic regurgitation (AR) and advanced LV failure present for operation today. Favorable operative and long-term results, and data demonstrating recovery of LV systolic function if patients are referred prior to the onset of systolic dysfunction have largely solved this problem in the context of AR. On the other hand, patients with critical aortic stenosis (AS) and severe LV systolic dysfunction constitute a more heterogeneous and even more challenging group. On one side of the continuum, patients with truly critical AS and low ejection fraction due to LV 'afterload mismatch' (depressed ejection performance resulting from excessively high systolic LV wall stress secondary to a very tight valve) generally respond well to aortic valve replacement, which immediately normalizes LV afterload. Conversely, patients with 'critical' aortic stenosis and advanced LV systolic dysfunction who present with a low transvalvular gradient and cardiac output constitute a subgroup at high operative risk, which also has a suboptimal prognosis after aortic valve replacement. This clinical situation has been termed the 'Gorlin Conundrum', and is punctuated by a low mean transvalvular gradient and low flow. The reason for the low transvalvular gradient is not always known, but can be secondary to some type of coexistent cardiomyopathy. Patients with only mild pathologic aortic valve sclerosis/stenosis and markedly depressed LV systolic function are frequently judged to have 'critical' aortic stenosis (AVA < 0.8 cm2 or AVAI < 0.4 cm2/m2) due to inherent flaws in the Gorlin equation and limitations of the Doppler continuity equation. Although alternative diagnostic techniques have been proposed, e.g. aortic valve resistance, stroke work loss, none has yet proven to be totally reliable. The suboptimal results of aortic valve replacement in low-gradient AS patients underscore our difficulty in currently predicting which patients will benefit from valve replacement. Newer diagnostic techniques, including dobutamine echocardiography, and novel new findings regarding the basic molecular mechanisms responsible for contractile dysfunction in pressure overload hypertrophy may ultimately improve the results of surgical treatment in these patients.

  View details for PubMedID 9427121

• Surgical treatment of endocarditis PROGRESS IN CARDIOVASCULAR DISEASES Moon, M. R., Stinson, E. B., Miller, D. C. 1997; 40 (3): 239-264

  Abstract

  Since early investigators first suggested that the treatment of endocarditis should include valve replacement for infections not readily controlled with medical therapy alone, the role of surgery has become expanded, yet refined, to improve the outcome of patients with this potentially fatal disease. Innovative surgical techniques have also been developed in an effort to improve the results of surgical treatment for complex sequelae of invasive infections. This article examines the current indications for surgical intervention, compares the various surgical options, and assesses the expected short-and long-term outcome after valve replacement for patients with native valve or prosthetic valve endocarditis.

  View details for PubMedID 9406678

• Surgical treatment of endocarditis: Is there a role for mechanical prostheses? Moon, M. R., Miller, D. C., Stinson, E. B., Mitchell, R. S., Oyer, P. E., Robbins, R. C., Shumway, N. E., Reitz, B. A. LIPPINCOTT WILLIAMS & WILKINS. 1997: 2409–

  View details for Web of Science ID A1997YC88002397

• Ascending aortic aneurysm and aortic valve disease: what is the most optimal surgical technique? Seminars in thoracic and cardiovascular surgery Yun, K. L., Miller, D. C. 1997; 9 (3): 233-245

  Abstract

  The merits of separate versus composite valve graft replacement for the treatment of patients with ascending aortic aneurysms or dissections associated with aortic valve disease remain a controversial issue. Considering all available clinical data, the early and late results surprisingly are quite similar between the two procedures. However, patient selection criteria and operative technique are important. In patients with the Marfan syndrome and in those with significantly diseased or destroyed sinuses, composite valve graft replacement is the procedure of choice. The "open" (Carrel button) method of coronary reimplantation is recommended in almost all cases to minimize the risk of late false aneurysm formation. If the aortic leaflets are normal, a valve-sparing aortic root remodeling procedure is a reasonable alternative in certain individuals. Separate valve graft replacement is still a satisfactory option in other (non-Marfan) patients; however, most of the sinuses should be resected, leaving only small tongues of aortic wall surrounding the coronary ostia to reduce the risk of late aortic root aneurysmal degeneration. In patients with complex prosthetic valve endocarditis or multiple paravalvular leaks, homograft aortic root replacement is a good option after radical debridement of all infected or devitalized tissue.

  View details for PubMedID 9263342

• Acute rupture of the descending thoracic aorta: Repair with use of endovascular stent-grafts JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Semba, C. P., Kato, N., Kee, S. T., Lee, G. K., Mitchell, R. S., Miller, D. C., Dake, M. D. 1997; 8 (3): 337-342

  Abstract

  To describe the use of endovascular stent-grafts to treat acute ruptures of the descending thoracic aorta as an alternative to surgery in high-risk patients.From July 1992 to August 1996, 95 patients underwent stent-grafting of the descending thoracic aorta for a variety of lesions. Of these, 11 patients with acute (< or = 7 days) rupture from aneurysms (n = 8) or trauma (n = 3) underwent repair with use of endovascular stent-grafts. Rupture was confirmed with preoperative imaging studies and occurred in the mediastinum (n = 9), the pleural space (n = 1), or the lung (n = 1). All patients were considered high surgical risk due to generalized cardiopulmonary disease and/or previous thoracotomies. Stent-grafts were constructed from Z stents covered with polyester fabric and delivered through a catheter under fluoroscopic control from a remote access site.Stent-graft deployment was successful in all patients. There were no complications of perigraft leak, stent migration, paraplegia, or intraoperative death. Two patients died in the follow-up period: one of ventricular perforation during unrelated thoracic surgery for tumor resection (day 1) and one of cardiac arrest (day 28). All others are alive (mean follow-up, 15.1 months).For acute rupture of the thoracic aorta, endovascular stent-graft repair is technically feasible and may be a therapeutic alternative to a surgical interposition graft in patients considered high risk for conventional thoracotomy. Long-term studies are necessary to determine the role of stent-grafts in preventing future aortic rupture.

  View details for PubMedID 9152904

• Effects of mechanical left ventricular support on right ventricular diastolic function 16th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation Moon, M. R., DeAnda, A., Castro, L. J., Daughters, G. T., Ingels, N. B., Miller, D. C. MOSBY-YEAR BOOK INC. 1997: 398–407

  Abstract

  Previous studies have shown that left ventricular (LV) unloading alters right ventricular (RV) systolic mechanics, but the effects of LV assist device (LVAD) support on RV diastolic function have not been examined in intact subjects.Seven closed-chest, sedated dogs were studied after placement of a LVAD and 27 myocardial markers; in four animals, a right coronary artery occluder was placed to induce acute RV free wall ischemia. Data were recorded with the LVAD off and LVAD on before (control) and during RV ischemia. Assessment of RV diastolic function included RV myocardial relaxation (time constant of isovolumic pressure decay [tau]), RV chamber stiffness (slope of the end-diastolic pressure-volume relation), and RV filling dynamics (peak filling rate and mean filling rate during early diastole).During control, full LVAD support did not alter RV tau (104 +/- 67 msec LVAD off versus 109 +/- 49 msec LVAD on, p > 0.50), RV diastolic stiffness (0.56 +/- 0.31 versus 0.51 +/- 0.25 mm Hg/ml, p > 0.20), peak filling rate (107 +/- 51 versus 119 +/- 82 ml/sec, p > 0.35) or mean filling rate during early diastole (32 +/- 28 versus 27 +/- 18 ml/sec, p > 0.40). With right coronary artery occlusion, RV tau rose to 136 +/- 33 msec (p < 0.001), and RV diastolic stiffness fell to 0.29 +/- 0.13 mm Hg/ml (p < 0.005), but there was no change in RV filling rates (p > 0.20). With mechanical LV support during acute RV ischemia, there was no additional change in RV tau, diastolic stiffness, or filling dynamics (p > 0.20).In intact animals, RV ischemia impaired RV relaxation and decreased chamber stiffness, but there was no change in RV filling rates. Mechanical LV support, during the control state and with RV ischemia, did not affect RV diastolic performance.

  View details for PubMedID 9154950

• Septal function during left ventricular unloading CIRCULATION Moon, M. R., Bolger, A. F., DeAnda, A., Komeda, M., Daughters, G. T., Nikolic, S. D., Miller, D. C., Ingels, N. B. 1997; 95 (5): 1320-1327

  Abstract

  Left ventricular (LV) unloading with mechanical support devices alters biventricular geometry and impairs right ventricular (RV) contractility, but its effect on septal systolic function remains unknown.To evaluate the effects of LV volume and pressure unloading on septal geometry and function, LV preload was abruptly reduced by clamping left atrial pressure between 0 and -2 mm Hg in seven open-chest, anesthetized dogs by use of a pressure-control servomechanism to withdraw blood from the left atrium. With left atrial pressure clamping, maximal LV pressure decreased 30 +/- 12% (mean +/- SD) (P < .0001) and LV end-diastolic cross-sectional area (determined by two-dimensional echocardiography) decreased by 53 +/- 16% (P < .0001). This caused the septum to shift toward the left (RV septal free-wall dimension increased; P < .004) and flatten (radius of curvature increased; P < .0002), while LV septal free-wall dimension fell (P < .0001). Septal end-diastolic thickness increased 23 +/- 15% (P < .0005), reflecting a decline in septal preload. Systolic septal thickening decreased (P < .002), while systolic septal output (Septal Output = Septal Thickening x Heart Rate) fell from 30 +/- 17 to 15 +/- 22 cm/min (P < .002). This was associated with movement along the septal Frank-Starling equivalent (septal output versus end-diastolic septal thickness [preload] relation) to a less productive portion of the curve.LV unloading not only altered interventricular septal geometry but also reduced septal systolic thickening and output, all of which may contribute to impaired RV contractility during mechanical LV support.

  View details for Web of Science ID A1997WK42100036

  View details for PubMedID 9054866

• Papillary muscle - Left ventricular wall ''complex'' 76th Annual Meeting of the American-Association-for-Thoracic-Surgery Komeda, M., Glasson, J. R., Bolger, A. F., Daughters, G. T., Ingels, N. B., Miller, D. C. MOSBY-YEAR BOOK INC. 1997: 292–300

  Abstract

  Mitral valve homografts, despite theoretical advantages, are not widely used, in part because of lack of basic information about the three-dimensional geometry of the mitral apparatus.Radiopaque markers were used in the study of eight closed-chest dogs under four conditions: (1) baseline, (2) caval occlusion, (3) tachycardia (atrial pacing), and (4) nitroprusside infusion. Using a cylindrical coordinate system. defined with the origin at the midpoint between the anterior and posterior commissures, and the left ventricular long axis (z-axis), defined by the origin and the left ventricular apex, DTIP-MA (the z-coordinate [millimeters] of the papillary muscle tip), was measured at 10 time points throughout the entire cardiac cycle. DBASE-MA (the z-coordinate of the papillary muscle base) and LPM (the length of the papillary muscle [millimeters]) were also measured.DTIP-MA varied slightly with time (p < 0.001 by analysis of variance), but the magnitude of change was negligible (< 0.9 mm) (e.g., DTIP-MA of the anterior papillary muscle was 20.7 +/- 2.7/20.8 +/- 2.8 [end-diastolic/end-systolic, mean +/- 1 standard deviation]; DTIP-MA of the posterior papillary muscle was 25.8 +/- 4.8/25.5 +/- 4.5). DTIP-MA was minimally influenced by the above perturbations. DBASE-MA and LPM of each papillary muscle, however, changed throughout the cardiac cycle (p < 0.001 by analysis of variance) by about 4 mm, and both parameters were dependent on loading conditions.Papillary muscle length changed to keep the DTIP-MA distance constant such that the papillary muscle and left ventricular wall functioned together as a unit ("J-shaped complex"). These results provide a physiologic rationale for measuring DTIP-MA, define its potential surgical usefulness, and imply that using the entire length of the donor's papillary muscle (i.e., maintaining the entire J-shaped complex) is important in operations in which homograft or stentless xenograft mitral valves are used.

  View details for PubMedID 9040623

• Simultaneous abdominal aortic replacement and thoracic stent-graft placement for multilevel aortic disease Joint Annual Meeting of the Society-for-Vascular-Surgery and the North-American-Chapter of the International-Society-for-Cardiovascular-Surgery Moon, M. R., Mitchell, R. S., Dake, M. D., Zarins, C. K., Fann, J. I., Miller, D. C. MOSBY-YEAR BOOK INC. 1997: 332–40

  Abstract

  Patients with aneurysmal disease involving both the descending thoracic and abdominal aorta have historically required simultaneous or sequential conventional operations, but the morbidity rate is high with either approach in these patients, who often exhibit coexisting cardiopulmonary disease. Transluminally placed endovascular grafts have recently been developed for repair of aortic aneurysms, and we have implemented these techniques to eliminate the need for a thoracotomy in patients with multilevel aortic disease.Since January 1994, 18 patients have undergone conventional abdominal aortic replacement with endovascular stent-graft placement into the descending thoracic aorta under fluoroscopic guidance through a 10 mm Dacron side limb off the abdominal graft. Abdominal aortic replacement required a tube graft in eight patients and bifurcated grafts in 10 patients. Thoracic stent-grafts (custom fabricated, woven Dacron covered, self-expandable stents) averaged 12.2 +/- 4.2 cm (mean +/- SD) in length.One patient died, resulting in a hospital mortality rate of 6%. No patients required further surgical intervention to treat their aortic disease. Seventeen patients (94%) are currently well 14 +/- 8 months after surgery (range, 3 to 29 months) with completely excluded thoracic aortic disease, no stent migration, and no change in stent configuration documented by serial radiologic examinations.Simultaneous abdominal aortic replacement and deployment of a thoracic stent-graft can safely exclude multilevel aortic aneurysmal disease and may be a valuable treatment option for these otherwise high-risk patients.

  View details for PubMedID 9052568

• Thoracic aortic aneurysm repair with endovascular stent-grafts. Vascular medicine Semba, C. P., Mitchell, R. S., Miller, D. C., Kato, N., Kee, S. T., Chen, J. T., Dake, M. D. 1997; 2 (2): 98-103

  Abstract

  The purpose of the study was to describe the clinical experience is using endoluminal stent-grafts for the treatment of thoracic aortic aneurysms in high-risk patients. Patients with aneurysms of the descending thoracic aorta who were considered high surgical risks underwent evaluation for endoluminal repair. The prosthesis was constructed from Z stents covered with polyester fabric using dimensions based upon preprocedural computed tomography scans and angiography. Through a femoral arteriotomy or left retroperitoneal flank incision, a 22-24 Fr delivery catheter was inserted and advanced through the aorta to the target site under fluoroscopic guidance in the operating suite. The stent-graft prosthesis was deployed at the site of the aneurysm. 44 patients (36 male, 8 female; mean age 36 years) underwent stent-graft repair for thoracic aneurysms (mean diameter 6.3 cm). The deployment was technically successful in all cases, with complete aneurysm thrombosis in 88%. The 30-day perioperative mortality rate was 6.8% and 35-month actuarial survival was 82%. There were no cases of stent migration, surgical conversion or intraprocedural death. Paraplegia occurred in two patients who underwent simultaneous surgical infrarenal aortic aneurysm repair immediately followed by stent-graft placement for a coexisting thoracic aneurysm. The conclusion was that placement of endoluminal stent-grafts for repair of thoracic aortic aneurysms is technically feasible in high-risk patients in whom conventional surgery is contraindicated. Long-term studies are needed to determine protection against aneurysm rupture and patient survival.

  View details for PubMedID 9546963

• Twenty-year clinical experience with porcine bioprostheses 32nd Annual Meeting of the Society-of-Thoracic-Surgeons Fann, J. I., Miller, D. C., Moore, K. A., Mitchell, R. S., Oyer, P. E., Stinson, E. B., Robbins, R. C., Reitz, B. A., Shumway, N. E. ELSEVIER SCIENCE INC. 1996: 1301–11

  Abstract

  For the past 25 years, porcine valves have been the most widely implanted bioprosthesis, thereby becoming the standard for comparison with newer bioprosthetic valves.We retrospectively analyzed 2,879 patients who underwent aortic (AVR; n = 1,594) or mitral (MVR; n = 1,285) valve replacement between 1971 and 1990. Follow-up was 97% complete and extended to 20 years (total, 17,976 patient-years). Patient age ranged from 16 to 94 years; mean age in patients who underwent AVR was 60 +/- 15 (+/- standard deviation) years; that for patients who underwent MVR was 58 +/- 13 years.The operative mortality rates were 7% +/- 1% (70% confidence limits) for AVR and 10% +/- 1% for MVR. Actuarial estimates of freedom from structural valve deterioration at 10 and 15 years were 78% +/- 2% (SE) and 49% +/- 4%, respectively, for the AVR subgroup; and 69% +/- 2% and 32% +/- 4%, respectively, for the MVR subgroup (AVR > MVR; p < 0.05). Estimates of freedom from reoperation at 10 and 15 years were 76% +/- 2% and 53% +/- 4%, respectively, for the AVR subgroup and 70% +/- 2% and 33% +/- 4%, respectively, for the MVR subgroup (AVR > MVR; p < 0.05). Estimates of freedom from thromboembolism at 10 and 15 years were 92% +/- 1% and 87% +/- 2%, respectively, for the AVR subgroup and 86% +/- 1% and 77% +/- 3%, respectively, for the MVR subgroup (AVR > MVR; p < 0.05). Estimates of freedom from anticoagulant-related hemorrhage at 10 and 15 years were both 96% +/- 1% for the AVR subgroup and 93% +/- 1% and 90% +/- 2%, respectively, for the MVR subgroup (AVR > MVR; p < 0.05). Estimates of freedom from valve-related mortality at 10 and 15 years were 86% +/- 1% and 78% +/- 3%, respectively, for the AVR subgroup and 84% +/- 2% and 70% +/- 4%, respectively, for the MVR subgroup (p = not significant). Multivariate analysis (Cox model) showed younger age, later year of operation, and valve site (MVR > AVR) to be significant risk factors for structural valve deterioration. Younger age, later year of operation, valve site (MVR > AVR), and renal insufficiency were the significant, independent risk factors for reoperation. Multivariate analysis revealed that higher New York Heart Association functional class, longer cardiopulmonary bypass time, congestive heart failure, renal insufficiency, and longer cross-clamp time were significant risk factors for valve-related mortality. Valve manufacturer did not emerge as a factor in any analysis.These long-term results with porcine bioprostheses were satisfactory, particularly in older patients and those undergoing AVR. As expected, younger age was a significant risk factor for structural valve deterioration and reoperation in both groups. Surprisingly, the durability of porcine bioprosthetic valves has not improved over time, which possibly can be attributed to more enhanced postoperative surveillance and earlier reintervention. These first-generation Hancock and Carpentier-Edwards porcine bioprostheses achieved similar long-term performance.

  View details for PubMedID 8893561

• Effects of chordal disruption on regional left ventricular torsional deformation Moon, M. R., DeAnda, A., Daughters, G. T., Ingels, N. B., Miller, C. AMER HEART ASSOC. 1996: 143-151

  View details for Web of Science ID A1996VP69000027

• Loss of three-dimensional canine mitral annular systolic contraction with reduced left ventricular volumes CIRCULATION Glasson, J. R., Komeda, M., Daughters, G. T., Bolger, A. F., Ingels, N. B., Miller, D. C. 1996; 94 (9): 152-158

  View details for Web of Science ID A1996VP69000028

• Three-dimensional dynamic geometry of the normal canine mitral annulus and papillary muscles. Circulation Komeda, M., Glasson, J. R., Bolger, A. F., Daughters, G. T., Niczyporuk, M. A., Ingels, N. B., Miller, D. C. 1996; 94 (9): II159-63

  Abstract

  Despite an incomplete knowledge of the geometry and dynamics of the mitral annulus (MA), papillary muscle (PM), and the chordae tendineac, chordal-sparing MVR is popular.The systolic reduction in three-dimensional distance between each PM tip and eight MA sites (DT-A) was measured in nine normal closed-chest dogs by use of surgically implanted radiopaque markers. Three loci (tip, junction, and base) on each PM were also projected onto the MA plane at end diastole and end systole to assess PM dynamics. The anterior PM tip showed significant shortening of DT-A toward the opposite side of the MA or the midanterior MA region (P < .005 or P < .05, respectively, versus same MA side [MANOVA]); conversely, the posterior PM tip DT-A shortened toward the opposite side of the MA near the anterior commissure or the area between the anterior commissure and midposterior MA (P < .005 versus same MA side). Annular projection revealed three-dimensional motion (relative to the MA) of the anterior PM tip, junction, and base toward the right trigone, while posterior PM motion was oriented toward the opposite side of the MA.Both PMs in normal canine hearts demonstrated systolic relative motion in a direction compatible with the "oblique" chordal configuration, ie, from the anterior PM to the anterior MA near the right trigone and from the posterior PM to the opposite side of the posterior MA. These observations warrant further investigation of three-dimensional PM-MA dynamics with various methods of chorda preservation during MVR to assess their impact on left ventricular systolic and diastolic function.

  View details for PubMedID 8901738

• Loss of three-dimensional canine mitral annular systolic contraction with reduced left ventricular volumes. Circulation Glasson, J. R., Komeda, M., Daughters, G. T., Bolger, A. F., Ingels, N. B., Miller, D. C. 1996; 94 (9): II152-8

  Abstract

  We have recently described an inhomogeneous pattern of systolic contraction of the mitral annulus (MA) in normovolemic dogs: the posterior annulus shortens, and the anterior annulus lengthens. MA dynamics, however, have not been studied in volume-depleted hearts.Eight radiopaque markers were placed equidistant from each other around the MA in seven dogs. As viewed from the left atrium, the segment between markers 1 and 2 (seg12) began at the posteromedial commissure, and remaining segments were numbered sequentially clockwise around the MA (ie, posterior MA encompassed seg12, seg23, seg34, and seg45; anterior MA encompassed seg56, seg67, seg78, and seg81). Marker images were obtained in sedated dogs by simultaneous biplane videofluoroscopy 7 to 12 days after marker implantation, and three-dimensional marker coordinates at end diastole (ED) and end systole (ES) were computed. Vena caval occlusion (VCO) was used to reduce left ventricular end-diastolic volume to 70 +/- 5% of baseline (BL). With VCO, mean MA area did not change from ED to ES (3.4 +/- 0.8 versus 3.6 +/- 0.7 cm2, P = NS) during the cardiac cycle. MA segmental systolic shortening values (negative values indicate lengthening) were as follows for BL and VCO, respectively (mean +/- SD): seg12, 7 +/- 9% and 0 +/- 13%; seg23, 8 +/- 10%* and 1 +/- 11%; seg34, 16 +/- 6%* and 4 +/- 9% seg45, 10 +/- 7%* and 2 +/- 13%; seg56, -4 +/- 5%* and -16 +/- 11%*; seg67, -7 +/- 7%* and -14 +/- 7%*; seg78, 3 +/- 2%* and -1 +/- 6%; and seg81, 6 +/- 5%* and -5 +/- 11% (*P < or = .05 versus zero changes, paired t test).With acute volume depletion, the five annular segments that shortened at BL no longer changed length; two anterior segments (seg56 and seg67) that lengthened at BL continued to lengthen significantly, and to a greater extent. These findings indicate that the anterior MA is a more dynamic structure than previously thought. Such dynamic motion may be important for normal mitral valvular function and possibly needs to be taken into account in the design of mitral valve reparative techniques.

  View details for PubMedID 8901737

• Effects of chordal disruption on regional left ventricular torsional deformation. Circulation Moon, M. R., DeAnda, A., Daughters, G. T., Ingels, N. B., Miller, D. C. 1996; 94 (9): II143-51

  Abstract

  Chordal excision during mitral valve replacement (MVR) impairs left ventricular (LV) systolic function, but the mechanisms responsible for this change remain unclear. This study was performed to determine the influence of annular papillary continuity on regional LV torsional deformation acutely following MVR with and without chordal preservation.Twenty-seven dogs underwent placement of LV subepicardial myocardial markers to measure regional LV systolic torsional deformation throughout the left ventricle. After 1 week, biplane fluoroscopic marker images were obtained pre-MVR in the baseline state and with inotropic stimulation (calcium, 15 mg/kg). Dogs were then randomized to undergo a sham procedure with cardiopulmonary bypass but no valve replacement (n = 6), conventional MVR with chordal excision (n = 7), or chordal-sparing MVR with preservation of the posterior leaflet and reattachment of the anterior leaflet chordae to either the anterior annulus (n = 7) or posterior annulus (n = 7). After chest closure and recovery from anesthesia, post-MVR data were acquired. At the LV apical level, maximal regional LV systolic torsional deformation (theta max) did not fall from pre-MVR values in the baseline state after the sham procedure or anterior or posterior chordal-sparing MVR procedure (P > or = .10). After conventional MVR, baseline theta max fell by 66% to 81% in the anteroseptal, anterior, anterolateral, and lateral regions (P < .05). With calcium, theta max fell in the anteroseptal through lateral regions and the septal wall (P < .05) but did not change in the posterior regions (P > or = .10). With calcium, theta max did not fall in any region after either the sham procedure or anterior MVR; however, after posterior chordal-sparing MVR, theta max fell in the lateral, posterior, and posteroseptal regions (P < .05).Sham operation and anterior chordal-sparing MVR did not affect regional LV torsion; however, loss of normal valvular-ventricular integrity with conventional MVR reduced regional LV systolic torsion in the anterior and lateral LV regions. Posterior chordal-sparing MVR impaired torsion only after calcium administration. The deleterious effects of chordal excision may be due in part to perturbation of regional systolic torsional deformation.

  View details for PubMedID 8901736

• Composite versus separate aortic valve and ascending aortic replacement - 30 year experience Yun, K. L., Fann, J. I., Miller, D. C., Mitchell, R. S., Robbins, R. C., Oyer, P. E., Stinson, E. B., Reitz, B. A., Shumway, N. E. LIPPINCOTT WILLIAMS & WILKINS. 1996: 1017–17

  View details for Web of Science ID A1996VN11901015

• Three-dimensional dynamics of the canine mitral annulus during ischemic mitral regurgitation 32nd Annual Meeting of the Society-of-Thoracic-Surgeons Glasson, J. R., Komeda, M., Daughters, G. T., Bolger, A. F., MacIsaac, A., Oesterle, S. N., Ingels, N. B., Miller, D. C. ELSEVIER SCIENCE INC. 1996: 1059–67

  Abstract

  It has been suggested that ischemic mitral regurgitation results, at least in part, from generalized end-systolic mitral annulus (MA) dilatation, but the role of the MA is incompletely understood and the segmental dynamics of the MA during left ventricular ischemia have not been described.We used radiopaque markers and simultaneous biplane videofluoroscopy to measure three-dimensional in vivo lengths of eight MA segments in 7 sedated dogs before and after induction of ischemic MR (produced by circumflex coronary artery balloon occlusion and verified by Doppler echocardiography). As viewed from the left atrium, the MA segment between markers 1 and 2 (S12) was defined as starting at the posteromedial commissure, and remaining segments were numbered sequentially clockwise around the MA (ie, the posterior MA encompassed S12, S23, S34, S45,; the anterior MA included S56, S67, S78, S81). Marker images obtained 7 to 12 days after implantation were used to construct x, y, and z coordinates of each marker at end-diastole and end-systole.During regional (posterolateral walls) left ventricular ischemia, the end-systolic MA area increased (4.9 +/- 0.8 cm2 [control] versus 5.9 +/- 0.6 cm2; p = 0.005). End-systolic MA segment lengths were as follows (control, ischemia [mm, mean +/- standard deviation]): S12 = 9 +/- 2, 10 +/- 3; S23 = 10 +/- 2, 12 +/- 3; S34 = 13 +/- 1, 15 +/- 1; S45 = 8 +/- 2, 9 +/- 2; S56 = 11 +/- 2, 11 +/- 2; S67 = 12 +/- 2, 12 +/- 2; S78 = 10 +/- 3, 11 +/- 2; and S81 = 11 +/- 1, 12 +/- 1. Values for S12, S23, S34, and S81 were significant (p < or = 0.05 for control versus ischemia by paired t test).During ischemic mitral regurgitation, the MA enlarged at end-systole, but in an asymmetric manner; most posterior annular segments lengthened, whereas most anterior annular segment lengths did not change. These data suggest that alterations in regional MA mechanics may be important in the pathogenesis of ischemic mitral regurgitation. Further three-dimensional studies of MA dynamics and shape should be conducted so that new knowledge may result in improved mitral valve surgical techniques.

  View details for PubMedID 8823090

• Radiographic detection of single strut leg separations as a putative basis for prophylactic explantation of Bjork-Shiley convexo-concave heart valves International Surgical Week Chandler, J. G., Hirsch, J. L., Oneill, W. W., Oesterle, S. N., Miller, D. C., Kennedy, J. A., Faichney, A. SPRINGER VERLAG. 1996: 953–60

  Abstract

  Cineradiography, using higher kVp and two or more specified profiles for each outlet strut leg, was used to evaluate Björk-Shiley convexo-concave (C/C) heart valves with epidemiologically defined > 0.1% per year estimated fracture rates. Among 828 mitral valves, eight radiographs were assessed as definite single leg separations (SLS) and 23 were read as probable SLS. Explantation confirmed SLS in 24 valves; 4 probables were false positives, and 3 patients with probable SLS ratings decided against explantation. Four patients with SLS died, an operative mortality of 14%. Only 23 mitral and 6 aortic valves receiving ratings ranging from apparently normal to suspicious have become available for verification; 1 rated apparently normal was found to have a SLS. Two patients experienced fatal fractures and 1 SLS valve was explanted 3 to 15 months after apparently normal x-ray studies; it cannot be known if a SLS was or was not present at the time of these examinations. As 97% of negatively rated valves remain in situ, the sensitivity of the test is similarly not known. Only 1 SLS has been detected among 136 aortic valves. Uncertainty about test accuracy and SLS progression condition the clinical utility of radiographic SLS detection, particularly with respect to assurance from apparently normal readings. However, radiographic identification of an SLS substantially enhances epidemiologically derived risk categorization as a basis for consideration of prophylactic replacement for the approximately 12,000 valves with a > 0.1% estimated annual fracture risk, currently thought to be implanted in living patients.

  View details for Web of Science ID A1996VH39700003

  View details for PubMedID 8798347

• True lumen obliteration in complicated aortic dissection: Endovascular treatment 1995 Annual Meeting of the Radiological-Society-of-North-America Slonim, S. M., NYMAN, U. R., Semba, C. P., Miller, D. C., Mitchell, R. S., Dake, M. D. RADIOLOGICAL SOC NORTH AMER. 1996: 161–66

  Abstract

  To evaluate endovascular treatment of ischemic complications caused by true lumen obliteration in aortic dissection.Endovascular techniques were used to treat true lumen obliteration in 11 patients with complicated aortic dissection. In all cases, the true lumen was compressed to a paper-thin sliver by the expanded false lumen. Two patients had Stanford type A (chronic) and nine had type B (six acute, three chronic) dissections. Obliteration of the true lumen was associated with branch vessel ischemia that included renal (n = 7), mesenteric (n = 6), and lower-extremity (n = 6) arterial compromise. Two patients were treated with aortic stents, four with balloon fenestration of the intimal flap, and three with both stent placement and fenestration. In two patients, ischemic complications caused by true lumen obliteration could not be treated with endovascular techniques.Revascularization was technically successful with relief of clinical symptoms in nine patients. Revascularization was unsuccessful in one patient in whom surgical revascularization of the superior mesenteric artery was necessary and in one in whom hypertension was managed medically. One patient developed thrombosis of a renal artery in which a stent had been placed. The 30-day mortality rate was 9%, and the mean follow-up was 10.1 months (range, 2 weeks to 39 months).True lumen obliteration can be safely and effectively treated with endovascular stent placement and balloon fenestration.

  View details for PubMedID 8816538

• Accuracy of biplane and multiplane transesophageal echocardiography in diagnosis of typical acute aortic dissection and intramural hematoma JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Keren, A., Kim, C. B., Hu, B. S., Eyngorina, I., Billingham, M. E., Mitchell, R. S., Miller, D. C., Popp, R. L., Schnittger, I. 1996; 28 (3): 627-636

  Abstract

  The purpose of this study was to evaluate the diagnostic accuracy of biplane and multiplane transesophageal echocardiography in patients with suspected aortic dissection, including intramural hematoma.Transesophageal echocardiography is a useful technique for rapid bedside evaluation of patients with suspected acute aortic dissection. The sensitivity of transesophageal echocardiography is high, but the diagnostic accuracy of biplane and multiplane transesophageal echocardiography for dissection and intramural hematoma is less well defined.We studied 112 consecutive patients at a major referral center who had undergone biplane or multiplane transesophageal echocardiography to identify aortic dissection. The presence, absence and type of aortic dissection (type A or B, typical dissection or intramural hematoma) were confirmed by operation or autopsy in 60 patients and by other imaging techniques in all. The accuracy of transesophageal echocardiography for ancillary findings of aortic dissection (intimal flap, fenestration and thrombosis) was assessed in the 60 patients with available surgical data.Of the 112 patients, aortic dissection was present in 49 (44%); 10 of these had intramural hematoma (5 with and 5 without involvement of the ascending aorta). Of the remaining 63 patients without dissection, 33 (29%) had aortic aneurysm and 30 (27%) had neither dissection nor aneurysm. The overall sensitivity and specificity of transesophageal echocardiography for the presence of dissection were 98% and 95%, respectively. The specificity for type A and type B dissection was 97% and 99%, respectively. The sensitivity and specificity for intramural hematoma was 90% and 99%, respectively. The accuracy of transesophageal echocardiography for diagnosis of acute significant aortic regurgitation and pericardial tamponade was 100%.Biplane and multiplane transesophageal echocardiography are highly accurate for prospective identification of the presence and site of aortic dissection, its ancillary findings and major complications in a large series of patients with varied aortic pathology. Intramural hematoma carries a high complication rate and should be treated identically with aortic dissection.

  View details for PubMedID 8772749

• Guidelines for reporting morbidity and mortality after cardiac valvular operations JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Edmunds, L. H., Clark, R. E., Cohn, L. H., Grunkemeier, G. L., Miller, D. C., Weisel, R. D. 1996; 112 (3): 708-711

  View details for Web of Science ID A1996VG35300019

  View details for PubMedID 8800159

• Guidelines for reporting morbidity and mortality after cardiac valvular operations EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Edmunds, L. H., Clark, R. E., Cohn, L. H., Grunkemeier, G. L., Miller, D. C., Weisel, R. D. 1996; 10 (9): 812-816

  Abstract

  At the request of the Councils of the Society of Thoracic Surgeons (STS) and the American Association of Thoracic Surgery (AATS) the Ad Hoc Liaison Committee for Standardizing Definitions of Prosthetic Heart Valve Morbidity reviewed the "Guidelines" published in September 1988 [3, 7, 8]. The purpose of the review was to update and clarify definitions within the guidelines and to consider recommendations made by other [2, 11]. The variety of cardiac valvular procedures has expanded since 1988; therefore, in this document the term "operated valve" indicates prosthetic and bioprosthetic heart valves of all types, operated or repaired native valves and allograft and autograft valves. The term "operated valve" includes any cardiac valve altered by a surgeon during an operation. Much morbidity and mortality is a direct consequence of the interaction between the patient and operated valve(s), although patient variables (e.g., age, degree of coronary arterial disease, follow-up care, etc.) may be more responsible for outcomes than an operated valve. However, no set of guidelines can identify all possible patient factors that may affect morbidity and mortality. General agreement regarding the following definitions of terms and suggestions for reporting data do not preclude more detailed analyses or constructive recommendations and investigators are encouraged to identify relevant patient factors in addition to factors related to operated valves. Purpose The purpose of these guidelines is to facilitate the analysis and reporting of results of operations on diseased cardiac valves. The definitions and recommendations that follow are guidelines, not standards, and are designed to facilitate comparisons between the experiences of different surgeons who treat different cohorts of patients at different times with different techniques and materials.

  View details for Web of Science ID A1996VP85800024

  View details for PubMedID 8905288

• Improving methods of chordal-sparing mitral valve replacement .3. Optimal direction for artificial chordae 68th Annual Meeting of the American-Heart-Association Komeda, M., DeAnda, A., Glasson, J. R., Daugthers, G. T., Bolger, A. F., Nikolic, S. D., Ingels, N. B., Miller, D. C. I C R PUBLISHERS. 1996: 484–90

  Abstract

  The optimal direction to preserve artificial chordae tendineae (CT) during mitral valve replacement (MVR) is not known, especially in regard to the response to inotropic stimulation which simulates exercise conditions.Using a non-distorting isovolumic balloon technique, we compared left ventricular (LV) systolic and diastolic mechanics in 11 dogs in a control state (no chordal sparing) and with four different methods of chordal preservation: posterior, anterior, oblique (anterior papillary muscle chordae directed anteriorly and others posteriorly, the direction which theoretically augments LV systolic twist), and counter-oblique (counter, chordae preserved in directions opposite to oblique).Before dobutamine, delta Emax from the control was: 0.32 +/- 0.82, 0.10 +/- 0.43, 0.64 +/- 1.07, and 0.51 +/- 0.78 (anterior, posterior, oblique, and counter method, respectively). With dobutamine (3 mg/kg/min), delta Emax (mmHg/ml) was: 0.41 +/- 1.21, -0.13 +/- 0.75, 0.59 +/- 0.82*, and -0.34 +/- 0.71. Before dobutamine, delta LV stiffness (Sd, mmHg/ml) was -0.01 +/- 0.09, -0.02 +/- 0.12, 0.02 +/- 0.10, and 0.01 +/- 0.12; with dobutamine it was 0.01 +/- 0.09, 0.00 +/- 0.15, 0.03 +/- 0.15, and -0.06 +/- 0.11. Similarly, before dobutamine delta LV equilibrium volume (Veq) was -1.2 +/- 3.8, -0.3 +/- 3.0, -0.7 +/- 2.7, and -0.2 +/- 3.5, whereas with dobutamine zeta eq was -0.1 +/- 1.1, -0.4 +/- 0.8, 0.6 +/- 1.7, and -0.4 +/- 1.1. (Mean +/- S.D.; *p = 0.005 posterior and counter by ANOVA; p = NS (< 0.06) versus counter and posterior by ANOVA).The oblique method enhanced systolic LV function both with and without dobutamine, while a tendency towards better diastolic LV function (Veq) was observed with dobutamine. The anterior method was next best in preserving systolic function, both with and without dobutamine. LV diastolic function tended to deteriorate with dobutamine in the posterior group. Systolic function with the counter method deteriorated with dobutamine. These results warrant further study in an ejecting model to investigate LV systolic and diastolic mechanics with the oblique method of CT preservation, including interactions with LV systolic twist and diastolic recoil.

  View details for PubMedID 8894987

• Improving methods of chordal-sparing mitral valve replacement .2. Optimal tension for chordal resuspension Chordal Replacement Colloquium Komeda, M., DeAnda, A., Glasson, J. R., Bolger, A. F., Nikolic, S. D., Ingels, N. B., Miller, D. C. I C R PUBLISHERS. 1996: 477–83

  Abstract

  Although chordal-sparing mitral valve replacement (MVR) is popular, the optimal tension for preserved or reattached chordae tendineae (CT) or for synthetic (ePTFE) CT is unknown.Changes in left ventricular (LV) systolic and diastolic function in nine dogs with anterior CT preservation with different levels of end-diastolic chordal tension (0, 10, 20, 30, and 40 gm, measured by spring scale) were compared using an isovolumic double-balloon technique.LV function data at each level of tension were compared to control data using 0 gm of tension. Systolic function assessed as Emax (mmHg/ml) at 10, 20, 30, and 40 gm versus control was: 5.7 +/- 2.6/4.9 +/- 2.7, 4.7 +/- 2.2/4.7 +/- 2.7, 4.8 +/- 3.1/4.7 +/- 2.8, and 5.0 +/- 3.5/5.1 +/- 2.9; delta improvement from the control at 10 gm was larger than that at 20 gm (p < 0.05 by paired t-test). Diastolic function assessed as diastolic stiffness (Sd, mmHg/ml) at the same CT tensions versus control was: 0.56 +/- 0.23/0.56 +/- 0.34, 0.53 +/- 0.30/0.57 +/- 0.37, 0.56 +/- 0.39/0.52 +/- 0.38, and 0.60 +/- 0.36/0.58 +/- 0.39; delta Sd was smaller at 20 gm than at 30 gm (p = 0.05 by ANOVA). LV equilibrium volume (Veq, ml) was: 10.7 +/- 3.9/10.1 +/- 3.9, 9.6 +/- 3.4/9.9 +/- 3.8, 10.8 +/- 4.0/10.3 +/- 3.4, and 10.6 +/- 4.0/10.6 +/- 3.5; delta Veq was larger (i.e., more compliant chamber) at 10 gm than at 40 gm (p < 0.05 by rm-ANOVA). Arrhythmias precluding satisfactory measurements occurred in two dogs at 30 or 40 gm CT tension.With chordal tension exceeding 10 gm, which is barely palpable, there was no additional enhancement in LV systolic function compared to zero CT tension. Veq was largest at the lowest tension; LV diastolic function (assessed as Sd) deteriorated with tensions of 30 gm or higher. The optimal end-diastolic tension of preserved CT should enhance systolic LV performance without adversely affecting diastolic function; in this isovolumic model, minimal CT tension (10 gm) best met these goals. Excessive tension may negate the potential hemodynamic benefits of chordal preservation during mitral valve replacement.

  View details for PubMedID 8894986

• Improving methods of chordal sparing mitral valve replacement .1. A new, non-distorting isovolumic balloon preparation for the left ventricle with intact mitral subvalvular apparatus Chordal Replacement Colloquium Komeda, M., Bolger, A. F., DeAnda, A., Tomizawa, Y., Ingels, N. B., Miller, C. I C R PUBLISHERS. 1996: 376–82

  Abstract

  The conventional isovolumic preparation with a single balloon, although employed for many years, distorts the chordae tendineae of the intact mitral apparatus.Anterior balloon (one balloon inserted via a slit in the anterior leaflet) and double balloon (two balloons through slits in both leaflets) methods were developed and compared to the conventional method and natural conditions (LV filled with saline, or 'gold standard') in six ex-vivo, non-beating porcine hearts.LV volumes measured by the double balloon, anterior balloon, and conventional techniques all correlated highly with natural conditions, but the conventional method had a lower correlation coefficient (r = 0.99, 0.98, p < 0.0001 and < 0.001; and 0.92 p < 0.01, respectively at a left ventricular (LV) pressure of 50 mmHg, while r = 1.00, 1.00, both p < 0.0001; and 0.92, p < 0.01, respectively at 70 mmHg). Epicardial echocardiography revealed that the double balloon technique filled the space behind the chordae while maintaining normal chordal geometry, but the anterior balloon alone did not (p < 0.001). Similarly, the conventional method did not fill the LV outflow tract (p < 0.001) and had a mitral annular shift toward the left atrium (p < 0.001). Photography of both leaflets showed that only the double balloon method maintained normal geometry as assessed by leaflet length ratio; the other methods produced distorted geometry compared to natural filling conditions.With an intact mitral valve, the double balloon method provides more precise LV pressure-volume measurements while preserving the normal geometry of the chordae tendineae and mitral annulus.

  View details for PubMedID 8858501

• Porcine valves: Hancock and Carpentier-Edwards aortic prostheses. Seminars in thoracic and cardiovascular surgery Fann, J. I., Miller, D. C. 1996; 8 (3): 259-268

  Abstract

  Hancock and Carpentier-Edwards porcine bioprostheses are the two most widely implanted biological valves and have become the standard by which the performance of newer tissue valves are measured. New guidelines for reporting valve-related complications have provided more comprehensive evaluations and meaningful comparison of the long-term results of valve substitutes. Clinical investigations directly comparing the Hancock and Carpentier-Edwards bioprostheses have shown no significant differences in the long-term performance of these two valves. The incidence of structural valve deterioration for porcine bioprostheses begins to increase 5 to 6 years after implantation. For patients undergoing aortic valve replacement, estimates of freedom from structural valve deterioration at 10 and 15 years range from 76% to 91% and 37% to 63%, respectively. The incidence of structural valve deterioration may be offset by the limited survival of older patients; thus, the durability of a bioprosthesis may be sufficient for the majority of these patients. The long-term results of the porcine bioprosthesis have been satisfactory, particularly in older patients and those undergoing aortic valve replacement. The performance of the Hancock modified orifice (MO) bioprosthesis is comparable with that of other bioprostheses despite its more complex fabrication process. Although it does not offer any distinct advantages in terms of durability, the Hancock MO valve is associated with lower pressure gradients and larger calculated valve areas compared with other porcine valves in the smaller sizes. Based on currently available data, there are no distinct differences in the performance of the second-generation porcine bioprostheses compared with the first-generation valves, and any purported advantages need to be confirmed with long-term evaluations.

  View details for PubMedID 8843517

• Endovascular stent-graft repair of thoracic aortic aneurysms 21st Annual Meeting of the Western-Thoracic-Surgical-Association Mitchell, R. S., Dake, M. D., Semba, C. P., Fogarty, T. J., Zarins, C. K., Liddell, R. P., Miller, D. C. MOSBY-YEAR BOOK INC. 1996: 1054–60

  Abstract

  Conventional repair of aneurysms of the descending thoracic aorta entails thoracotomy and graft interposition. For elderly patients and those with previous operations, obesity, respiratory insufficiency, or other comorbidities, such a procedure entails significant mortality and morbidity. Transluminal stent-graft placement offers an alternative approach with potentially less morbidity and quicker recovery; however, the effectiveness and durability of stent-grafts remain uncertain.Since July 1992, thoracic aortic stent-grafts have been placed in 44 patients with a variety of pathologic conditions. Each graft was individually constructed from self- expanding, stainless-steel Z stents covered with a woven Dacron polyester fabric graft. Craft dimensions were determined from spiral computed tomographic scans. All implants were performed in the operating theater under fluoroscopic and transesophageal echocardiographic guidance. Follow-up was by computed tomography and contrast angiography in all cases. PATIENT DATA: There were 36 men and 8 women. Mean age was 66 years (range 35 to 88 years). Mean aneurysmal diameter was 6.3 cm (range 4.0 to 9.4 cm). Etiologies included 23 degenerative aneurysms, four posttraumatic aneurysms, four pseudoaneurysms, and one chronic aortic dissection.There were three early deaths (<30 days) and two late deaths. One early death resulted from graft failure. There were two instances of paraparesis or paraplegia, with one associated early death. A single stent was deployed in 27 patients, two stents were required in 14 patients, and three stents were required in three patients. In 23 patients, vascular access was attained through the femoral artery; abdominal aortic access, either native or graft, was necessary in the remaining 21 patients. Twelve grafts were placed in conjunction with open abdominal aortic surgical procedures. Mean follow-up (98% complete) was 12.6 months (range 1 to 34 months). One late death occurred from aneurysmal expansion and rupture in a patient with a persistent midgraft leak. The second late death may have resulted from aneurysmal rupture. Immediate thrombosis was achieved in 36 patients, and late thrombosis was achieved in three others. Failure to achieve complete aneurysmal thrombosis occurred in five patients, however, and one individual (previously noted) died of aneurysmal expansion and rupture; the remaining four are being carefully monitored. Only one patient has required conversion of the stent to an open procedure; a contained rupture of the false lumen of a chronic dissection eventually necessitated total descending thoracic aortic exclusion.These early results support the hypothesis that endovascular stent-graft placement may be a safe and durable treatment for selected patients with aneurysmal disease of the descending thoracic aorta. Large introducer size (26F outer diameter) and relatively limited angulation capability, as well as imprecise deployment techniques, currently limit its applicability. Distal embolization and stent migration have not been observed. Failure to achieve complete aneurysmal thrombosis may allow continued aneurysmal expansion and rupture. Further follow-up is clearly necessary to evaluate the true long-term effectiveness of this procedure.

  View details for PubMedID 8622303

• Left ventricular diastolic suction with zero left atrial pressure in open-chest dogs AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Ingels, N. B., Daughters, G. T., Nikolic, S. D., DeAnda, A., Moon, M. R., Bolger, A. F., Komeda, M., Derby, G. C., Yellin, E. L., Miller, D. C. 1996; 270 (4): H1217-H1224

  Abstract

  We investigated left ventricular (LV) diastolic volume changes (suction inflows) with left atrial pressure (LAP) clamped to ambient pressure in six open-chest, anesthetized dogs. The left atrium was cannulated and connected to a servo pump, and LAP was clamped to a set point near 0 mmHg for four beats by withdrawing blood. LAP averaged 5.88 +/- 1.44 mmHg before the clamp and fell to 0.74 +/- 0.61 mmHg (P < 0.0001) after the clamp. During the first clamped beat a transmitral pressure gradient of 1.0 +/- 0.6 mmHg was observed, resulting in LV filling of 2.6 +/- 1.8 ml. Subsequent beats developed suction-driven (mean negative LV pressure: -1.5 +/- 1.3 mmHg; P < 0.005 vs. zero) LV filling of 4.5 +/- 2.8 ml/beat with a peak transmitral pressure gradient of 1.7 +/- 0.6 mmHg. These data are consistent with the hypothesis that LV suction can be an important filling mechanism under condition in which LV end-systolic volume is reduced, e.g., reduced filling pressures, high heart rates, exercise, or increased inotropic drive.

  View details for Web of Science ID A1996UE41600010

  View details for PubMedID 8967359

• Three-dimensional regional dynamics of the normal mitral anulus during left ventricular ejection JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Glasson, J. R., Komeda, M., Daughters, G. T., Niczyporuk, M. A., Bolger, A. F., Ingels, N. B., Miller, D. C. 1996; 111 (3): 574-584

  Abstract

  The mitral anulus is a dynamic structure that undergoes alterations in size and shape throughout the cardiac cycle, contracting during systole. Numerous reports have shown this systolic orifice reduction to be due chiefly to posterior annular contraction, whereas the anterior perimeter was unchanged. Segmental motion of the mitral anulus from true in vivo three-dimensional data, however, has not been described. We used radiopaque markers and simultaneous biplane videofluoroscopy to measure the lengths of mitral anular segments in seven closed-chest, sedated dogs. Eight markers were placed equidistant from each other around the mitral anulus, As viewed from the left atrium, segment 1 began at the posteromedial commissure, and the remaining segments were numbered sequentially clockwise around the anulus (that is, the posterior mitral anulus encompassed segments 1 to 4 and the anterior anulus encompassed segments 5 to 8). Marker image coordinates obtained from two orthogonal views 7 to 12 days after implantation were merged to construct three-dimensional marker coordinates at end-diastole and end-systole. From end-diastole to end-systole, mean annular area decreased by 11% +/- 8% (5.5 +/- 0.9 cm2 to 4.9 +/- 0.8 cm2, p = 0.005) and perimeter by 5% +/- 4% (8.8 +/- 0.7 cm to 8.3 +/- 0.7 cm, p < 0.01). Mitral annular segmental percent systolic shortening (negative values indicate lengthening) were as follows (mean +/- standard deviation): segment 1, 7% +/- 9%; segment 2, 8% +/- 10%; segment 3, 16% +/- 6%; segment 4, 10% +/- 7%; segment 5, -4% +/- 5%, segment 6, -7% +/-7%; segment 7, 3% +/- 2%; and segment 8, 6% +/- 5%. With the exception of segment 1, all posterior (2 to 4) and two anterior (7 and 8) mitral annular segments contracted significantly (p < or = vs zero, paired t test). Two anterior annular segments (5 and 6, regions overlapping aortic-mitral continuity), however, unexpectedly lengthened during left ventricular systole. We conclude that the anterior mitral anulus may be a much more dynamic component of the mitral apparatus that previously thought. Such heterogeneous dynamic annular motion should be taken into account when various mitral valve reparative techniques are being designed.

  View details for PubMedID 8601972

• Aortic dissection: Percutaneous management of ischemic complications with endovascular stents and balloon fenestration 49th Annual Meeting of the Society-for-Vascular-Surgery Slonim, S. M., Nyman, U., Semba, C. P., Miller, D. C., Mitchell, R. S., Dake, M. D. MOSBY-ELSEVIER. 1996: 241–51

  Abstract

  The purpose of this study was to evaluate endovascular stenting (EVS) and balloon fenestration (BF) of intimal flaps for the management of lower extremity, renal, and visceral ischemia in acute or chronic aortic dissection.Twenty-two patients (16 male, 6 female) with a median age of 53 years (range 35 to 77 years) underwent percutaneous treatment for peripheral ischemic complications of 12 type A (five acute, seven chronic) and 10 type B (nine acute, one chronic) aortic dissections.Ten patients had leg ischemia, 13 had renal ischemia, and 6 had visceral ischemia. Sixteen patients were treated with EVS including 11 with renal, 6 with lower extremity, 2 with superior mesenteric artery, and 2 with aortic stents. Three patients had BF of the intimal flap, and three had BF in combination with EVS. Revascularization with clinical success was achieved in all 22 patients. Two patients died 3 days and 13.4 months after the procedure was performed, respectively. Of the remaining 20 patients, 1 is lost to follow-up, and 19 have persistent relief of clinical symptoms. Mean follow-up time is 13.7 months (range 1.1 to 46.5 months). One case was complicated by guidewire-induced perinephric hematoma.EVS and BF provide a safe and effective percutaneous method for managing peripheral ischemic complications of aortic dissection.

  View details for PubMedID 8637101

• Exploring better methods to preserve the chordae tendineae during mitral valve replacement 31st Annual Meeting of the Society-of-Thoracic-Surgeons Komeda, M., DeAnda, A., Glasson, J. R., Bolger, A. F., Tomizawa, Y., Daughters, G. T., Tye, T. L., Ingels, N. B., Miller, D. C. ELSEVIER SCIENCE INC. 1995: 1652–57

  Abstract

  It is not known how best to resuspend the mitral chordae tendineae during mitral valve replacement to optimize postoperative left ventricular (LV) systolic and diastolic function.Six different techniques to preserve the chordae during mitral valve replacement were compared in 12 dogs using a nondistorting isovolumic technique: conventional, all chordae severed; anterior, all chordae preserved anteriorly; partial, anterior papillary muscle chordae preserved anteriorly; posterior, all chordae preserved posteriorly; oblique, anterior papillary muscle chordae directed anteriorly and posterior papillary muscle chordae posteriorly; and counter, opposite of oblique chordal direction. Control measurements (no chordal tension) were recorded between each experimental condition.The oblique method tended to have the best LV systolic function versus the conventional method (Emax = 4.0 +/- 1.8 versus 3.3 +/- 1.2 mm Hg/mL [mean +/- standard deviation]; p = 0.08 by repeated-measures analysis of variance; physiologic intercept Ees100 = 20.3 +/- 8.6 mL [p < 0.05 versus control]), with no major change in LV diastolic stiffness. The posterior method had a lower Emax (3.3 +/- 1.2 mm Hg/mL) than the oblique method, but a similar Ees100 (20.8 +/-8.1 mL; p < 0.05 versus control) and the best diastolic LV performance (LV diastolic stiffness = 0.46 +/- 0.23 mm Hg/mL). The counter method also had good systolic function (Emax = 3.8 +/- 1.2 mm Hg/mL; Ees100 = 19.7 +/- 7.5 mL; p < 0.05 versus control), but had less favorable diastolic properties (0.65 +/- 0.37 mm Hg/mL; p < 0.05 by repeated-measures analysis of variance versus posterior).In this isovolumic preparation in normal canine hearts, the oblique method of chordal resuspension was associated with the best LV systolic function, whereas the counter technique impaired LV diastolic function. These preliminary results warrant further study in ejecting and failing hearts to determine conclusively which chordal orientation best preserves LV performance after mitral valve replacement.

  View details for PubMedID 8787458

• Surgical management of aortic dissection during a 30-year period. Circulation Fann, J. I., Smith, J. A., Miller, D. C., Mitchell, R. S., Moore, K. A., Grunkemeier, G., Stinson, E. B., Oyer, P. E., Reitz, B. A., Shumway, N. E. 1995; 92 (9): II113-21

  Abstract

  Certain recent studies have demonstrated improved surgical outcome in patients with aortic dissection. We analyzed the surgical survival rates of patients with acute aortic dissections and the late prognosis of those with aortic dissection during a 30-year period.Between 1963 and 1992, 360 patients (256 men and 104 women; mean +/- 1 SD age, 57 +/- 14 years) underwent surgery for aortic dissection: 174 patients had an acute type A (AcA), 46 an acute type B (AcB), 106 a chronic type A (ChA), and 34 a chronic type B (ChB) aortic dissection. The overall operative mortality rate was 24 +/- 8% (26 +/- 3% for AcA, 39 +/- 8% for AcB, 17 +/- 4% for ChA, and 15 +/- 6% for ChB, [+/- 70% confidence limit]). The operative mortality rates for patients with acute aortic dissection (AcA or AcB) were assessed for five time "windows": 1963 to 1972 (42 +/- 8%), 1973 to 1977 (37 +/- 8%), 1978 to 1982 (15 +/- 6%), 1983 to 1987 (27 +/- 6%), and 1988 to 1992 (26 +/- 6%). Logistic regression analysis suggested that the low operative mortality rate during the 1978-to-1982 interval occurred by chance. Multivariate analysis showed earlier operative year, hypertension, cardiac tamponade, renal dysfunction, and older age were independent determinants of operative death. Actuarial survival rates (including early deaths) after 5, 10, and 15 years for AcA patients were 55%, 37%, and 24%; for AcB, 48%, 29%, and 11%; for ChA, 65%, 45%, and 27%; and for ChB, 59%, 45%, and 27%. Multivariate analysis revealed that older age and previous operation were significant predictors for late death. Freedom from reoperation for all patients was 84%, 67%, and 57% at 5, 10, and 15 years, respectively.Although the operative mortality rate decreased over time for patients with aortic dissection, the risk for those with acute aortic dissection during the last 10 years (1983 to 1992) is probably more realistic than that observed in the preceding 5-year interval (1978 to 1982). The operative mortality rates for patients with chronic aortic dissection have remained relatively static. Earlier diagnosis of acute aortic dissection before development of cardiac tamponade and renal impairment is critical to improve the operative salvage rate. Long-term outcome still is not optimal, which emphasizes the need for better serial postoperative aortic imaging surveillance and medical follow-up and blood pressure control.

  View details for PubMedID 7586393

• LEFT-VENTRICULAR FUNCTION, TWIST, AND RECOIL AFTER MITRAL-VALVE REPLACEMENT CIRCULATION DeAnda, A., Komeda, M., Nikolic, S. D., Daughters, G. T., Ingels, N. B., Miller, D. C. 1995; 92 (9): 458-466

  View details for Web of Science ID A1995TE55900076

• SURGICAL-MANAGEMENT OF AORTIC DISSECTION DURING A 30-YEAR PERIOD CIRCULATION Fann, J. I., Smith, J. A., Miller, D. C., Mitchell, R. S., Moore, K. A., Grunkemeier, G., Stinson, E. B., Oyer, P. E., Reitz, B. A., Shumway, N. E. 1995; 92 (9): 113-121

  View details for Web of Science ID A1995TE55900020

• Left ventricular function, twist, and recoil after mitral valve replacement. Circulation DeAnda, A., Komeda, M., Nikolic, S. D., Daughters, G. T., Ingels, N. B., Miller, D. C. 1995; 92 (9): II458-66

  Abstract

  Preservation of the mitral subvalvular apparatus during mitral valve replacement (MVR) has become more popular, in part because of the clinically and experimentally demonstrated more optimal left ventricular (LV) performance after surgery; the mechanisms responsible for this beneficial influence, however, have not been clearly elucidated.Fourteen dogs underwent placement of 26 myocardial markers into the LV and septum. One week later, the animals were studied while awake, sedated, and atrially paced (120 beats per minute) both under baseline conditions and after inotropic stimulation (calcium). The animals then underwent MVR and were randomized into either chord-sparing (MVR-Intact) or chord-severing (MVR-Cut) techniques. Two weeks later, the animals were studied under the same conditions. LV systolic function was assessed by the slope of the end-systolic pressure-volume relation (Ees); early LV diastolic filling was analyzed by the pressure-time constant of relaxation (tau). The instantaneous longitudinal gradient of torsional deformation for the LV (twist) was also calculated, as were the changes in twist with respect to time during systole and early diastole (LV recoil). Intergroup comparison showed a trend toward increased contractility (Ees, P = .061, before versus after MVR), as well as faster relaxation for the MVR-Intact group. Concurrent analysis of LV systolic function and the rate of systolic twist revealed a significant inverse relation, which disappeared after MVR when the chordae were severed.These observations suggest that the mitral subvalvular apparatus acts as a modulator of LV systolic torsional deformation into LV pump (or ejection) performance.

  View details for PubMedID 7586455

• ENDOVASCULAR STENT-GRAFTING AFTER ARCH ANEURYSM REPAIR USING THE ELEPHANT TRUNK ANNALS OF THORACIC SURGERY Fann, J. I., Dake, M. D., Semba, C. P., Liddell, R. P., Pfeffer, T. A., Miller, D. C. 1995; 60 (4): 1102-1105

  Abstract

  A 68-year-old woman with severe chronic obstructive pulmonary disease, aortic valvular insufficiency, and diffuse thoracic aortic aneurysm underwent aortic valve replacement and separate Dacron graft replacement of the ascending aortic and arch aneurysms using the elephant trunk technique. She was discharged on the tenth postoperative day. Five months later, she underwent endovascular stent-graft repair of the descending thoracic aortic aneurysm. She recovered uneventfully, and was discharged on the third postoperative day. Follow-up computed tomography at 6 months demonstrated exclusion of all flow into the descending thoracic aortic aneurysm. The elephant trunk technique followed by endovascular stent-grafting of the descending thoracic component is a potential therapeutic option in selected high-risk patients with diffuse aortic aneurysmal disease.

  View details for PubMedID 7574959

• Torsional deformation of the left ventricle. journal of heart valve disease Yun, K. L., Miller, D. C. 1995; 4: S214-20

  View details for PubMedID 8563999

• DURABILITY OF THE HANCOCK-MO BIOPROSTHESIS COMPARED WITH STANDARD AORTIC-VALVE BIOPROSTHESES VI International Symposium for Cardiac Bioprostheses Yun, K. L., Miller, D. C., Moore, K. A., Mitchell, R. S., Oyer, P. E., Stinson, E. B., Robbins, R. C., Reitz, B. A., Shumway, N. E. ELSEVIER SCIENCE INC. 1995: S221–S228

  Abstract

  To compare the durability of the Hancock modified orifice (Hancock MO, model 250 [H-MO]) valve with two other commonly used standard aortic valve bioprostheses, a cohort of 1,602 patients undergoing aortic valve replacement using porcine valves between 1971 and 1990 (excluding simultaneous mitral valve replacement) was analyzed retrospectively using Cox model multivariate techniques. Five hundred sixty-one patients received a composite H-MO valve, 652 received a standard Hancock model 242 (H) valve, and 389 received a Carpentier-Edwards model 2625 (C-E) valve. Mean age was 60 +/- 15 years (+/- 1 standard deviation) (71% male). Follow-up (10,247 patient-years) extended to 15 years and was 97% complete. The main focus of this study was bioprosthetic durability, using The American Association for Thoracic Surgery/The Society of Thoracic Surgeons guidelines to define structural valve deterioration (SVD). Multivariate analysis revealed that (younger) age (p < 10(-5), liver disease (p = 0.02), and 1981 to 1985 operative period (p = 0.012) were the only significant, independent predictors of SVD. In concordance with previous reports, the SVD freedom estimate was greater than 90% at 15 years for patients older than 70 years of age. Hepatic dysfunction had an adverse effect on SVD (estimated freedom from event at 10 years was 34 +/- 17% [standard error of mean] versus 78 +/- 2% for those without liver disease), but this affected only 3% of patients. Interestingly, one operative period (1981 to 1985) was associated with a slightly higher risk of SVD compared to the three other 5-year time windows. Valve type did not emerge as a significant risk factor for SVD.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for PubMedID 7646163

• PREGNANCY AND BIOPROSTHESES - INFLUENCE ON STRUCTURAL VALVE DETERIORATION JAMIESON, W. R., MILLER, D. C., AKINS, C. W., MUNRO, A. I., GLOWER, D. D., MOORE, K. A., HENDERSON, C. ELSEVIER SCIENCE PUBL CO INC. 1995: S282–S287

  Abstract

  The long-term performance of bioprostheses was evaluated in women 35 years of age or less to determine the influence of pregnancy on structural valve deterioration. Between 1972 and 1992, 237 female patients received 255 biological prostheses. Of the total operations, 53 were performed in patients who experienced pregnancy (P) and 202 in patients who were never pregnant (nonpregnant [NP]). The mean age of the P group was 23.0 +/- 5.8 years (standard deviation) (12 to 34 years) and of the NP group it was 27.1 +/- 6.3 years (8 to 35 years) (p < 0.05). The mean follow-up for the NP group was 6.8 years and for the P group it was 7.9 years. The late mortality was 2.26%/patient-year overall, 2.71%/patient-year for the NP group and 0.89%/patient-year for the P group (p = not significant [NS]). The P group of 52 patients had 94 pregnancies: 70 deliveries (74.5%) and 24 abortions (25.5%) (therapeutic, 14 [15%]). There were a total of 143 valve-related complications (P, 35; NP, 108); the majority for structural valve deterioration (SVD) 43% (109 patients), P 51% (27 patients) and NP 41% (82 patients) (p = NS). The valve-related reoperation rate paralleled the SVD rate at 42% (107 patients), P 51% (27 patients) and NP 40% (80 patients) (p = NS). The overall reoperative mortality rate was 6.0%. The interval from initial implant to reoperation was 99.6 +/- 3.6 months (p = NS groups P and NP).(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for Web of Science ID A1995RT15700045

  View details for PubMedID 7646173

• A METHOD TO ASSESS ENDOCARDIAL REGIONAL LONGITUDINAL CURVATURE OF THE LEFT-VENTRICLE AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY DeAnda, A., Moon, M. R., Nikolic, S. D., Castro, L. J., Fann, J. I., Daughters, G. T., Ingels, N. B., Miller, D. C. 1995; 268 (6): H2553-H2560

  Abstract

  Knowledge of the instantaneous geometry of the left ventricular (LV) chamber is necessary to calculate LV function and wall stresses. We describe a method utilizing myocardial markers that does not rely on any a priori assumptions of global LV geometry. Five dogs underwent placement of 25 endocardial and 3 epicardial miniature LV markers. Six weeks later, the animals were studied during conscious closed-chest conditions. The three-dimensional coordinates of the LV markers were used to compute longitudinal fitted curves for LV walls and septum during steady-state conditions; endocardial radii of curvature (rcurv) were then computed for each region at the midequatorial (rcurv-eq) and apical levels. There was a uniform decrease in rcurv in each LV wall during systole (compared with diastole, P < 0.01); at end systole, rcurv was regionally heterogeneous between opposing walls, e.g., anterior and posterior rcurv-eq values were 17.2 +/- 2.0 and 17.7 +/- 1.8 (SD) cm, respectively (P < 0.05). At end diastole, only septal-lateral rcurv-eq was different (16.9 +/- 2.1 vs. 18.7 +/- 1.3 cm: P < 0.05). Normalization of rcurv (to instantaneous LV volume) removed the systolic-diastolic differences, but a similar pattern of regional heterogeneity persisted. The data presented pertain to the LV endocardial surface, but the method described can be applied to the epicardial surface as well; this new method offers promise in assessing dynamic changes in longitudinal LV endocardial curvature.

  View details for PubMedID 7611505

• A METHOD TO ASSESS ENDOCARDIAL REGIONAL LONGITUDINAL CURVATURE OF THE LEFT-VENTRICLE AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY DEANDA, A., MOON, M. R., NIKOLIC, S. D., CASTRO, L. J., FANN, J. I., DAUGHTERS, G. T., INGELS, N. B., MILLER, D. C. 1995; 268 (6): H2553-H2560

  View details for DOI 10.1152/ajpheart.1995.268.6.H2553

  View details for Web of Science ID A1995RE37300045

• A GLY1127SER MUTATION IN AN EGF-LIKE DOMAIN OF THE FIBRILLIN-1 GENE IS A RISK FACTOR FOR ASCENDING AORTIC-ANEURYSM AND DISSECTION AMERICAN JOURNAL OF HUMAN GENETICS FRANCKE, U., Berg, M. A., Tynan, K., Brenn, T., Liu, W. G., Aoyama, T., Gasner, C., Miller, D. C., FURTHMAYR, H. 1995; 56 (6): 1287-1296

  Abstract

  Ascending aortic disease, ranging from mild aortic root enlargement to aneurysm and/or dissection, has been identified in 10 individuals of a kindred, none of whom had classical Marfan syndrome (MFS). Single-strand conformation analysis of the entire fibrillin-1 (FBN1) cDNA of an affected family member revealed a G-to-A transition at nucleotide 3379, predicting a Gly1127Ser substitution. The glycine in this position is highly conserved in EGF-like domains of FBN1 and other proteins. This mutation was present in 9 of 10 affected family members and in 1 young unaffected member but was not found in other unaffected members, in 168 chromosomes from normal controls, and in 188 chromosomes from other individuals with MFS or related phenotypes. FBN1 intragenic marker haplotypes ruled out the possibility that the other allele played a significant role in modulating the phenotype in this family. Pulse-chase studies revealed normal fibrillin synthesis but reduced fibrillin deposition into the extracellular matrix in cultured fibroblasts from a Gly1127Ser carrier. We postulate that the Gly1127Ser FBN1 mutation is responsible for reduced matrix deposition. We suggest that mutations such as this one may disrupt EGF-like domain folding less drastically than do substitutions of cysteine or of other amino acids important for calcium-binding that cause classical MFS. The Gly1127Ser mutation, therefore, produces a mild form of autosomal dominantly inherited weakness of elastic tissue, which predisposes to ascending aortic aneurysm and dissection later in life.

  View details for PubMedID 7762551

• AORTIC DISSECTION ANNALS OF VASCULAR SURGERY Fann, J. I., Miller, D. C. 1995; 9 (3): 311-323

  View details for PubMedID 7632561

• EVALUATION OF MYOCARDIAL MOTION TRACKING WITH CINE-PHASE CONTRAST MAGNETIC-RESONANCE-IMAGING INVESTIGATIVE RADIOLOGY Pelc, L. R., Sayre, J., Yun, K., Castro, L. J., Herfkens, R. J., Miller, D. C., Pelc, N. J. 1994; 29 (12): 1038-1042

  Abstract

  The accuracy of myocardial motion measurements, computed from cine-phase contrast (cine-PC) magnetic resonance (MR) velocity data, was compared with directly visualized motion of MR signal voids caused by implanted tantalum markers in anesthetized dogs.Magnetic resonance imaging (MRI) data were electrocardiogram-gated and divided into 16 phases per cardiac cycle. Myocardial trajectories as a function of time in the cardiac cycle were measured using both methods for four to seven markers in each of eight animals.The peak observed in-plane excursion was 4.0 +/- 2.1 mm. The average deviation between displacements derived from velocity data versus displacements visualized directly was 1.1 +/- 0.7 mm (27.5% of the peak displacement). The difference was less if three separate MR scans were used to measure each velocity component in the cine-PC method. This improvement is probably caused by improved temporal resolution.Cine-PC MRI offers a noninvasive method for accurate quantification of myocardial motion.

  View details for PubMedID 7721545

• Coronary bypass grafting with biological grafts in a canine model. Circulation Tomizawa, Y., Moon, M. R., DeAnda, A., Castro, L. J., Kosek, J., Miller, D. C. 1994; 90 (5): II160-6

  Abstract

  Poor patency rates have limited the success of biological vascular grafts in the coronary artery position. Recently, two bovine internal mammary arterial grafts have been developed for possible use as coronary artery bypass graft (CABG) conduits: (1) Denaflex grafts (Baxter Health-care Co, 3-mm ID) treated with polyepoxy compounds and with heparin ionically bound to the luminal surface and (2) Bioflow grafts (Bio-Vascular, Inc, 3-mm ID) treated with dialdehyde starch.Thirty dogs underwent CABG with either a Denaflex (n = 20) or Bioflow (n = 10) graft to the left circumflex coronary artery (LCx). The left main coronary artery (n = 12) or proximal LCx (n = 18) was then ligated. Six-month patency (Kaplan-Meier) for Denaflex grafts was 44 +/- 13% (+/- SEM), compared with 12 +/- 11% for Bioflow grafts, but this difference did not reach statistical significance (P = .56). Among grafts open at 14 days, however, there were no occlusions among six Denaflex grafts versus five occlusions among seven Bioflow grafts. At 6 months, all six surviving Denaflex grafts appeared normal, while the only remaining patent Bioflow graft was angiographically dilated and had diffuse luminal irregularities. At 1 year, three Denaflex grafts angiographically had no dilation, stenosis, or luminal irregularities. Macroscopically, all explanted long-term (6 to 12 months) Denaflex grafts had a smooth, clean luminal surface, whereas the only patent Bioflow graft had multifocal thrombi. Microscopically, all Denaflex grafts had minimal degenerative changes, but the Bioflow graft had transmural linear cracks and medial deterioration.These data suggest that long-term (> 6-month) patency is possible with small-caliber, low-flow biological grafts in the canine coronary position, although both types of grafts are prone to early occlusion. If these early failures are excluded, the Denaflex graft appears to be associated with better long-term patency and an absence of degenerative changes.

  View details for PubMedID 7955246

• LEFT-VENTRICULAR TORSIONAL DYNAMICS IMMEDIATELY AFTER MITRAL-VALVE REPLACEMENT 66th Scientific Sessions of the American-Heart-Association:Cardiovascular Surgery 1993 DeAnda, A., Moon, M. R., Yun, K. L., Daughters, G. T., Ingels, N. B., Miller, D. C. AMER HEART ASSOC. 1994: 339–46

  View details for Web of Science ID A1994PR28700059

• SOMATOSENSORY-EVOKED POTENTIALS DURING EXCLUSION AND REPERFUSION OF CRITICAL AORTIC SEGMENTS IN THORACOABDOMINAL AORTIC-ANEURYSM SURGERY - DISCUSSION JOURNAL OF CARDIAC SURGERY Cooley, D. A., Coselli, J. S., Cunningham, J. N., Ergin, M. A., Miller, D. C. 1994; 9 (6): 703-712

  View details for Web of Science ID A1994PR94600010

• EFFECTS OF LEFT-VENTRICULAR SUPPORT ON RIGHT-VENTRICULAR MECHANICS DURING EXPERIMENTAL RIGHT-VENTRICULAR ISCHEMIA 66th Scientific Sessions of the American-Heart-Association:Cardiovascular Surgery 1993 Moon, M. R., Castro, L. J., DeAnda, A., Daughters, G. T., Ingels, N. B., Miller, D. C. AMER HEART ASSOC. 1994: 92–101

  View details for Web of Science ID A1994PR28700018

• CORONARY-BYPASS GRAFTING WITH BIOLOGICAL GRAFTS IN A CANINE MODEL 66th Scientific Sessions of the American-Heart-Association:Cardiovascular Surgery 1993 Tomizawa, Y., Moon, M. R., DeAnda, A., Castro, L. J., Kosek, J., Miller, D. C. AMER HEART ASSOC. 1994: 160–66

  View details for Web of Science ID A1994PR28700030

• SURGICAL-MANAGEMENT OF AORTIC DISSECTION IN PATIENTS WITH THE MARFAN-SYNDROME 66th Scientific Sessions of the American-Heart-Association:Cardiovascular Surgery 1993 Smith, J. A., Fann, J. I., Miller, D. C., Moore, K. A., DeAnda, A., Mitchell, R. S., Stinson, E. B., Oyer, P. E., Reitz, B. A., Shumway, N. E. AMER HEART ASSOC. 1994: 235–42

  View details for Web of Science ID A1994PR28700043

• Left ventricular torsional dynamics immediately after mitral valve replacement. Circulation DeAnda, A., Moon, M. R., Yun, K. L., Daughters, G. T., Ingels, N. B., Miller, D. C. 1994; 90 (5): II339-46

  Abstract

  Cardiac operations and cardiopulmonary bypass are associated with a host of unphysiological consequences that have widespread systemic effects. Since previous investigations in human cardiac transplant recipients had demonstrated that left ventricular (LV) torsional deformation was a sensitive method to detect subclinical LV dysfunction during acute rejection, we studied LV systolic torsion and diastolic recoil preoperatively and postoperatively in a canine model using myocardial marker techniques.Seven dogs underwent placement of LV subepicardial myocardial markers and creation of mitral regurgitation. Three months later, the animals underwent high-speed, biplane videofluoroscopic analysis for determination of LV systolic function and regional LV systolic torsional deformation and diastolic recoil. The animals then underwent chordal-sparing mitral valve replacement and were restudied 1 to 2 hours postoperatively. One to 2 hours after the cardiac operation, regional maximal systolic torsional deformation decreased significantly in all three LV regions on the lateral LV wall, as well as in the apical and apical-equatorial regions on the anterior wall. During early systole, minimal regional systolic torsion increased significantly in all regions on the lateral wall, as well as in the apical level of the posterior wall. Heterogeneous decreases in torsional deformation were also seen during the early diastolic filling period.Regional systolic torsional deformation and diastolic recoil are markedly perturbed early after a cardiac operation and its associated manipulations. Such changes, however, may potentially serve as sensitive tools to assess the impact of different techniques of intraoperative management, including newer methods of myocardial protection.

  View details for PubMedID 7955276

• Surgical management of aortic dissection in patients with the Marfan syndrome. Circulation Smith, J. A., Fann, J. I., Miller, D. C., Moore, K. A., DeAnda, A., Mitchell, R. S., Stinson, E. B., Oyer, P. E., Reitz, B. A., Shumway, N. E. 1994; 90 (5): II235-42

  Abstract

  Aortic dissection is one of the most lethal potential complications in patients with the Marfan syndrome.Among 360 patients undergoing operative treatment of aortic dissection between 1963 and 1992, 40 had the Marfan syndrome. There were 24 men and 16 women with a mean age of 35 +/- 9 years (+/- 1 SD; range, 15 to 54 years). These patients included 16 with acute type A, 2 with acute type B, 18 with chronic type A, and 4 with chronic type B aortic dissections. The aortic arch was involved in 29 cases. Preoperative complications included acute aortic valvular insufficiency in 13 patients, rupture into the pericardial space in 3, and loss of peripheral pulses in 9. The site of primary intimal tear was the ascending aorta in 25 patients, the aortic arch in 2, the descending aorta in 7, and not identified in 6. Operations included ascending aortic and aortic valvular replacement (with or without coronary artery reimplantation) in 22 patients, ascending aortic replacement alone in 5, and descending thoracic aortic replacement in 9. Four operative deaths (10 +/- 5% [+/- 70% confidence limits]) occurred in 3 acute patient-years and 1 chronic type A patient-years. Long-term follow-up (216 patient-years; range, 1 month to 22 years; mean, 5.4 years) revealed 15 late deaths, 7 from late aortic sequelae. The overall actuarial survival estimates were 71 +/- 8%, 54 +/- 10%, and 22 +/- 11% at 5, 10, and 15 years, respectively. Twenty late aortic operations were required in 14 patients.Despite satisfactory early results, the long-term survival of patients with the Marfan syndrome was suboptimal (albeit similar to those without the Marfan syndrome). Future progress will pivot on reducing the incidence of aortic dissection in these patients with medical therapy and/or earlier surgical intervention and enhanced postoperative serial imaging surveillance of the entire aorta.

  View details for PubMedID 7955259

• Effects of left ventricular support on right ventricular mechanics during experimental right ventricular ischemia. Circulation Moon, M. R., Castro, L. J., DeAnda, A., Daughters, G. T., Ingels, N. B., Miller, D. C. 1994; 90 (5): II92-101

  Abstract

  Left ventricular (LV) assist device (LVAD) support has been associated with right ventricular (RV) failure in humans, but the etiology remains unknown. Mechanical LV support apparently does not induce RV pump failure in normal hearts, but controlled studies of LV assistance in hearts with preexistent RV dysfunction have been limited. Therefore, this study was performed to determine if LVAD support impairs RV systolic mechanics during acute RV ischemia.Five closed-chest, autonomically blocked, sedated dogs were studied after placement of an LVAD (LV-femoral artery bypass), right coronary artery (RCA) occluder, and 27 miniature radiopaque tantalum markers into the LV and RV walls for independent computation of RV and LV volumes. Biplane videofluoroscopic marker images and hemodynamic data were recorded before RCA occlusion with the LVAD off (maximum LV pressure [LVPmax] = 119 +/- 25 mm Hg), after 3 minutes of RCA occlusion with the LVAD off (LVPmax = 84 +/- 18 mm Hg), and then with the LVAD on (LVPmax = 26 +/- 32 mm Hg). Global RV contractility (end-systolic elastance [RV Ees] and preload recruitable stroke work [RV PRSW]), RV power output, and the mechanical (pump) efficiency of converting potential energy to external work (ratio of RV stroke work/total pressure-volume area) were calculated. As expected, with RCA occlusion there were major decreases in RV Ees (from 2.5 +/- 1.2 to 1.4 +/- 0.5 mm Hg/mL, P < .005) and RV PRSW (15 +/- 4 versus 9 +/- 4 mm Hg, P < .001). RV power output (overall pump performance) declined by 39 +/- 20% (P < .025), and mechanical efficiency fell by 38 +/- 13% (P < .001). After initiation of mechanical LV support, however, there was no further impairment of RV contractility or power output (P > .80). Pulmonary artery input impedance (RV afterload) decreased from 848 +/- 628 to 673 +/- 577 dyne.sec-1.cm-5 (P < .01), which led to a 26 +/- 29% improvement in RV pump efficiency (P < .001).While right coronary artery occlusion significantly reduced RV systolic performance, LVAD support during acute RV ischemia did not further impair RV contractility or power output. Furthermore, since RV afterload fell with LV unloading, the mechanical pump efficiency of the right ventricle actually improved. These observations demonstrate that LVAD support does not directly induce RV failure in canine hearts with acute isolated RV ischemia.

  View details for PubMedID 7955292

• EXPERIMENTAL EVALUATION OF DIFFERENT CHORDAL PRESERVATION METHODS DURING MITRAL-VALVE REPLACEMENT 30th Annual Meeting of the Society-of-Thoracic-Surgeons Moon, M. R., DeAnda, A., Daughters, G. T., Ingels, N. B., Miller, D. C. ELSEVIER SCIENCE INC. 1994: 931–44

  Abstract

  During chordal-sparing mitral valve replacement (MVR), some recommend anatomic reattachment of the anterior leaflet chordae to the anterior annulus; others advocate shifting the chordae to the posterior annulus. To compare the results of these techniques with those of conventional MVR (total chordal excision), 21 dogs were studied 5 to 12 days after implantation of tantalum markers to measure left ventricular volume and geometry. One to 3 weeks later, animals underwent conventional MVR (n = 7) or chordal-sparing MVR with either anterior chordal reattachment (n = 7) or posterior transposition (n = 7). Contractility was assessed using physiologic volume intercepts for end-systolic elastance, preload recruitable stroke work, and the relationship of the maximum rate of change of left ventricular pressure to the end-diastolic volume. The physiologic intercept for end-systolic elastance did not change after anterior or posterior MVR, but increased from 60 +/- 14 mL before MVR to 72 +/- 17 mL with conventional MVR (p < 0.002), indicating impaired left ventricular contractility. Similarly, the physiologic intercept for preload recruitable stroke work and the relationship of the maximum rate of change of left ventricular pressure to the end-diastolic volume increased 22% +/- 13% and 28% +/- 13%, respectively, after conventional MVR, but neither changed after anterior or posterior MVR. Although the end-diastolic pressure-volume relationship did not change with either chordal-sparing technique, its slope increased 98% +/- 73% after conventional MVR (p < 0.008). Thus, although chordal preservation maintained better systolic and diastolic function, there was no substantial difference between the results of the anterior and posterior chordal-sparing techniques in this model.

  View details for PubMedID 7944814

• ACTUARIAL VERSUS ACTUAL RISK OF PORCINE STRUCTURAL VALVE DETERIORATION JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Grunkemeier, G. L., Jamieson, W. R., Miller, D. C., Starr, A. 1994; 108 (4): 709-718

  Abstract

  Actuarial analysis, using nonparametric (e.g., life table or Kaplan-Meier) or parametric (statistical modeling) methods, is used to describe and compare survival probabilities by allowing for partial survival times (censoring). Although devised to describe freedom from death, this method has been extended to nonfatal complications, such as freedom from tissue valve failure. However, the risk described for nonfatal events is that which a patient would experience provided he were immortal. And patients with valve disease have a relatively high risk of dying, generating the question: "What is the chance the valve will fail before the patient dies?" To answer this more practical (for individual patient management and population resource allocation) question requires an estimate of what we call actual failure, that is, the percentage of patients whose valve will actually fail before they die. This risk is less than the risk which the usual actuarial curve describes. This difference increases with patient age, because older patients have a lower risk of tissue failure and a higher risk of death than younger patients.

  View details for Web of Science ID A1994PK51400017

  View details for PubMedID 7934107

• PERCUTANEOUS BALLOON FENESTRATION OF THE AORTA TO RELIEVE ISCHEMIC COMPLICATIONS OF AORTIC DISSECTION Williams, D. M., Marx, M. V., Dake, M. D., Semba, C. P., Andrews, J. C., Deeb, G. M., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 1994: 10–10

  View details for Web of Science ID A1994PN41700086

• SURGICAL-MANAGEMENT OF AORTIC DISSECTION OVER 30 YEARS Fann, J. I., Smith, J. A., Miller, D. C., Mitchell, R. S., Moore, K., Oyer, P. E., STINSOUN, E. B., Reitz, B. A., Shumway, N. E. LIPPINCOTT WILLIAMS & WILKINS. 1994: 96–96

  View details for Web of Science ID A1994PN41700549

• TRANSLUMINALLY PLACED ENDOVASCULAR STENT GRAFTS FOR THE TREATMENT OF ABDOMINAL AORTIC AND NON-AORTIC ANEURYSMS Dake, M. D., Semba, C. P., Mitchell, R. S., Zarins, C. K., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 1994: 206–

  View details for Web of Science ID A1994PN41701137

• SYNTHETIC PEPTIDE THROMBIN INHIBITOR CIRCULATION DeAnda, A., Coutre, S., Miller, D. C. 1994; 90 (3): 1581-1582

  View details for Web of Science ID A1994PG60200061

  View details for PubMedID 8087972

• THE AORTIC-ARCH - DISCUSSION JOURNAL OF CARDIAC SURGERY Borst, H. G., Coselli, J. S., Ergin, M. A., Griepp, R. B., Kouchoukos, N., Miller, D. C., YONKS, Murphy, Melo, RAMMOS, BRAIS, Bavaria, AKI, MEADORS, Westaby 1994; 9 (5): 614-623

  View details for Web of Science ID A1994PJ90500017

• PILOT-STUDY OF THE EFFICACY OF A THROMBIN INHIBITOR FOR USE DURING CARDIOPULMONARY BYPASS 30th Annual Meeting of the Society-of-Thoracic-Surgeons DeAnda, A., Coutre, S. E., Moon, M. R., Vial, C. M., Griffin, L. C., Law, V. S., Komeda, M., Leung, L. L., Miller, D. C. ELSEVIER SCIENCE INC. 1994: 344–50

  Abstract

  Heparin is normally used for anticoagulation during cardiopulmonary bypass (CPB), but its use is contraindicated in patients with a history of heparin-induced thrombocytopenia, heparin-provoked thrombosis, or both. Heparin therapy can also be ineffective due to heparin resistance. A short-acting, oligonucleotide-based thrombin inhibitor (thrombin aptamer) may potentially serve as a substitute for heparin in these and other clinical situations. We tested a novel thrombin aptamer in a canine CPB pilot study to determine its anticoagulant efficacy, the resultant changes in coagulation variables, and the aptamer's clearance mechanisms and pharmacokinetics. Seven dogs were studied initially: Four received varied doses of the aptamer (to establish the pharmacokinetic profile) and 3 received heparin. Subsequently, 4 other dogs underwent CPB, receiving a constant infusion of the aptamer before CPB (to characterize the baseline coagulation status), with partial CPB and hemodilution, during 60 minutes of total CPB, and, finally, after a 2-hour recovery period. At a 0.5 mg.kg-1.min-1 dose, the activated clotting time rose with aptamer infusion from 106 +/- 12 seconds to 187 +/- 8 seconds (+/- 1 standard deviation) (p = 0.014), increased further with hemodilution (to 259 +/- 41 seconds; p = 0.017), and was even more prolonged during total CPB (> 1,500 seconds; p < 0.001). This later increase in the activated clotting time paralleled a rise in the plasma concentration of the thrombin aptamer during total CPB, as determined by high-performance liquid chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for Web of Science ID A1994PD58900014

  View details for PubMedID 8067830

• LEFT ATRIAL PRESSURE-CLAMP SERVOMECHANISM DEMONSTRATES LV-SUCTION IN CANINE HEARTS WITH NORMAL MITRAL-VALVES AMERICAN JOURNAL OF PHYSIOLOGY Ingels, N. B., Daughters, G. T., Nikolic, S. D., DeAnda, A., Moon, M. R., Bolger, A. F., Komeda, M., Derby, G. C., Yellin, E. L., Miller, D. C. 1994; 267 (1): H354-H362

  Abstract

  A novel technique is presented to study suction of the in situ left ventricle in open-chest experimental animals without requiring cardiopulmonary bypass or disturbing the native mitral valvular apparatus. In 17 dogs, left ventricular pressure (LVP) and left atrial pressure (LAP) were measured, the left atrium was cannulated and connected to a servo pump, and LAP was controlled to a setpoint near 0 mmHg by withdrawing blood from the left atrium. Heart rate [103 +/- 17 (SD) min-1], peak pressure (100 +/- 13 mmHg), minimum pressure (1.4 +/- 0.8 mmHg), and maximum rate of change of pressure with respect to time during isovolumic contraction and relaxation (2,506 +/- 775 and -1,761 +/- 855 mmHg/s, respectively) were normal. Servo control of LAP was possible to +/- 1 mmHg. LV suction was demonstrated in each heart (mean negative LVP -2.3 +/- 1.1 mmHg; P < 0.0001). This new technique demonstrates that the left ventricle can generate negative diastolic suction pressures when examined in vivo and in situ with an undisturbed mitral valve and physiologically normal preload and afterload. This adds to a growing body of evidence that, under appropriate circumstances, the heart can suck blood into itself and thereby aid in its own filling.

  View details for Web of Science ID A1994NY98500044

  View details for PubMedID 8048601

• DYNAMICS OF NORMAL AND ISCHEMIC CANINE PAPILLARY-MUSCLES CIRCULATION RESEARCH Rayhill, S. C., Daughters, G. T., Castro, L. J., Niczyporuk, M. A., Moon, M. R., Ingels, N. B., Stadius, M. L., Derby, G. C., Bolger, A. F., Miller, D. C. 1994; 74 (6): 1179-1187

  Abstract

  This investigation was designed to elucidate the dynamics of the left ventricular (LV) papillary muscles. Miniature tantalum myocardial markers were placed on the tip and base of each papillary muscle in six dogs. Markers were also implanted into the LV myocardium to define two orthogonal equatorial diameters and the long-axis dimension. Two weeks later, after recovery from thoracotomy, markers were visualized by biplane fluoroscopy, and video images were recorded during control conditions, after autonomic blockade, after inotropic stimulation with calcium, after methoxamine infusion (to increase afterload), and after blood volume augmentation (to increase preload). Two days later, radiographic recordings were made before and after occlusion of the left circumflex coronary artery. Computer-aided analysis of the video recordings was used to determine three-dimensional coordinates of the markers. It was found that before circumflex coronary occlusion, the dynamics of both papillary muscles closely mimicked the dynamics of the LV as a whole. The papillary muscles shortened during ejection and lengthened during diastole. Their lengths changed minimally during the isovolumic periods, and this behavior was not altered by any of the interventions except coronary occlusion. During circumflex coronary artery occlusion, the ischemic posterior papillary muscle lengthened during isovolumic contraction and most of ejection and shortened only when LV pressure began to fall. Hence, we believe that previous studies demonstrating papillary muscle lengthening during isovolumic contraction and shortening during isovolumic relaxation may have been confounded by coexistent myocardial ischemia or stunning.

  View details for PubMedID 8187284

• 1986: Pharmacological, hematological, and physiological effects of a new thromboxane synthetase inhibitor (CGS-13080) during cardiopulmonary bypass in dogs. Updated in 1994. Annals of thoracic surgery DeAnda, A., Miller, D. C. 1994; 57 (3): 778-780

  View details for PubMedID 7511885

• IN-VIVO LOAD INDEPENDENCE OF LEFT ATRIAL ELASTANCE DEANDA, A., MOON, M. R., KOMEDA, M., HANDEN, C. E., TYE, T., DAUGHTERS, G. T., INGELS, N. B., MILLER, D. C., NIKOLIC, S. D. ELSEVIER SCIENCE INC. 1994: A164

  View details for Web of Science ID A1994PP51800646

• AORTIC COBWEBS - AN ANATOMIC MARKER IDENTIFYING THE FALSE LUMEN IN AORTIC DISSECTION - IMAGING AND PATHOLOGICAL CORRELATION RADIOLOGY Williams, D. M., Joshi, A., Dake, M. D., Deeb, G. M., Miller, D. C., Abrams, G. D. 1994; 190 (1): 167-174

  Abstract

  To describe and estimate the frequency of fibroelastic cords or bands projecting from the false lumen wall ("aortic cobwebs") in acute and chronic dissections.Pathologic specimens (n = 23), routine magnetic resonance (MR) images (n = 27), and intravascular (n = 5) and transesophageal (n = 3) ultrasound (US) images from 43 patients with aortic dissection were reviewed, and the presence and configuration of cobwebs were noted.Aortic cobwebs usually bridge the junction of the dissection flap with the outer wall of the false lumen (the line of dissection) but occasionally project like small tendrils from the false lumen wall remote from the line of dissection. Cobwebs were found in 17 of 23 pathologic specimens and on six of 27 MR images, two of five intravascular US scans, and one of three transesophageal US scans.Aortic cobwebs most likely represent residual ribbons of media that have been incompletely sheared from the aortic wall during the dissection process. As such, they can serve as an anatomic marker of the false lumen. They are occasionally seen on routine aortic images and may, therefore, prove useful for orientation during percutaneous or surgical interventional procedures to relieve ischemic complications of aortic dissection.

  View details for Web of Science ID A1994MW25300034

  View details for PubMedID 8259399

• ALTERATIONS IN LEFT-VENTRICULAR TWIST MECHANICS WITH INOTROPIC STIMULATION AND VOLUME LOADING IN HUMAN-SUBJECTS 65TH Scientific Sessions of the American-Heart-Association Moon, M. R., Ingels, N. B., Daughters, G. T., Stinson, E. B., Hansen, D. E., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 1994: 142–50

  Abstract

  Left ventricular (LV) twist, the longitudinal gradient of circumferential rotation about the LV long axis, may play an important role in the storage of potential energy at end systole and its subsequent release as elastic recoil during early diastole; however, the effects of load and inotropic state on LV systolic twist and diastolic untwist in human subjects have not previously been characterized.Six cardiac transplant recipients with 12 implanted radiopaque midwall LV myocardial markers were studied 1 year after transplantation. Biplane cinefluoroscopic marker images and LV pressure were recorded during control conditions and after afterload augmentation (methoxamine, 5 to 10 micrograms.kg-1 x min-1), inotropic stimulation (dobutamine, 5 micrograms.kg-1 x min-1), and preload augmentation (volume loading with normal saline). Systolic twist dynamics were assessed by maximum twist (Tmax[rad/cm]), peak negative twist rate (-dT/dtmin[rad.cm-1 x s-1]), and the slope of the twist normalized-ejection fraction relation (T-nEFR, Msys[rad/cm]) during systole. Diastolic untwist was assessed by the peak positive untwist rate (+dT/dtmax [rad.cm-1 x s-1]) and the slopes (rad/cm) of the T-nEFR during early diastole (Mear-dia) and mid diastole (Mmid-dia). Compared with control values, LV pressure and volume loading had no significant effect on Tmax, -dT/dtmin, or Msys; however, inotropic stimulation significantly increased all parameters describing systolic twist (Tmax: -0.10 +/- 0.03 versus -0.06 +/- 0.02 rad/cm, P < .001; -dT/dtmin: -0.72 +/- 0.19 versus -0.44 +/- 0.22 rad.cm-1 x s-1, P < .001; Msys: -0.10 +/- 0.03 versus -0.06 +/- 0.01 rad/cm, P < .001). Pressure loading had no effect on early diastolic untwisting; however, dobutamine significantly increased M(ear)-dia (-0.24 +/- 0.06 versus -0.13 +/- 0.04 rad/cm, P < .0001) and +dT/dtmax (0.78 +/- 0.24 versus 0.45 +/- 0.16 rad.cm-1 x s-1, P < .001). Conversely, volume loading significantly decreased M(ear)-dia (-0.08 +/- 0.04 versus -0.13 +/- 0.04 rad/cm, P < .05). M(ear)-dia correlated directly with LV contractile state (as assessed as maximum dP/dt, r = .60, P < .0001) and inversely with end-systolic volume (r = -.87, P < .0001) but was unrelated to stroke volume (r = .08, P = .30) or LV afterload (estimated as effective arterial elastance, r = .08, P = .29). Mmid-dia did not change during any intervention.In conscious human transplant patients, (1) pressure and volume loading do not affect systolic LV twist; (2) dobutamine augments systolic twist and early diastolic untwisting, suggesting more end-systolic potential energy storage and early diastolic elastic recoil with enhanced inotropic state; (3) volume loading decreases early diastolic untwisting, possibly reflecting diminished recoil forces after preload augmentation associated with larger end-systolic volumes (ESV); and (4) M(ear)-dia correlates strongly with ESV (in an inverse fashion), and less strongly, but directly, with LV dP/dtmax.

  View details for PubMedID 8281641

• THE USE OF ENDOVASCULAR TECHNIQUES FOR THE TREATMENT OF COMPLICATIONS OF AORTIC DISSECTION JOURNAL OF VASCULAR SURGERY Walker, P. J., Dake, M. D., Mitchell, R. S., Miller, D. C. 1993; 18 (6): 1042-1051

  Abstract

  Intravascular ultrasonography, balloon angioplasty, stent placement, and endovascular septal fenestration have been used in the evaluation and treatment of vascular complications of acute and chronic aortic dissection in five patients. There were three men and two women with an average age of 52 years (range 39 to 64 years). There were three chronic type A dissections, one acute type B, and one subacute type B dissection. Intravascular ultrasonography was used in all five cases. The three patients with chronic type A dissections underwent unilateral renal artery angioplasty (RA PTA) and stent placement; one patient with an acute type B dissection and associated fibromuscular dysplasia underwent bilateral RA PTA without stent placement. These procedures were performed to ameliorate severe hypertension. The final patient, with a subacute type B dissection, underwent iliac artery stenting to correct severe lower extremity ischemia. During a second intervention, this patient, who also had bowel ischemia and nonresolving acute renal failure, underwent balloon dilatation of a preexisting septal fenestration to augment visceral blood supply and bilateral RA PTA and stent placement in an effort to improve renal function. This patient eventually died of gut ischemia. After RA PTA and stent placement, one patient had a major intrarenal hemorrhage that required coil embolization and transfusion. In the four survivors, RA PTA and stent placement resulted in immediate improvement in blood pressure control. This response has been sustained during follow-up intervals ranging from 8 to 18 months (average 10 months). Intravascular ultrasonography can clearly demonstrate the pathologic anatomy associated with aortic dissection (even when angiography is ambiguous) and is essential for guiding therapeutic endovascular interventions. Further exploration of the efficacy of these endovascular techniques is warranted in this high-risk group of patients with aortic dissection who have appropriate clinical indications.

  View details for PubMedID 8264033

• Management of patients with intramural hematoma of the thoracic aorta. Circulation Robbins, R. C., McManus, R. P., Mitchell, R. S., LATTER, D. R., Moon, M. R., Olinger, G. N., Miller, D. C. 1993; 88 (5): II1-10

  Abstract

  Intramural hematoma of the thoracic aorta (IMH) is a diagnosis of exclusion and represents spontaneous, localized hemorrhage into the wall of the thoracic aorta in the absence of bona fide aortic dissection, intimal tear, or penetrating atherosclerotic ulcer. This process may arise from primary vasa vasorum hemorrhage within the aortic media or rupture of an atherosclerotic plaque. The clinical presentation of patients with IMH mimics that of acute aortic dissection; moreover, considerable diagnostic confusion exists despite the use of many different imaging modalities. The optimal mode of management of patients with IMH (medical versus medical plus surgical) remains problematic because of the paucity of information available.Thirteen patients with IMH were managed at two medical centers between 1983 and 1992. Patients with IMH caused by giant penetrating atherosclerotic ulcers were specifically excluded. There were 8 women and 5 men (mean age, 70 years [range, 54 to 82 years]). The admitting clinical diagnosis was acute aortic dissection, and all patients had a history of hypertension. There was no evidence of aortic dissection or intimal disruption as assessed by computed tomographic (CT) scan (n = 11), aortography (n = 10), magnetic resonance imaging (MRI) scan (n = 9), transesophageal echocardiography (TEE) (n = 6), or intravascular ultrasound (n = 1). The diagnosis of IMH was established by exclusion. The descending thoracic aorta was involved in 10 cases and the ascending/arch in 3. Conservative medical management was attempted initially. All 3 patients with IMH involving the ascending aorta ultimately required operative intervention, and 2 individuals died; 2 of 10 patients with descending aortic involvement eventually underwent surgery. Average hospital stay was 11 days; the mean follow-up interval for discharged patients was 29 months.IMH is a distinct pathological entity, should not be confused with aortic dissection, and probably will be identified more frequently in the future. All patients with IMH should be monitored carefully and treated with aggressive antihypertensive therapy. Frequent serial assessment is necessary using TEE or MRI/CT scans. Based on this small experience, patients with ascending/arch IMH, ongoing pain, or IMH expansion should probably undergo early graft replacement. Patients with IMH involving the descending thoracic aorta who have no evidence of progression and become pain free can probably be treated conservatively but require antihypertensive therapy and serial aortic imaging surveillance indefinitely.

  View details for PubMedID 8222144

• RANDOMIZED, PROSPECTIVE ASSESSMENT OF BIOPROSTHETIC VALVE DURABILITY - HANCOCK VERSUS CARPENTIER-EDWARDS VALVES CIRCULATION Sarris, G. E., Robbins, R. C., Miller, D. C., Mitchell, R. S., Moore, K. A., Stinson, E. B., Oyer, P. E., Reitz, B. A., Shumway, N. E. 1993; 88 (5): 55-64

  View details for Web of Science ID A1993ME83400009

• MANAGEMENT OF PATIENTS WITH INTRAMURAL HEMATOMA OF THE THORACIC AORTA 65TH Scientific Sessions of the American-Heart-Association Robbins, R. C., McManus, R. P., Mitchell, R. S., LATTER, D. R., Moon, M. R., Olinger, G. N., Miller, D. C. AMER HEART ASSOC. 1993: 1–10

  View details for Web of Science ID A1993ME83400001

• MUTATION SCREENING OF COMPLETE FIBRILLIN-1 CODING SEQUENCE - REPORT OF 5 NEW MUTATIONS, INCLUDING 2 IN 8-CYSTEINE DOMAINS HUMAN MOLECULAR GENETICS Tynan, K., COMEAU, K., Pearson, M., Wilgenbus, P., Levitt, D., Gasner, C., Berg, M. A., Miller, D. C., FRANCKE, U. 1993; 2 (11): 1813-1821

  Abstract

  Marfan syndrome (MFS) is an autosomal dominantly inherited connective tissue disorder characterized by cardiovascular, ocular and skeletal manifestations. Previously, mutations in the fibrillin-1 gene on chromosome 15 (FBN1) have been reported to cause MFS. We have now screened 44 probands with MFS or related phenotypes for alterations in the entire fibrillin coding sequence (9.3 kb) by single strand conformation analysis. We report four unique mutations in the fibrillin gene of unrelated MFS patients. One is a 17 bp deletion and three are missense mutations, two of which involve 8-cysteine motifs. Another missense mutation was found in two unrelated individuals with annuloaortic ectasia but was also present in unaffected relatives and controls from various ethnic backgrounds. By using allele-specific oligonucleotide hybridization, we screened 65 unrelated MFS patients, 29 patients with related phenotypes and 84 control individuals for these mutations as well as for a previously reported mutation and two polymorphisms. Our results suggest that most MFS families carry unique mutations and that the fibrillin genotype is not the sole determinant of the connective tissue phenotype.

  View details for PubMedID 8281141

• Randomized, prospective assessment of bioprosthetic valve durability. Hancock versus Carpentier-Edwards valves. Circulation Sarris, G. E., Robbins, R. C., Miller, D. C., Mitchell, R. S., Moore, K. A., Stinson, E. B., Oyer, P. E., Reitz, B. A., Shumway, N. E. 1993; 88 (5): II55-64

  Abstract

  Although the major limitation of porcine valves is their finite durability, no controlled clinical data exist regarding the relative durability of the two porcine bioprostheses implanted most commonly today, the Carpentier-Edwards (C-E) and Medtronic Hancock I (H) valves.To assess this question, 174 patients undergoing aortic (AVR) or mitral (MVR) valve replacement with a bioprosthesis between March 1980 and March 1982 were randomized to receive either a C-E or a H valve. There were 102 AVRs (54 C-E and 48 H) and 74 MVRs (39 C-E and 35 H). For both the AVR and MVR cohorts, the average patient age was 58 +/- 14 years (+/- SD). The male/female ratio was 2.2:1 for AVR and 0.57:1 for MVR. Clinical follow-up was undertaken periodically; the most recent follow-up closing interval was July through October 1992, and current follow-up was 96% complete. Cumulative follow-up totaled 1369 patient-years (mean, 7.7 +/- 3.6 years; median, 9.1 years; maximum, 12.0 years). The main focus of this analysis was bioprosthetic durability, using the AATS/STS guidelines defining "Structural Valve Deterioration" (SVD). Multivariate analysis revealed that (younger) age was the only significant (P = .024) independent predictor of SVD. Valve manufacturer (C-E versus H) and valve site (aortic versus mitral) did not emerge as significant independent risk factors for SVD. Actuarial rates (Cutler-Ederer) expressed as percent free of SVD (+/- SEM) at 10 years (n = number of patients remaining at risk) were 71 +/- 7% and 59 +/- 9% for the C-E (n = 26) and H (n = 17) groups, respectively, for the AVR cohort; for the MVR cohort, these estimates were 60 +/- 10% (n = 12) and 72 +/- 10% (n = 11), respectively, but these differences were not statistically significant (P = NS, Lee-Desu).After 10 years, there was no statistically significant difference in durability or other valve-related complications between the H and C-E aortic or mitral valves. Based on current information, the choice of a porcine bioprosthesis should be based on factors other than durability, including ease of implantation, hemodynamic performance, and cost.

  View details for PubMedID 8222197

• 3-DIMENSIONAL SPIRAL COMPUTED TOMOGRAPHIC ANGIOGRAPHY - AN ALTERNATIVE IMAGING MODALITY FOR THE ABDOMINAL-AORTA AND ITS BRANCHES 8TH ANNUAL MEETING OF THE WESTERN-VASCULAR-SOC Rubin, G. D., Walker, P. J., Dake, M. D., Napel, S., Jeffrey, R. B., McDonnell, C. H., Mitchell, R. S., Miller, D. C. MOSBY-ELSEVIER. 1993: 656–65

  Abstract

  We sought to apply a new technique of computed tomographic angiography (CTA) to the preoperative and postoperative assessment of the abdominal aorta and its branches.After a peripheral intravenous contrast injection, the patient is continuously advanced through a spiral CT scanner, while maintaining a 30-second breath-hold. Thirty-five patients with abdominal aortic, renal, and visceral arterial disease have undergone CTA.Diagnostic three-dimensional images were obtained in patients with aortic aneurysms (n = 9), aortic dissections (n = 4), and mesenteric artery stenoses (n = 4). The technique has also been used to assess vessels after operative reconstruction or endovascular intervention in 18 patients. These preliminary studies have correlated well with conventional arteriographic findings. In aneurysmal disease both the lumen and mural thrombus and associated renal artery stenoses are visualized. The true and false channels of aortic dissections and the perfusion source of the visceral vessels are clearly shown; patency of visceral and renal reconstruction or stent placement are confirmed. CTA is relatively noninvasive and can be completed in less time than conventional angiography with less radiation exposure.This initial experience suggests that CTA may be a valuable alternative to conventional arteriography in the evaluation of the aorta and its branches.

  View details for PubMedID 8411473

• Utilization of manufacturers' implant card data to estimate heart valve failure. journal of heart valve disease Grunkemeier, G. L., Chandler, J. G., Miller, D. C., Jamieson, W. R., Starr, A. 1993; 2 (5): 493-503

  Abstract

  Heart valve manufacturers possess the most complete inventory of world-wide mechanical valve failures, but to convert failures to time-related risks requires estimates of patient follow up. Since manufacturers did not actively track patients, they needed a model that incorporates an assumed death rate to decrease the numbers of patients at risk. We present a method for using a manufacturer's implant card database to estimate time-related complication rates for patient subsets, and illustrate its use by examining the risk of outlet strut fracture (OSF) with the Björk-Shiley 60 degrees Convexo-Concave valve (CC60). We developed a parametric model for valve patient survival based on actively followed valve patients from three centers using only variables typically available from implant cards. Using this survival model, a simulated lifetime was produced for each valve in the CC60 implant database for which the required covariates were known. These lifetimes were then used to analyze OSF as if they were true follow up times. This allowed the use of conventional methods of univariate and multivariate analysis for OSF, including parametric statistical models. According to the approximate linearity of the cumulative hazard functions, OSF risk over time appeared to be fairly constant. Several risk factors were identified, including valve size, patient age at implant and valve position. Using parametric models for both patient survival and OSF permits the estimation of the probability of OSF before death for an individual patient (as opposed to the usual actuarial probability of OSF given that the patient does not die). Because the patient may die before his valve would have failed, this cumulative incidence of OSF is always less than the actuarial risk. For all but the very highest risk patients, the cumulative incidence over their relatively short remaining lifetimes is very small.

  View details for PubMedID 8269157

• ABNORMAL POSTOPERATIVE INTERVENTRICULAR MOTION - NEW INTRAOPERATIVE TRANSESOPHAGEAL ECHOCARDIOGRAPHIC EVIDENCE SUPPORTS A NOVEL HYPOTHESIS AMERICAN HEART JOURNAL Wranne, B., Pinto, F. J., Siegel, L. C., Miller, D. C., Schnittger, I. 1993; 126 (1): 161-167

  Abstract

  Abnormal interventricular septal motion is a frequent finding after cardiac surgery. However, the time course and underlying mechanisms are not well understood. Nineteen patients, mean age 54 years (range 20 to 82 years), were studied with intraoperative transesophageal echocardiography at five specific times: with the chest closed (baseline), with the chest open and the pericardium closed, with both chest and pericardium open, after cardiopulmonary bypass with the chest open, and after cardiopulmonary bypass with the chest closed. In each patient interventricular septal motion was recorded from the transgastric view; tricuspid annular motion and Doppler color flow mapping of tricuspid regurgitation were obtained from the four-chamber view. All the echocardiographic data were stored on videotape and were later viewed in random sequence by one investigator who was aware of the baseline stage but was blinded to the other stages. All patients had normal septal motion before cardiopulmonary bypass. After cardiopulmonary bypass, with the chest still open, 5 of 17 patients (29%) with adequate recordings had abnormal septal motion while 13 of 17 patients (76%) with adequate recordings had abnormal tricuspid annular motion. After chest closure, only three patients (14%) had normal septal motion and one patient (6%) had normal tricuspid annular motion. Significant tricuspid regurgitation was an infrequent finding in all cases. It is concluded that abnormal interventricular septal motion occurs after cardiopulmonary bypass and is related to abnormal tricuspid annular motion. We hypothesize that suboptimal right ventricular myocardial preservation impairs the motion pattern of the right ventricle, including the tricuspid annulus.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for PubMedID 8322660

• RIGHT-VENTRICULAR DYNAMICS DURING LEFT-VENTRICULAR ASSISTANCE IN CLOSED-CHEST DOGS 29TH ANNUAL MEETING OF THE SOC OF THORACIC SURGEONS Moon, M. R., Castro, L. J., DeAnda, A., Tomizawa, Y., Daughters, G. T., Ingels, N. B., Miller, D. C. ELSEVIER SCIENCE INC. 1993: 54–67

  Abstract

  To determine the effects of left ventricular assist device (LVAD) support on global right ventricular (RV) systolic mechanics, 8 closed-chest, conscious, sedated dogs were studied after placement of an LVAD (left ventricle to femoral artery bypass) and implantation of 27 tantalum markers into the left ventricular and RV walls for computation of biventricular volumes and geometry. Biplane cinefluoroscopic marker images and hemodynamic parameters were recorded during transient vena caval occlusion at various levels of LVAD support. Right ventricular contractility was assessed using end-systolic elastance and preload recruitable stroke work, and the myocardial (pump) efficiency of converting mechanical energy to external work (stroke work/total pressure-volume area) was calculated. With full LVAD support, RV end-diastolic volume increased from 60 +/- 15 to 62 +/- 17 mL (p < 0.002), pulmonary artery input impedance decreased from 940 +/- 636 to 587 +/- 347 dyne.s/cm5 (p < 0.007), and measurement of RV and left ventricular septal-free wall dimensions demonstrated a significant leftward septal shift (p < 0.0005). Global RV end-systolic elastance and preload recruitable stroke work decreased from 2.4 +/- 1.0 to 1.7 +/- 0.7 mm Hg/mL (p < 0.004) and 14.1 +/- 3.3 to 12.1 +/- 3.9 mm Hg (p < 0.02), respectively; however, RV power output and myocardial efficiency did not change significantly (p > 0.74 and p > 0.33, respectively). Therefore, during LVAD support, global RV contractility is impaired with leftward septal shifting, but RV myocardial efficiency and power output are maintained through a decrease in RV afterload and an increase in RV preload.

  View details for PubMedID 8328877

• THROMBIN APTAMER AS AN ANTICOAGULANT FOR CANINE CARDIOPULMONARY BYPASS Coutre, S. E., Griffin, L. C., Moon, M. R., DeAnda, A., Law, V. S., Leung, L. L., Miller, D. C. SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN. 1993: 540–40

  View details for Web of Science ID A1993LT57700004

• INTRAVASCULAR STENTING OF ACUTE EXPERIMENTAL TYPE-B DISSECTIONS 1992 Annual Meeting of the Association-for-Academic-Surgery Moon, M. R., Dake, M. D., Pelc, L. R., Liddell, R., Castro, L. J., Mitchell, R. S., Miller, D. C. ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS. 1993: 381–88

  Abstract

  To evaluate the efficacy of intravascular stenting for acute aortic dissection, 12 dogs underwent surgical creation of an acute type B dissection. Intravascular ultrasound evaluated luminal diameter, distal propagation, and branch involvement. Three animals underwent no further treatment (control). In 9 dogs, balloon-expandable intravascular stents (15-20 mm) were placed proximally to compress the intimal flap. One dog with a small dissection had complete obliteration of the false lumen after initial stent placement. Six dogs with extension below the diaphragm were initially stented proximally to restore flow; 3 were left with a residual distal false lumen, while 3 had additional stents placed to obliterate their entire false lumen. In the final 2 dogs, proximal stenting resulted only in partial compression of the false lumen. Two animals died within 24 hr due to prolonged hemodynamic instability and aortic rupture at the intimal flap, respectively. Six weeks later, radiologic and histologic evaluation was performed on the 10 surviving animals. All stented true lumens were patent without thrombus formation, and stents were covered by neointima. In dogs with stenting of the entire dissection, the aortic wall had healed and no false lumen was present. However, in all dogs with only proximal obliteration, 1/2 with partial compression, and 2/3 controls, a patent false channel was present indicative of a chronic dissection. Thus, we found that intravascular stents can restore true lumen flow and obliterate the false lumen in experimental dissections; however, stenting limited to the proximal dissection does not prevent formation of a chronic residual patent false lumen.

  View details for PubMedID 8331933

• ANNULOPLASTY WITH FLEXIBLE OR RIGID RING DOES NOT ALTER LEFT-VENTRICULAR SYSTOLIC PERFORMANCE, ENERGETICS, OR VENTRICULAR-ARTERIAL COUPLING IN CONSCIOUS, CLOSED-CHEST DOGS JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Castro, L. J., Moon, M. R., Rayhill, S. C., Niczyporuk, M. A., Ingels, N. B., Daughters, G. T., Derby, G. C., Miller, D. C. 1993; 105 (4): 643-659

  Abstract

  Eighteen dogs were randomly chosen to undergo mitral annuloplasty with either a Carpentier-Edwards rigid ring (n = 6 in each group) or a Duran-Medtronic flexible ring or to undergo a sham procedure with an operation, but no ring. Tantalum markers were inserted to measure left ventricular volume and geometry. After 1 and 6 weeks, biplane videofluoroscopic images were obtained during steady-state conditions and during vena caval occlusion. Global and regional systolic function was assessed with load-insensitive indexes. Comparison of all three groups and both times (1 and 6 weeks) showed no significant differences among the three groups in global or regional (basal, equatorial, and apical) left ventricular systolic performance. Furthermore, neither type of annuloplasty ring significantly affected left ventricular pump efficiency, ventricular-arterial coupling ratio, or systolic circumferential contraction and rotation of the basal left ventricular sites.

  View details for PubMedID 8468998

• EVALUATION OF REGIONAL LONGITUDINAL CURVATURE OF THE LEFT-VENTRICLE DURING THE CARDIAC CYCLE DEANDA, A., NIKOLIC, S. D., MOON, M. R., CASTRO, L. J., DAUGHTERS, G. T., INGELS, N. B., MILLER, D. C. FEDERATION AMER SOC EXP BIOL. 1993: A651

  View details for Web of Science ID A1993KP97500767

• VALVULAR DISEASE IN THE ELDERLY - INFLUENCE ON SURGICAL RESULTS ANNALS OF THORACIC SURGERY Davis, E. A., Gardner, T. J., Gillinov, A. M., Baumgartner, W. A., Cameron, D. E., Gott, V. L., Stuart, R. S., Watkins, L., Reitz, B. A., Akins, C. W., Miller, D. C., Reitz, B. A., David, T. E., Cosgrove, D. M. 1993; 55 (2): 333-338

  Abstract

  Aortic valve disease in the elderly is primarily calcific stenosis with preservation of left ventricular function. In contrast, mitral valve disease in the elderly often is ischemic in nature with damage occurring to both valve and myocardium. The present study was undertaken to compare results of aortic (AVR) and mitral valve replacement (MVR) in the elderly and to ascertain predictors of poor outcome. Because patients who had concomitant coronary artery bypass grafting (CABG) are included (51% for AVR, 55% for MVR), patients who had isolated CABG were used as a comparison group. Between January 1, 1984, and June 30, 1991, 1,386 patients aged 70 years and older underwent CABG (n = 1,043), AVR (n = 245), or MVR (n = 98). The operative mortality rates were 5.3% for AVR, 20.4% for MVR, and 5.8% for CABG. Late follow-up of patients undergoing operation in 1984 and 1985 was available for 98% (231/237). Overall survival was comparable for all three groups through the first 5 years of follow-up (AVR, 68% +/- 8%; MVR, 73% +/- 8%; CABG, 78% +/- 3%). After 5 years, survival for patients having AVR and MVR was less than that for those having CABG. Patient age, sex, New York Heart Association functional class, concomitant CABG, prosthetic valve type, native valve pathology, and preoperative catheterization data were examined as possible predictors of outcome by multivariate logistic regression.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for Web of Science ID A1993KK91400004

  View details for PubMedID 8431037

• Composite aortic valve replacement and graft replacement of the ascending aorta plus coronary ostial reimplantation: how I do it. Seminars in thoracic and cardiovascular surgery Miller, D. C., Mitchell, R. S. 1993; 5 (1): 74-83

  View details for PubMedID 8425007

• ARTERIAL AND VENOUS-BLOOD FLOW - NONINVASIVE QUANTITATION WITH MR IMAGING RADIOLOGY Pelc, L. R., Pelc, N. J., Rayhill, S. C., Castro, L. J., Glover, G. H., Herfkens, R. J., Miller, D. C., Jeffrey, R. B. 1992; 185 (3): 809-812

  Abstract

  Quantitative measurements of arterial and venous blood flow were obtained with phase-contrast cine magnetic resonance (MR) imaging and compared with such measurements obtained by means of implanted ultrasound (US) blood flow probes in anesthetized dogs. The US flowmeter was enabled during a portion of each MR imaging sequence to allow virtually simultaneous data acquisition with the two techniques. MR imaging data were gated by means of electrocardiography and divided into 16 phases per cardiac cycle. The rates of portal venous blood flow measured with MR imaging and averaged across the cardiac cycle (710 mL/min +/- 230 [standard deviation]) correlated well with those measured with the flowmeter and averaged in like fashion (751 mL/min +/- 238) (r = .995, slope = 1.053). The correspondence in arterial blood flow was almost as good. No statistically significant difference existed between the paired measurements of blood flow obtained with MR imaging and the implanted probe. It is concluded that, as a noninvasive means of accurate quantification of blood flow, phase-contrast MR imaging may be especially useful in deep blood vessels in humans.

  View details for PubMedID 1438767

• Rigid ring fixation of the mitral annulus does not impair left ventricular systolic function in the normal canine heart. Circulation Rayhill, S. C., Castro, L. J., NIZYPORUK, M. A., Ingels, N. B., Daughters, G. T., Derby, G. C., Tye, T. L., Bolger, A. F., Miller, D. C. 1992; 86 (5): II26-38

  Abstract

  Previous studies suggest that rigid fixation of the mitral annulus with an annuloplasty ring may impair left ventricular (LV) systolic performance. We used load-insensitive indexes of global and regional LV contractile mechanics to test the hypothesis that rigid fixation of the mitral annulus alters LV systolic function.Global and regional LV systolic mechanics were compared in 10 dogs during two mitral annular conditions: rigidly fixed and freely mobile. Carpentier-Edwards annuloplasty rings (20-24 mm) were inserted using a special buttressing suture technique that permitted alternate cinching of the ring down onto the annulus and subsequent removal away from the annulus. Aortic flow was measured with an electromagnetic flow probe, LV pressure by a micromanometer, and LV wall thickness and three near-orthogonal LV endocardial chamber dimensions using piezoelectric crystals during four sequential ring conditions: 1) down, 2) away, 3) down, and 4) away. The following parameters were analyzed during each ring condition to assess global LV systolic function: end-systolic chamber elastance (end-systolic pressure-volume relation), fiber elastance (end-systolic stress-volume relation), preload recruitable stroke work, and myocardial stress-strain relation. Additionally, regional LV systolic performance was assessed using the end-systolic pressure-diameter relation and a regional analog of preload recruitable stroke work. No significant differences in any of these measurements of LV systolic mechanics were observed between the two mitral annular conditions.Rigid fixation of the mitral annulus alters neither global nor regional LV systolic function in anesthetized, open-chest dogs with normal ventricles.

  View details for PubMedID 1424010

• CLINICAL USE OF INTRAVASCULAR ULTRASOUND IN STENTING ISCHEMIC COMPLICATIONS OF AORTIC DISSECTION Dake, M. D., Wexler, L., Walker, P. J., Mitchell, R. S., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 1992: 364–64

  View details for Web of Science ID A1992JT66001471

• EFFECTS OF THE PERICARDIUM ON LEFT-VENTRICULAR DIASTOLIC FILLING AND SYSTOLIC PERFORMANCE EARLY AFTER CARDIAC OPERATIONS JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Daughters, G. T., Frist, W. H., Alderman, E. L., Derby, G. C., Ingels, N. B., Miller, D. C. 1992; 104 (4): 1084-1091

  Abstract

  To determine whether closure of the pericardium after cardiac operations affects the filling characteristics and systolic performance of the left ventricle, we measured left ventricular volume, pressure, cardiac index, and stroke work index in 10 patients between 11 and 15 hours after cardiac operations, with the pericardium first closed and then open. At the time of operation, radiopaque tantalum markers were inserted in the left ventricular myocardium to outline the chamber in the 30-degree right anterior oblique projection, and the pericardium was closed by a continuous polypropylene suture exteriorized at both ends of the sternotomy. The patient was then transferred to the surgical intensive care unit, where left atrial pressure was measured via a fluid-filled catheter, left ventricular pressure with a micromanometer-tipped catheter, and myocardial oxygen consumption via a coronary sinus catheter. Left ventricular volume was measured by computer-aided analysis of fluoroscopic images (recorded at 30 frames per second) of the implanted myocardial markers. Left atrial pressure was maintained at target values of 10, 15, and 20 mm Hg by intravenous augmentation of blood volume. Left ventricular and left atrial pressures and volumes were measured with the pericardium closed; the pericardium was then opened by withdrawal of the pericardial suture. Radiopaque clips on the pericardial edges confirmed opening of the pericardium seconds after withdrawal of the suture. Repeated measurements of left ventricular pressures and volumes were then made at the target left atrial pressures with the pericardium open. End-diastolic volume index, peak positive time derivative of pressure, stroke work index, and cardiac index all increased significantly when the pericardium was opened (p < 0.001). Thus we found the following: (1) At physiologic pressures, the pericardium had a significant constraining effect on diastolic filling of the left ventricle, and (2) opening of the pericardium resulted in increased cardiac index and stroke work index. These increases may be attributed to the Frank-Starling response to increased left ventricular preload. The demonstrated improvement in left ventricular systolic performance should be considered when contemplating closure of the pericardium after cardiac operations, especially in patients with preoperative left ventricular dysfunction.

  View details for Web of Science ID A1992JT19800033

  View details for PubMedID 1405667

• RANDOMIZED, PROSPECTIVE ASSESSMENT OF BIOPROSTHESIS DURABILITY - HANCOCK VS CARPENTIER-EDWARDS VALVES Sarris, G. E., Robbins, R. C., Miller, D. C., Mitchell, R. S., Moore, K. A., Stinson, E. B., Oyer, P. E., Starnes, V. A., Shumway, N. E. LIPPINCOTT WILLIAMS & WILKINS. 1992: 496–96

  View details for Web of Science ID A1992JT66001991

• MANAGEMENT OF INTRAMURAL HEMATOMA OF THE THORACIC AORTA Robbins, R. C., MACMANUS, R. P., Mitchell, R. S., LATTER, D. R., Olinger, G. N., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 1992: 12–12

  View details for Web of Science ID A1992JT66000078

• LEFT-VENTRICULAR MECHANICS AND ENERGETICS IN THE DILATED CANINE HEART - ACUTE VERSUS CHRONIC MITRAL REGURGITATION JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Yun, K. L., Rayhill, S. C., NICZPORUK, M. A., Fann, J. I., Derby, G. C., Daughters, G. T., Ingels, N. B., Miller, D. C. 1992; 104 (1): 26-39

  Abstract

  The effects of volume overload associated with mitral regurgitation on left ventricular systolic mechanics, energetics, mechanical to external stroke work efficiency, and ventriculoarterial coupling were examined in 11 conscious, closed-chest dogs. Miniature radiopaque tantalum markers were implanted into the myocardium to measure left ventricular volume, and biplane cinefluoroscopic images were obtained 1 week and 3 months after creation of mitral regurgitation. Echocardiographically determined left ventricular mass increased from 116 +/- 28 to 152 +/- 29 gm (p less than 0.001). Left ventricular end-diastolic and end-ejection volumes increased by 24% and 27%, respectively. Global left ventricular systolic performance was assessed by the slopes (linear regression) of the end-systolic pressure-volume and end-systolic stress-volume relationships corrected for change in end-diastolic volume; normalized end-systolic pressure-volume relationships fell by 36% (p less than 0.001), and normalized end-systolic stress-volume relationships declined by 21% (p less than 0.005). The normalized end-systolic volume at 100 mm Hg end-systolic left ventricular pressure increased from 0.63 to 0.75 (p less than 0.05). Similar results were observed based on a nonlinear (quadratic) fit of the end-systolic pressure-volume data. In terms of energetics, the slopes of the stroke volume-end-diastolic volume and pressure-volume area-end-diastolic volume relationships fell significantly, indicating reduced external stroke work and mechanical energy at any given level of preload. Additionally, the efficiency of energy transfer from pressure-volume area to external pressure-volume work at matched end-diastolic volume was 25% lower (p = 0.006) at 3 months compared with the 1-week measurements. While overall effective arterial (or total vascular) elastance tended to decrease after a period of time, the effective ventriculovascular coupling ratio increased from 1.6 +/- 0.6 to 2.7 +/- 1.1 (p less than 0.005), indicating a greater degree of mismatch between the left ventricle and the total (forward and regurgitant) vascular load. Therefore the low pressure-volume overload of mitral regurgitation not only resulted in depressed left ventricular systolic mechanics but also was associated with deterioration of global left ventricular energetics and efficiency and exacerbated mismatch in coupling between the left ventricle and the systemic arterial bed and left atrium.

  View details for PubMedID 1614212

• CONCOMITANT ARCH REPAIR IN ACUTE TYPE-A AORTIC DISSECTION JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY MILLER, D. C. 1992; 104 (1): 206–8

  View details for Web of Science ID A1992JD13800028

  View details for PubMedID 1614206

• DURABILITY OF PORCINE VALVES AT 15 YEARS IN A REPRESENTATIVE NORTH-AMERICAN PATIENT POPULATION JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Burdon, T. A., Miller, D. C., Oyer, P. E., Mitchell, R. S., Stinson, E. B., Starnes, V. A., Shumway, N. E. 1992; 103 (2): 238-252

  Abstract

  Isolated aortic (n = 857) or mitral (n = 793) valve replacement with a porcine bioprosthesis was performed in 1650 patients between 1971 and 1980. Follow-up (total = 12,012 patient-years) extended to more than 15 years and was 96% complete. Patient age ranged from 16 to 87 years; mean age was 59 +/- 11 years (+/- 1 standard deviation) for the aortic valve replacement cohort and 56 +/- 12 years for the mitral valve replacement cohort. The operative mortality rates were 5% +/- 1% (+/- 70% confidence limits) and 8% +/- 1%, respectively, for the aortic and mitral subgroups. Estimated freedom from structural valve deterioration (+/- 1 standard error of the mean) after 10 and 15 years was significantly higher for the aortic than for the mitral valve replacement subgroup (85% +/- 0.4% and 63% +/- 3% versus 78% +/- 2% and 45% +/- 3%, respectively, p = 0.001). Reoperation-free actuarial estimates were also significantly greater for the aortic valve replacement cohort: 83% +/- 2% and 57% +/- 3% versus 78% +/- 2% and 43% +/- 3% for mitral valve replacement at 10 and 15 years, respectively. The mortality rate for reoperative aortic valve replacement was 11% +/- 1%; it was 8% +/- 1% for reoperative mitral valve replacement. Importantly, the estimates of freedom from valve-related death (including sudden, unexplained deaths) were relatively high at 10 and 15 years: 78% +/- 2% and 69% +/- 3% in the aortic cohort and 74% +/- 2% and 63% +/- 3% in the mitral cohort (p = not significant). Excluding sudden, unexplained deaths, these estimates were 81% +/- 3% (aortic) and 73% +/- 4% (mitral) at 15 years. Thromboembolism-free rates were 84% +/- 3% (aortic) and 78% +/- 6% (mitral) at 15 years, and freedom from anticoagulant-related hemorrhage was 96% +/- 1% and 89% +/- 2%, respectively. At the time of current follow-up, 13% of patients having aortic valve replacement and 50% of patients having mitral valve replacement were receiving warfarin sodium. The hazard functions for thromboembolism and prosthetic valve endocarditis were constant and remained less than 1%/pt-yr over the entire follow-up period.(ABSTRACT TRUNCATED AT 400 WORDS)

  View details for PubMedID 1735989

• EFFECTS OF FISH OIL ON GRAFT ARTERIOSCLEROSIS AND MHC CLASS-II ANTIGEN EXPRESSION IN RAT HETEROTOPIC CARDIAC ALLOGRAFTS JOURNAL OF HEART AND LUNG TRANSPLANTATION Yun, K. L., Michie, S. A., Fann, J. I., Billingham, M. E., Miller, D. C. 1991; 10 (6): 1004-1111

  Abstract

  The effect of fish oil on accelerated graft coronary arteriosclerosis was assessed in Lewis to Brown-Norway rat heterotopic cardiac allografts. Twelve Brown-Norway rats were supplemented with 2 ml/kg/day of fish oil (68.3 mg eicosopentaenoic acid and 47.5 mg decosahexaenoic acid per milliliter). Eleven additional animals, receiving an isocaloric amount of safflower oil, served as control. All diets began 1 week before operation. Immunosuppression was obtained with low-dose cyclosporine (2 mg/kg/d). When killed (100 days), there were no significant differences in percentage weight gain, graft function, or histologic rejection score. Although lipid profiles were comparable, total cholesterol:high-density lipoprotein ratio was marginally higher in animals treated with fish oil (p = 0.069). Mean percentage luminal occlusion (before and after correcting for differences in size between coronary vessels analyzed) and average intimal thickness were similar between animals treated with fish oil and safflower oil as assessed by computer-assisted digitized, morphometric planimetry. In all allografts, donor interstitial dendritic cells were repopulated with recipient dendritic cells. The major histocompatibility complex class II cell density in the fish oil group did not differ significantly from rats supplemented with safflower oil (1.48 +/- 0.68 vs 1.48 +/- 0.65 cells per mm2, p = 0.995). In conclusion, fish oil did not exert any beneficial effect over safflower oil in terms of graft coronary arteriosclerosis, histologic rejection, or plasma lipids.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for PubMedID 1756147

• REGIONAL EPICARDIAL AND ENDOCARDIAL 2-DIMENSIONAL FINITE DEFORMATIONS IN CANINE LEFT-VENTRICLE AMERICAN JOURNAL OF PHYSIOLOGY FANN, J. I., SARRIS, G. E., INGELS, N. B., NICZYPORUK, M. A., YUN, K. L., DAUGHTERS, G. T., DERBY, G. C., MILLER, D. C. 1991; 261 (5): H1402-H1410

  View details for DOI 10.1152/ajpheart.1991.261.5.H1402

  View details for Web of Science ID A1991GQ78100009

• REGIONAL EPICARDIAL AND ENDOCARDIAL 2-DIMENSIONAL FINITE DEFORMATIONS IN CANINE LEFT-VENTRICLE AMERICAN JOURNAL OF PHYSIOLOGY Fann, J. I., Sarris, G. E., Ingels, N. B., Niczyporuk, M. A., Yun, K. L., Daughters, G. T., Derby, G. C., Miller, D. C. 1991; 261 (5): H1402-H1410

  Abstract

  We evaluated subepicardial and subendocardial two-dimensional finite deformations in the left ventricular (LV) anterior, lateral, and posterior regions in the closed-chest, conscious dog heart. Eight dogs underwent placement of 22 radiopaque markers in the LV myocardium. Sets of three markers were implanted in the anterior, lateral, and posterior subepicardium and subendocardium at the mid-ventricular level; reference markers were placed at apical and basal sites. Eight hours later, biplane videofluoroscopy was performed. Finite deformations for each subepicardial and subendocardial region were analyzed during three consecutive beats at end expiration. Circumferential shortening occurred in all layers and regions; similarly, longitudinal shortening occurred in all layers except that of the posterior endocardium. Values of principal strain were -0.19 +/- 0.08 (SD) and -0.10 +/- 0.03 for the anterior subendocardium and subepicardium, -0.20 +/- 0.07 and -0.10 +/- 0.02 for the lateral subendocardium and subepicardium, and -0.13 +/- 0.02 and -0.10 +/- 0.03 for the posterior subendocardium and subepicardium respectively (P less than 0.05 subendocardium vs. subepicardium). Second principal strain tended to be near zero or positive (from -0.01 +/- 0.05 to 0.04 +/- 0.05) in all regions. The end-systolic direction of principal strain was -29 +/- 32 degrees and -34 +/- 29 degrees in the anterior subepicardium and subendocardium, -47 +/- 10 degrees and -30 +/- 37 degrees in the lateral subepicardium and subendocardium, and -4 +/- 29 degrees and +7 +/- 23 degrees in the posterior subepicardium and subendocardium. Anterior and lateral directions of principal strain were similar in the subepicardial and subendocardial layers and oriented along the epicardial fiber axis, but the posterior direction tended to be circumferentially oriented.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for PubMedID 1951727

• Improved follow-up for patients with chronic dissections. Seminars in thoracic and cardiovascular surgery Miller, D. C. 1991; 3 (4): 270-276

  View details for PubMedID 1793763

• AORTIC DISSECTION RESULTING FROM TEAR OF TRANSVERSE ARCH - IS CONCOMITANT ARCH REPAIR WARRANTED 16TH ANNUAL MEETING OF THE WESTERN THORACIC SURGICAL ASSOC Yun, K. L., Glower, D. D., Miller, D. C., Fann, J. I., Mitchell, R. S., White, W. D., Rankin, J. S., Wolfe, W. G., Shumway, N. E. MOSBY-ELSEVIER. 1991: 355–70

  Abstract

  Forty-seven patients with aortic dissection resulting from a primary tear located in the transverse aortic arch underwent surgical treatment. Twenty-six patients had acute type A, 7 had acute type B, 7 had chronic type A, and 7 had chronic type B aortic dissections. Of the 33 patients with acute dissections, 11 (7 acute type A and 4 acute type B) underwent concomitant arch repair with an operative (less than or equal to 30 days) mortality rate of 55% (35% to 73%, +/- 1 asymmetric 70% confidence limit) (2 of 7 acute type A and 4 of 4 acute type B). Concomitant arch repair was omitted in 22 patients with acute dissections (19 acute type A and 3 acute type B); the operative mortality rate was 41% (29% to 54%) (7 of 19 acute type A and 2 of 3 acute type B) (p = not significant versus arch repair). The overall survival rate for those with arch repair was 45% +/- 15% (+/- 1 standard error of the estimate) at 4 years, compared with 43% +/- 11% for patients without arch repair (p = not significant). Considering the type of dissection, the 4-year survival estimate for patients with acute type A dissections who underwent arch repair (5 hemiarch and 2 total arch) was 71% +/- 17% (versus 44% +/- 12% for acute type A patients without arch repair). There were no survivors among the 4 patients with acute type B dissections who had an arch repair (1 hemiarch and 3 total arch), whereas patients with acute type B dissections who did not undergo concomitant arch repair had a 4-year survival estimate of 33% +/- 27% (p = not significant versus arch repair). Four other patients with acute type B dissections resulting from an arch tear were managed medically and tended to have a slightly better prognosis (2-year survival estimate of 75% +/- 22% versus 14% +/- 13% for all surgically treated acute type B patients), but again this difference was not statistically significant. Multivariate analysis of the 47 surgical patients revealed that advanced age (p = 0.0008), preoperative dissection complications (p = 0.02), and other coexistent medical problems (p = 0.03) were the only significant, independent determinants of overall mortality. Initial arch repair was not a significant predictor. Nine percent (2/22) of patients with acute type A dissections who initially underwent isolated ascending aortic replacement required subsequent arch replacement; 1 died after reoperation.(ABSTRACT TRUNCATED AT 400 WORDS)

  View details for PubMedID 1881176

• DOSE-RESPONSE OF FISH OIL VERSUS SAFFLOWER OIL ON GRAFT ARTERIOSCLEROSIS IN RABBIT HETEROTOPIC CARDIAC ALLOGRAFTS ANNALS OF SURGERY Yun, K. L., Fann, J. I., Sokoloff, M. H., Fong, L. G., Sarris, G. E., Billingham, M. E., Miller, D. C. 1991; 214 (2): 155-167

  Abstract

  With the advent of cyclosporin A, accelerated coronary arteriosclerosis has become the major impediment to the long-term survival of heart transplant recipients. Due to epidemiologic reports suggesting a salutary effect of fish oil, the dose response of fish oil on graft coronary arteriosclerosis in a rabbit heterotopic cardiac allograft model was assessed using safflower oil as a caloric control. Seven groups of New Zealand White rabbits (n = 10/group) received heterotropic heart transplants from Dutch-Belted donors and were immunosuppressed with low-dose cyclosporin A (7.5 mg/kg/day). Group 1 animals were fed a normal diet and served as control. Group 2, 3, and 4 animals received a daily supplement of low- (0.25 mL/kg/day), medium- (0.75 mL/kg/day), and high- (1.5 mL/kg/day) dose fish oil (116 mg n-3 polyunsaturated fatty acid/mL), respectively. Group 5, 6, and 7 animals were supplemented with equivalent dose of safflower oil (i.e., 0.25, 0.75, and 1.5 mL/kg/day). Oil-supplemented rabbits were pretreated for 3 weeks before transplantation and maintained on the same diet for 6 weeks after operation. The extent of graft coronary arteriosclerosis was quantified using computer-assisted, morphometric planimetry. When the animals were killed, cyclosporin A was associated with elevated plasma total cholesterol and triglyceride levels in the control group. While safflower oil prevented the increase in plasma lipids at all dosages, fish oil ameliorated the cyclosporin-induced increase in total cholesterol only with high doses. Compared to control animals, there was a trend for more graft vessel disease with increasing fish oil dose, as assessed by mean luminal occlusion and intimal thickness. A steeper trend was observed for increasing doses of safflower oil; compared to the high-dose safflower oil group, animals supplemented with low-dose safflower oil had less mean luminal occlusion (16.3% +/- 5.9% versus 41.4% +/- 7.6%, p less than 0.017) and intimal thickness (7.9 +/- 1.9 microns versus 34.0 +/- 13.0 microns, analysis of variance: p = 0.054). Low-dose safflower oil also had a slight, but nonsignificant, beneficial effect on graft vessel disease when compared to control rabbits. The same trends were observed in the degree of histologic rejection (0 = none to 3 = severe) in fish oil- and safflower oil-treated animals. Rejection score correlated weakly but significantly (p = 0.0001) with mean luminal occlusion (r = 0.52) and intimal thickness (r = 0.46). Therefore allograft coronary disease in this model appeared to exhibit an unfavorable, direct-dose response to fish oil and safflower oil, independent of effects on plasma lipids.(ABSTRACT TRUNCATED AT 400 WORDS)

  View details for PubMedID 1867523

• Surgical management of acute aortic dissection: new data. Seminars in thoracic and cardiovascular surgery Miller, D. C. 1991; 3 (3): 225-237

  View details for PubMedID 1958743

• PRESERVATION OF AORTIC-VALVE IN TYPE-A AORTIC DISSECTION COMPLICATED BY AORTIC REGURGITATION 70TH ANNUAL MEETING OF THE AMERICAN ASSOC FOR THORACIC SURGERY Fann, J. I., Glower, D. D., Miller, D. C., Yun, K. L., Rankin, J. S., White, W. D., Smith, L. R., Wolfe, W. G., Shumway, N. E. MOSBY-YEAR BOOK INC. 1991: 62–75

  Abstract

  Two hundred fifty-two patients underwent operation for type A aortic dissection at Stanford University Medical Center from 1963 to 1987 and Duke University Medical Center from 1975 to 1988. Sixty-seven percent had an acute type A dissection and 33% had a chronic type A dissection. In addition to repair or replacement of the ascending aorta, 121 patients (48%) required an aortic valve procedure. Valve resuspension was performed in 46 (39 acute type A and 7 chronic type A), with an operative mortality rate of 13% +/- 5% (+/- 70% confidence limits), and aortic valve replacement in 75 (36 acute type A and 39 chronic type A), with an operative mortality rate of 20% +/- 5% (p = not significant versus resuspension). The operative mortality rate for patients requiring only repair or replacement of the ascending aorta was 32% +/- 4%. Indications for valve replacement included coexistent (nonacute) aortic valve disease, Marfan's syndrome, annuloaortic ectasia, and cases in which successful resuspension could not be accomplished. The overall actuarial survival rate for all patients was 59% +/- 3% (+/- 1 standard error of the mean), 40% +/- 4%, and 25% +/- 5% at 5, 10, and 15 years, respectively. Survival rates at these same times for patients with valve resuspension were 67% +/- 8%, 52% +/- 10%, and 26% +/- 19%, respectively; for patients who required aortic valve replacement, these survival rates were 70% +/- 5%, 39% +/- 8%, and 21% +/- 11%; finally, patients who received only an ascending aortic procedure had survival probabilities of 51% +/- 5%, 37% +/- 6%, and 23% +/- 6% (p = not significant versus resuspension versus aortic valve replacement). Multivariate analysis showed advanced age (p less than 0.001), previous cardiac or aortic operation (p less than 0.001), more preoperative dissection complications (p = 0.002), and earlier operative date (p = 0.038) to be the only significant, independent factors that increased the likelihood of early or late death. The type of aortic valve procedure (resuspension versus aortic valve replacement versus none) was not a significant predictor of mortality. Two of 46 patients with valve resuspension required late aortic valve replacement (freedom from aortic valve replacement: 100% and 80% +/- 13% at 5 and 10 years, respectively), as did 4 of 75 patients with initial aortic valve replacement (freedom from repeat aortic valve replacement: 98% +/- 2% and 73% +/- 13%, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

  View details for PubMedID 2072730

• HUMAN VENTRICULAR REPOLARIZATION AND T-WAVE GENESIS PROGRESS IN CARDIOVASCULAR DISEASES Franz, M. R., BARGHEER, K., COSTARDJACKLE, A., Miller, D. C., Lichtlen, P. R. 1991; 33 (6): 369-384

  View details for PubMedID 2028018

• Mitral valve repair versus replacement. Cardiology clinics Yun, K. L., Miller, D. C. 1991; 9 (2): 315-327

  Abstract

  When considering all the major series comparing the early and late results of mitral valve repair versus prosthetic or bioprosthetic mitral valve replacement, the operative mortality rate is slightly lower for patients undergoing valve reconstruction. Late survival is also superior after valve repair. Although these modest differences may be related to patient selection bias, a lower rate of thromboembolic and endocarditis-related complications and improved LV function remain as rather compelling factors favoring valve repair. The durability of valve repair is comparable to valve replacement in terms of reoperation rate, except in cases of rheumatic valve abnormality (in which reoperation rates are higher after valvuloplasty). Definitive, objective evidence favoring mitral valve repair is lacking given the short period of followup in all studies and absence of controlled, randomized clinical trials. The success of mitral valve reconstruction relies heavily on the experience and technical expertise of the surgeon. The wide variability in observed survival rates, however, is unlikely to be due to differences in surgical skill between experienced groups; it more likely represents the results of differing criteria for mitral valve repair, various followup intervals, and comparisons between distinctly different cohorts. Although a prospective randomized trial would be ideal to compare the results of mitral valve reconstruction versus mitral valve replacement for patients with mitral valve regurgitation, it is unlikely and unrealistic that such a study will ever be conducted. The universal applicability of the results of such a study would also be dubious, given the widely varying extent of surgical expertise with mitral valve repair. Furthermore, not all types of mitral regurgitation are amendable to reconstruction short of using patch techniques (usually autologous pericardium treated with glutaraldehyde) or resorting to artificial chordae (e.g., extensive leaflet destruction from rheumatic changes or infective endocarditis, and substantial anterior leaflet redundancy). In cases in which mitral valve replacement is necessary, preservation of the mitral subvalvular apparatus promises to be an important concept to preserve optimal systolic LV function postoperatively.

  View details for PubMedID 2054820

• AUTOMATIC TRACKING AND DIGITIZATION OF MULTIPLE RADIOPAQUE MYOCARDIAL MARKERS COMPUTERS AND BIOMEDICAL RESEARCH Niczyporuk, M. A., Miller, D. C. 1991; 24 (2): 129-142

  Abstract

  An 80386 PC-based system was designed to track automatically multiple, miniature radiopaque markers implanted in the heart wall. This system eliminated the need for tedious, time-consuming manual digitization of marker coordinates. Use of a MATROX MVP-AT/NP image processing board incorporated advanced image processing and graphics features into the low-cost PC environment. Digital image enhancement and segmentation techniques (such as limiting analysis to predefined windows of interest, spatial band-pass and matched filtering, contrast stretching and clipping, linear adaptive prediction, intensity histogram analysis, adaptive binary thresholding, region growing, expanding region of analysis, and feature extraction) were incorporated into a user-friendly integrated marker processing software environment. Improved speed, accuracy, and reproducibility of the marker digitizing process were realized. These basic techniques have broad applications to other image processing needs in biomedical research.

  View details for PubMedID 2036779

• EFFECT OF VOLUME LOADING, PRESSURE LOADING, AND INOTROPIC STIMULATION ON LEFT-VENTRICULAR TORSION IN HUMANS CIRCULATION Hansen, D. E., Daughters, G. T., Alderman, E. L., Ingels, N. B., Stinson, E. B., Miller, D. C. 1991; 83 (4): 1315-1326

  Abstract

  The transmural distribution of fiber angles and the extent of shortening among obliquely oriented fibers are likely to be major determinants of the twisting motion that accompanies left ventricular (LV) ejection. As such, measurements of torsion may provide useful information about LV contractile function, but other factors, such as ventricular loading conditions, may also regulate this motion.Torsion angles (theta i) of midventricular and apical regions were measured relative to a reference minor axis near the base in seven human cardiac allografts from biplane radiographic images of metallic midwall markers. Pressure loading with methoxamine (5-10 muk/kg/min) increased LV end-systolic pressure by 41 +/- 14 mm Hg (p less than 0.0001). Volume loading with normal saline raised LV end-diastolic pressure from 9.9 +/- 5.2 to 19.6 +/- 4.9 mm Hg (p less than 0.0001). These alterations in LV loading conditions were associated with no change in theta i (difference not significant) for any marker site. Inotropic stimulation with dobutamine (5 micrograms/kg/min) increased values of theta i by as much as twofold (p less than 0.05); this response varied considerably depending on marker location, with the middle and apical inferior wall and the apical lateral wall being the most sensitive. When the marker site associated with the largest torsion angle (theta max) was considered in each patient, dobutamine increased theta max in all cases (25.2 +/- 10.5 degrees versus 15.8 +/- 7.7 degrees, p less than 0.001), whereas pressure and volume loading had negligible effects. This 59% increase in theta max was greater than that of conventional load-dependent indexes of LV systolic performance such as stroke volume (16%), ejection fraction (22%), and maximum rate of LV pressure rise (52%).This component of LV motion is relatively insensitive to alterations in preload and afterload, while changes in contractile state influence LV torsion in a regionally heterogeneous manner. Quantification of LV torsion may, therefore, provide a sensitive and relatively load-independent measure of contractile performance that may prove to be useful in the serial assessment of LV function.

  View details for Web of Science ID A1991FF41900016

  View details for PubMedID 2013149

• ALTERATIONS IN LEFT-VENTRICULAR DIASTOLIC TWIST MECHANICS DURING ACUTE HUMAN CARDIAC ALLOGRAFT-REJECTION CIRCULATION Yun, K. L., Niczyporuk, M. A., Daughters, G. T., Ingels, N. B., Stinson, E. B., Alderman, E. L., Hansen, D. E., Miller, D. C. 1991; 83 (3): 962-973

  Abstract

  Contraction of obliquely oriented left ventricular (LV) fibers results in a twisting motion of the left ventricle. The purpose of this study was to assess the effects of acute human cardiac allograft rejection on LV twist pattern and the twist-volume relation.Tantalum markers were implanted into the LV midwall in 15 transplant recipients to measure time-varying, three-dimensional chamber twist using computer-assisted analysis of biplane cinefluoroscopic images. Twist was defined as the mean longitudinal gradient of circumferential rotation about the LV long axis. When plotted against normalized percent ejection fraction (%EF), the resulting twist-normalized %EF relation could be divided into three phases. In systole, LV twist was linearly related to ejection of blood. In contrast, diastolic untwist was characterized by early rapid recoil with little change in LV volume, followed by more gradual untwisting when the bulk of diastolic filling occurred. During 10 acute rejection episodes in 10 patients, maximum twist, peak systolic twist rate, and the slope of the systolic twist-normalized %EF relation did not change. In contrast, the slope of the early (first 15% of filling) diastolic twist-normalized %EF relation (M(early-dia)) decreased significantly (-0.194 +/- 0.062 [prerejection] versus -0.103 +/- 0.054 rad/cm [rejection], p = 0.0003), resulting in a prolonged tau 1/2 (time required to untwist by 50% [20 +/- 5% versus 28 +/- 5% of diastole], p = 0.0003) and decrease in percent untwisting at 15% diastolic LV filling (62 +/- 11% versus 36 +/- 13%, p = 0.0003). Therefore, a greater proportion of LV untwisting occurred later in diastole during rejection, as reflected by an increase in the slope (M(mid-dia)) of the middle to late (from 15 to 90% filling) diastolic twist-normalized %EF relation (-0.018 +/- 0.009 versus -0.030 +/- 0.010 rad/cm, p = 0.0015). Peak rate of untwist was not affected. With resolution of rejection, M(early-dia) and percent untwist during early diastole returned to baseline levels (p = NS versus baseline). There was also a trend for M(mid-dia) to return toward prerejection values (p = NS versus baseline), but this change did not reach statistical significance compared with rejection values.Acute cardiac allograft rejection is associated with altered diastolic twist mechanics in the absence of any demonstratable systolic abnormalities. During rejection, myocardial edema and other factors may result in intrinsic changes of the elastic properties of the myocardium, thereby leading to modification of recoil forces responsible for the early, rapid unwinding of the deformed ventricle.

  View details for PubMedID 1999044

• FREEHAND ALLOGRAFT AORTIC-VALVE REPLACEMENT AND AORTIC ROOT REPLACEMENT - UTILITY OF INTRAOPERATIVE ECHOCARDIOGRAPHY AND DOPPLER COLOR FLOW MAPPING JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY BARTZOKIS, T., STGOAR, F., Dibiase, A., Miller, D. C., Bolger, A. F. 1991; 101 (3): 545-554

  Abstract

  Seventeen consecutive patients undergoing 20 planned aortic valve replacements with allograft valves at Stanford University Medical Center were studied with intraoperative epicardial echocardiography and Doppler color flow mapping before and after cardiopulmonary bypass. Native aortic valves were replaced in 12 of the 20 patients, and eight patients underwent second aortic valve procedures. In 17 of 20 patients allograft selection was guided by prebypass echocardiographic estimates of annular diameter and/or length of allograft aortic root required. Other prebypass findings included unanticipated severe mitral regurgitation in one patient (which precluded allograft aortic valve replacement), left-to-right shunts in five patients, ascending aortic dissection in one, and aortic root disease necessitating coronary reimplantation or bypass in two. Postbypass echocardiography demonstrated acceptable competency of 18 of 19 allograft valves (mild or no aortic insufficiency). Postbypass echocardiography also documented successful repair of four of five shunts and mild mitral regurgitation in 15 of 19 patients (versus 11 of 19 before bypass). Conclusions: Intraoperative echocardiography-Doppler mapping is a useful adjunct for allograft aortic valve or aortic root replacement; it allows confident selection of appropriate tissue size before aortic cross clamping, which minimizes delay from allograft thawing procedures. It also provides helpful information about the extent of aortic root disease and coronary ostial anatomy before bypass, confirms allograft competency after bypass, and detects accompanying valvular and other hemodynamic lesions before and after allograft valve replacement.

  View details for PubMedID 1999949

• IMPORTANCE OF MITRAL SUBVALVULAR APPARATUS IN TERMS OF CARDIAC ENERGETICS AND SYSTOLIC MECHANICS IN THE EJECTING CANINE HEART JOURNAL OF CLINICAL INVESTIGATION Yun, K. L., Niczyporuk, M. A., Sarris, G. E., Fann, J. I., Miller, D. C., Derby, G. C., Handen, C. E. 1991; 87 (1): 247-254

  Abstract

  To assess the importance of the intact mitral subvalvular apparatus for left ventricular (LV) energetics, data from nine open-chest ejecting canine hearts were analyzed using piezoelectric crystals to measure LV volume. After mitral valve replacement with preservation of all chordae tendineae, baseline LV function was assessed during transient caval occlusion: A quadratic fit of the LV end-systolic pressure-volume data was used to determine the curvilinear end-systolic pressure-volume relationship (ESPVR). All chordae were then divided with exteriorized snares. Reassessment revealed deterioration of global LV pump function: (a) the coefficient of nonlinearity, decreased (less negative) by 90% (P = 0.06); (b) slope of the curvilinear ESPVR at the volume axis intercept, decreased by 75% (P = 0.01); and V100, end-systolic volume at 100 mmHg end-systolic pressure, increased by 42% (P less than 0.02). Similarly, preload recruitable stroke work fell significantly (-14%) and Vw1,000 (end-diastolic volume [EDV] at stroke work [SW] of 1,000 mmHg.ml) rose by 17% (P less than 0.04). With respect to LV energetics, the total mechanical energy generated by the ventricle decreased, as indicated by a decline in the slope of the pressure volume area (PVA)-EDV relationship (120 +/- 13 [mean +/- SD] vs. 105 +/- 13 mmHg, P less than 0.001). Additionally, comparison of LV SW and PVA from single beats with matched EDV showed that the efficiency of converting mechanical energy to external work (SW/PVA) declined by 14% (0.65 +/- 0.13 vs. 0.56 +/- 0.08, P less than 0.03) after chordal division. While effective systemic arterial elastance, Ea, also fell significantly (P = 0.03) after the chordae were severed, the Ea/Ees ratio (Ees = slope of the linear ESPVR) increased by 124% (0.91 +/- 0.53 vs. 2.04 +/- 0.87, P = 0.001) due to a proportionally greater decline in Ees. This indicates a mismatch in ventriculo-arterial interaction, deviating from that required for maximal external output (viz., Ea/Ees = 1). These adverse effects of chordal division may be related to the observed changes in LV geometry (i.e., eccentricity). We conclude that the intact mitral subvalvular apparatus is important in optimizing LV energetics and ventriculo-vascular coupling in addition to the enhancement of LV systolic performance.

  View details for PubMedID 1985098

• TREATMENT OF PATIENTS WITH AORTIC DISSECTION PRESENTING WITH PERIPHERAL VASCULAR COMPLICATIONS ANNALS OF SURGERY Fann, J. I., Sarris, G. E., Mitchell, R. S., Shumway, N. E., Stinson, E. B., Oyer, P. E., Miller, D. C. 1990; 212 (6): 705-713

  Abstract

  The incidence of peripheral vascular complications in 272 patients with aortic dissection during a 25-year span was determined, as was outcome after a uniform, aggressive surgical approach directed at repair of the thoracic aorta. One hundred twenty-eight patients (47%) presented with acute type A dissection, 70 (26%) with chronic type A, 40 (15%) with acute type B, and 34 (12%) with chronic type B dissections. Eighty-five patients (31%) sustained one or more peripheral vascular complications: Seven (3%) had a stroke, nine (3%) had paraplegia, 66 (24%) sustained loss of a peripheral pulse, 22 (8%) had impaired renal perfusion, and 14 patients (5%) had compromised visceral perfusion. Following repair of the thoracic aorta, local peripheral vascular procedures were unnecessary in 92% of patients who presented with absence of a peripheral pulse. The operative mortality rate for all patients was 25% +/- 3% (68 of 272 patients). For the subsets of individuals with paraplegia, loss of renal perfusion, and compromised visceral perfusion, the operative mortality rates (+/- 70% confidence limits) were high: 44% +/- 17% (4 of 9 patients), 50% +/- 11% (11 of 22 patients), and 43% +/- 14% (6 of 14 patients), respectively. The mortality rates were lower for patients presenting with stroke (14% +/- 14% [1 of 7 patients]) or loss of peripheral pulse (27% +/- 6% [18 of 66 patients]). Multivariate analysis revealed that impaired renal perfusion was the only peripheral vascular complication that was a significant independent predictor of increased operative mortality risk (p = 0.024); earlier surgical referral (replacement of the appropriate section of the thoracic aorta) or more expeditious diagnosis followed by surgical renal artery revascularization after a thoracic procedure may represent the only way to improve outcome in this high-risk patient subset. Early, aggressive thoracic aortic repair (followed by aortic fenestration and/or abdominal exploration with or without direct visceral or renal vascular reconstruction when necessary) can save some patients with compromised visceral perfusion; however, once visceral infarction develops the prognosis is also poor. Increased awareness of these devastating complications of aortic dissection and the availability of better diagnostic tools today may improve the survival rate for these patients in the future. The initial surgical procedure should include repair of the thoracic aorta in most patients.

  View details for PubMedID 2256762

• Importance of the mitral subvalvular apparatus for left ventricular segmental systolic mechanics. Circulation Yun, K. L., Fann, J. I., Rayhill, S. C., NASSERBAKHT, F., Derby, G. C., Handen, C. E., Bolger, A. F., Miller, D. C. 1990; 82 (5): IV89-104

  Abstract

  The relative importance of the anterolateral (ANTLAT) and posteromedial (POSTMED) papillary muscle (PM) chordae tendineae for left ventricular (LV) segmental wall function was assessed in 12 in situ ejecting canine hearts. Pairs of piezoelectric crystals were placed in the regions subtending PM insertions and the ANTLAT LV free wall to measure wall thickness. After mitral valve replacement with complete preservation of the subvalvular apparatus, chordal attachments to either the ANTLAT PM or POSTMED PM were randomly severed using exteriorized snares, followed by subsequent division of the remaining chordae tendineae. Segmental wall function in each region was determined at each stage by segmental preload recruitable stroke work (sPRSW, slope of the segmental stroke work-end-diastolic wall thickness relation). The order in which the chordae were severed was unimportant (p greater than 0.530 in all regions). When the ANTLAT PM chordae were severed first, there were significant declines in sPRSW without a change in the wall thickness intercept in both the ANTLAT (-71.0 +/- 18.3 vs. -57.7 +/- 16.8 mmHg, p less than 0.05) and POSTMED (-81.8 +/- 23.1 vs. -65.4 +/- 17.3 mmHg, p less than 0.05) PM insertion sites. No further significant reductions in sPRSW in either region were detected after severing the remaining chordal attachments to the POSTMED PM. sPRSW in the ANTLAT LV free wall decreased progressively, reaching statistical significance when both sets of chordae tendineae were divided (-88.3 +/- 14.3 vs. -74.0 +/- 15.2 mm Hg, p less than 0.05). When the POSTMED PM chordae were severed first, no significant changes in sPRSW or the wall thickness intercept in either region of PM insertion were detected. Subsequent division of the ANTLAT PM chordal attachments reduced sPRSW significantly in both the ANTLAT PM (-65.9 +/- 21.1 vs. -56.1 +/- 22.1 mm Hg, p less than 0.05) and POSTMED PM (-78.8 +/- 24.7 vs. -67.2 +/- 24.0 mm Hg, p less than 0.05) insertion sites, without a shift in the wall thickness intercept. In the ANTLAT LV free wall, sPRSW again fell progressively, achieving statistical significance only when both chordal attachments were severed (-78.6 +/- 14.8 vs. -62.2 +/- 13.7 mm Hg, p less than 0.05). In conclusion, division of the chordae tendineae resulted in a decline in segmental LV function not only in the areas subtending PM insertions but also in remote LV regions. Furthermore, the influence of the ANTLAT PM chordae predominated local LV systolic function at both PM insertion sites.(ABSTRACT TRUNCATED AT 400 WORDS)

  View details for PubMedID 2225439

• Hemodynamic comparison of Hancock and Carpentier-Edwards mitral bioprosthetic valves. Circulation Khan, S., Mitchell, R. S., Derby, G. C., Oyer, P. E., Miller, D. C. 1990; 82 (5): IV75-81

  Abstract

  Although it is known that pressure gradients and calculated valve areas in bioprosthetic valves are highly flow dependent, no studies have compared bioprosthetic valve performances while adjusting for differences in flow rate. We therefore studied 75 patients undergoing mitral valve replacement who were randomized to receive either Hancock (n = 35) or Carpentier-Edwards (n = 40) bioprosthetic valves. Pressure gradients were measured using transducer-tipped catheters to record left ventricular and left atrial pressures and cardiac outputs by thermodilution. Repeated measurements were made in each patient after either pacing, fluid infusion, or pharmacological intervention to vary flow rates for a total of 239 measurements (mean, 3.2 measurements per patient). Using analyses of variance and covariance, mean valve gradients and the calculated Gorlin area were adjusted for flow rate, valve size, valve type, and interpatient differences to compare hemodynamics. Without flow and interpatient adjustment, the univariate analysis suggested higher mean gradients in the Carpentier-Edwards 29-mm valves (p = 0.038), with a trend toward higher gradients and smaller areas in the Hancock 33-mm valves (p = 0.057 and 0.059, respectively). After adjustment for flow rate and interpatient differences, however, there was no difference at any valve size in the mean pressure gradients (p = 0.13-0.89) or Gorlin valve areas (p = 0.34-0.96). Although measurements within a given patient were consistent, marked interpatient variabilities in gradients and areas were observed for identical valve types and sizes, which were as significant as flow-dependent or size-dependent changes. We conclude that comparisons of valve performance should adjust for variations in flow rate and for interpatient differences with the use of repeated-measures designs.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for PubMedID 2225438

• Differences in Hancock and Carpentier-Edwards porcine xenograft aortic valve hemodynamics. Effect of valve size. Circulation Khan, S. S., Mitchell, R. S., Derby, G. C., Oyer, P. E., Miller, D. C. 1990; 82 (5): IV117-24

  Abstract

  We prospectively compared the hemodynamic performance of Hancock and Carpentier-Edwards bioprosthetic aortic valves in a randomized study of 100 patients. A total of 47 patients received the Hancock valve, and 53 received the Carpentier-Edwards valve. Mean pressure gradients were measured using micromanometer catheters and cardiac outputs by thermodilution. Multiple measurements were made in each patient with atrial pacing, volume infusion, and inotropic drugs for a total of 319 observations. The pressure gradients and Gorlin valve areas showed significant scatter caused by both flow-dependent and patient-dependent variability. Mean transvalvular pressure gradients were therefore compared after adjustment for flow rate and for random interpatient differences using analysis of variance and covariance. Pressure gradients were lower and Gorlin valve areas larger for the Hancock valve than for the Carpentier-Edwards valve, but the differences were significant only for the smaller valve sizes. Compared with the Carpentier-Edwards valve, the mean pressure gradients were significantly lower for the Hancock 19-mm modified orifice (MO) valves (16.9 versus 31.7 mm Hg, p = 0.04), for the 21-mm valves (15.2 versus 22.4 mm Hg, p = 0.003), and for the 23-mm MO valve (9.2 versus 13.8 mm Hg, p = 0.04). The Gorlin areas were also significantly larger for the Hancock 19-mm MO valve (0.85 versus 0.77 cm2, p = 0.004) and the 21-mm MO valve (1.11 versus 0.89 cm2, p = 0.0009) but not for the 23-mm MO valve (1.59 versus 1.14, p = 0.08). Mean gradients and valve areas were not different for any of the larger valve sizes.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for PubMedID 2225396

• Comparison of medical and surgical therapy for uncomplicated descending aortic dissection. Circulation Glower, D. D., Fann, J. I., SPEIER, R. H., Morrison, L., White, W. D., Smith, L. R., Rankin, J. S., Miller, D. C., Wolfe, W. G. 1990; 82 (5): IV39-46

  Abstract

  To guide the choice of medical versus surgical therapy for patients with descending (type B) aortic dissection (tear in the descending aorta without involvement of the ascending aorta), multivariate survival analysis was applied to 136 patients admitted to two medical centers between 1975 and 1988 with acute (n = 89) or chronic (n = 47) descending dissection: group 1, all 136 patients; group 2, 106 patients without rupture, pulse loss, or visceral organ compromise; and group 3, 56 patients from group 2 without major cardiac or renal disease (23 surgical and 33 medical). Group 3 medical and surgical subgroups were well matched for baseline characteristics and were potential candidates for either mode of therapy. By Cox model analysis, significant predictors of mortality were pleural rupture, other dissection complications, increasing age, and cardiac disease (all p less than 0.01). Surgical versus medical therapy was not an independent determinant of survival in any of the three groups for acute or chronic dissection. Survival probabilities for all group 3 patients at 1, 5, and 10 years were 0.94, 0.87, and 0.32 (medical) and 0.90, 0.80, and 0.50 (surgical). Despite the limitations of this retrospective study (including the possibility of undefined treatment selection biases), these data suggest that medical or early surgical therapy is associated with equivalent outcome in selected patients with uncomplicated acute or chronic descending aortic dissection.

  View details for PubMedID 1977532

• COMPARISON OF MEDICAL AND SURGICAL THERAPY FOR UNCOMPLICATED DESCENDING AORTIC DISSECTION CIRCULATION Glower, D. D., Fann, J. I., SPEIER, R. H., Morrison, L., White, W. D., Smith, L. R., Rankin, J. S., Miller, D. C., Wolfe, W. G. 1990; 82 (5): 39-46

  View details for Web of Science ID A1990EJ51000006

• THE REVERSIBILITY OF CANINE VEIN-GRAFT ARTERIALIZATION CIRCULATION Fann, J. I., Sokoloff, M. H., Sarris, G. E., Yun, K. L., Kosek, J. C., Miller, D. C. 1990; 82 (5): 9-18

  View details for Web of Science ID A1990EJ51000003

• IMPORTANCE OF THE MITRAL SUBVALVULAR APPARATUS FOR LEFT-VENTRICULAR SEGMENTAL SYSTOLIC MECHANICS CIRCULATION Yun, K. L., Fann, J. I., Rayhill, S. C., NASSERBAKHT, F., Derby, G. C., Handen, C. E., Bolger, A. F., Miller, D. C. 1990; 82 (5): 89-104

  View details for Web of Science ID A1990EJ51000013

• DIFFERENCES IN HANCOCK AND CARPENTIER-EDWARDS PORCINE XENOGRAFT AORTIC-VALVE HEMODYNAMICS - EFFECT OF VALVE SIZE CIRCULATION Khan, S. S., Mitchell, R. S., Derby, G. C., Oyer, P. E., Miller, D. C. 1990; 82 (5): 117-124

  View details for Web of Science ID A1990EJ51000016

• HEMODYNAMIC COMPARISON OF HANCOCK AND CARPENTIER-EDWARDS MITRAL BIOPROSTHETIC VALVES CIRCULATION Khan, S., Mitchell, R. S., Derby, G. C., Oyer, P. E., Miller, D. C. 1990; 82 (5): 75-81

  View details for Web of Science ID A1990EJ51000011

• The reversibility of canine vein-graft arterialization. Circulation Fann, J. I., Sokoloff, M. H., Sarris, G. E., Yun, K. L., Kosek, J. C., Miller, D. C. 1990; 82 (5): IV9-18

  Abstract

  We assessed the reversibility of functional and morphological changes of arterialized vein segments by returning them to the venous circulation. Thirteen dogs underwent right carotid and femoral veno-arterial grafting. After 12 weeks, veno-arterial grafts were removed for contractility (norepinephrine [NE] and 5-hydroxytryptamine [5-HT]), luminal prostacyclin (PGI2), and morphometric analyses; the remaining segments were used as left jugular and femoral veno-venous grafts. After another 12 weeks, the veno-venous grafts were harvested. To NE, veno-arterial grafts (ED50, 5.4 +/- 0.1 [-log M]) were less sensitive than control veins (ED50, 6.0 +/- 0.2) or veno-venous grafts (ED50, 6.4 +/- 0.2) but were more sensitive than control arteries (ED50, 4.0 +/- 0.1); the maximum tension of veno-arterial grafts (6.2 +/- 0.6 g) was greater than that of veins, less than that of arteries (9.8 +/- 1.0 g), and comparable with that of veno-venous grafts (5.1 +/- 1.1 g). To 5-HT, veno-arterial (ED50, 7.5 +/- 0.1) and veno-venous (ED50, 7.3 +/- 0.2) grafts were more sensitive than arteries (ED50, 6.0 +/- 0.3), while the vein was unresponsive; the maximum tension of veno-arterial grafts (5.0 +/- 0.7 g) was less than that of arteries (6.9 +/- 0.9 g) and greater than that of veno-venous grafts (1.4 +/- 0.3 g). PGI2 production in veins (3.6 +/- 0.8 ng/ml), veno-arterial grafts (3.9 +/- 0.8 ng/ml), and veno-venous grafts (3.3 +/- 0.9 ng/ml) was comparable and less than that of arteries (6.4 +/- 0.9 ng/ml). Veno-arterial graft intimal thickness (127 +/- 8 microns) and intimal area (15.6 +/- 1.8 x 10(3) microns 2) tended to be greater than that in the veno-venous graft (113 +/- 9 microns and 12.4 +/- 1.8 x 10(3) microns 2); also, the veno-arterial graft medial area (103.0 +/- 7.3 x 10(3) microns 2) was greater than that of the veno-venous graft (80.3 +/- 6.9 x 10(3) microns 2), thereby resulting in a similar relative intimal area (13 +/- 1%). Therefore, some changes associated with arterialization, for example, adrenergic sensitivity, maximum tension to 5-HT, medial thickening, and perhaps intimal hyperplasia, reverted toward venous values when replaced in the venous environment, possibly due to variations in pressure, flow, shear stress, and/or graft preparation techniques. Luminal PGI2 was unchanged in the grafts, implying that graft contractility was not modulated by luminal PGI2.

  View details for PubMedID 2225440

• CONGENITAL LEFT ATRIAL APPENDAGE ANEURYSM WITH INTACT PERICARDIUM - DIAGNOSIS BY TRANSESOPHAGEAL ECHOCARDIOGRAPHY AMERICAN HEART JOURNAL COMESS, K. A., LABATE, D. P., WINTER, J. A., HILL, A. C., MILLER, D. C. 1990; 120 (4): 992–96

  View details for DOI 10.1016/0002-8703(90)90226-N

  View details for Web of Science ID A1990EC24400035

  View details for PubMedID 2220557

• 3-DIMENSIONAL LEFT-VENTRICULAR MIDWALL DYNAMICS IN THE TRANSPLANTED HUMAN HEART CIRCULATION Ingels, N. B., Daughters, G. T., Stinson, E. B., Alderman, E. L., Miller, D. C. 1990; 81 (6): 1837-1848

  Abstract

  To quantify the three-dimensional regional dynamics of the left ventricular (LV) midwall and the centroid and cross-sectional shape of the LV chamber in the transplanted human heart, 12 miniature radiopaque tantalum markers were implanted in the LV midwall of the donor heart at the time of cardiac transplantation in 15 patients. Stereo cineradiography in the late postoperative period (mean, 52 days after surgery) allowed computer-aided measurements of the three-dimensional coordinates of multiple sites in anterior, inferior, lateral, and septal LV regions at 16.7-msec intervals throughout the cardiac cycle. In awake, supine patients, from maximum to minimum LV volume, group mean translations of free wall markers ranged from 0.80 to 1.24 cm, directed toward the LV interior, whereas translations of septal wall markers were significantly less, 0.46 and 0.34 cm (p less than 0.01), directed away from the LV interior. A component of this translation along the septal-lateral axis was also significantly less (p less than 0.01) in the septum (0.19 and 0.20 cm) than in the free wall, where it ranged from 0.32 to 0.97 cm. The LV cross section was not circular, and anterior-inferior dimensions (7.18 +/- 0.66 and 6.13 +/- 0.79 cm, at maximum and minimum volumes, respectively) were significantly greater (p less than 0.01) than septal-lateral dimensions (5.78 +/- 0.65 and 5.12 +/- 0.48 cm), yielding an unchanging transverse elliptical LV eccentricity (0.58 +/- 0.13). The position of the LV center of volume did not change significantly from maximum to minimum volume in the direction of either the LV long axis or the anterior-inferior axis, but it did change significantly (0.55 +/- 0.23 cm, p less than 0.01) along the septal-lateral axis. We conclude 1) as viewed in a fixed external reference system, midwall sites in the interventricular septum of the transplanted human heart move paradoxically yet are relatively immobile compared with the three-dimensional dynamics of midwall sites in the LV free wall; 2) the transverse cross-sectional shape of the LV in the transplanted human heart is decidedly oval, with significantly greater anterior-posterior than septal-lateral dimensions at the time of maximum and minimum LV volumes; and 3) the center of volume in the transplanted human LV is remarkably stable in the directions of the LV long axis and anterior-posterior axis, suggesting a balance of forces along these axes, yet it moves significantly toward the interventricular septum, presumably counterbalancing the opposite translation during systole of the right ventricular (RV) center of volume.(ABSTRACT TRUNCATED AT 400 WORDS)

  View details for Web of Science ID A1990DH02100013

  View details for PubMedID 2344679

• Intraoperative echocardiography and Doppler color flow mapping in freehand allograft aortic valve and root replacement. Echocardiography (Mount Kisco, N.Y.) Bolger, A. F., BARTZOKIS, T., Miller, D. C. 1990; 7 (3): 229-240

  Abstract

  Intraoperative epicardial echocardiography and color flow Doppler were performed before and after cardiopulmonary bypass in 17 consecutive patients undergoing 20 freehand allograft aortic valve replacements. Native aortic valves were replaced in 12, and prostheses in 8 patients. Precardiopulmonary bypass echocardiography estimates of annular diameter guided allograft selection and predicted length of allograft aortic root required, defined coronary situs, and revealed other cardiac abnormalities. These included unanticipated severe mitral regurgitation (which precluded allograft aortic valve replacements in one patient), left-to-right shunts in the membranous septum, ascending aortic dissection, and aortic root pathology requiring coronary reimplantation or bypass. Postcardiopulmonary bypass echocardiography demonstrated acceptable competency of 18/19 allograft valves (mild or no aortic insufficiency), and successful repair of 3/4 shunts. Mild mitral regurgitation was detected more often at postcardiopulmonary bypass than precardiopulmonary bypass (15 vs 11 cases) and postcardiopulmonary bypass estimates of mitral regurgitation severity corollated well with subsequent postoperative follow-up. IOE allows selection and thawing of the allograft valves prior to aortic cross clamping, minimizing cross-clamp time. It detects important concomitant cardiac abnormalities, and predicts postoperative allograft valve and mitral competency. Intraoperative echocardiography Doppler, is therefore, a useful adjunct for allograft aortic valve replacements or aortic root replacement.

  View details for PubMedID 10149225

• DETERMINANTS OF SURVIVAL AND LEFT-VENTRICULAR PERFORMANCE AFTER MITRAL-VALVE REPLACEMENT CIRCULATION Crawford, M. H., Souchek, J., Oprian, C. A., Miller, D. C., Rahimtoola, S., Giacomini, J. C., Sethi, G., Hammermeister, K. E. 1990; 81 (4): 1173-1181

  Abstract

  To determine how survival and clinical status were related to left ventricular (LV) size and systolic function after mitral valve replacement, 104 patients (48 mitral regurgitation [MR], 33 mitral stenosis [MS], and 23 MS/MR) with isolated mitral valve replacement were evaluated before and after surgery. Preoperative hemodynamic abnormalities by cardiac catheterization were improved 6 months after surgery in all three patient groups. The patients with MR exhibited reductions in LV end-diastolic volume index (EDVI) (117 +/- 51 to 89 +/- 27 ml/m2, p less than 0.001) and ejection fraction (EF) (0.56 +/- 0.15 to 0.45 +/- 0.13, p less than 0.001); however, the ratio of forward stroke volume to end-diastolic volume increased (0.32 +/- 0.21 to 0.45 +/- 0.17, p less than 0.001) because of the elimination of regurgitant volume. Survival analysis revealed that mortality was significantly higher in MS or MS/MR patients with postoperative EDVI more than 101 ml/m2 (p less than 0.001 and p less than 0.042, respectively) and in MR patients with postoperative EF less than or equal to 0.50 (p less than 0.031). Also, the majority of patients with MR or MS/MR and postoperative EDVI more than 101 ml/m2 and EF less than or equal to 0.50 were in New York Heart Association class III or IV. Multivariate logistic regression analysis in the patients with MR revealed that the strongest predictor of postoperative EF was preoperative EF (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for Web of Science ID A1990CX49900002

  View details for PubMedID 2317900

• Predictors of outcome in patients with prosthetic valve endocarditis (PVE) and potential advantages of homograft aortic root replacement for prosthetic ascending aortic valve-graft infections. Journal of cardiac surgery Miller, D. C. 1990; 5 (1): 53-62

  Abstract

  Seventy-five surgically treated patients with prosthetic valve endocarditis were treated at the Stanford University Medical Center. This was a multivariate analysis analyzing both patient related factors, bacteriology, and surgical findings. The conclusions among 10 patients with allograft valves, 20% had an annular abscess; this occurred in 36% of 29 patients with porcine valves, and 65% of these with mechanical prosthesis. Though prevention, again, is key in this especially devastating disease, once infection has been established and an aggressive approach is indicated, it would appear that a homograft re-replacement or free aortic homograft valve replacement can deal with severe tissue destruction to prevent recurrence.

  View details for PubMedID 2133823

• Determinants of outcome in surgically treated patients with native valve endocarditis (NVE). Journal of cardiac surgery Miller, D. C. 1989; 4 (4): 331-339

  Abstract

  This is a multivariate analysis of patients treated with native valve endocarditis at Stanford University. The analysis indicates that the preoperative cardiovascular condition and other organ system functions are important determinants of postoperative outcome in conjunction with the pathology denoted at the time of operation, particularly annular abscess. These two negative factors suggest more intense scrutiny of patients preoperatively and a more aggressive approach to surgery before these two extremely adverse prognostic factors occur. Prevention of native valve endocarditis will also be a major key to overall improvement in the future for prophylaxis of dental hygiene and other minor surgery, particularly in patients with known valvular heart disease.

  View details for PubMedID 2520015

• Role of the mitral subvalvular apparatus in left ventricular systolic mechanics. Seminars in thoracic and cardiovascular surgery Sarris, G. E., Miller, D. C. 1989; 1 (2): 133-143

  View details for PubMedID 2488417

• Surgical management of acute aortic dissection complicated by stroke. Circulation Fann, J. I., Sarris, G. E., Miller, D. C., Mitchell, R. S., Oyer, P. E., Stinson, E. B., Shumway, N. E. 1989; 80 (3): I257-63

  Abstract

  Although patients with acute type A aortic dissection are best managed by emergency surgical intervention, preoperative stroke is known to be an independent predictor of late mortality and is considered by some to be a contraindication to operation because of the risk of precipitating hemorrhagic cerebral infarction and poor long-term outcome. In a series of 272 consecutive, unselected patients with aortic dissection undergoing surgical treatment during a 25-year span (1963-1987), 128 (47 +/- 3% [+/- 70% confidence level (CL)]) had an acute type A dissection. A total of seven patients with acute type A dissection (2.6 +/- 1% of all patients, 5.5 +/- 2% of the acute type A cohort) developed a new stroke preoperatively. Thirteen (4.8 +/- 1%) patients had a diminished or absent carotid pulse, only four (31 +/- 13%) of whom sustained a stroke. One patient died in the immediate postoperative period due to severe brain injury, yielding an operative mortality rate of 14 +/- 14%. Two patients had persistent neurological deficits and died within 4 months of operation; the actuarial survival estimate at 1 year was 57 +/- 19% (mean +/- SEM). One patient recovered function of one upper extremity (preoperative left hemiparesis compounded by paraplegia) but died 6 years later. The remaining three long-term survivors (43 +/- 19%) had major resolution of their neurological deficits and are clinically well 2-8 years postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for PubMedID 2766534

• MECHANISMS RESPONSIBLE FOR INHIBITION OF VEIN-GRAFT ARTERIOSCLEROSIS BY FISH OIL CIRCULATION Sarris, G. E., Fann, J. I., Sokoloff, M. H., Smith, D. L., LOVEDAY, M., Kosek, J. C., Stephens, R. J., Cooper, A. D., May, K., Willis, A. L., Miller, D. C. 1989; 80 (3): 109-123

  View details for Web of Science ID A1989AR92500012

• GLOBAL AND REGIONAL LEFT-VENTRICULAR SYSTOLIC PERFORMANCE IN THE INSITU EJECTING CANINE HEART - IMPORTANCE OF THE MITRAL APPARATUS CIRCULATION Sarris, G. E., Fann, J. I., Niczyporuk, M. A., Derby, G. C., Handen, C. E., Miller, D. C. 1989; 80 (3): 24-42

  View details for Web of Science ID A1989AR92500004

• SURGICAL-MANAGEMENT OF ACUTE AORTIC DISSECTION COMPLICATED BY STROKE CIRCULATION Fann, J. I., Sarris, G. E., Miller, D. C., Mitchell, R. S., Oyer, P. E., Stinson, E. B., Shumway, N. E. 1989; 80 (3): 257-263

  View details for Web of Science ID A1989AR92500030

• REPLACEMENT OF THE TRANSVERSE AORTIC-ARCH DURING EMERGENCY OPERATIONS FOR TYPE-A ACUTE AORTIC DISSECTION JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY MILLER, D. C. 1989; 98 (2): 310–12

  View details for Web of Science ID A1989AJ72300041

  View details for PubMedID 2755171

• EFFECTS OF FISH OIL ON ARTERIOSCLEROSIS IN THE JAPANESE QUAIL CARDIOVASCULAR RESEARCH Fann, J. I., Angell, S. K., CAHILL, P. D., Kosek, J. C., Miller, D. C. 1989; 23 (7): 631-638

  Abstract

  The effects of fish oil on the development of arteriosclerosis were assessed using a special susceptible strain (SEA) of Japanese quail (Coturnix coturnix japonica). Sixty four quail were randomly divided into two groups and placed on isocaloric and approximately isocholesterolic (2% by weight) diets. Group A (control) was supplemented with 10% beef tallow oil, while group B received 10% Menhaden fish oil. The birds were sacrificed at 10 weeks (early) and 15-16 weeks (late). Based on semiquantitative histological grading of the arteriosclerotic lesions in the proximal aorta and brachiocephalic arteries, a score from 1 (no lesion) to 5 (severe, diffuse lesions) was assigned. A total of 57 quail were evaluated (seven died prior to scheduled sacrifice). At the early period, the mean arteriosclerosis scores for group A (n = 8) and group B (n = 8) were 3.3 (SD 1.0) and 1.9(1.0) respectively (p less than 0.017); 63% of the quail in group A and 13% of those in group B had a score greater than or equal to 3 (p less than 0.25, NS). At the late period, the scores for group A (n = 20) and group B (n = 21) were 3.8(0.6) and 2.6(0.9), respectively (p less than 0.001); 95% of the birds in group A and 43% of those in group B had a score greater than or equal to 3 (p less than 0.005). Histopathological examination of the arteriosclerotic lesions revealed disruption of the innermost elastic lamina, increased proteoglycan deposition in the medial interlamellar spaces, and the distinct involvement of macrophage like cells. Compared to human disease, arteriosclerosis in the quail is marked by distinct similarities, as well as differences. The SEA strain of Japanese quail appears to be a practical model for the study of arteriosclerosis; fish oil reduces the severity of disease in these birds when fed a high cholesterol diet.

  View details for PubMedID 2598217

• INHIBITION OF ACCELERATED CARDIAC ALLOGRAFT ARTERIOSCLEROSIS BY FISH OIL JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Sarris, G. E., Mitchell, R. S., Billingham, M. E., Glasson, J. R., CAHILL, P. D., Miller, D. C. 1989; 97 (6): 841-855

  Abstract

  Accelerated coronary arteriosclerosis remains the most important factor limiting long-term survival of heart transplant recipients, and dietary fish oil supplementation with omega-3 polyunsaturated fatty acids has been suggested to have a protective effect against coronary disease in epidemiologic studies and to inhibit arteriosclerosis in animal experiments. Therefore we tested the hypothesis that fish oil administration inhibits the development of allograft coronary arteriosclerosis by using a heterotopic heart transplant model. Three groups of Lewis rats (n = 10 each) received heterotopic heart transplants from Brown-Norway donors and were treated with cyclosporine intraperitoneally on a tapering schedule. Group 1 received fish oil daily by gavage (2 ml/kg/day; Emulsified Super MaxEpa, Twin Labs, Ronkonkona, N.Y.). Group 2 received an equal amount of safflower oil, as well as aspirin (1 mg/kg/day) and dipyridamole (3 mg/kg/day). Group 3 received safflower oil only. All rats were put to death 110 days later, at which time there was no statistically significant difference in graft function as assessed by palpation (scale 0 to 4, mean = 3.7 +/- 0.5 [+/- standard deviation]; analysis of variance: p = 0.72) or in microscopic grade of rejection (scale, 0 = none to 3 = severe, mean 2.1 +/- 0.6; analysis of variance: p = 0.68) between any of the groups. The coronary arteries were histologically scored for the degree of arteriosclerosis (scale, 0 = normal to 3 = occluded), and a mean grade of coronary disease was calculated for each heart. The fish oil-treated group had significantly less severe allograft coronary arteriosclerosis (analysis of variance: p = 0.005) than did groups 2 and 3 (mean grade 0.23 +/- 0.22 versus 1.04 +/- 0.75 and 0.96 +/- 0.55 (p less than 0.05, Scheffe F test), whereas groups 2 and 3 had similar degrees of coronary disease (p = no significant difference). These data demonstrate that fish oil supplementation inhibited accelerated coronary arteriosclerosis in this cyclosporine-treated heart allograft rat model, whereas antiplatelet agents in these doses were ineffective. Although the mechanism of this protective effect remains incompletely understood, it does not appear to involve enhanced immunosuppression. Fish oil and specific omega-3 polyunsaturated fatty acids should be further investigated as potentially useful agents to ameliorate accelerated allograft coronary arteriosclerosis in other animal species and perhaps eventually in man.

  View details for PubMedID 2657223

• REGIONAL VARIABILITY OF PROSTACYCLIN BIOSYNTHESIS ARTERIOSCLEROSIS Fann, J. I., CAHILL, P. D., Mitchell, R. S., Miller, D. C. 1989; 9 (3): 368-373

  Abstract

  To investigate the regional variability in arterial and venous endothelial prostacyclin (PGI2) biosynthesis, we obtained 1-cm segments of carotid arteries, external jugular veins, femoral arteries and veins, iliac arteries and veins, inferior venae cavae (IVC), and aortas from 17 dogs. Vessel luminal PGI2 production was measured in the basal state by radioimmunoassay of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha). A total of 90 arterial specimens (57, 19, and 14 segments, respectively, of femoral/carotid arteries, iliac arteries, and aorta) and 41 venous specimens (15, 10, and 16 segments, respectively, of femoral/jugular veins, iliac veins, and IVC) were analyzed. Overall, arterial endothelial 6-keto-PGF1 alpha was higher than venous (8.1 +/- 0.5 ng/ml vs. 4.9 +/- 0.7 ng/ml, p less than 0.0004); 6-keto-PGF1 alpha levels were greater in the arteries than in their corresponding veins [femoral/carotid arteries (6.3 +/- 0.4 ng/ml) vs. femoral/jugular vein (2.1 +/- 0.4 ng/ml), p less than 0.0002; iliac arteries (9.3 +/- 1.0 ng/ml) vs. iliac veins (4.8 +/- 0.9 ng/ml), p less than 0.005; aorta (14.0 +/- 1.6 ng/ml) vs. IVC (7.5 +/- 1.4 ng/ml), p less than 0.006].(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for PubMedID 2655571

• MORE ATTEMPTS TO MONITOR QUALITY ASSURANCE FOR MYOCARDIAL REVASCULARIZATION ANNALS OF THORACIC SURGERY MILLER, D. C. 1989; 47 (5): 641–42

  View details for DOI 10.1016/0003-4975(89)90108-2

  View details for Web of Science ID A1989U853700001

  View details for PubMedID 2786390

• RELATION BETWEEN LONGITUDINAL, CIRCUMFERENTIAL, AND OBLIQUE SHORTENING AND TORSIONAL DEFORMATION IN THE LEFT-VENTRICLE OF THE TRANSPLANTED HUMAN-HEART CIRCULATION RESEARCH Ingels, N. B., Hansen, D. E., Daughters, G. T., Stinson, E. B., Alderman, E. L., Miller, D. C. 1989; 64 (5): 915-927

  Abstract

  The present study was designed to investigate the anisotropy of systolic chord shortening in the lateral, inferior, septal, and anterior regions of the human left ventricle. At the time of surgery, 12 miniature radiopaque markers were implanted into the left ventricular midwall of the donor heart in 15 cardiac transplant recipients. Postoperative biplane cineradiograms were computer-analyzed to yield the three-dimensional coordinates of these markers at 16.7-msec intervals. In each of the four left ventricular regions, chords were constructed from a central marker to outlying markers, and the percent systolic shortening of each chord was calculated. In each region, chord angles were measured with respect to the circumferential direction (positive angles counterclockwise) and each chord was assigned to one of four angular groups: I. oblique, -45 +/- 22.5 degrees or 135 +/- 22.5 degrees; II. circumferential, 0 +/- 22.5 degrees or 180 +/- 22.5 degrees; III. oblique, 45 +/- 22.5 degrees or -135 +/- 22.5 degrees; or IV. longitudinal, 90 +/- 22.5 degrees. In the lateral, inferior, and septal regions, respectively, systolic shortening (mean +/- SD%) was significantly greater in Group I chords (19 +/- 5%, 17 +/- 5%, and 15 +/- 4%) than those in Group II (15 +/- 5%, 12 +/- 4%, and 11 +/- 4%), Group III (12 +/- 4%, 12 +/- 5%, and 11 +/- 4%), or Group IV (13 +/- 5%, 13 +/- 6%, and 12 +/- 5%). The anterior region was unique in exhibiting equal shortening in both Group I and Group II chords (16 +/- 5%), although the shortening of these chords was significantly greater than that of Group III and Group IV (12 +/- 5%) in this region. A cylindrical mathematical model was developed to relate longitudinal, circumferential, and oblique systolic shortening to torsional deformation about the long axis of the left ventricle. Torsional deformations measured in these 15 hearts were of sufficient magnitude and correct sense to agree with model predictions. These data suggest that torsional deformations of the left ventricle are of fundamental importance in linking the one-dimensional contraction of the helically wound myocytes to the three-dimensional anisotropic systolic shortening encountered in the transplanted human heart.

  View details for Web of Science ID A1989U428000007

  View details for PubMedID 2650919

• OCCLUSIVE CORONARY-ARTERY SPASM AS A CAUSE OF ACUTE MYOCARDIAL-INFARCTION AFTER CORONARY-ARTERY BYPASS-GRAFTING NEW ENGLAND JOURNAL OF MEDICINE Fischell, T. A., McDonald, T. V., GRATTAN, M. T., Miller, D. C., Stadius, M. L. 1989; 320 (6): 400-401

  View details for Web of Science ID A1989T128500024

  View details for PubMedID 2783623

• ASYNERGY OF RIGHT VENTRICULAR WALL MOTION IN MAN JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Chin, K. W., Daughters, G. T., Alderman, E. L., Miller, D. C. 1989; 97 (1): 104-109

  Abstract

  Canine studies have shown a correlation between instantaneous segmental lengths in the right ventricular free wall and chamber volume, pressure, and stroke work. To determine whether such correlations exist in intact man, we studied the temporal relationships between chord dynamics in various regions of the right ventricle in 21 heart transplant recipients with apparently normal right ventricular function. Patients were examined by biplane radiography while performing various maneuvers (e.g., Valsalva maneuver). Computer-aided analysis of biplane radiograms of five surgically inserted radiopaque tantalum right ventricular myocardial markers was used to calculate interpoint chord lengths at 33 msec sampling intervals. Two patterns of right ventricular chord asynergy were defined: (1) An akinetic chord had an amplitude of less than 2.0 mm during the course of at least one beat; (2) an out-of-phase chord was more than a quarter period out of phase from the average curve (derived from all concurrently measured marker pairs during each maneuver) for at least one beat. Considering all chords (n = 978), 60 chords (6.1%) were akinetic and nine chords (0.9%) were out of phase. Excluding the outflow tract markers (n = 581), 33 chords (5.7%) were akinetic and five chords (0.9%) showed out-of-phase movement. During some maneuver, at least one akinetic chord occurred in 57% of patients and out-of-phase chords in 33% of patients. Most right ventricular regions were implicated in asynergic motion, including the right ventricular free wall, acute margin, and outflow tract. The frequency and distribution of asynergy in right ventricular chord dynamics observed in this study suggests that changes in a single right ventricular dimension may not accurately reflect global right ventricular events.

  View details for Web of Science ID A1989R753800016

  View details for PubMedID 2911185

• EFFECTS OF ASPIRIN, DIPYRIDAMOLE, AND COD LIVER OIL ON ACCELERATED MYOINTIMAL PROLIFERATION IN CANINE VENOARTERIAL ALLOGRAFTS ANNALS OF SURGERY DeCampli, W. M., Kosek, J. C., Mitchell, R. S., Handen, C. E., Miller, D. C. 1988; 208 (6): 746-754

  Abstract

  The effects of the administration of aspirin (ASA), dipyridamole (DPM), and cod liver oil (CLO) on graft patency rate and degree of intimal hyperplasia were investigated in a canine, hypercholesterolemic veno-arterial allograft model in an attempt to modify this immunologically mediated vascular injury. The drug regimens were ASA 1 mg/kg/day, DPM 10 mg/kg/day, combined ASA and DPM (ASA + DPM), and CLO (1.8 g/day eicosapentanoic acid [EPA] and 1.2 g/day docosahexanoic acid [DHA]), and control. The early angiographic patency rate (1-3 weeks) was 81% +/- 10% (+/- 70% confidence limits); the 90-day overall patency rate was 60% +/- 4% (87/144), with no statistically significant differences among the groups (range 46 +/- 10-71 +/- 9%). Qualitatively, there was no difference in luminal thrombus, intimal hemorrhage, or lesion eccentricity. Considering the relatively short time of graft implantation, an extensive amount of microscopic disease was observed; quantitatively, the mean intimal thickness was 515 +/- 17 microgram overall but was not statistically different between the groups. The fraction of potential lumenal area occupied by intimal thickening was 0.37 +/- 0.01 but again did not differ significantly between the groups. These doses of ASA, DPM, ASA + DPM, and CLO did not alter graft occlusion or retard the marked degree of subintimal myointimal cell hyperplasia that was generated in this hypercholesterolemic canine veno-arterial allograft preparation. Possible explanations for these negative findings include inadequate dosage or form of omega-3 fatty acids and the antiplatelet drugs administered, excessive variability in graft response due to uncharacterized immunologic histocompatibility, and the possible influence of non-platelet-mediated mechanisms. Nevertheless, this preparation is attractive as a reproducible model of accelerated (immunologically mediated) experimental arteriosclerosis.

  View details for PubMedID 3196097

• OUTLET STRUT FRACTURE OF THE BJORK-SHILEY 60-DEGREES CONVEXO-CONCAVE VALVE - CURRENT INFORMATION AND RECOMMENDATIONS FOR PATIENT-CARE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Hiratzka, L. F., Kouchoukos, N. T., Grunkemeier, G. L., Miller, D. C., Scully, H. E., Wechsler, A. S. 1988; 11 (5): 1130-1137

  Abstract

  Mechanical failure of artificial heart valves can be a catastrophic event. The problem of outlet strut fracture of the Björk-Shiley 60 degrees Convexo-Concave tilting disc prosthesis has received much attention in the medical literature and generated both concern and confusion among patients and physicians. Analysis of current data from the manufacturer, as well as a review of the medical literature, suggests that the overall risk of outlet strut fracture is low and that elective explantation of a well functioning Björk-Shiley 60 degrees Convexo-Concave valve prosthesis is not warranted. Diagnostic features of outlet strut fracture can be seen with overpenetrated chest X-ray films so that diagnosis can be established promptly. Early operation to replace the fractured prosthesis is essential for patient survival.

  View details for Web of Science ID A1988N246700032

  View details for PubMedID 3281994

• A simple technique for aortic valve replacement using freehand allografts. Journal of cardiac surgery Moreno-Cabral, C. E., Miller, D. C., Shumway, N. E. 1988; 3 (1): 69-76

  Abstract

  Given the recent resurgence of interest in the use of "fresh" and cryopreserved allograft valves for aortic valve replacement, the fact that many cardiac surgeons were not exposed to the operative techniques involved in freehand implantation of allograft valves during their residency training, and the paucity of teaching materials that clearly portray such techniques, details of a simplified method of subcoronary, freehand allograft valve implantation in the aortic position are described and illustrated.

  View details for PubMedID 2980005

• INHIBITION OF VEIN GRAFT INTIMAL THICKENING BY EICOSAPENTANOIC ACID - REDUCED THROMBOXANE PRODUCTION WITHOUT CHANGE IN LIPOPROTEIN LEVELS OR LOW-DENSITY LIPOPROTEIN RECEPTOR DENSITY JOURNAL OF VASCULAR SURGERY CAHILL, P. D., Sarris, G. E., Cooper, A. D., Wood, P. D., Kosek, J. C., Mitchell, R. S., Miller, D. C. 1988; 7 (1): 108-118

  Abstract

  Marine lipids containing omega-3 fatty acids (chiefly, eicosapentanoic acid [EPA] and docosahexanoic acid [DHA]) may inhibit the development of atherosclerotic vascular disease, but the mechanisms responsible for this putative beneficial effect are unknown. We investigated the effects of EPA and DHA in a canine model of accelerated vein graft arteriosclerosis during a 3-month period. Twenty-five dogs were divided into three dietary groups: group I (control), group II (2.5% cholesterol), and group III (2.5% cholesterol plus 2 gm EPA/day [as MaxEPA]). The effects of EPA on vein graft intimal thickening, platelet and vascular prostaglandin metabolism, lipid and lipoprotein receptor metabolism, and hematologic parameters were assessed. Cholesterol feeding caused a significant 54% increase in graft intimal thickness compared with control animals (124.9 +/- 50.4 vs 81.2 +/- 32.4 micron; p = 0.013), which was prevented by supplementation with EPA in group III (56.9 +/- 30.0 micron; p = 0.001 vs group II). Intimal thickness in group III was not significantly different from that of control. EPA supplementation was also associated with a 38% decline in serum thromboxane levels from 457.0 +/- 129.3 pg/0.1 ml in group II to 283.5 +/- 96.9 pg/0.1 ml in group III (p = 0.007). The alterations in lipoprotein metabolism associated with cholesterol feeding were not affected by EPA: in both groups II and III, serum cholesterol and high-density lipoproteins and liver cholesterol content were elevated and hepatic low-density lipoproteins (LDL) receptor content was reduced. There were no differences between the three groups in terms of vein graft or native vessel prostacyclin production, hematocrit, platelet count, or coagulation parameters. In this canine model, dietary supplementation with marine omega-3 fatty acids reduced the extent and magnitude of accelerated vein graft intimal thickening induced by hypercholesterolemia; moreover, this beneficial effect was associated with lower serum thromboxane production and appeared to be independent of alterations in lipoprotein metabolism or LDL receptor density.

  View details for PubMedID 3336117

• CARDIAC CRYOLESIONS AS AN EXPERIMENTAL-MODEL OF MYOCARDIAL WOUND-HEALING ANNALS OF SURGERY Jensen, J. A., Kosek, J. C., Hunt, T. K., Goodson, W. H., Miller, D. C. 1987; 206 (6): 798-803

  Abstract

  The standard coronary ligation model for experimental myocardial infarction results in variable areas and patterns of necrosis; therefore, the healing of such infarctions is also variable. The authors developed an experimental myocardial injury model using simple cryoinjury, which allows standardization of the size, depth, and location of the wound. Thirty-eight left ventricular cryolesions were created in 19 dogs, which were then killed from 3 to 35 days after injury. A consistent decrease in the depth of scar (p less than 0.005) and accumulation of collagen (p less than 0.0001) over time characterized this healing myocardial wound. Histologic examination revealed that the cellular pattern of healing myocardial cryolesions is similar to that of a healing myocardial infarction but with less variability. The authors advocate the use of cardiac cryolesions as a model of experimental myocardial wound healing.

  View details for PubMedID 3689016

• EFFECT OF ACUTE HUMAN CARDIAC ALLOGRAFT-REJECTION ON LEFT-VENTRICULAR SYSTOLIC TORSION AND DIASTOLIC RECOIL MEASURED BY INTRAMYOCARDIAL MARKERS CIRCULATION Hansen, D. E., Daughters, G. T., Alderman, E. L., Stinson, E. B., Baldwin, J. C., Miller, D. C. 1987; 76 (5): 998-1008

  Abstract

  Left ventricular systolic torsion and diastolic recoil were quantified in 12 human cardiac transplant recipients with surgically implanted intramyocardial markers with the use of computer-aided analysis of biplane cineradiographic images. Measurements were performed between 6 and 16 weeks after surgery and related to the presence or absence of rejection as determined by cardiac biopsy. Torsional deformation, defined as twisting about the left ventricular long axis of the apical region with respect to the base, was characterized in terms of the rate and amplitude of systolic torsion and the rate of diastolic recoil by means of an internal reference system. Comparison of measurements before, during, and after recovery from 14 rejection episodes allowed assessment of the effects of acute reversible cardiomyopathy on left ventricular torsion and recoil. Compared with prerejection values, the amplitude of torsional deformation in the maximally deforming segment (theta max) decreased by 25% from 21.1 +/- 15.2 to 16.0 +/- 5.7 degrees (p less than .005) during acute rejection with myocyte necrosis; this was associated with significant (p less than .05) decreases in the peak systolic torsion rate (+d theta/dtmax), whereas the peak diastolic recoil rate (-d theta/dtmax) was unchanged. This suggests that the stiffness of elastic components of the myocardium may have increased, maintaining the rate of diastolic recoil when these elements are stretched less. With successful treatment of rejection episodes, the torsional deformation characteristics normalized. Heart rate, mean arterial pressure, left ventricular end-diastolic volume, stroke volume, ejection fraction, and peak left ventricular filling rate were unchanged with rejection episodes, whereas left ventricular end-systolic volume increased (p less than .05) during acute rejection and returned to normal with resolution of the rejection process. These data suggest that left ventricular torsional deformation amplitude and rate are sensitive to episodes of subclinical left ventricular dysfunction and that such intramyocardial marker techniques may provide new insights regarding the elastic properties of the ventricular myocardium and their impact on left ventricular mechanics.

  View details for PubMedID 3311453

• INCOMPLETE BIOCHEMICAL ADAPTATION OF VEIN GRAFTS TO THE ARTERIAL ENVIRONMENT IN TERMS OF PROSTACYCLIN PRODUCTION JOURNAL OF VASCULAR SURGERY CAHILL, P. D., Brown, B. A., Handen, C. E., Kosek, J. C., Miller, D. C. 1987; 6 (5): 496-503

  Abstract

  Biochemical (or functional) adaptation of venoarterial grafts has been demonstrated recently. We reexamined one aspect of this biochemical "arterialization" process: prostacyclin (PGI2) production by canine venoarterial autologous grafts and the responsiveness of this biosynthetic pathway to maximal stimulation with substrate enhancement. Four reversed autologous grafts (femoral vein) were interposed into both carotid and femoral arteries in eight dogs. After 12 weeks, the grafts were removed, and radioimmunoassay was used to determine luminal surface production of 6-keto-PGF1 alpha (the stable metabolite of PGI2) in both the basal and stimulated (27 mumol/L arachidonic acid [AA]) states. PGI2 production by the venous autologous grafts was compared with that of control native artery and vein. We confirmed that PGI2 production (measured in nanograms per milliliter) by control artery was greater than vein under both basal conditions (5.8 +/- 0.4 [+/- SEM] vs. 2.7 +/- 0.5, p less than 0.001) and stimulated conditions (8.8 +/- 0.8 vs. 5.5 +/- 0.4, p = 0.002); moreover, AA stimulation significantly increased PGI2 production in both native artery and vein compared with basal PGI2 production. Under basal conditions, graft PGI2 production (6.3 +/- 1.6 ng/ml) was not significantly different than basal arterial levels (p = 0.8) but was higher than basal venous levels (p = 0.05). However, in marked contrast to both native artery and vein, the vein graft flow surface showed no significant response to substrate enhancement with AA: basal (6.3 +/- 1.6 ng/ml) vs. stimulated (5.9 +/- 0.9 ng/ml) (p = 0.8). These observations confirm that canine venoarterial autologous grafts undergo biochemical "arterialization"; however, this process appears to be an incomplete one.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for PubMedID 3312650

• WHEN SHOULD DOPPLER-DETERMINED VALVE AREA BE BETTER THAN THE GORLIN FORMULA - VARIATION IN HYDRAULIC CONSTANTS IN LOW FLOW STATES JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Segal, J., Lerner, D. J., Miller, D. C., Mitchell, R. S., Alderman, E. A., Popp, R. L. 1987; 9 (6): 1294-1305

  Abstract

  In low flow states, underestimation errors occur when the Gorlin formula is used to calculate valve area. A model of valvular stenosis designed to examine changes in the hydraulic discharge coefficient (Cd) and coefficient of orifice contraction (Cc) may explain these errors. Unsteady flow was examined in a pulsatile pump model and in a dog model. Valve areas were calculated from pressure and flow data using: a modified form of the Gorlin formula (assuming constant values for Cd and Cc) and a corrected formula (with values of Cd and Cc obtained from steady state data). Valve area was also calculated using the continuity equation with velocity and flow data (constant Cc). Flow velocities were measured using a newly designed ultrasound Doppler catheter capable of resolving flow velocities of up to 5.5 m/s. Both the corrected formula and continuity equation were highly predictive of actual valve area (r = 0.99, slope or M = 0.96 and r = 0.99, M = 1.06, respectively). The modified Gorlin equation was less accurate and tended to underestimate valve areas (r = 0.87, M = 0.83). This underestimation was most notable at low rates of flow (Gorlin: r = 0.94, M = 0.53; continuity: r = 0.93, M = 0.81 and r = 0.94, M = 0.89, respectively) more accurately than the modified Gorlin formula (r = 0.69, M = 0.49). In patients with low cardiac output, hemodynamic formulas, such as the Gorlin formula, which assume a constant value for the hydraulic discharge coefficient (Cd), may be less accurate than formulas using either a corrected value of Cd or Doppler-determined flow velocity and mean systolic flow.

  View details for Web of Science ID A1987H646300013

  View details for PubMedID 3294968

• PRIMARY CARDIAC NEOPLASMS - EARLY AND LATE RESULTS OF SURGICAL-TREATMENT IN 42 PATIENTS JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY DEIN, J. R., Frist, W. H., Stinson, E. B., Miller, C., Baldwin, J. C., Oyer, P. E., Jamieson, S., Mitchell, R. S., Shumway, N. E. 1987; 93 (4): 502-511

  Abstract

  Forty-two patients underwent resection of primary cardiac neoplasms at Stanford University Medical Center and the Palo Alto Veterans Administration Medical Center between 1961 and 1986. A total of 27 atrial myxomas, seven benign nonmyxomatous tumors, and eight malignant tumors were resected. The mean age was 47 years (range 8 to 79) in 27 female and 15 male patients. The clinical presentations included congestive heart failure in 24 patients, palpitations in nine, neurologic symptoms in six, recurrent cardiac tamponade in three, vasculitis in two, and chest pain in two. Thirty-one of 34 benign lesions were completely resected, although one patient required cardiac transplantation to resect completely an "inoperable" benign tumor. All gross tumor was resected in four of eight patients with malignant lesions. All patients survived operation, but three with malignant disease died within 30 days. Late outcome was known for 41 of 42 (98%) patients. Total follow-up for the series was 200.1 patient-years, for an average of 4.7 years (range 1 month to 18 years). Excellent early and late results were obtained in patients with benign lesions, as there was no known tumor recurrence even if resection was incomplete. Effective palliation and local control of disease is possible with extensive resection of malignant primary tumors, but more effective adjuvant therapy will be necessary to improve long-term prognosis.

  View details for Web of Science ID A1987G751000003

  View details for PubMedID 3560997

• "Fresh" aortic allografts: long-term results with free-hand aortic valve replacement. Journal of cardiac surgery Miller, D. C., Shumway, N. E. 1987; 2 (1): 185-191

  Abstract

  Renewed interest in the use of "fresh" and cryopreserved allograft valves for aortic valve replacement (AVR) prompted an updated analysis of the long-term results of our old experience (1964-1971) with free-hand AVR. Eighty-three patients received "fresh" (antibiotic stored at 4 degrees C for intervals between 24 hrs and 18 days), free-hand allograft valves. Current (1986) follow-up was 96% complete; cumulative follow-up included 773 patient-years (pt-yr) and averaged 9 yrs. Importantly, 37 patients were still at risk with their original allograft valve at ten yrs, and 12 patients at 17 yrs. Standard conservative criteria were used to assess valve-related complications. Thromboembolism (TE) occurred at a linearized incidence of 1.0%/pt-yr, anticoagulation-related hemorrhage (ACH) at 0.2%/pt-yr), and fatal prosthetic valve endocarditis (PVE) at 0.5%/pt-yr. In actuarial terms, the incidence of degenerative valve failure was 30 +/- 6% (+/- SEM) at ten yrs and 40 +/- 7% at 15 yrs. Valve failure due to all causes (including sudden, unexplained deaths and PVE) occurred in 38 +/- 6% of patients at ten yrs and 57 +/- 7% after 15 yrs. The incidence of fatal valve failure was 11 +/- 4% at six yrs (the time of the last event). The rate of reoperation was 33 +/- 6% at ten yrs and 52 +/- 7% at 15 yrs. Given the relatively crude methods of allograft valve preparation and storage during this remote era, we believe that these long-term results with free-hand allograft AVR are satisfactory, albeit far from optimal.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for PubMedID 2979970

• A TRI-INSTITUTIONAL COMPARISON OF TISSUE AND MECHANICAL VALVES USING A PATIENT-ORIENTED DEFINITION OF TREATMENT FAILURE ANNALS OF THORACIC SURGERY Cobanoglu, A., Jamieson, W. R., Miller, D. C., McKinley, C., Grunkemeier, G. L., Floten, H. S., Miyagishima, R. T., Tyers, G. F., Shumway, N. E., Starr, A. 1987; 43 (3): 245-253

  Abstract

  Selection of valve type for predominant usage is obscured by limiting the analysis to prosthesis-related rather than patient-oriented failure modes. In this report, "treatment failure" is defined as a valve-related death or permanent patient disability; successful reoperations are excluded, and emboli with permanent residua are included. Results with the Starr-Edwards Silastic ball valve (Oregon) and the Hancock (Stanford) and Carpentier-Edwards (Vancouver) porcine valves are compared using this new definition of treatment failure. Evaluated according to structural failure, the mechanical valve is superior to the tissue valve, and using the Stanford definition of valve failure, it becomes so between 5 and 10 years. Using treatment failure, tissue valves are superior at 5 years; at 10 years in the aortic position, the results are comparable; and in the mitral position at 8 to 10 years, tissue valves show a continued but small advantage.

  View details for Web of Science ID A1987G482000002

  View details for PubMedID 3493739

• PATHOPHYSIOLOGY AND PREVENTION OF ACUTE-RENAL-FAILURE ASSOCIATED WITH THORACOABDOMINAL OR ABDOMINAL AORTIC-SURGERY JOURNAL OF VASCULAR SURGERY Miller, D. C., Myers, B. D. 1987; 5 (3): 518-523

  View details for PubMedID 3334683

• MYOVENTRICULOPLASTY AND NEOVENTRICLE MYOGRAFT CARDIAC AUGMENTATION TO ESTABLISH PULMONARY BLOOD-FLOW - PRELIMINARY-OBSERVATIONS AND FEASIBILITY STUDIES JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Macoviak, J. A., Stinson, E. B., Starkey, T. D., Hansen, D. E., CAHILL, P. D., Miller, D. C., Shumway, N. E. 1987; 93 (2): 212-220

  Abstract

  In 10 dogs, a latissimus dorsi muscle (myograft) was neuroelectrically stimulated at 120 cycles/min for as long as 80 days. The higher thresholds and multiple lead penetrations required of direct muscle stimulation for muscle conditioning were avoided. Vascular delay and protective wrapping of the myograft in four dogs resulted in rapid seroma and fibrous sheath formation, which precluded further study. Of the six other myografts that were stimulated, two were used as functional right ventricular myoventriculoplasties and four were employed as neoventricle myografts with inflow and outflow valved conduits that were used to provide total pulmonary blood flow. Myoventriculoplasty produced functional enlargement of the right ventricle with synchronously contractile muscle. Neoventricles provided hemodynamically stable total pulmonary blood flow for as long as 20 hours, until internal chamber thrombus formed. Transpulmonary blood pressure generation by the neoventricle was found to be programmable up to physiologic systemic pressures by modulation of chamber preload and burst stimulation frequency at 50 msec intervals, delivered 120 times per minute. Synchronization capabilities for implantable burst pulse generators would further improve the efficacy of these myograft techniques designed to augment or supplant ventricular function, particularly to provide transpulmonary blood flow at programmable pressures.

  View details for Web of Science ID A1987F936800006

  View details for PubMedID 3807397

• RELATIVE CONTRIBUTIONS OF THE ANTERIOR AND POSTERIOR MITRAL CHORDAE TENDINEAE TO CANINE GLOBAL LEFT-VENTRICULAR SYSTOLIC FUNCTION JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Hansen, D. E., CAHILL, P. D., Derby, G. C., Miller, D. C. 1987; 93 (1): 45-55

  Abstract

  The relative importance of the anterior and posterior mitral chordae tendineae to global left ventricular performance, independent of load, was determined by sequentially measuring the slope of the left ventricular peak isovolumetric pressure-volume relation in a canine model with the chordae of both, either, and neither mitral leaflet(s) intact. The order in which the chordae were severed was randomly assigned. Compared to baseline values (both chordae intact), severing the chordae of the anterior leaflet (posterior leaflet chordae intact) reduced the slope of the pressure-volume relation by 27% (p = 0.005) in 10 dogs; the slope decreased by an additional 16% (p = 0.017) when the posterior chordae were subsequently severed in this group. In 10 dogs randomized to the reverse order, the slope of the pressure-volume relation decreased by 17% (p = 0.021) after the posterior chordae were severed (anterior leaflet chordae intact); an additional 24% decrease in the slope (p = 0.001) occurred when the chordae of the anterior leaflet were subsequently severed in this group. The chordae of the anterior and posterior mitral leaflets have an additive, but statistically indistinguishable (p = 0.140), influence upon global left ventricular systolic performance; however, the contribution of the anterior chordae tends to be more important. Thus preservation of the anterior mitral leaflet and its chordal attachments to the papillary muscles during mitral valve replacement may have an equal or greater impact upon postoperative left ventricular function than mitral valve replacement with preservation of the posterior chordae; however, severing either the anterior or posterior chordae appears to be detrimental.

  View details for Web of Science ID A1987F617300006

  View details for PubMedID 3796031

• Aneurysms of ascending thoracic aorta and transverse aortic arch. Cardiovascular clinics Frist, W. H., Miller, D. C. 1987; 17 (3): 263-287

  Abstract

  Recent chapters in the relatively brief history of surgical treatment of patients with ascending aortic aneurysms and aortic arch aneurysms continue to be punctuated by substantial clinical improvements. More precise diagnostic methods, increased awareness of the dismal natural history of patients with these aneurysms, improved methods of myocardial and cerebral protection, refined vascular grafts and prosthetic valves, widespread availability of specific coagulation components, more sophisticated anesthetic and postoperative management, and more timely referral of patients (prior to rupture or irreversible deterioration of left ventricular function, or both) have all been instrumental in promoting these improving results. The thrust of future efforts should be directed to the appropriate identification, diagnosis, and treatment of remote aneurysms and atherosclerotic disease in the cerebral and coronary circulation, detection of patients predisposed to aortic dissection, and ultimately to the development of pharmacologic methods to prevent aortic dissection and atherosclerotic aneurysm development. Eventually, it is hoped, more complete understanding of the genetics, molecular biology, and biochemistry of both acquired and congenital degenerative thoracic aortic aneurysms will also lead to preventive measures for these patients.

  View details for PubMedID 3555812

• PHARMACOLOGICAL, HEMATOLOGICAL, AND PHYSIOLOGICAL-EFFECTS OF A NEW THROMBOXANE SYNTHETASE INHIBITOR (CGS-13080) DURING CARDIOPULMONARY BYPASS IN DOGS ANNALS OF THORACIC SURGERY DeCampli, W. M., Goodwin, D., Kosek, J. C., Handen, C. E., Mitchell, R. S., Miller, D. C. 1986; 42 (6): 690-696

  Abstract

  The hematological and pharmacological effects of a new thromboxane synthetase inhibitor, CGS-13080 (imidazo[1,5-alpha]pyridine-5-hexanoic acid), were investigated during cardiopulmonary bypass in a blinded, randomized manner in dogs. Compared with placebo, CGS-13080 suppressed thrombin-stimulated platelet thromboxane B2 production by 90% during cardiopulmonary bypass (p less than .001), an effect that persisted for two hours after stopping the infusion. In the CGS-13080-treated group, plasma 6-keto-prostaglandin F1 alpha levels significantly increased over time (p less than .03) and were somewhat higher when compared with those in the placebo-treated group. This observation suggests that an "endoperoxide shunt" may have occurred. In the control group, an inverse correlation between platelet count and level of thromboxane B2 per platelet following in vitro thrombin stimulation (r = .5, p less than .001) was apparent, but there was no correlation between these two variables (r = .18, p less than .10) in the CGS-13080-treated group. No adverse hemodynamic or other effects attributable to CGS-13080 occurred during or immediately following cardiopulmonary bypass. These results suggest that CGS-13080 is an effective inhibitor of thromboxane B2 production during cardiopulmonary bypass in dogs and has no adverse physiological effects.

  View details for Web of Science ID A1986F174300017

  View details for PubMedID 3789860

• AUTOLOGOUS PERICARDIUM VERSUS A XENOGRAFT SUBSTITUTE IN MYOCARDIAL WOUND-HEALING JOURNAL OF SURGICAL RESEARCH Cohen, R. G., DeCampli, W. M., Weiss, L. M., Henderson, V. J., Gaudiani, V. A., GOODSON, W., Billingham, M. E., Miller, D. C. 1986; 41 (4): 352-361

  Abstract

  This study compared repair of myocardial wounds covered with autologous pericardium to healing of wounds covered with glutaraldehyde-preserved bovine pericardium in an experimental canine model. Right (RV) and left (LV) full thickness ventriculotomies were made and closed. In the control group (n = 12), the pericardium was closed over the wound; in the experimental group (n = 12), wounds were covered with bovine pericardium. Animals were sacrificed at 14, 21, 28, and 42 days. After excising the pericardium, 6 mm punch biopsies of normal RV, RV wound, normal LV, and LV wound were assayed for hydroxyproline (HPro). Both autologous and bovine pericardium became densely adherent to the wounds. Bovine pericardium was mildly adherent over unwounded areas, while autologous pericardium was usually free. Normal RV contained more than twice as much HPro as normal LV (5.4 +/- 0.57 micrograms/mg vs 1.7 +/- 0.35 micrograms/mg, P less than 0.0002). A gradual rise in HPro over time was seen in both groups, but this increase was statistically significant only at 42 days (P less than 0.05). There was no significant difference in HPro between wounds covered with autologous pericardium and those covered with bovine grafts (P = 0.13) at any of the sample times in this study. In this experimental canine model, the pericardium does not appear to play a prominent role in myocardial wound healing by contributing collagen-producing fibroblasts. Furthermore, the bovine pericardial xenograft becomes densely adherent to LV and RV incisions. In the clinical setting, such may make reoperation more hazardous when the heart has been previously incised or coronary bypass grafts have been constructed.

  View details for Web of Science ID A1986E615200003

  View details for PubMedID 3773495

• A RECONSIDERATION OF CEREBRAL PERFUSION IN AORTIC-ARCH REPLACEMENT ANNALS OF THORACIC SURGERY Frist, W. H., Baldwin, J. C., Starnes, V. A., Stinson, E. B., Oyer, P. E., Miller, D. C., Jamieson, S. W., Mitchell, R. S., Shumway, N. E. 1986; 42 (3): 273-281

  Abstract

  Ten patients underwent aortic arch replacement for aneurysmal disease from 1970 to 1985 using a simplified cardiopulmonary bypass (CPB) technique with partial brachiocephalic perfusion, low CPB flow (30 to 50 ml/kg/min), moderate systemic cooling (26 degrees to 28 degrees C), and topical hypothermic myocardial protection. The arterial line from a single pump head has a Y shape to perfuse the femoral artery (20F cannula) and either the innominate or left carotid artery (14F). Of the 10 patients (mean age, 58 years) with arch aneurysm (6 atherosclerotic, 2 dissections, and 2 degenerative), 3 had previously undergone major cardiovascular operations. Concomitant procedures included aortic valve replacement in 4 and coronary artery bypass grafting in 3. Eight patients survived the procedure, and 1 died three weeks after operation of a ruptured abdominal aneurysm. Among the survivors, CPB time was 119 +/- 36 minutes (+/- standard deviation), myocardial ischemia time was 79 +/- 32 minutes, and intraoperative blood requirement was 5.9 +/- 3.4 units. There were no postoperative strokes. Neurological complications were only minor and included an asymptomatic miosis and ulnar nerve paresthesias in 1 patient and transient vocal cord palsy in another. Applicable in most patients undergoing elective resection of degenerative and atherosclerotic arch aneurysms and in selected patients with arch dissections, this simplified technique of brachiocephalic perfusion without circulatory arrest provides an attractive and safe alternative; the potential advantages are technical simplicity, reduced CPB and operating times, and satisfactory cerebral protection.

  View details for Web of Science ID A1986E046200010

  View details for PubMedID 3489444

• USE OF THE INTRAAORTIC BALLOON PUMP AFTER VALVE-REPLACEMENT - PREDICTIVE INDEXES, CORRELATIVE PARAMETERS, AND PATIENT SURVIVAL JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY DOWNING, T. P., Miller, D. C., STOFER, R., Shumway, N. E. 1986; 92 (2): 210-217

  Abstract

  Intra-aortic balloon pump counterpulsation required as an adjunct during weaning from cardiopulmonary bypass or for circulatory support in the immediate postoperative period was analyzed in 2,498 patients undergoing valve replacement between December, 1972, and September, 1981. A total of 140 successful insertions were performed in 155 attempts. Ninety-five of these patients were from a homogeneous cohort of 1,908 patients undergoing valve replacement with porcine xenografts and were analyzed for factors that might be useful predictors of the need for balloon pump support. Univariate analysis of individual factors delineated preoperative characteristics in patients having mitral valve replacement and intraoperative factors in all patients that correlated with use of the balloon pump. Multivariate analysis revealed a subset of male patients with mitral valve and coronary disease most likely to require counterpulsation. Overall survival rate was markedly reduced at 30 days (balloon counterpulsation plus valve replacement, 50% +/- 5%; valve replacement only, 96% +/- 5%; p less than 0.001) and at 1 year (balloon counterpulsation plus valve replacement, 38% +/- 5%; valve replacement only, 89% +/- 1%, p less than 0.001) if balloon pumping was required. The entire group of 140 patients were retrospectively analyzed for factors predictive of survival. Patients requiring balloon pumping who had a preoperative diagnosis of aortic regurgitation had a lower 1 year survival rate (13% +/- 9%) than the total subgroup undergoing balloon counterpulsation (36% +/- 4.0%) (p = 0.002). Similarly patients treated by balloon counterpulsation who had postoperative renal failure had a significantly lower 1 year survival rate (17% +/- 5%) than those without renal failure (66% +/- 6%) (p = 0.003). The survival rate of patients who required this therapeutic modality after valve replacement is poor. Other methods of hemodynamic support are necessary.

  View details for Web of Science ID A1986D556200005

  View details for PubMedID 3488470

• NATURALLY CORRECTED DOUBLE-OUTLET RIGHT VENTRICLE WITH BIVENTRICULAR OUTFLOW TRACT OBSTRUCTION JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY ZUSMAN, D. R., FRENCH, J. W., GUTHANER, D. F., WALLINGTON, J., MILLER, D. C. 1986; 92 (1): 155–59

  Abstract

  A 5-year-old girl had presyncopal episodes associated with exertion. Diagnostic evaluation revealed a combination of congenital abnormalities: double-outlet right ventricle with apparent "natural correction" of a large subaortic ventricular septal defect and severe biventricular outflow tract obstruction. Intraoperative and postoperative studies confirmed satisfactory relief of the biventricular outflow tract obstruction.

  View details for Web of Science ID A1986D068800024

  View details for PubMedID 3724221

• SIGNIFICANT PATIENT-RELATED DETERMINANTS OF PROSTHETIC VALVE PERFORMANCE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Mitchell, R. S., Miller, D. C., Stinson, E. B., Oyer, P. E., Jamieson, S. W., Baldwin, J. C., Shumway, N. E. 1986; 91 (6): 807-817

  Abstract

  With rare exception, the bulk of out knowledge concerning the performance of any particular valve substitute originates from one institution; thus, if valve-related complications are more a function of the patient substrate undergoing operation than the prosthesis per se, the usefulness of inter-institutional comparisons would be severely limited. To address this question, the outcome of 2,719 patients after mitral or aortic valve replacement over 12,955 patient-years of follow-up was analyzed by time-dependent multivariate statistical methods with respect to thromboembolic events, anticoagulant-related hemorrhage, valve failure, fatal valve failure, all valve-related morbidity and mortality, necessity for reoperation, and late survival. Many patient-related factors were significant predictors of the probability of certain patient groups for sustaining these valve-related complications. Hence, comparisons of results of valve performance from different institutions may be misleading unless patient populations are comparable.

  View details for Web of Science ID A1986C716600001

  View details for PubMedID 3713234

• VALVULAR-VENTRICULAR INTERACTION - IMPORTANCE OF THE MITRAL APPARATUS IN CANINE LEFT-VENTRICULAR SYSTOLIC PERFORMANCE CIRCULATION Hansen, D. E., CAHILL, P. D., DeCampli, W. M., HARRISON, D. C., Derby, G. C., Mitchell, R. S., Miller, D. C. 1986; 73 (6): 1310-1320

  Abstract

  As the mitral valvular apparatus tenses during systole, forces transmitted along the chordae tendineae to the left ventricular chamber may influence left ventricular performance. To test this hypothesis, 10 dogs anesthetized with fentanyl were studied during cardiopulmonary bypass. The importance of the mitral apparatus in left ventricular systolic function was assessed independent of load by means of the slope of the contractile state-dependent left ventricular peak isovolumetric pressure-volume relationship (Emax), which was measured at constant heart rate and aortic pressure with a micromanometer inside a left ventricular intracavitary balloon before and immediately after all chordae tendineae were severed. Herniation of the balloon was prevented by a disk secured to the mitral anulus. Emax decreased from 11.97 +/- 3.35 (+/- SD) to 6.38 +/- 0.96 mm Hg/ml (p less than .001) with chordal severing. The volume intercept (Vo) was unchanged. Fluoroscopic studies of the balloon contour in eight additional dogs revealed dyskinesia in the area of the papillary muscle insertion and substantial alterations in chamber geometry during systole after the chordae were severed. Accordingly, we conclude that global left ventricular systolic performance is impaired when chordal attachments of the mitral valve are disrupted. Changes in left ventricular geometry or loss of inward force normally transmitted to the left ventricular wall as the valve tense may underlie these changes. These findings suggest that postoperative left ventricular dysfunction after mitral valve replacement may be attributable, in part, to excision of the native mitral apparatus at the time of surgery and support efforts to spare chordae during mitral valve surgery.

  View details for Web of Science ID A1986C525700028

  View details for PubMedID 3698258

• BIOCHEMICAL (FUNCTIONAL) ADAPTATION OF ARTERIALIZED VEIN GRAFTS ANNALS OF SURGERY Henderson, V. J., Mitchell, R. S., Kosek, J. C., Cohen, R. G., Miller, D. C. 1986; 203 (4): 339-345

  Abstract

  Canine venous autografts and allografts were interposed in the femoral and carotid arterial positions in 29 dogs; grafts were harvested at three postoperative intervals (1-2 weeks, 4-6 weeks, and 8-10 weeks) for light and scanning electron (SEM) microscopy and lumenal surface prostacyclin (PGI2) production. Normal veins and arteries were used as controls. Radioimmunoassay for tritiated 6-k-PGF1 alpha, the stable metabolite of PGI2, was performed using a flow surface template incubation chamber during basal and arachidonic acid stimulated conditions. Using SEM, the autografts revealed normal endothelial cell (EC) surfaces at all time intervals; conversely, allografts exhibited extensive EC loss at 1-2 weeks with gradual reparation by 10-12 weeks (such that the EC surface was virtually indistinguishable from that of control veins or autografts). PGI2 production was significantly greater in control arteries than veins (p = 0.0001). At 1-2 weeks and 4-6 weeks, lumenal production of PGI2 in both the autografts and allografts was not significantly different from control vein; however, PGI2 production after 10-12 weeks was identical to normal arterial levels (and significantly [p less than 0.0044] higher than venous levels) in both basal and stimulated conditions. Although the mechanisms responsible for this functional (biochemical) "arterialization" process remain conjectural, increased biosynthesis and/or release of PGI2 by endothelial cells, acute phase inflammatory cells (allografts) mediated by interleukin-1 or myointimal cells seems most likely. Further elucidation of these sources of PGI2 is necessary, but these data demonstrate for the first time that venous grafts placed in the arterial circulation undergo complete functional adaptation (in addition to the well known morphological changes).

  View details for Web of Science ID A1986A591200001

  View details for PubMedID 3516084

  View details for PubMedCentralID PMC1251115

• TIMING OF ABNORMAL INTERVENTRICULAR SEPTAL MOTION AFTER CARDIOPULMONARY BYPASS OPERATIONS - LACK OF INJURY PROVED BY PREOPERATIVE, INTRAOPERATIVE, AND POSTOPERATIVE ECHOCARDIOGRAPHY JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Schnittger, I., Keren, A., Yock, P. G., Allen, M. D., Modry, D. L., Zusman, D. R., Mitchell, R. S., Miller, D. C., Popp, R. L. 1986; 91 (4): 619-623

  Abstract

  Abnormal interventricular septal motion after cardiopulmonary bypass is a widely known occurrence. The cause and exact timing of this phenomenon remain unclear. We have studied 21 patients prospectively with preoperative, intraoperative, and postoperative two-dimensional and M-mode echocardiograms. Intraoperative studies were obtained with the pericardium closed and open and after completion of procedures performed with cardiopulmonary bypass. Fourteen patients had coronary artery bypass graft operations alone. Six patients had valve replacement with or without coronary bypass, and one patient had removal of a left atrial myxoma. All patients had normal interventricular septal motion before the operation, and none had abnormal septal motion intraoperatively. Four to eight days postoperatively, the septum still thickened normally in all patients, with five patients having normal, nine patients abnormal, and seven patients paradoxical interventricular septal motion. Studies in 11 patients 1 to 4 months postoperatively showed no change from the early postoperative study. The pericardium was left open postoperatively in all patients. Six patients were studied a few hours after sternal closure and all had abnormal interventricular septal motion. We conclude that abnormal interventricular septal motion after cardiac operations is not due to injury of the septum, adhesion formation, or loss of pericardial constraint. Closure of the chest wall itself, with the pericardium left open, is associated with this abnormality.

  View details for Web of Science ID A1986A823600019

  View details for PubMedID 3959582

• Repair of ascending aortic aneurysms and dissections. Journal of cardiac surgery Frist, W. H., Miller, D. C. 1986; 1 (1): 33-52

  View details for PubMedID 2979914

• IMPORTANCE OF THE ANTERIOR AND POSTERIOR MITRAL CHORDAE ON GLOBAL LEFT-VENTRICULAR SYSTOLIC FUNCTION Hansen, D. E., CAHILL, P. D., DeCampli, W. M., HARRISON, D. C., HANDEN, C., Derby, G., Mitchell, R. S., Miller, D. C. ELSEVIER SCIENCE INC. 1986: A249–A249

  View details for Web of Science ID A1986A165000992

• SUPERIORITY OF CARDIAC DIMENSIONAL CHANGES COMPARED TO STANDARD HEMODYNAMIC INDEXES FOR THE DETECTION OF HUMAN ALLOGRAFT-REJECTION HANSEN, D. E., DAUGHTERS, G. T., ALDERMAN, E. L., INGELS, N. B., STINSON, E. B., MILLER, D. C., BALDWIN, J. C., OYER, P. E., DERBY, G. C. ELSEVIER SCIENCE INC. 1986: A96

  View details for Web of Science ID A1986A165000380

• TORSIONAL DEFORMATION OF THE HUMAN LEFT-VENTRICLE - ALTERATIONS DURING CARDIAC ALLOGRAFT-REJECTION HANSEN, D. E., DAUGHTERS, G. T., ALDERMAN, E. L., BALDWIN, J. C., OYER, P. E., INGELS, N. B., STINSON, E. B., MILLER, D. C. ELSEVIER SCIENCE INC. 1986: A244

  View details for Web of Science ID A1986A165000972

• PROSTHETIC GRAFT INFECTION - LIMITATIONS OF INDIUM WHITE BLOOD-CELL SCANNING JOURNAL OF VASCULAR SURGERY Brunner, M. C., Mitchell, R. S., Baldwin, J. C., James, D. R., Olcott, C., MEHIGAN, J. T., McDougall, I. R., Miller, D. C. 1986; 3 (1): 42-48

  Abstract

  The lack of a rapid, noninvasive, and accurate method to confirm or rule out prosthetic graft infection continues to constitute a compelling and vexing clinical problem. A host of adjunctive diagnostic techniques has been used in the past, but early promising results subsequently have usually not yielded acceptable sensitivity (reflecting false negatives) and specificity (reflecting false positive) data. White blood cell (WBC) indium 111 scanning has recently been added to this list. The utility and accuracy of 111In WBC scans were assessed by retrospective review of WBC scan results in 70 patients undergoing evaluation for possible prosthetic graft infection over a 7-year period. Operative and autopsy data (mean follow-up, 18 months for survivors with negative scans) were used to confirm the 22 positive, 45 negative, and three equivocal WBC scans. The false positive rate (+/- 70% confidence limits) was 36% +/- 6% (n = 8) among the 22 patients with positive scans (44% +/- 6% [11 of 25] if the three equivocal scans are included as false positive), yielding a specificity of 85% +/- 5% and an overall accuracy rate of 88% +/- 4% (80% +/- 5% and 84% +/- 5%, respectively, if the three equivocal cases are considered as false positive). All three patients with equivocal scans ultimately were judged not to have prosthetic graft infection. As implied by the high accuracy rate, the sensitivity of the test was absolute (100% [14 of 14]); there were no false negative results. (ABSTRACT TRUNCATED AT 250 WORDS)

  View details for Web of Science ID A1986AYC3400005

  View details for PubMedID 3079840

• Acute and chronic aortic dissections--determinants of long-term outcome for operative survivors. Circulation Haverich, A., Miller, D. C., Scott, W. C., Mitchell, R. S., Oyer, P. E., Stinson, E. B., Shumway, N. E. 1985; 72 (3): II22-34

  Abstract

  A total of 135 survivors of surgical treatment of aortic dissection was followed for up to 15 years after surgery. Actuarial survival rates were 82 +/- 4% at 5 years and 64 +/- 6% at 10 years. There were no significant differences in long-term survival rates of patients in four subsets based on type and acuity of dissections. The incidence of late reoperation (dissection-related) was 13 +/- 4% at 5 years and 23 +/- 6% at 10 years; again, there was no significant difference among patients with different types or acuity of dissection. Multiple variables were investigated by multivariate discriminant analysis. Significant independent risk factors for late death included stroke, chronic renal dysfunction, remote myocardial infarction, and operation in the early years of this study. Younger age, site of intimal tear (arch), and cardiac tamponade portended a significantly higher likelihood of late reoperation. Except for stroke, no complication of the dissection or intraoperative factor significantly influenced late survival. Patients in whom the intimal tear was located in the aortic arch had the highest probability of late reoperation. Thus, dissection type, acuity, and distal extent, whether or not the tear was resected or concomitant aortic valve replacement performed, and a host of patient-related characteristics had no significant influence on the generally excellent long-term prognosis after surgical treatment. Indefinite surveillance of the remaining natural aorta is imperative (with reoperation when indicated) to attain such results.

  View details for PubMedID 3928189

• Effect of early postoperative volume loading on left ventricular systolic function (including left ventricular ejection fraction determined by myocardial marker) after myocardial revascularization. Circulation Miller, D. C., Daughters, G. T., Derby, G. C., Mitchell, R. S., Ingels, N. B., Stinson, E. B., Alderman, E. L. 1985; 72 (3): II207-15

  Abstract

  The effects of early volume loading in terms of isovolumetric-phase and ejection-phase indexes of left ventricular systolic function were studied in 12 patients 5 hr after myocardial revascularization, with myocardial markers used to measure left ventricular volume directly and with simultaneous transmural left ventricular pressure measurements by micromanometers. Volume loading (increasing transmural left ventricular end-diastolic pressure from 11 +/- 4 to 15 +/- 5 mm Hg) induced a significant 14% increase in left ventricular end-diastolic volume index (LVEDVI), which was associated (as expected) with significant (p less than .005) augmentation of stroke work (+26%), left ventricular pressure-volume loop area (+35%), and stroke volume index (+22%) and with increments in left ventricular dP/dt and mean velocity of circumferential fiber shortening despite a simultaneous increase in left ventricular afterload. In contrast to previous radionuclide studies, however, left ventricular ejection fraction increased significantly (+9%) and the left ventricular end-systolic pressure-volume ratio did not fall. The relative change in ejection fraction was directly proportional to the increment in LVEDVI (r = .54, p = .03) and inversely related to the change in left ventricular end-systolic volume index (r = -.71, p = .0005). Patients who demonstrated a small or no increase in ejection fraction generally had a larger simultaneous increase in afterload, but one patient exhibited exhaustion of preload reserve. Ejection fraction, as an ejection-phase index of left ventricular performance, is highly dependent on afterload; therefore, interpretation of postoperative changes in ejection fraction must be undertaken only with strict caution.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for PubMedID 3896554

• Operative risk of mitral valve replacement: discriminant analysis of 1329 procedures. Circulation Scott, W. C., Miller, D. C., Haverich, A., Mitchell, R. S., Oyer, P. E., Stinson, E. B., Jamieson, S. W., Baldwin, J. C., Shumway, N. E. 1985; 72 (3): II108-19

  Abstract

  The influence of 34 variables on the operative mortality rate for isolated mitral valve replacement (MVR) was assessed by univariate and multivariate logistic regression analysis. The physiologic lesions were classified as stenosis (20%, operative mortality rate 8 +/- 1%), regurgitation (44%, operative mortality rate 13 +/- 2%), and mixed (34%, operative mortality rate 8 +/- 1%). Functional class (NYHA), previous myocardial infarction, and hepatic dysfunction were powerful independent clinical determinants of operative mortality (p less than .001), along with age at operation and emergency operation (p = .001, p = .04). Concomitant coronary artery bypass grafting or tricuspid annuloplasty, angina, ischemic etiology, and physiologic lesion were not significant independent determinants of operative risk. Interestingly, year of operation, prosthetic valve dysfunction, and previous cardiac surgery had no important effect on operative mortality. Early operative risk for MVR was related to preoperative cardiac and hepatic function. Prior myocardial infarction substantially increased the risk even if the mitral valve disease was not ischemic in origin. Increased operative mortality rate in the subgroup with mitral regurgitation was related to advanced left ventricular failure and myocardial infarction rather than the etiology of the mitral regurgitation. These clinical factors coupled with more refined measurements of left ventricular systolic pump function (independent of loading conditions) should permit more intelligent decision making regarding the optimal timing of MVR, at least in terms of early operative risk.

  View details for PubMedID 4028353

• Surgical treatment of constrictive pericarditis: analysis of outcome and diagnostic error. Circulation Seifert, F. C., Miller, D. C., Oesterle, S. N., Oyer, P. E., Stinson, E. B., Shumway, N. E. 1985; 72 (3): II264-73

  Abstract

  The records of 81 patients with a diagnosis of constrictive pericarditis who underwent surgical treatment were examined to assess the effectiveness of diagnosis and therapy. A false-positive diagnosis occurred in 10 patients (12%); seven had restrictive cardiomyopathy. Of 51 variables examined, only a low right ventricular end-diastolic pressure (RVEDP) significantly and independently predicted diagnostic error. Seventy-one patients with constrictive pericarditis underwent pericardiectomy. Mean follow-up was 4.7 years (maximum 12), and only two patients were untraceable. The study population was notable: 42 patients had visceral as well as parietal pericardial involvement; 32 had idiopathic disease and 25 had pericarditis related to radiation therapy. Results were favorable in 83% of the population. There were seven in-hospital deaths (10%). Actuarial survival estimates were 74% and 64% at 5 and 10 years, respectively. Compared with a normal population, the survival rate of patients with postradiation constrictive pericarditis was significantly inferior, whereas the survival rate of the remaining patients was not significantly different. Patients with constrictive pericarditis and restrictive cardiomyopathy did no better than those with restrictive cardiomyopathy alone. Additionally, patients in NYHA functional class IV had a significantly worse prognosis. Multivariate analysis of 38 preoperative variables identified high RVEDP as a significant independent predictor of in-hospital death, and renal dysfunction and diuretic use were significant independent predictors of overall poor outcome. Differentiation between the diagnosis of constrictive pericarditis and restrictive cardiomyopathy remains a problem. Radiation therapy, pericarditis with restrictive cardiomyopathy, high RVEDP, NYHA class IV status, renal dysfunction, and diuretic use adversely influenced outcome in patients undergoing pericardiectomy.

  View details for PubMedID 4028364

• ACUTE AND CHRONIC AORTIC DISSECTIONS - DETERMINANTS OF LONG-TERM OUTCOME FOR OPERATIVE SURVIVORS CIRCULATION Haverich, A., Miller, D. C., Scott, W. C., Mitchell, R. S., Oyer, P. E., Stinson, E. B., Shumway, N. E. 1985; 72 (3): 22-34

  View details for Web of Science ID A1985APY7900005

• LEFT-VENTRICULAR PRESSURE-VOLUME AREA CORRELATES WELL WITH MYOCARDIAL OXYGEN-CONSUMPTION IN INTACT MAN DAUGHTERS, G. T., MEAD, C. W., DERBY, G. C., SCHWARZKOPF, A., ALDERMAN, E. L., FOWLER, M. B., MILLER, D. C. ELSEVIER SCIENCE INC. 1985: 418

  View details for Web of Science ID A1985ABL1000131

• FLOW DETERMINATION USING COMPUTED-TOMOGRAPHY - APPLICATION TO AORTIC DISSECTION GUTHANER, D. F., NASSI, M., BRADLEY, B., TELLO, R., MILLER, D. C. LIPPINCOTT-RAVEN PUBL. 1985: S27

  View details for DOI 10.1097/00004424-198509000-00135

  View details for Web of Science ID A1985ARG0500123

• INDEPENDENCE OF LEFT-VENTRICULAR PRESSURE-VOLUME RATIO FROM PRELOAD IN MAN EARLY AFTER CORONARY-ARTERY BYPASS GRAFT-SURGERY CIRCULATION Daughters, G. T., Derby, G. C., Alderman, E. L., Schwarzkopf, A., MEAD, C. W., Ingels, N. B., Miller, D. C. 1985; 71 (5): 945-950

  Abstract

  The response of the maximum value of the left ventricular pressure-volume ratio to preload augmentation by blood or plasma expanders was studied in 11 patients during the first 24 hr after coronary artery bypass graft surgery. Increasing the mean left atrial pressure from 10 to 15 and 20 mm Hg resulted in no change in the maximum pressure-volume ratio in the group as a whole. In certain individual patients, however, the maximum pressure-volume ratio changed with volume infusion, and these changes were accompanied by simultaneous changes in afterload. The observed changes in pressure-volume ratio were in the same direction as the changes in afterload (systolic pressure), suggesting a dependence of maximum pressure-volume ratio on afterload. These results show that the maximum pressure-volume ratio is independent of preload in the first 24 hr after coronary artery bypass graft surgery with the pericardium open; thus the maximum pressure-volume ratio is a useful index of postoperative left ventricular function when afterload is unchanged. However, because this ratio (a single-point assessment of the pressure-volume relationship) may not be a good estimate of Emax, we recommend a more complete determination of the locus of the "upper left corners" of the pressure-volume loops for measurement of Emax to provide a more accurate indicator of the myocardial contractile state.

  View details for Web of Science ID A1985AGC5100015

  View details for PubMedID 3872741

• SURGICAL REPAIR OF TETRALOGY OF FALLOT - LONG-TERM FOLLOW-UP WITH PARTICULAR EMPHASIS ON LATE DEATH AND REOPERATION JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Zhao, H. X., Miller, D. C., Reitz, B. A., Shumway, N. E. 1985; 89 (2): 204-220

  Abstract

  Early and late results in 309 patients undergoing repair of tetralogy of Fallot between 1960 and 1982 were analyzed with respect to independent determinants of operative mortality, late reoperation, and late death. Follow-up extended to 22 years and totaled 2,743 patient-years. The operative mortality rate was 4.9% +/- 1.3%. Multivariate logistic regression analysis revealed that only young age, long cardiopulmonary bypass time, and (probably) extent of right ventricular outflow tract patch were independent significant determinants of operative mortality. Patients who required a transannular right ventricular outflow tract patch and those who underwent repair without any outflow tract patch were at higher risk than those who received a separate right ventricular and/or pulmonary artery patch. The long-term results were highly satisfactory: Only 15% +/- 3% of patients required reoperation 13 years postoperatively, and 85% +/- 4% of discharged patients were alive 16 years later. Time-dependent linear stepwise multivariate discriminant analysis showed that extent of right ventricular outflow tract patch (transannular greater than none greater than right ventricular and/or [separate] pulmonary arterial), longer ischemic arrest time, previous palliative shunt, and primary suture closure of the ventricular septal defect were the only covariates that independently portended a higher likelihood of reoperation. Similarly, only older age, absence of hypoxic spells, and reoperation were significantly and independently related to the probability of late death. The results of these analyses demonstrate that intracardiac repair of tetralogy is a durable procedure for upwards of 20 years; however, high-risk subsets of patients can be identified in terms of operative mortality, reoperation, and late death. Thus, there is still a need for improvement, particularly future research devoted to better understanding of the electrophysiological mechanisms responsible for arrhythmias, electrosurgical and medical arrhythmia therapy, and right and left ventricular mechanics after repair of tetralogy of Fallot.

  View details for Web of Science ID A1985ABW9100006

  View details for PubMedID 3968904

• 10 YEAR DURABILITY AND PERFORMANCE OF PORCINE BIOPROSTHESES ZEITSCHRIFT FUR KARDIOLOGIE Miller, D. C., Oyer, P. E., Stinson, E. B., Shumway, N. E. 1985; 74: 15-18

  Abstract

  The results presented herein describe the prognosis over the first 10 postoperative years for patients operated upon at Stanford University Medical Center who received a first generation, commercially-manufactured porcine bioprosthetic valve. Extrapolation of these results to 15 and 20 years cannot be justified at this time. Conversely, newer tissue valves are believed to be superior, in terms of both hemodynamic performance and long-term durability. Indeed, the newer pericardial valves (Hancock Laboratories and American-Edwards Laboratories) have hemodynamic characteristics that do not differ markedly from those of the tilting disk and bi-leaflet mechanical valves. This promise of potential superior durability in terms of resistance to fibrocalcification will only be able to be determined after patients with these second and third generation tissue valves have been followed for 10 to 15 years postoperatively. Speculation regarding the comparative performance between a durable mechanical valve and a bioprosthesis in the 10 to 15 year time frame is also probably not prudent at this time. We continue to submit, however, that the balance between lower cumulative complication and death rates and finite durability--which currently favors the tissue valve at 10 years--will continue to predominate beyond ten years. This is due for the most part to the constant rate of serious (and frequently fatal) valve-related complications which occur in patients with mechanical valves over the years; having 20 to 40% of patients with mechanical valves succumb within 10 to 15 years due to the complications of TE, ACH, and valve thrombosis is not acceptable, in our opinion, as the magnitude of the risk associated with porcine valve PTF and resultant REOP is lower.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for Web of Science ID A1985AXE7200004

  View details for PubMedID 4096073

• SURGICAL-TREATMENT OF CONSTRICTIVE PERICARDITIS - ANALYSIS OF OUTCOME AND DIAGNOSTIC ERROR CIRCULATION Seifert, F. C., Miller, D. C., Oesterle, S. N., Oyer, P. E., Stinson, E. B., Shumway, N. E. 1985; 72 (3): 264-273

  View details for Web of Science ID A1985APY7900040

• FLOW DETERMINATION USING COMPUTED-TOMOGRAPHY - APPLICATION TO AORTIC DISSECTION .2. INVESTIGATIVE RADIOLOGY GUTHANER, D. F., Nassi, M., Bradley, B., Miller, D. C. 1985; 20 (7): 682-686

  Abstract

  Dynamic CT is not only useful in imaging an aortic dissection but may provide additional information concerning the hemodynamic significance of differing flow patterns in the false channel compared with the true channel. Once validated, the computed tomographic (CT) method of flow determination (See Part I) was applied to an experimental animal model with a surgically created aortic dissection. Good correlation was obtained for the flow estimates of cardiac output derived for the true and false channel (r = .82). The shapes of the curves, however, were distinct, reflecting different flow patterns for the true and false channels. Curve parameters, such as peak CT number (P = .0001), variance (P = .006), and, in particular, the number of mixers (a parameter used to quantify the degree of mixing) (P = .0001), demonstrated significant differences between the two channels of the dissection. The curve parameters derived can therefore be used to differentiate the true and false channels and may then predict the long-term outcome of the false channel, and the aortic branches derived from it.

  View details for Web of Science ID A1985ASP4400006

  View details for PubMedID 4066238

• VALVE-REPLACEMENT IN PATIENTS WITH NATIVE VALVE ENDOCARDITIS - WHAT REALLY DETERMINES OPERATIVE OUTCOME ANNALS OF THORACIC SURGERY DAGOSTINO, R. S., Miller, D. C., Stinson, E. B., Mitchell, R. S., Oyer, P. E., Jamieson, S. W., Baldwin, J. C., Shumway, N. E. 1985; 40 (5): 429-438

  Abstract

  The influence of 27 variables on operative mortality and late complications (defined as residual or recurrent endocarditis or late bland periprosthetic leak) was determined using discriminant analysis for 108 patients undergoing valve replacement for native valve endocarditis at Stanford University Medical Center from March, 1964, to January, 1983. Congestive heart failure was the indication for valve replacement in 86% of patients. Aortic valve replacement was required in 68% and mitral valve replacement, in 26%. Patients were arbitrarily defined as having active (58%) or healed (42%) endocarditis. Follow-up included 515 patient-years and extended to a maximum of 19 years. Operative mortality was 15 +/- 4%, and 17 patients had late complications (linearized rate, 3.3% per patient-year). Seven variables were significantly related to operative mortality in the univariate analysis, but only organism (Staphylococcus aureus versus all others, p = 0.0302) was a significant independent predictor of operative mortality. For late complications, only 2 of 7 significant univariate covariates proved to be significant independent determinants: organisms on valve culture or gram stain and the presence of annular abscess. Patients with S. aureus endocarditis not showing prompt response to antibiotic treatment must be considered for early operation. Similarly, timely operative intervention for patients with annular abscess will be essential in decreasing late valve infections and perivalvular leaks.

  View details for Web of Science ID A1985AUP5300004

  View details for PubMedID 4062397

• DETERMINANTS OF OPERATIVE MORTALITY FOR PATIENTS UNDERGOING AORTIC-VALVE REPLACEMENT - DISCRIMINANT-ANALYSIS OF 1,479 OPERATIONS JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Scott, W. C., Miller, D. C., Haverich, A., Dawkins, K., Mitchell, R. S., Jamieson, S. W., Oyer, P. E., Stinson, E. B., Baldwin, J. C., Shumway, N. E. 1985; 89 (3): 400-413

  Abstract

  The influence of 35 preoperative and intraoperative characteristics on operative mortality risk after 1,479 isolated aortic valve replacement procedures (1967 to 1981) was investigated utilizing univariate and multivariate logistic regression analyses. Mean age at operation was 58 +/- 13 years; 72% of patients were men. Physiology was classified as aortic stenosis (58%), regurgitation (30%), or both (9%). The overall operative mortality rate was 7% +/- 1%, but there were substantial differences in operative mortality rates among physiological subgroups (aortic regurgitation, 10% +/- 2%; aortic stenosis, 6% +/- 1%; stenosis/regurgitation, 5% +/- 2%). Independent determinants of operative mortality rate in the entire group were advanced New York Heart Association functional class, renal dysfunction, physiological subgroup, atrial fibrillation, and older age. In the aortic regurgitation subgroup, functional class, atrial fibrillation, and operative year were independent predictors. In the aortic stenosis subgroup, the significant determinants were functional class, renal dysfunction, age, prosthetic valve dysfunction, and absence of angina. Concomitant coronary bypass grafting, previous operation, endocarditis, and ascending aortic replacement had no independent predictive effect on operative mortality rate. Thus, the early results of aortic valve replacement can be related to several specific variables describing the functional and physiological status of the patient. Operative mortality rate is not independently related to previous operation or concomitant operative procedures. Specific differences in risk factors exist among the various physiological subgroups, probably reflecting the pathophysiology of the different hemodynamic lesions. This information should provide for a more rational approach to aortic valve replacement, at least in terms of early risk/benefit deliberations.

  View details for Web of Science ID A1985ADH6100009

  View details for PubMedID 3974275

• QUANTITATION OF HYDRAULIC CONSTANTS IN THE GORLIN AND HOLEN-HATLE EQUATIONS IS IMPORTANT IN LOW OUTPUT STATES Segal, J., Lerner, D. J., Miller, D. C., Mitchell, R. S., Alderman, E. A., Popp, R. L. LIPPINCOTT WILLIAMS & WILKINS. 1985: 373–73

  View details for Web of Science ID A1985ARW1101491

• SEVERING THE CHORDAE TENDINEAE REDUCES LEFT-VENTRICULAR SYSTOLIC PERFORMANCE IN DOGS Hansen, D. E., DeCampli, W. M., Mitchell, R. S., Derby, G. C., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 1985: 485–85

  View details for Web of Science ID A1985ARW1101940

• CRITICAL-EVALUATION OF 111-IN-WHITE CELL SCAN FOR DIAGNOSING PROSTHETIC GRAFT INFECTION McDougall, I. R., Brunner, M. C., Mitchell, R. S., Baldwin, J. C., James, D. R., Olcott, C., MEHIGAN, J. T., Miller, D. C. LIPPINCOTT-RAVEN PUBL. 1985: P18–P18

  View details for Web of Science ID A1985ARV0700035

• EFFECT OF EARLY POSTOPERATIVE VOLUME LOADING ON LEFT-VENTRICULAR SYSTOLIC FUNCTION (INCLUDING LEFT-VENTRICULAR EJECTION FRACTION DETERMINED BY MYOCARDIAL MARKER) AFTER MYOCARDIAL REVASCULARIZATION CIRCULATION Miller, D. C., Daughters, G. T., Derby, G. C., Mitchell, R. S., Ingels, N. B., Stinson, E. B., Alderman, E. L. 1985; 72 (3): 207-215

  View details for Web of Science ID A1985APY7900032

• OPERATIVE RISK OF MITRAL-VALVE REPLACEMENT - DISCRIMINANT-ANALYSIS OF 1329 PROCEDURES CIRCULATION Scott, W. C., Miller, D. C., Haverich, A., Mitchell, R. S., Oyer, P. E., Stinson, E. B., Jamieson, S. W., Baldwin, J. C., Shumway, N. E. 1985; 72 (3): 108-119

  View details for Web of Science ID A1985APY7900017

• Independent determinants of operative mortality for patients with aortic dissections. Circulation Miller, D. C., Mitchell, R. S., Oyer, P. E., Stinson, E. B., Jamieson, S. W., Shumway, N. E. 1984; 70 (3): I153-64

  Abstract

  A 20 year (1963 to 1982) surgical experience including 175 consecutive patients with aortic dissections was analyzed by logistic discriminant analyses to identify predictors of high operative risk. The patient population had characteristics similar to those in large autopsy series. Sixty-nine percent had type A and 58% had acute dissections. The intimal tear was located in the ascending aorta in 60% of the patients, the descending aorta in 27%, and the transverse arch in 13%. The overall operative mortality rate was 23 +/- 3%. The operative mortality rates were substantially lower between 1977 and 1982: mortality in patients with acute type A dissections, 7 +/- 5%; in those with chronic type A, 11 +/- 7%; in those with acute type B, 13 +/- 12%; and in those with chronic type B, 11 +/- 11%. After preliminary univariate screening, the following factors were determined to be significant independent predictors of operative mortality (in rank order of declining predictive power): type A patients (n = 121), renal dysfunction, tamponade, renal/visceral ischemia, and operative date; type B patients (n = 54), rupture, renal/visceral ischemia, and age; all patients (n = 175), renal dysfunction, renal/visceral ischemia, site of tear (ascending less than descending less than arch), tamponade, operative date, and pulmonary disease. Interestingly, several variables had no important bearing on operative mortality, including type (acute vs chronic) of dissection, age, previous operation, rupture, stroke, paraplegia, Marfan's syndrome, concomitant aortic valve replacement and/or coronary artery bypass grafting, site of tear, and whether or not the tear was resected in type A patients; emergency operation, hypertension, previous cardiac symptoms, paraplegia, site of tear, and resection of tear in type B patients; and, when all patients were considered together, age, sex, cardiac symptoms, prior operation, stroke, paraplegia, acute myocardial infarction, acute aortic regurgitation, Marfan's syndrome, and tear resection. These data allow calculation of any individual patient's operative risk and document that the operative mortality rate today is relatively low for all patients with aortic dissections, irrespective of type or acuity. Earlier surgical referral of patients with acute type A or acute type B dissection before irreversible major end-organ ischemia and/or infarction is probably in part responsible for the substantially improved results since 1977.

  View details for PubMedID 6235061

• Dobutamine and dopamine after cardiac surgery: greater augmentation of myocardial blood flow with dobutamine. Circulation Fowler, M. B., Alderman, E. L., Oesterle, S. N., Derby, G., Daughters, G. T., Stinson, E. B., Ingels, N. B., Mitchell, R. S., Miller, D. C. 1984; 70 (3): I103-11

  Abstract

  Left ventricular hemodynamics, dimensions and coronary sinus blood flows were measured simultaneously after infusions of dobutamine and dopamine. Ten patients were studied 6, 10 to 15, and 24 hr after cardiopulmonary bypass surgery. The dose of each drug was adjusted to increase cardiac output by 25%. Heart rate was held constant with atrial pacing. Dobutamine and dopamine increased peak left ventricular dP/dt from baseline values by 72% vs 58% during the early study, 77% vs 78% in the intermediate study, and 95% vs 79% in the late study (all NS, difference between drugs). Similarly, there were no significant differences in hemodynamic response or in cardiac dimensions after the two drugs in any period. Both drugs increased myocardial oxygen uptake during the intermediate and late studies (32% vs 33% and 34% vs 25%). With dobutamine this increase was matched by a similar increase in coronary blood flow; however, failure of the expected increase in coronary blood flow with dopamine suggested coronary constriction. Although dobutamine and dopamine have similar hemodynamic effects, dobutamine has the advantage of not limiting the increase in coronary blood flow associated with increased oxygen demand.

  View details for PubMedID 6744557

• DOBUTAMINE AND DOPAMINE AFTER CARDIAC-SURGERY - GREATER AUGMENTATION OF MYOCARDIAL BLOOD-FLOW WITH DOBUTAMINE CIRCULATION Fowler, M. B., Alderman, E. L., Oesterle, S. N., Derby, G., Daughters, G. T., Stinson, E. B., Ingels, N. B., Mitchell, R. S., Miller, D. C. 1984; 70 (3): 103-111

  View details for Web of Science ID A1984TF85700018

• NONVALVED RIGHT VENTRICULAR-PULMONARY ARTERY DACRON CONDUITS - IMPROVED LONG-TERM PERFORMANCE WITH DOUBLE VELOUR GRAFTS SURGICAL FORUM HAVERICH, A., MILLER, C., BORST, H. G. 1984; 35: 344–46

  View details for Web of Science ID A1984TW53800145

• WHEN TO SUSPECT AORTIC DISSECTION - WHAT TREATMENT CARDIOVASCULAR MEDICINE MILLER, D. C. 1984; 9 (10): 811–18

  View details for Web of Science ID A1984TT73600004

• THE DIURETIC PROPERTIES OF DOPAMINE IN PATIENTS AFTER OPEN-HEART OPERATION ANESTHESIOLOGY Hilberman, M., Maseda, J., Stinson, E. B., Derby, G. C., Spencer, R. J., Miller, D. C., Oyer, P. E., Myers, B. D. 1984; 61 (5): 489-494

  Abstract

  Dopamine and dobutamine were administered to 12 patients who had undergone open cardiac operations. To eliminate the effects of variation in systemic blood flow upon renal function the drug infusion rates were adjusted to achieve equal cardiac outputs. Under conditions of equivalent systemic pressure and flow, dopamine (5.0 +/- 1 micrograms X kg-1 X min-1) and dobutamine (3.5 +/- 1.8 micrograms X kg-1 X min-1) had similar effects upon glomerular filtration rate (90 +/- 29 vs. 83 +/- 27 ml X min-1 X 1.73 m-2) and effective renal plasma flow (375 +/- 119 vs. 357 +/- 126 ml X min-1 X 1.73 m-2). However, dopamine administration resulted in a significantly greater diuresis (2.8 +/- 2.7 vs. 1.0 +/- 0.3 ml/min), natriuresis (0.32 +/- 0.39 vs. 0.07 +/- 0.10 mEq Na+/min), and kaliuresis (0.15 +/- 0.06 vs. 0.10 +/- 0.03 mEq K+/min) (P less than 0.05). In patients with modest depression of cardiac performance and renal vasoconstriction, dopamine's selective renal vasodilator effects were not evident. Furthermore, these data suggest that dopamine inhibits tubular solute reabsorption directly. Thus, the diuresis and natriuresis that frequently accompany dopamine administration may occur independently of any effects of dopamine upon renal blood flow.

  View details for Web of Science ID A1984TP66500002

  View details for PubMedID 6496987

• CALCIFICATION OF AORTIC VERSUS MITRAL PORCINE BIOPROSTHETIC HEART-VALVES - A RADIOGRAPHIC STUDY COMPARING AMOUNTS OF CALCIFIC DEPOSITS IN VALVES EXPLANTED FROM THE SAME PATIENT AMERICAN JOURNAL OF CARDIOLOGY Cipriano, P. R., Billingham, M. E., Miller, D. C. 1984; 54 (8): 1030-1032

  Abstract

  Calcium detected by radiography was compared in 10 pairs of aortic and mitral glutaraldehyde-treated porcine bioprosthetic heart valves explanted from 10 patients (7 men and 3 women), aged 19 to 68 years (mean 43). Both valves of 6 pairs of valves had undergone primary tissue failure (revealed by cardiac catheterization and angiography) and 1 valve of the other 4 pairs of valves had undergone primary tissue failure. These porcine valves had been implanted from 2 1/4 to 9 years (mean 5 3/4). All 20 explanted valves contained calcium. The grade of calcium was the same in 4 pairs of valves (grade 2+ or 3+), and 1 grade different in 4 pairs of valves (grade 1+ to 4+), with the greater calcium evenly divided between the 2 valve positions. There was more than 1 grade greater mitral valve calcium in 2 pairs of valves (grade 3+ and 4+ mitral vs 1+ and 2+ aortic, respectively). Thus, calcium is usually present in both aortic and mitral valve positions when bioprosthetic valves of this type in either valve position fail as a result of primary tissue failure, and radiographic calcium in porcine bioprosthetic valves is usually similar in grade in both the aortic and mitral valve positions.

  View details for Web of Science ID A1984TQ43000017

  View details for PubMedID 6496325

• DETERMINANTS OF OPERATIVE MORTALITY (OM) IN 1329 PATIENTS UNDERGOING MITRAL-VALVE REPLACEMENT (MVR) Scott, W. C., Haverich, A., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 1984: 328–28

  View details for Web of Science ID A1984TN45401321

• NATURE OF THE RENAL INJURY FOLLOWING TOTAL RENAL ISCHEMIA IN MAN JOURNAL OF CLINICAL INVESTIGATION Myers, B. D., Miller, D. C., MEHIGAN, J. T., Olcott, C., GOLBETZ, H., Robertson, C. R., Derby, G., Spencer, R., Friedman, S. 1984; 73 (2): 329-341

  Abstract

  The effects of total renal ischemia (TRI) of 15-87 min duration due to suprarenal clamping of the aorta were studied in 15 mannitol-treated patients undergoing abdominal aortic surgery. 15 patients undergoing similar surgery but requiring only infrarenal clamping served as controls. 1-2 h following TRI, GFR was reduced to only 39% of that in controls, 23 +/- 5 vs. 59 +/- 7 ml/min (P less than 0.001). This could not be ascribed to impaired renal plasma flow (RPF), which was mildly reduced to 331 +/- 71 and was not different from the value in controls, 407 +/- 66 ml/min. However, impaired PAH extraction (43 +/- 7%) and isosthenuria, not present in controls, suggest a primary role for tubular injury in lowering GFR at this time. 24 h following TRI, the GFR remained depressed below controls, 45 +/- 8 vs. 84 +/- 8 ml/min (P less than 0.005), while the transglomerular sieving of neutral dextrans was significantly enhanced (radius interval, 24-40 A). A theoretical analysis of transcapillary solute exchange revealed that these findings could be largely explained by a selective reduction of either RPF (-61%) or of transmembrane hydraulic pressure difference (-18%) below control values. Alternately, a combination of these two factors with changes of smaller magnitude could explain the findings. In contrast, a selective increase in oncotic pressure or decrease of the glomerular ultrafiltration coefficient could be excluded as a cause of hypofiltration 24 h after TRI. These observations lead us to suggest that the transient azotemia observed following TRI is due to a self-limited injury to the nephron that is identical to that seen in overt and sustained forms of acute renal failure.

  View details for Web of Science ID A1984SD74800006

  View details for PubMedID 6421876

  View details for PubMedCentralID PMC425022

• THROMBOEMBOLIC RISK AND DURABILITY OF THE HANCOCK BIOPROSTHETIC CARDIAC-VALVE EUROPEAN HEART JOURNAL Oyer, P. E., Stinson, E. B., Miller, D. C., Jamieson, S. W., Mitchell, R. S., Shumway, N. E. 1984; 5: 81-85

  View details for Web of Science ID A1984ACF9100015

  View details for PubMedID 6519106

• DEGENERATIVE AND ATHEROSCLEROTIC ANEURYSMS OF THE THORACIC AORTA - DETERMINANTS OF EARLY AND LATE SURGICAL OUTCOME JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY MORENOCABRAL, C. E., Miller, D. C., Mitchell, R. S., Stinson, E. B., Oyer, P. E., Jamieson, S. W., Shumway, N. E. 1984; 88 (6): 1020-1032

  Abstract

  To identify significant predictors of early and late mortality, multivariate discriminant analyses were applied to the clinical outcome of 175 consecutive patients with thoracic aortic aneurysms operated upon over a 20 year span. Only atherosclerotic and degenerative aneurysms were included; the patients were segregated into two groups according to location of the aneurysm. The ascending aortic aneurysm group consisted of 124 patients, 85% of whom required concomitant aortic valve replacement. There were 51 patients in the descending aortic aneurysm group. Mean follow-up was 4.9 years (maximum of 19 years), with a total of 860 patient-years of follow-up. Multivariate analyses revealed that surgical priority and advanced age were independent determinants of hospital mortality in the ascending group; for the descending group, surgical priority and the presence of congestive heart failure were the strongest predictors of hospital mortality. Late mortality in the ascending group correlated with advanced age. Hypertension and the presence of preoperative congestive heart failure were independent determinants of late mortality in the descending group. Several variables did not have any independent bearing on hospital or late mortality, including etiology and location of the aneurysm, previous myocardial infarction, chronic lung disease, and concomitant aortic valve replacement. High-risk subgroups of patients with thoracic aortic aneurysms can be identified by these variables. Aggressive medical plus surgical management and operation prior to aneurysm rupture is necessary to improve both early and long-term survival rates.

  View details for Web of Science ID A1984TV42000015

  View details for PubMedID 6503314

• PERFORMANCE-CHARACTERISTICS OF THE STARR-EDWARDS MODEL 1260 AORTIC-VALVE PROSTHESIS BEYOND 10 YEARS JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Miller, D. C., Oyer, P. E., Mitchell, R. S., Stinson, E. B., Jamieson, S. W., Baldwin, J. C., Shumway, N. E. 1984; 88 (2): 193-207

  Abstract

  The Starr-Edwards non-cloth-covered silicone ball (Model 1260) aortic valve prosthesis has been widely used for over 15 years and remains a standard against which newer values are compared. To define more completely the performance characteristics of this prosthesis, this study (including 449 patients) analyzed the long-term function of this specific valve over a cumulative total of 2,896 patient-years (pt-yrs) of follow-up which extended beyond 13 years. Expressed in both actuarial (% [+/- standard error of the mean] free at 10 years) and linearized (%/pt-yr) terms, respectively, valve-related complications occurred at the following rates: thromboembolism, 76 +/- 3 and 2.7; anticoagulant-related hemorrhage, 74 +/- 3 and 3.1; prosthetic valve endocarditis, 92 +/- 2 and 0.9; reoperation, 90 +/- 2 and 1.1; valve failure, 82 +/- 2 and 2.2; all valve-related morbidity and mortality, 51 +/- 3 and 6.0; and valve-related death, 88 +/- 2 and 1.3. Thirteen percent of hospital and 18% of late deaths were due to valve-related causes. No case of structural failure was documented. This prosthesis has an admirable structural durability record out to 13 years, and its long-term performance is satisfactory, albeit not optimal. Despite the indestructable design and construction of this mechanical valve substitute, 12% +/- 2% of patients had died of valve-related complications by 10 years, and fully 49% +/- 3% had had some form of serious valve-related complication. The long-term data reported herein can be used for analytical comparison when follow-up of patients with newer mechanical prostheses and tissue bioprostheses reaches 10 years to elucidate whether or not these newer valves truly represent improvements and which type of valve substitute proffers the most possible net benefit to the patient.

  View details for Web of Science ID A1984TE45900006

  View details for PubMedID 6748713

• RECOVERY OF PROSTACYCLIN PRODUCTION IN VENOARTERIAL AUTOGRAFTS AND ALLOGRAFTS SURGICAL FORUM Henderson, V. J., Mitchell, R. S., Cohen, R. G., Kosek, J. C., Miller, D. C. 1984; 35: 421-422

  View details for Web of Science ID A1984TW53800177

• INDEPENDENT DETERMINANTS OF OPERATIVE MORTALITY FOR PATIENTS WITH AORTIC DISSECTIONS CIRCULATION Miller, D. C., Mitchell, R. S., Oyer, P. E., Stinson, E. B., Jamieson, S. W., Shumway, N. E. 1984; 70 (3): 153-164

  View details for Web of Science ID A1984TF85700025

• 10 TO 15 YEAR REASSESSMENT OF THE PERFORMANCE-CHARACTERISTICS OF THE STARR-EDWARDS MODEL 6120 MITRAL-VALVE PROSTHESIS JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Miller, D. C., Oyer, P. E., Stinson, E. B., Reitz, B. A., Jamieson, S. W., Baumgartner, W. A., Mitchell, R. S., Shumway, N. E. 1983; 85 (1): 1-20

  View details for Web of Science ID A1983PY87000001

• PROLIFERATIVE VARIABILITY OF ENDOTHELIAL CLONES DERIVED FROM ADULT BOVINE AORTA - INFLUENCE OF FIBROBLAST GROWTH-FACTOR AND SMOOTH-MUSCLE CELL EXTRACELLULAR-MATRIX JOURNAL OF CELLULAR PHYSIOLOGY LONGENECKER, J. P., KILTY, L. A., RIDGE, J. A., MILLER, D. C., JOHNSON, L. K. 1983; 114 (1): 7–15

  Abstract

  Four endothelial cell clones derived from adult bovine aorta were examined with respect to their proliferative characteristics in vitro. Three of these clones, derived in the absence of fibroblast growth factor (FGF), displayed variable basal proliferative rates. One of these non-FGF derived clones grew at a maximal rate which could not be further enhanced with FGF. The other two clones grew at a suboptimal rate which was stimulated by low doses of FGF (10-50 ng/ml) and inhibited by higher doses (100-250 ng/ml). The fourth clone, derived in the presence of FGF, was stimulated by FGF in a dose-dependent manner (10-250 ng/ml) and was not growth inhibited at high FGF concentrations (250-1,000 ng/ml). Growth of all four clones on extracellular matrix (ECM) derived from bovine aortic smooth muscle (BASM) cells was optimal in the absence of FGF. ECM-coated dishes also significantly increased the sensitivity of all clones by at least fivefold to mitogenic stimulation by serum. The proliferative lifespans of the clones ranged between 60 and 120 generations with the most actively proliferating clones attaining the greatest lifespan. Continuous subculture of two of the endothelial clones in the presence of FGF or on ECM-coated dishes did not induce a dependence of the cells on either factor for subsequent growth in its absence. The results indicate that aortic endothelial cells display considerable clonal variability in ther basal proliferative rate and in their response to FGF. This clonal variability is not observed when the cells are maintained on ECM-coated dishes derived from vascular smooth muscle cells.

  View details for Web of Science ID A1983PZ45300002

  View details for PubMedID 6219118

• SIMPLE ADJUNCTS WHICH MAINTAIN SEPTAL TEMPERATURE BELOW 20-DEGREES-C DURING ISCHEMIC ARREST FOR CORONARY-ARTERY BYPASS-GRAFTING AMERICAN HEART JOURNAL Baumgartner, W. A., Miller, D. C., Stinson, E. B., Reitz, B. A., Oyer, P. E., Jamieson, S. W. 1983; 105 (3): 440-444

  View details for Web of Science ID A1983QF05800013

  View details for PubMedID 6338684

• SURGICAL-TREATMENT OF PROSTHETIC VALVE ENDOCARDITIS ANNALS OF THORACIC SURGERY Baumgartner, W. A., Miller, D. C., Reitz, B. A., Oyer, P. E., Jamieson, S. W., Stinson, E. B., Shumway, N. E. 1983; 35 (1): 87-104

  View details for Web of Science ID A1983PX59600012

  View details for PubMedID 6849584

• Ten to fifteen year reassessment of the performance characteristics of the Starr-Edwards Model 6120 mitral valve prosthesis. journal of thoracic and cardiovascular surgery Miller, D. C., Oyer, P. E., Stinson, E. B., Reitz, B. A., Jamieson, S. W., Baumgartner, W. A., Mitchell, R. S., Shumway, N. E. 1983; 85 (1): 1-20

  View details for PubMedID 6848878

• DIGITAL SUBTRACTION ANGIOGRAPHY OF AORTIC DISSECTION AMERICAN JOURNAL OF ROENTGENOLOGY GUTHANER, D. F., Miller, D. C. 1983; 141 (1): 157-161

  Abstract

  Digital subtraction angiography (DSA) was used to study six patients with aortic dissection, five of whom had undergone surgical repair. One patient had both pre- and postoperative evaluations. DSA with intravenous contrast administration is a relatively noninvasive procedure that provides diagnostic images in projection format allowing assessment of the extent of aortic dissection and involvement of important aortic branches. Postacquisition reprocessing techniques unique to DSA optimize the imaging information regarding flow dynamics of the true and false channels.

  View details for Web of Science ID A1983QV95400032

  View details for PubMedID 6344601

• VENO-VENOUS ALLOGRAFTS - PATENCY, SUBENDOTHELIAL PROLIFERATION, AND THE ROLE OF PLATELET-ACTIVE AGENTS JOURNAL OF SURGICAL RESEARCH Gaudiani, V. A., MILLER, D. G., Kosek, J. C., Burg, J., Jamieson, S. W. 1983; 34 (3): 263-270

  Abstract

  Patency and histology of 81 vein allografts and 10 autografts in the canine femoral venous system were compared and the effect of platelet active agents in altering patency rates and subendothelial proliferation in allografts was examined. It was found that allografts thrombose at a predictable interval after operation (18 +/- 7 days) and have significantly worse survival than autografts (P less than 0.001). Platelet-active agents did not alter allograft patency rate of the incidence of subendothelial proliferation in this model.

  View details for Web of Science ID A1983QJ47400010

  View details for PubMedID 6834811

• ANEURYSM OF THE DIVERTICULUM OF THE DUCTUS-ARTERIOSUS IN THE ADULT - SUCCESSFUL SURGICAL-TREATMENT IN 5 PATIENTS AND REVIEW OF THE LITERATURE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Mitchell, R. S., Seifert, F. C., Miller, D. C., Jamieson, S. W., Shumway, N. E. 1983; 86 (3): 400-408

  Abstract

  Sixteen aneurysms of the diverticulum of the ductus arteriosus in adults have been previously reported. Ten patients died of rupture of the aneurysm or died at surgical exploration. Only one previous patient underwent successful aneurysmectomy. Five new cases of aneurysm of the adult ductal diverticulum, all diagnosed preoperatively and successfully repaired, are presented. All five patients are alive 6 to 33 months postoperatively. Our experience with these patients suggests several important features of these aneurysms: (1) Diagnosis may be difficult and may require multiple-view aortography or computed tomographic (CT) scanning to differentiate from tumor. (2) The operative approach, either left thoracotomy or median sternotomy, may be determined by the necessity for concomitant procedures. (3) Unlike true atherosclerotic aneurysms of the aortic arch, these aneurysms can be repaired effectively by aneurysmorrhaphy. (4) Because of their critical location and the high incidence of complications in reported cases, aneurysms greater than 3 cm in diameter, those producing symptoms, or those showing progressive enlargement should be surgically resected.

  View details for Web of Science ID A1983RG46200010

  View details for PubMedID 6604198

• PULMONARY-ARTERY SURGICAL ANEURYSMORRHAPHY - WHERE DO WE GO FROM HERE AMERICAN HEART JOURNAL FINCH, E. L., Mitchell, R. S., GUTHANER, D. F., FOWLES, R. F., Miller, D. C. 1983; 106 (3): 614-618

  View details for Web of Science ID A1983RE66300042

  View details for PubMedID 6881048

• DISCRIMINANT-ANALYSIS OF THE CHANGING RISKS OF CORONARY-ARTERY OPERATIONS - 1971-1979 JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Miller, D. C., Stinson, E. B., Oyer, P. E., Jamieson, S. W., Mitchell, R. S., Reitz, B. A., Baumgartner, W. A., Shumway, N. E. 1983; 85 (2): 197-213

  Abstract

  The risk of perioperative myocardial infarction (PMI) and operative mortality (OM) associated with coronary artery bypass grafting (CABG) has declined since the introduction of this procedure 15 years ago. Rigorous scientific investigation of the reasons for this trend has been hindered by the complex interactions between changing indications for operation, criteria for patient selection, and management methods. Using univariate and multivariate logistic regression analyses, we investigated the effects of 42 variables on PMI and OM for two cohorts undergoing CABG between 1971 and 1975 (Group A) and 1977 and 1979 (Group B). According to previously identified risk factors, Group B patients were at higher potential risk than those in Group A. Nevertheless, the PMI and OM rates declined from 8.7% +/- 0.9% to 4.6% +/- 0.7% (p = 0.005) and from 2.4% +/- 0.5% to 1.2% +/- 0.4% (p = 0.07), respectively. In calendar year 1979 (N = 438), the PMI and OM rates were 2.8% +/- 0.8% and 0.7% +/- 0.4%. More importantly, the independent determinants of PMI and OM for the two time intervals were distinctly different. Factors which affected the PMI rate in Group A were no longer determinants of PMI in Group B; with the exception of emergency operation and, to a modest extent, congestive heart failure (CHF), predictors of OM in Group A were not determinants of OM in Group B. Thus the adverse impact of multiple patient-related and disease-related determinants of PMI and OM has been neutralized over this decade by the real improvements in patient management. The specific factors and management concepts responsible for these superior results in sicker patients remain uncharacterized; however, in general terms, more sophisticated medical, anesthetic, and nursing management and more refined surgical expertise have essentially nullified the concept of high-risk candidates. Furthermore, the more propitious early results being attained currently may translate directly into parallel long-term improvements in functional benefit and survival.

  View details for Web of Science ID A1983QC22500005

  View details for PubMedID 6600507

• INDEPENDENT DETERMINANTS OF OPERATIVE MORTALITY FOR PATIENTS WITH AORTIC DISSECTIONS Miller, D. C., Oyer, P. E., Mitchell, R. S., Stinson, E. B., Jamieson, S. W., Shumway, N. E. AMER HEART ASSOC. 1983: 15–15

  View details for Web of Science ID A1983RJ59300069

• The durability of porcine xenograft valves and conduits in children. Circulation Miller, D. C., Stinson, E. B., Oyer, P. E., Billingham, M. E., Pitlick, P. T., Reitz, B. A., Jamieson, S. W., Baumgartner, W. A., Shumway, N. E. 1982; 66 (2): I172-85

  Abstract

  One hundred four patients younger than 20 years of age underwent intracardiac xenograft valve replacement (n = 41) or extracardiac conduit implantation (n = 63). Long-term follow-up averaged 4.5 and 4.3 years, respectively, and cumulative follow-up totaled 344 patient-years (pt-yr). Thirty patients were followed more than 5 years. Functional results and survival were satisfactory, but valve failure and conduit failure prompted 23 reoperations at linearized rates of 10.1 +/- 2.6% and 4.1 +/- 1.5%/pt-yr, respectively. The rate of valve failure due to leaflet fibrocalcification (primary tissue failure [PTF] was 8.1 +/- 2.4%/pt-yr. Among patients who underwent valve replacement, 52 +/- 13% were free of reoperation at 5 years (59 +/- 13% for PTF only), as were 80 +/- 9% of patients who received an extracardiac conduit. There were no deaths associated with the 22 late reoperations or with the 21 reoperations for PTF. Valve failure was due to PTF in 80% of cases; conversely, isolated valvular PTF was the cause of conduit failure in only one of eight patients. The most common cause of conduit failure was exuberant pseudointimal proliferation in the proximal conduit, which was seen in six of eight patients (75%) with or without other sites of obstruction and responsible for nine of the 15 obstructions (60%). These results underscore the palliative nature of these procedures, militate against indiscriminant use of conduits, prompt consideration of alternative nonconduit techniques where possible, and reemphasize the clinical need for superior valve substitutes and biomaterials for use in the pediatric age group.

  View details for PubMedID 7083540

• Diagnosis of arterial prosthetic graft infection by indium-111 oxine white blood cell scans. Circulation Mckeown, P. P., Miller, D. C., Jamieson, S. W., Mitchell, R. S., Reitz, B. A., Olcott, C., MEHIGAN, J. T., SILBERSTEIN, R. J., McDougall, I. R. 1982; 66 (2): I130-4

  Abstract

  Early and accurate diagnosis of infected prosthetic arterial grafts is difficult, despite the application of diverse diagnostic modalities. Delay in making the diagnosis is largely responsible for the high amputation and mortality rates associated with this complication. In nine patients with suspected graft infections, indium-111 white blood cell scanning was useful and accurate. Graft infection was proved in five cases and ruled out in three. One false-positive scan was due to a sigmoid diverticular abscess overlying the graft. Indium-111 white blood cell scans may improve the accuracy of diagnosing infected prosthetic grafts, which may result in better limb and patient salvage rates.

  View details for PubMedID 7083531

• DIAGNOSIS OF ARTERIAL PROSTHETIC GRAFT INFECTION BY IN-111 OXINE WHITE BLOOD-CELL SCANS CIRCULATION Mckeown, P. P., Miller, D. C., Jamieson, S. W., Mitchell, R. S., Reitz, B. A., Olcott, C., MEHIGAN, J. T., SILBERSTEIN, R. J., McDougall, I. R. 1982; 66 (2): 130-134

  View details for Web of Science ID A1982NY67800024

• COLLAGEN-SYNTHESIS AND WOUND REPAIR AFTER MYOCARDIAL INCISION SURGICAL FORUM Gaudiani, V. A., Miller, D. C., Goodson, W. H., Billingham, M. E., Reitz, B. A., Stinson, E. B., Shumway, N. E. 1982; 33: 56-58

  View details for Web of Science ID A1982QD33400027

• TWO-DIMENSIONAL ECHOCARDIOGRAPHIC ANALYSIS OF SEGMENTAL LEFT-VENTRICULAR WALL MOTION BEFORE AND AFTER CORONARY-ARTERY BYPASS-SURGERY CIRCULATION Rubenson, D. S., Tucker, C. R., London, E., Miller, D. C., Stinson, E. B., Popp, R. L. 1982; 66 (5): 1025-1035

  Abstract

  Twenty patients with coronary artery disease were studied with two-dimensional echocardiography the day before saphenous vein bypass graft surgery. Serial studies were obtained 7.4 +/- 2.5 (+/- SD) and 43.4 +/- 13.1 days postoperatively to qualitatively assess the effect of bypass surgery on regional wall motion. Changes in segmental wall motion were assessed semiquantitatively by assigning a segmental wall motion score to each of nine echocardiographically defined segments. Preoperatively, 18% of the segments moved abnormally. The mean overall segmental wall motion score did not change significantly, as shown by comparing the postoperative studies with the preoperative study. However, there was a significant worsening in the septal motion (apical and basal) and a significant improvement in posterior wall motion (apical and basal) after bypass surgery. Anterior and lateral wall motion were not significantly changed. Nonseptal segments that were normal preoperatively usually remained normal; abnormal nonseptal segments usually improved or were unchanged by surgery. The motion of septal segments, however, generally worsened postoperatively whether they were normal or abnormal preoperatively. We conclude that segmental wall motion assessed by two-dimensional echocardiography may improve after revascularization surgery, but the interventricular septum shows impaired motion. This effect of coronary artery bypass on wall motion is better demonstrated relatively late after operation than early in the postoperative course, as has been done in some previous studies.

  View details for Web of Science ID A1982PM98800018

  View details for PubMedID 6982113

• THE DURABILITY OF PORCINE XENOGRAFT VALVES AND CONDUITS IN CHILDREN CIRCULATION Miller, D. C., Stinson, E. B., Oyer, P. E., Billingham, M. E., Pitlick, P. T., Reitz, B. A., Jamieson, S. W., Baumgartner, W. A., Shumway, N. E. 1982; 66 (2): 172-185

  View details for Web of Science ID A1982NY67800034

• Therapeutic efficacy of intraaortic balloon pump counterpulsation. Analysis with concurrent "control" subjects. Circulation DOWNING, T. P., Miller, D. C., Stinson, E. B., Burton, N. A., Oyer, P. E., Reitz, B. A., Jamieson, S. W., Shumway, N. E. 1981; 64 (2): II108-13

  Abstract

  During a 7-year period, intraaortic balloon pumping (IABP) was attempted in 319 cardiac surgical patients. The indications for IABP were stringent and consisted of unsuccessful discontinuation of cardiopulmonary bypass (39%), anticipated failure (40%) to wean from cardiopulmonary bypass, postoperative low cardiac output, or intractable ventricular tachyarrhythmias (15%). IABP support was successfully instituted in 280 patients and was unsuccessful in 39 patients ("controls"). These two groups were comparable except for an older mean age and a higher ejection fraction in controls. Operative mortality rates were 45% and 62% for IABP and control groups, respectively (p = 0.077). This difference was most evident in coronary artery bypass patients, in whom the decision to institute IABP counterpulsation was made intraoperatively before attempted discontinuation of cardiopulmonary bypass. Two years postoperatively the actuarial survival rate was 45 +/- 3% for the IABP group and 23 +/- 9% for the control group (p = 0.006). After exclusion of operative deaths, however, these survival rates were 81 +/- 3% and 60 +/- 20%, respectively (p = NS). The average hospital charge incurred by IABP patients was threefold greater than that of uncomplicated cardiac surgical procedures. We conclude that IABP counterpulsation is therapeutic for some cardiac surgical patients, but its benefits cannot be defined easily. The long-term survival rates for patients with advanced disease requiring IABP support perioperatively are poor and warrant continued development of more effective methods of mechanical circulatory assistance and heart replacement.

  View details for PubMedID 6788404

• WHIPPLES DISEASE PRESENTING AS AORTIC-INSUFFICIENCY NEW ENGLAND JOURNAL OF MEDICINE Bostwick, D. G., Bensch, K. G., Burke, J. S., Billingham, M. E., Miller, D. C., Smith, J. C., Keren, D. F. 1981; 305 (17): 995-998

  View details for Web of Science ID A1981ML04900008

  View details for PubMedID 6168911

• SURGICAL-MANAGEMENT OF ACUTE MECHANICAL DEFECTS SECONDARY TO MYOCARDIAL-INFARCTION AMERICAN JOURNAL OF SURGERY Miller, D. C., Stinson, E. B. 1981; 141 (6): 677-683

  View details for Web of Science ID A1981LU29500011

  View details for PubMedID 7246858

• SURGICAL-TREATMENT OF ISCHEMIC CARDIOMYOPATHY - IS IT EVER TOO LATE AMERICAN JOURNAL OF SURGERY Miller, D. C., Stinson, E. B., Alderman, E. L. 1981; 141 (6): 688-693

  View details for Web of Science ID A1981LU29500013

  View details for PubMedID 7018278

• LONG-TERM CLINICAL-ASSESSMENT OF THE EFFICACY OF ADJUNCTIVE CORONARY ENDARTERECTOMY JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Miller, D. C., Stinson, E. B., Oyer, P. E., Reitz, B. A., Jamieson, S. W., MORENOCABRAL, R. J., Shumway, N. E. 1981; 81 (1): 21-29

  View details for Web of Science ID A1981KY44100003

  View details for PubMedID 6969824

• POST-INFARCTION VENTRICULAR SEPTAL-DEFECT - AN ARGUMENT FOR EARLY OPERATION SURGERY Gaudiani, V. A., Miller, D. C., Stinson, E. B., Oyer, P. E., Reitz, B. A., MORENOCABRAL, R. J., Shumway, N. E. 1981; 89 (1): 48-55

  Abstract

  We reviewed our experience with 43 consecutive patients who underwent operations for postinfarction ventricular septal defect to determine optimal time for operative intervention, to identify factors responsible for failure of operative treatment, and to determine long-term survival rates. Patients were referred for operation after expectant medical management had failed or after 6 weeks electively. The operative mortality rate was 42% and ranged from 90% for those who required operation within 1 day of 11% for those underwent surgery after 1 month. In a multivariate discriminant analysis of preoperative variables, we found that inferior infarction with perforation (P less than 0.02) and preoperative multisystem failure (evidenced by abnormal mental status, P less than 0.02) were the major factors correlating with high operative risk. Early operation per se did not affect operative mortality rates. Technical problems with early operation were not a source of major morbidity and mortality. Actuarial long-term survival was good, and 88.5% of survivors were alive 5 years after surgery. Because preoperative multisystem failure is often progressive, we recommend immediate operation for all patients with postinfarction ventricular septal defect unless no deterioration is present. Moreover, because of the high risk of those patients with inferior infarction and perforation, we recommended immediate surgery for this group regardless of symptomatic status.

  View details for Web of Science ID A1981KY49800008

  View details for PubMedID 7466611

• INTRAVENOUS AORTOGRAPHY AFTER AORTIC DISSECTION REPAIR AMERICAN JOURNAL OF ROENTGENOLOGY GUTHANER, D. F., Brody, W. R., Miller, D. C. 1981; 137 (5): 1019-1022

  View details for Web of Science ID A1981MN28900025

  View details for PubMedID 7027772

• DIAGNOSIS OF INFECTED PROSTHETIC GRAFTS USING IN-111 WHITE CELL SCANS Miller, D. C., Mckeown, P. P., Jamieson, S. W., Mitchell, R. S., McDougall, I. R. LIPPINCOTT WILLIAMS & WILKINS. 1981: 21–21

  View details for Web of Science ID A1981MJ18900054

• THERAPEUTIC EFFICACY OF INTRA-AORTIC BALLOON PUMP COUNTERPULSATION - ANALYSIS WITH CONCURRENT CONTROL SUBJECTS CIRCULATION DOWNING, T. P., Miller, D. C., Stinson, E. B., Burton, N. A., Oyer, P. E., Reitz, B. A., Jamieson, S. W., Shumway, N. E. 1981; 64 (2): 108-113

  View details for Web of Science ID A1981LZ33700021

• Realistic expectations of surgical treatment of aortic dissections: the Stanford experience. World journal of surgery Miller, D. C., Stinson, E. B., Shumway, N. E. 1980; 4 (5): 571-578

  View details for PubMedID 7233927

• COMPREHENSIVE ASSESSMENT OF THE SAFETY, DURABILITY, CLINICAL-PERFORMANCE, AND HEALING CHARACTERISTICS OF A DOUBLE VELOUR KNITTED DACRON ARTERIAL PROSTHESIS VASCULAR SURGERY Mitchell, R. S., Miller, D. C., Billingham, M. E., MEHIGAN, J. T., Olcott, C., Stinson, E. B. 1980; 14 (3): 197-212

  View details for Web of Science ID A1980KE87600007

• SURGICAL APPROACH FOR S,L,L SINGLE VENTRICLE INCORPORATING TOTAL RIGHT ATRIUM-PULMONARY ARTERY DIVERSION JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY MORENOCABRAL, R. J., Miller, D. C., Oyer, P. E., Stinson, E. B., Reitz, B. A., Shumway, N. E. 1980; 79 (2): 202-210

  Abstract

  Patients with single ventricle and unfavorable anatomy for partitioning procedures have been considered inoperable. Such was the case in two patients with single ventricle and subaortic inverted (hypoplastic) infundibulum associated with subaortic obstruction and levo-transposition of the great vessels (S,L,L). Both had undergone pulmonary artery banding in infancy and presented 11 and 14 years later, cyanotic and severely incapacitated. Both patients were treated surgically by resection of the subaortic obstruction, patch closure of the right artrioventricular valve, closure of the proximal pulmonary artery, and diversion of systemic venous flow through a xenograft valved conduit from the right atrium to the distal pulmonary artery. Early postoperative complications included atrial dysrhythmias and right-sided congestion. The first patient, who had massive cardiomegaly and complete heart block preoperatively, developed congestive failure 20 months postoperatively. The second patient has an excellent functional result and is leading a normal life 1 years after operation. This procedure may be of value for patients with single ventricle in whom corrective ventricular septation is considered too risky or technically unfeasible.

  View details for Web of Science ID A1980JE62300008

  View details for PubMedID 7188708

• CLINICAL DURABILITY OF THE HANCOCK PORCINE BIOPROSTHETIC VALVE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Oyer, P. E., Miller, D. C., Stinson, E. B., Reitz, B. A., MORENOCABRAL, R. J., Shumway, N. E. 1980; 80 (6): 824-833

  Abstract

  The principal feature of the Hancock xenograft bioprosthesis which remains to be completely defined is long-term durability. This report provides extended data regarding valve durability derived from a data base of 1,407 patients (707 aortic [AVR] and 700 mitral [MVR] replacements) who received Hancock bioprostheses between 1971 and 1979; cumulative duration of follow-up was 1,732 patient-years for AVR and 1,843 for MVR patients, with a maximum follow-up duration of 8.4 years. One hundred seventy-nine patients were followed for more than 5 years and 67 for more than 6 years. Valve failure was defined on the basis of one or more of the following criteria: (1) postoperative development of a new regurgitant murmur, (2) thrombotic valvular occlusion, (3) infective endocarditis resulting in reoperation or death, and (4) hemodynamic valvular dysfunction confirmed by catheterization and resulting in reoperation or death. Twenty-one such failures occurred among all AVR patients and 23 among all MVR patients. The actuarial probability of freedom from valve failure (all causes) was 95.4% +/- 1.2% (+/- SEM) for adult AVR patients 5 years postoperatively and 90.9% +/- 2.6% for adult MVR patients 6 years postoperatively. The probability of freedom from primary tissue failure in adults was 99% +/- 1% in AVR patients at 5 years and 94.3% +/- 2.4% in MVR patients at 6 years. The linearized incidence of primary tissue failure in children (< 15 years old) was 9.8% per patient-year (combined AVR and MVR patients), compared to 0.2% per patient-year among all adult patients in the analysis. The combined actuarial incidence of primary tissue failure among adults with AVR and MVR was 98.6% +/- 0.7% at 5 years and 94.2% +/- 2.3% at 6 years; thus there appears to be a slight acceleration in the rate of valve tissue failure between 5 and 6 years after operation. The incidence of failure, however, remains acceptably low through 6 years of follow-up, and continued clinical use of the xenograft bioprosthesis seems warranted.

  View details for Web of Science ID A1980KT96500002

  View details for PubMedID 7431981

• POSTOPERATIVE ENHANCEMENT OF LEFT-VENTRICULAR PERFORMANCE BY COMBINED INOTROPIC-VASODILATOR THERAPY WITH PRELOAD CONTROL SURGERY Miller, D. C., Stinson, E. B., Oyer, P. E., Derby, G. C., Reitz, B. A., Shumway, N. E. 1980; 88 (1): 108-117

  View details for Web of Science ID A1980JZ48400014

  View details for PubMedID 7385014

• CONCOMITANT RESECTION OF ASCENDING AORTIC-ANEURYSM AND REPLACEMENT OF THE AORTIC-VALVE - OPERATIVE AND LONG-TERM RESULTS WITH CONVENTIONAL TECHNIQUES IN 90 PATIENTS JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Miller, D. C., Stinson, E. B., Oyer, P. E., MORENOCABRAL, R. J., Reitz, B. A., Rossiter, S. J., Shumway, N. E. 1980; 79 (3): 388-401

  Abstract

  We reviewed a consecutive series of 90 patients undergoing concomitant resection of ascending aortic anerysm and aortic valve replacement (AVR) utilizing noncomposite "conventional" techniques in order to assess the early and late results, to define limitations of this operative approach, and thereby to clarify the indications for composite reconstruction of the aortic root. Mean age was 55 years. Twenty percent had Marfan's syndrome, and 13% had aortic dissections. The cause of the aneurysm was dissection in 13% of cases, syphilis in 11%, atherosclerosis in 9%, and degeneration (with or without cystic medionecrosis) in 67%. Follow-up averaged 3.8 years and extended to 11.5 years maximum. AVR and complete excision of the aneurysm (preserving small tongues of aortic wall circumscribing the coronary artery ostia) coupled with tubular graft replacement of the ascending aorta were performed. Nineteen percent of patients required individual technical modifications relating to the coronary arteries. Operative mortality rate was 13%, with the majority of deaths being due to cardiac causes. Contemporary (1975 to 1978) operative mortality rate was 4.3%. Seven percent required re-exploration for hemorrhage and 2.4% had perioperative myocardial infarctions. Late functional results were generally good (average N.Y.H.A. Class 1.4). Late thromboembolism, angina, myocardial infarction, and congestive heart failure occurred at linearized rates of 3.4% per patient-year, 4.9% per patient-year, 1.1% per patient-year, and 5.2% per patient-year, respectively. No prosthetic valve endocarditis, graft infection, or recurrent aneurysms of the aortic root were observed. Late reoperation was necessary in eight patients (3% per patient-year), but reoperation for disease confined to the ascending aorta accounted for only three of these cases (1.1% per patient-year). Overall actuarial survival rates were 67% +/- 5% at 5 years and 50% +/- 9% at 10 years; survival rates for the 78 operative survivors were 77% +/- 5% and 57% +/- 10% at the same time intervals, respectively. Only one late death could be attributed to complications arising in the reconstructed aortic root. These results confirm that such simple, noncomposite techniques are safe, portend minimal risk of late complications and the attendant necessity for reoperation, and provide satisfactory long-term survival. We believe that composite techniques should be primarily reserved for selected cases of advanced necrotizing prosthetic or natural endocarditis.

  View details for Web of Science ID A1980JJ18300009

  View details for PubMedID 6986512

• CAROTID BACK PRESSURES IN CONJUNCTION WITH CEREBRAL-ANGIOGRAPHY RADIOLOGY Enzmann, D. R., Miller, D. C., Olcott, C., MEHIGAN, J. T. 1980; 134 (2): 415-419

  Abstract

  A method for obtaining carotid back pressures at the time of cerebral angiography is described. These preoperative measurements were compared to intraoperative measurements in 18 patients. Preoperative mean carotid back pressures (usually common carotid pressures) were obtained by occluding the artery with a double-lumen balloon catheter and recording the pressure distal to the balloon. Although the mean arterial blood pressure and the arterial carbon dioxide tension proved to be variables, the correlation of the pressures measured at angiography and at surgery was high (p less than 0.001).

  View details for Web of Science ID A1980JD98200026

  View details for PubMedID 7352221

• RETROSPECTIVE COMPARISON OF MEDICAL VS SURGICAL-TREATMENT OF CORONARY-DISEASE IN PATIENTS WITH SEVERE LV DYSFUNCTION Alderman, E. L., Mace, J., Miller, D. C., Kusnick, C., Sanders, G., Schwarzkopf, A., Stinson, E. B. LIPPINCOTT WILLIAMS & WILKINS. 1980: 94–94

  View details for Web of Science ID A1980KK12300353

• HEMODYNAMIC AND CLINICAL COMPARISON OF THE HANCOCK MODIFIED ORIFICE AND STANDARD ORIFICE BIOPROSTHESES IN THE AORTIC POSITION JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Rossiter, S. J., Miller, D. C., Stinson, E. B., Oyer, P. E., Reitz, B. A., MORENOCABRAL, R. J., MACE, J. G., ROBERT, E. W., TSAGARIS, T. J., Sutton, R. B., Alderman, E. L., Shumway, N. E. 1980; 80 (1): 54-60

  Abstract

  Bioprosthetic aortic valve replacement in patients with a small aortic root has been associated with postoperative transvalvular gradients. A modified orifice Hancock xenograft bioprosthesis has been developed and is purported to increase significantly the effective orifice area (as evaluated by in vitro testing) compared to the standard orifice Hancock bioprosthesis. To assess the in vivo differences, we compared 481 patients with standard orifice prostheses with 156 patients with modified orifice prostheses. Postoperative catheterization was performed in 24 patients with modified orifice (valve diameters 19 to 25 mm) with 14 with standard orifice valves (valve diameters 21 to 25 mm). Actuarial rates of survival, valve failure, endocarditis, and thromboembolism did not differ significantly between the two subgroups. Peak aortic valve gradients on the whole were less in the modified orifice subgroup than in the standard origice subgroup (12 +/- 1 torr versus 20 +/- 6 torr [mean +/- SEM]), but the difference was not statistically significant (p greather than 0.05). The calculated in vivo aortic valve areas were slightly, but insignificantly, greater in the modified orifice subgroup than in the standard orifice subgroup (p greater than 0.05). These in vivo data partially corroborate the in vitro findings of increased effective orifice area and internal-to-external diameter ratio for the modified orifice bioprosthesis. The hemodynamic differences between the two valve types are small, however, and the putative clinical advantages inherent in the use of the modified orifice bioprosthesis remain to be completely defined.

  View details for Web of Science ID A1980JZ53400012

  View details for PubMedID 7382536

• PULMONARY-ARTERY BALLOON COUNTERPULSATION FOR ACUTE RIGHT VENTRICULAR FAILURE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Miller, D. C., MORENOCABRAL, R. J., Stinson, E. B., SHINN, J. A., Shumway, N. E. 1980; 80 (5): 760-763

  Abstract

  The development and availability of right ventricular assist devices has not kept pace with the evolution of devices designed to mechanically support the systemic circulation. This report describes the application of the counterpulsation concept to the pulmonary circuit to unload the failing right ventricle and augment pulmonary blood flow. Conventional, widely available balloon pumping equipment was employed. Use of this double balloon pump system enabled a patient to be weaned from cardiopulmonary bypass after all other measures had failed. Other relevant potential clinical applications for this technique are discussed.

  View details for Web of Science ID A1980KQ47900016

  View details for PubMedID 7431972

• Operative treatment of aortic dissections. Experience with 125 patients over a sixteen-year period. journal of thoracic and cardiovascular surgery Miller, D. C., Stinson, E. B., Oyer, P. E., Rossiter, S. J., Reitz, B. A., Griepp, R. B., Shumway, N. E. 1979; 78 (3): 365-382

  Abstract

  An unselected, consecutive cohort of 125 patients underwent operative repair of acute and chronic aortic dissections with tubular graft interposition over a 16 year span. The absence of remote geographical referral biases and the unselected nature of this series provided a patient population that was representative of the disease process (as assessed heretofore only from autopsy series). Furthermore, this enabled high-risk subsets to be defined by retrospective analysis. Patients were classified according to whether the ascending aorta was involved (type A with involvement, type B without), irrespective of the site of intimal tear, and according to age of the dissection: Fifty-three patients had acute type A (Ac-A), 29 had chronic type A (Ch-A), 20 had acute type B (Ac-B), and 23 had chronic type B (Ch-B) dissections. Fourteen percent (17/125) of the dissections had ruptured. Concomitant aortic valve replacement (AVR) was performed in 11% (6/53) for Ac-A cases and 38% (11/29) of the Ch-A cases. A total of 391 patient-years of follow-up was analyzed; follow-up averaged 4.5 years and extended to 13.7 years. Over-all operative mortality rate was 34% (18/53) for Ac-A, 14% (4/29) for Ch-A, 45% (9/20) for Ac-B, and 22% (5/23) for Ch-B; during the most recent 5 year interval these figures were lower: 27%, 8%, 20%, and 20%, respectively, N = 50. Multiple preoperative variables were found to correlate significantly with both operative death and long-term survival. Operative survivors generally experienced satisfactory functional benefit. Late attrition averaged 8% per year; 61% of all late deaths were related to cardiac or cerebral causes. Over-all actuarial survival (+/- SEM) for the entire cohort was 54% +/- 5% at 5 years and 26% +/- 7% at 10 years; for the 89 patients surviving operation, these figures were 76% +/- 5% and 37% +/- 10%, respectively. No significant differences in long-term survival were evident between the different subgroups. Whether the primary intimal tear had been resected or concomitant AVR had been performed had no statistically significant bearing on operative mortality, functional result, necessity for late reoperation, or late attrition. The long-term "natural" history of surgically treated patients with aortic dissections, as defined in this study, should facilitate comparison with other treatment modalities. Results of the present analysis support immediate operative intervention for patients with Ac-A dissections and probably for those with Ac-B dissections. Additionally, surgical treatment of patients with symptomatic or enlarging Ch-A and Ch-B dissections provides satisfactory rehabilitation and long-term survival. Finally, we re-emphasize our recommendation for simplified classification of aortic dissections, based solely upon the presence or absence of ascending aortic involvement. Pathophysiology and expected biologic behavior pivot on this feature, and appropriate clinical strategy can thereby be defined.

  View details for PubMedID 470417

• OPERATIVE TREATMENT OF AORTIC DISSECTIONS - EXPERIENCE WITH 125 PATIENTS OVER A 16-YEAR PERIOD JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Miller, D. C., Stinson, E. B., Oyer, P. E., Rossiter, S. J., Reitz, B. A., Griepp, R. B., Shumway, N. E., WHEAT, M. W., Cohn, L. H. 1979; 78 (3): 365-382

  Abstract

  An unselected, consecutive cohort of 125 patients underwent operative repair of acute and chronic aortic dissections with tubular graft interposition over a 16 year span. The absence of remote geographical referral biases and the unselected nature of this series provided a patient population that was representative of the disease process (as assessed heretofore only from autopsy series). Furthermore, this enabled high-risk subsets to be defined by retrospective analysis. Patients were classified according to whether the ascending aorta was involved (type A with involvement, type B without), irrespective of the site of intimal tear, and according to age of the dissection: Fifty-three patients had acute type A (Ac-A), 29 had chronic type A (Ch-A), 20 had acute type B (Ac-B), and 23 had chronic type B (Ch-B) dissections. Fourteen percent (17/125) of the dissections had ruptured. Concomitant aortic valve replacement (AVR) was performed in 11% (6/53) for Ac-A cases and 38% (11/29) of the Ch-A cases. A total of 391 patient-years of follow-up was analyzed; follow-up averaged 4.5 years and extended to 13.7 years. Over-all operative mortality rate was 34% (18/53) for Ac-A, 14% (4/29) for Ch-A, 45% (9/20) for Ac-B, and 22% (5/23) for Ch-B; during the most recent 5 year interval these figures were lower: 27%, 8%, 20%, and 20%, respectively, N = 50. Multiple preoperative variables were found to correlate significantly with both operative death and long-term survival. Operative survivors generally experienced satisfactory functional benefit. Late attrition averaged 8% per year; 61% of all late deaths were related to cardiac or cerebral causes. Over-all actuarial survival (+/- SEM) for the entire cohort was 54% +/- 5% at 5 years and 26% +/- 7% at 10 years; for the 89 patients surviving operation, these figures were 76% +/- 5% and 37% +/- 10%, respectively. No significant differences in long-term survival were evident between the different subgroups. Whether the primary intimal tear had been resected or concomitant AVR had been performed had no statistically significant bearing on operative mortality, functional result, necessity for late reoperation, or late attrition. The long-term "natural" history of surgically treated patients with aortic dissections, as defined in this study, should facilitate comparison with other treatment modalities. Results of the present analysis support immediate operative intervention for patients with Ac-A dissections and probably for those with Ac-B dissections. Additionally, surgical treatment of patients with symptomatic or enlarging Ch-A and Ch-B dissections provides satisfactory rehabilitation and long-term survival. Finally, we re-emphasize our recommendation for simplified classification of aortic dissections, based solely upon the presence or absence of ascending aortic involvement. Pathophysiology and expected biologic behavior pivot on this feature, and appropriate clinical strategy can thereby be defined.

  View details for Web of Science ID A1979HL52600005

• LATE RIGHT HEART RECONSTRUCTION FOLLOWING REPAIR OF TETRALOGY OF FALLOT ANNALS OF THORACIC SURGERY Miller, D. C., Rossiter, S. J., Stinson, E. B., Oyer, P. E., Reitz, B. A., Shumway, N. E. 1979; 28 (3): 239-251

  Abstract

  Twenty-two symptomatic patients underwent a total of 28 reoperative procedures after initial surgical repair of tetralogy of Fallot. Sixteen of the patients were considered to have unfavorable anatomy of the right ventricular outflow tract (RVOT) or pulmonary artery at the time of initial repair. Pulmonary or tricuspid valve replacement, or replacement of both valves, utilizing a xenograft bioprosthesis was performed in 1 of the 22 initial repairs, 7 of the 22 first reoperations, and 5 of the 6 second reoperations. Ultimately, 14 patients received transannular RVOT patches. The interval between the first and second reoperations for 6 patients who required 2 late reconstructive procedures was 5.8 years. No operative deaths occurred. There were 2 late deaths (1 sudden and 1 due to aspiration). Actuarial survival probability (+/- standard error of the mean) 16 years after initial repair was 72 +/- 21%. Eighteen of the 20 current survivors in the present series are completely asymptomatic without physical restrictions; the other 2 are considered to be in New York Heart Association Functional Class II. No xenograft bioprosthetic dysfunction has occurred to date, but cumulative valve follow-up is limited (13 patient-years). In selected patients, earlier pulmonary or tricuspid valve replacement or replacement of both of these valves can provide some degree of protection against recurrent deterioration.

  View details for Web of Science ID A1979HK73000008

  View details for PubMedID 485625

• HEPATITIS RISK IN CARDIAC-SURGERY PATIENTS RECEIVING FACTOR-IX CONCENTRATES JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Rossiter, S. J., Miller, D. C., Raney, A. A., Oyer, P. E., Reitz, B. A., Stinson, E. B., Shumway, N. E. 1979; 78 (2): 203-207

  Abstract

  Experience with the clinical use and hepatitis risks of factor IX concentrate (Proplex) in cardiac surgical patients is presented in this report. Seventy-five patients received the concentrate for severe intraoperative or postoperative hemorrhage and 75 patients constituted matched controls. The incidence of probable type B viral hepatitis in patients receiving factor IX concentrate was 13.8 percent (four of 29) versus zero percent (zero of 29) in control patients (difference not significant). However, there was a greater incidence (p less than 0.05) of anti-HBs in patients receiving factor IX concentrate as compared to control subjects. No hepatitis-associated deaths or major morbidity were noted in these patients. It is confirmed that factor IX concentrate carries an associated significant risk of hepatitis. However, its use is justified in certain severe, acquired coagulopathies in which conventional platelet and fresh-frozen plasma therapy is inadequate.

  View details for Web of Science ID A1979HG27100008

  View details for PubMedID 459527

• AORTIC AND MITRAL PROSTHETIC VALVE REOPERATIONS - EARLY AND LATE RESULTS ARCHIVES OF SURGERY Rossiter, S. J., Miller, D. C., Stinson, E. B., Oyer, P. E., Reitz, B. A., Shumway, N. E. 1979; 114 (11): 1279-1283

  Abstract

  A total of 232 valvular reoperations (123 mitral valve reoperations [RMVR] and 109 aortic valve reoperations [RAVR] were performed in 194 patients with previously implanted prosthetic valves. Early mortality was 10% (12/123) for the RMVR subgroup and 14% (15/109) for the RAVR subgroup (P = NS). Late mortality was 16% (18/111) for the RMVR subgroup and 25% (23/94) for the RAVR subgroup (P = NS). Patients with prosthetic endocarditis or prosthetic stenosis constituted higher-risk subpopulations. Principal determinants of both operative mortality and late attrition were preoperative cardiac functional status and the nature of the pathology mandating valve replacement. Early prosthetic valve replacement is advocated to correct hemodynamic abnormalities before advanced ventricular decompensation ensues, especially when prosthetic valvular endocarditis or prosthetic stenosis exists.

  View details for Web of Science ID A1979HS43800008

  View details for PubMedID 496629

• SURGICAL IMPLICATIONS AND RESULTS OF COMBINED AORTIC-VALVE REPLACEMENT AND MYOCARDIAL REVASCULARIZATION AMERICAN JOURNAL OF CARDIOLOGY Miller, D. C., Stinson, E. B., Oyer, P. E., Rossiter, S. J., Reitz, B. A., Shumway, N. E. 1979; 43 (3): 494-501

  View details for Web of Science ID A1979GL34000005

  View details for PubMedID 420100

• LONG-TERM EVALUATION OF THE PORCINE XENOGRAFT BIOPROSTHESIS JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Oyer, P. E., Stinson, E. B., Reitz, B. A., Miller, D. C., Rossiter, S. J., Shumway, N. E. 1979; 78 (3): 343-350

  View details for Web of Science ID A1979HL52600003

  View details for PubMedID 470415

• A modern view of the surgical treatment of peripheral arterial disease. JAMA : the journal of the American Medical Association Miller, D. C., Griepp, R. B. 1978; 240 (14): 1542-1547

  Abstract

  As life expectancy increases, more patients will harbor atherosclerotic conditions that portend disability and death. Due basically to a communication gap, sizable numbers of these patients who stand to benefit from vascular reconstruction are not being referred or are being referred too late to vascular surgeons. Vascular surgery currently can save limbs, extend productivity and life expectancy, ameliorate hypertension, and prevent stroke more reliably and with less risk than ever before. As the subspeciality of vascular surgery has matured, has incorporated additional fellowship training, and now approaches potential recognition in some yet to be determined form by The American Board of Surgery, it is incumbent on general physicians and vascular surgeons alike to develop appropriate channels that can transmit clinical concepts, educational information, and clinical results, as well as refer patients.

  View details for PubMedID 682363

• IMPACT OF SIMULTANEOUS MYOCARDIAL REVASCULARIZATION ON OPERATIVE RISK, FUNCTIONAL RESULT, AND SURVIVAL FOLLOWING MITRAL-VALVE REPLACEMENT SURGERY Miller, D. C., Stinson, E. B., Rossiter, S. J., Oyer, P. E., Reitz, B. A., Shumway, N. E. 1978; 84 (6): 848-857

  Abstract

  A cohort of 282 patients who underwent mitral valve replacement with a xenograft bioprosthesis was strictly segregated according to etiology of mitral dysfunction and analyzed regarding the impact of arteriographic coronary artery disease (CAD) and concomitant coronary artery bypass grafting (CABG) on operative risk, functional result, and survival. CAD was present in 21% of the 122 patients with predominant mitral stenosis (MS) and 59% of the 155 patients with mitral regurgitation (MR); moreover, discordance between the presence of angina and anatomic CAD was found in 27% (33 of 122) of the MS subgroup and 36% (56 of 155) of the MR subgroup. Etiology of the valvular dysfunction was rheumatic in 148 patients, myxomatous degeneration in 83, and ischemic in 32. Within these subgroups, 41 patients (27%), 40 patients (48%), and 32 patients (100%), respectively, had CAD. Of those patients with CAD, 85% of the rheumatic subgroup, 90% of the degenerative subgroup, and 81% of the ischemic subgroup underwent concomitant CABG at the time of valve replacement. Within each subgroup no statistically significant (P greater than 0.05) differences in operative mortality rate, perioperative myocardial infarction rate, incidence of late angina or late infarction, or late actuarial survival were evident when compared on the basis of CAD, and/or CABG, with one exception. The exception was the 10% incidence of perioperative myocardial infarction in the rheumatic subgrohp with coronary disease versus 2% in the rheumatic subgroup without coronary disease (P = 0.05). Within the time constraints of this study (mean follow-up = 2.3 years; maximum follow-up = 5.9 years), these results support simultaneous MVR and CABG when hemodynamically appreciable CAD is found. Moreover, the overall 43% incidence of arteriographic CAD warrants routine coronary angiography in most adults undergoing preoperative catheterization for mitral valvular disease.

  View details for Web of Science ID A1978FY91700014

  View details for PubMedID 568831

• RECURRENT MEDIASTINAL BRONCHOGENIC CYST - CAUSE OF BRONCHIAL OBSTRUCTION AND COMPRESSION OF SUPERIOR VENA-CAVA AND PULMONARY-ARTERY CHEST MILLER, D. C., WALTER, J. P., GUTHANER, D. F., MARK, J. B. 1978; 74 (2): 218–20

  Abstract

  The recurrence of a benign mediastinal bronchogenic cyst 20 years after partial excision precipitated potentially serious vascular and pulmonary complications. Aggressive total surgical excision should be feasible in the majority of cases. An approach via a median sternotomy offers distinct advantages in certain cases and should be considered. Computerized axial tomographic scanning promises to provide improved definition of mediastinal anatomic features and should be a valuable noninvasive diagnostic method in selected cases.

  View details for DOI 10.1378/chest.74.2.218

  View details for Web of Science ID A1978FJ94600025

  View details for PubMedID 679757

• MODERN VIEW OF SURGICAL TREATMENT OF PERIPHERAL ARTERIAL-DISEASE JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Miller, D. C., Griepp, R. B. 1978; 240 (14): 1524-1527

  View details for Web of Science ID A1978FQ17200026

• LEFT VENTRICULAR CORONARY SINUS FISTULA FOLLOWING REPEATED MITRAL-VALVE REPLACEMENTS JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Miller, D. C., SCHAPIRA, J. N., Stinson, E. B., Shumway, N. E. 1978; 76 (1): 43-45

  Abstract

  After mitral valve replacement, symptomatic deterioration and new murmurs characterstistic of atrioventricular valvular regurgitation are usually the result of periprosthetic leaks or prosthetic dysfunction with or without endocarditis. In the case which we are reporting, an iatrogenic fistula between the left ventricle and coronary sinus was responsible for the murmur and symptoms. This type of shunt has not been previously reported. Thorough debridement of the anulus is necessary during mitral valve replacement; additionally, previously implanted prostheses are occasionally embedded in the endocardial wall and must be excised. Hematoma in the atrioventricular groove and perforations of the posterior left ventricular wall are widely recognized complications of mitral valve replacement. Similar mechanisms of injury can cause other problems such as left ventricular-right atrial communications and the unique anatomic shunt described in this report.

  View details for Web of Science ID A1978FG72000007

  View details for PubMedID 661365

• LOCALIZED TAMPONADE OF RIGHT ATRIUM AND RIGHT VENTRICLE - INDUCTION OF INTRA-CARDIAC RIGHT-TO-LEFT SHUNTING AFTER USE OF A GOTT SHUNT ARCHIVES OF SURGERY Miller, D. C., Oyer, P. E., RICKS, W., Cipriano, P. R., Shumway, N. E. 1978; 113 (6): 764-766

  Abstract

  After repair of a traumatic tear of the descending aorta, using a Gott shunt between the left ventricle and the distal descending aorta, a patient was readmitted with profound postural cyanosis and dyspnea. Catheterization showed right-to-left shunting at the atrial level caused by extrinsic deformation of the right atrium and right ventricle. Sternotomy showed selective pericardial tamponade on the right side of the heart caused by a localized collection of organizing thrombus and old blood. The previously unsuspected large patent foramen ovale was closed. This complication represents a form of iatrogenic cyanosis tardice and is thought to be attributable to the method of shunting used during the first operation. Moreover, this complication should be easily preventable if the pooled blood and clot in the most dependent portion of the pericardial cavity is adequately evacuated.

  View details for Web of Science ID A1978FB53200021

  View details for PubMedID 655856

• PROSTHETIC VALVE ENDOCARDITIS - COMPARISON OF HETEROGRAFT TISSUE VALVES AND MECHANICAL VALVES JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Rossiter, S. J., Stinson, E. B., Oyer, P. E., Miller, D. C., SCHAPIRA, J. N., Martin, R. P., Shumway, N. E. 1978; 76 (6): 795-803

  View details for Web of Science ID A1978GA20800007

  View details for PubMedID 713586

• Changes in survival and symptom relief in a longitudinal study of patients after bypass surgery. Circulation TECKLENBERG, P. L., Alderman, E. L., Miller, D. C., Shumway, N. E., HARRISON, D. C. 1975; 52 (2): I98-104

  Abstract

  The first 350 patients having coronary surgery at Stanford Medical Center (excluding patients with aneurysmectomy or valve replacement) have been followed sequentially utilizing a computer-based information system. Our experience spans 72 months (900 patient-years), with an average follow-up of 30 months. Hospital mortality was 4.9%. Actuarial analysis revealed survival of 91% at 1 year and 80% at 6 years. Forty patients (11.5%) had 43 late myocardial infarctions, of which 5 were fatal. Analyses of selected patient subgroups revealed significantly poorer survival in patients with prior myocardial infarction (P less than 0.05), significant congestive heart failure, or mitral regurgitation (P less than 0.01). Survival in multigrafted (and multivessel) patients was not significantly different from survival in single-grafted (predominantly single-vessel) patients. Actuarial studies suggest improved survival in patients with multivessel disease after coronary artery surgery. Between an initial evaluation at 9 months postoperatively (range: 2 to 40 months) and the most recent evaluation after 30 months (range: 6 to 72 months), 13% of patients showed further clinical improvement, 47% were unchanged, while 40% deteriorated with respect to chest pain. We conclude that initial symptomatic benefits may not be maintained in late follow-up studies owing to progression of underlying vascular disease.

  View details for PubMedID 1080447

• CHANGES IN SURVIVAL AND SYMPTOM RELIEF IN A LONGITUDINAL STUDY OF PATIENTS AFTER BYPASS SURGERY CIRCULATION TECKLENBERG, P. L., Alderman, E. L., Miller, D. C., Shumway, N. E., HARRISON, D. C. 1975; 52 (2): 98-104

  View details for Web of Science ID A1975AM55300015

• LONG-TERM FOLLOW-UP OF PATIENTS UNDERGOING SAPHENOUS-VEIN BYPASS SURGERY CIRCULATION Cannom, D. S., Miller, D. C., Shumway, N. E., Fogarty, T. J., Daily, P. O., Hu, M., Brown, B., HARRISON, D. C. 1974; 49 (1): 77-85

  View details for Web of Science ID A1974R794700012

  View details for PubMedID 4543527

• SURGICAL TREATMENT OF REFRACTORY LIFE-THREATENING VENTRICULAR TACHYCARDIA AMERICAN JOURNAL OF CARDIOLOGY Graham, A. F., Miller, D. C., Stinson, E. B., Daily, P. O., Fogarty, T. J., HARRISON, D. C. 1973; 32 (7): 909-912

  View details for Web of Science ID A1973R494400004

  View details for PubMedID 4543267