Joseph Woo, MD, FACS, FACC, FAHA

All Publications

• A 3D-Printed Externally Adjustable Symmetrically Extensible (EASE) Aortic Annuloplasty Ring for Root Repair and Aortic Valve Regurgitation. Cardiovascular engineering and technology Zhu, Y., Park, M. H., Wilkerson, R. J., Joo, H. C., Pandya, P. K., Woo, Y. J. 2024

  Abstract

  The valve-sparing aortic root replacement (VSARR) procedure was developed to preserve the aortic valve apparatus to replace aneurysmal aortic roots with synthetic grafts and to eliminate associated aortic regurgitation (AR). However, residual post-repair AR is not uncommon and has been found to be associated with recurrent AR and future reoperation.We designed and manufactured a 3D-printed, external adjustable symmetrically extensible (EASE) aortic annuloplasty ring that can symmetrically reduce the aortic annulus diameter via a radial constriction, compliant mechanism. An ex vivo porcine VSARR model with annular dilation and AR was developed (n = 4) and used for hemodynamic, echocardiography, and high-speed videography data collection.After ring annuloplasty repair using the EASE aortic ring, the regurgitant fraction decreased from 23.6 ± 6.9% from the VSARR model to 7.4 ± 5.6% (p = 0.05), which was similar to that measured from baseline with a regurgitant fraction of 10.2 ± 3.9% (p = 0.34). The leaflet coaptation height after annuloplasty repair also significantly increased from that measured in VSARR model (0.4 ± 0.1 cm) to 0.9 ± 0.1 cm (p = 0.0004), a level similar to that measured in baseline (1.1 ± 0.1 cm, p = 0.28).Using an ex vivo VSARR model, the EASE ring successfully reduced AR by reducing the annular diameter and improving leaflet coaptation. With its broad applicability and ease of use, this device has the potential to have a significant impact on patients suffering worldwide from AR due to root aneurysms.

  View details for DOI 10.1007/s13239-024-00709-2

  View details for PubMedID 38238600

  View details for PubMedCentralID 6562077

• Discussion to: Contemporary surgical techniques for mitral valve replacement in extensive mitral annular calcification JTCVS TECHNIQUES El-Eshmawi, A., Woo, J. 2023; 22: 13-15

  View details for DOI 10.1016/j.xjtc.2023.10.019

  View details for Web of Science ID 001134251400001

  View details for PubMedID 38152169

  View details for PubMedCentralID PMC10750993

• Neochords: How long, how many, too many? JTCVS techniques Elde, S., Woo, Y. J. 2023; 22: 59-64

  View details for DOI 10.1016/j.xjtc.2023.10.018

  View details for PubMedID 38152190

  View details for PubMedCentralID PMC10750996

• Diversifying cardiac intensive care unit models: Successful example of an operating surgeon-led unit. JTCVS open Choi, P. S., Pines, K. C., Swaminathan, A., Nilkant, R., Mendez, M. A., He, H., Woo, Y. J., Martin, B. 2023; 16: 524-531

  Abstract

  Objective: The intensivist-led cardiovascular intensive care unit model is the standard of care in cardiac surgery. This study examines whether a cardiovascular intensive care unit model that uses operating cardiac surgeons, cardiothoracic surgery residents, and advanced practice providers is associated with comparable outcomes.Methods: This is a single-institution review of the first 400 cardiac surgery patients admitted to an operating surgeon-led cardiovascular intensive care unit from 2020 to 2022. Inclusion criteria are elective status and operations managed by both cardiovascular intensive care unit models (aortic operations, valve operations, coronary operations, septal myectomy). Patients from the surgeon-led cardiovascular intensive care unit were exact matched by operation type and 1:1 propensity score matched with controls from the traditional cardiovascular intensive care unit using a logistic regression model that included age, sex, preoperative mortality risk, incision type, and use of cardiopulmonary bypass and circulatory arrest. Primary outcome was total postoperative length of stay. Secondary outcomes included postoperative intensive care unit length of stay, 30-day mortality, 30-day Society of Thoracic Surgeons-defined morbidity (permanent stroke, renal failure, cardiac reoperation, prolonged intubation, deep sternal infection), packed red cell transfusions, and vasopressor use. Outcomes between the 2 groups were compared using chi-square, Fisher exact test, or 2-sample t test as appropriate.Results: A total of 400 patients from the surgeon-led cardiovascular intensive care unit (mean age 61.2±12.8years, 131 female patients [33%], 346 patients [86.5%] with European System for Cardiac Operative Risk Evaluation II <2%) and their matched controls were included. The most common operations across both units were coronary artery bypass grafting (n=318, 39.8%) and mitral valve repair or replacement (n=238, 29.8%). Approximately half of the operations were performed via sternotomy (n=462, 57.8%). There were 3 (0.2%) in-hospital deaths, and 47 patients (5.9%) had a 30-day complication. The total length of stay was significantly shorter for the surgeon-led cardiovascular intensive care unit patients (6.3 vs 7.0days, P=.028), and intensive care unit length of stay trended in the same direction (2.5 vs 2.9days, P=.16). Intensive care unit readmission rates, 30-day mortality, and 30-day morbidity were not significantly different between cardiovascular intensive care unit models. The surgeon-led cardiovascular intensive care unit was associated with fewer postoperative red blood cell transfusions in the cardiovascular intensive care unit (P=.002) and decreased vasopressor use (P=.001).Conclusions: In its first 2years, the surgeon-led cardiovascular intensive care unit demonstrated comparable outcomes to the traditional cardiovascular intensive care unit with significant improvements in total length of stay, postoperative transfusions in the cardiovascular intensive care unit, and vasopressor use. This early success exemplifies how an operating surgeon-led cardiovascular intensive care unit can provide similar outcomes to the standard-of-care model for patients undergoing elective cardiac surgery.

  View details for DOI 10.1016/j.xjon.2023.09.040

  View details for PubMedID 38204639

• Electrophysiological mapping of the epicardium via 3D-printed flexible arrays. Bioengineering & translational medicine Pong, T., Cyr, K. J., Carlton, C., Aparicio-Valenzuela, J., Wang, H., Babakhanian, M., Maiuolo, A., Lucian, H., Wang, P. J., Woo, Y. J., Lee, A. M. 2023; 8 (6): e10575

  Abstract

  Cardiac electrophysiology mapping and ablation are widely used to treat heart rhythm disorders such as atrial fibrillation (AF) and ventricular tachycardia (VT). Here, we describe an approach for rapid production of three dimensional (3D)-printed mapping devices derived from magnetic resonance imaging. The mapping devices are equipped with flexible electronic arrays that are shaped to match the epicardial contours of the atria and ventricle and allow for epicardial electrical mapping procedures. We validate that these flexible arrays provide high-resolution mapping of epicardial signals in vivo using porcine models of AF and myocardial infarction. Specifically, global coverage of the epicardial surface allows for mapping and ablation of myocardial substrate and the capture of premature ventricular complexes with precise spatial-temporal resolution. We further show, as proof-of-concept, the localization of sites of VT by means of beat-to-beat whole-chamber ventricular mapping of ex vivo Langendorff-perfused human hearts.

  View details for DOI 10.1002/btm2.10575

  View details for PubMedID 38023702

  View details for PubMedCentralID PMC10658567

• Sex Differences in Patients With 3-Vessel Coronary Artery Disease Undergoing FFR-Guided PCI or CABG: A Prespecified Analysis of the FAME 3 Trial Takahashi, K., Otsuki, H., Zimmermann, F., Ding, V., Oldroyd, K., Wendler, O., Reardon, M., Woo, J., Yeung, A., Fearon, W. ELSEVIER SCIENCE INC. 2023: B136

  View details for Web of Science ID 001108754600331

• Outcomes Based on Angiographic vs Functional Significance of Complex 3-Vessel Coronary Disease: FAME 3 Trial. JACC. Cardiovascular interventions Kobayashi, Y., Takahashi, T., Zimmermann, F. M., Otsuki, H., El Farissi, M., Oldroyd, K. G., Wendler, O., Reardon, M. J., Woo, Y. J., Yeung, A. C., De Bruyne, B., Pijls, N. H., Fearon, W. F., FAME 3 Trial Investigators 2023; 16 (17): 2112-2119

  Abstract

  BACKGROUND: The functional SYNTAX score (FSS), which incorporates functional information as assessed by fractional flow reserve (FFR), is a better predictor of outcome after percutaneous coronary intervention (PCI) in patients with less complex coronary artery disease (CAD).OBJECTIVES: This study sought to test the prognostic value of the FSS in patients with complex CAD eligible for coronary artery bypass grafting (CABG).METHODS: The FAME 3 (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation 3) trial compared FFR-guided PCI with CABG in patients with angiographic 3-vessel CAD. In this prespecified substudy, the angiographic core laboratory calculated the SYNTAX score (SS) and then the FSS by eliminating lesions that were not significant based on FFR. Outcomes in the PCI patients based on the FSS and the SS were compared to each other and to the patients treated with CABG.RESULTS: The FSS reclassified more than one-quarter of patients from an SS >22 to an FSS≤22. In the 50% of PCI patients who had an FSS≤22, the primary endpoint occurred at a similar rate to patients treated with CABG (P = 0.77). The primary endpoint in patients without functionally significant 3-vessel CAD was similar to the CABG group (P = 0.97). The rate of myocardial infarction and revascularization among all deferred lesions was 0.5% and 3.2%, respectively.CONCLUSIONS: By measuring the FSS, one can identify 50% of patients who have a similar outcome at 1 year with PCIcompared with CABG. Lesions deferred from PCI based on FFR have a low event rate.

  View details for DOI 10.1016/j.jcin.2023.06.023

  View details for PubMedID 37704297

• Chordal force profile after neochordal repair of anterior mitral valve prolapse: An ex vivo study. JTCVS open Yajima, S., Zhu, Y., Stark, C. J., Wilkerson, R. J., Park, M. H., Stefan, E., Woo, Y. J. 2023; 15: 164-172

  Abstract

  This study aimed to biomechanically evaluate the force profiles on the anterior primary and secondary chordae after neochord repair for anterior valve prolapse with varied degrees of residual mitral regurgitation using an ex vivo heart simulator.The experiment used 8 healthy porcine mitral valves. Chordal forces were measured using fiber Bragg grating sensors on primary and secondary chordae from A2 segments. The anterior valve prolapse model was generated by excising 2 primary chordae at the A2 segment. Neochord repair was performed with 2 pairs of neochords. Varying neochord lengths simulated postrepair residual mitral regurgitation with regurgitant fraction at >30% (moderate), 10% to 30% (mild), and <10% (perfect repair).Regurgitant fractions of baseline, moderate, mild, and perfect repair were 4.7% ± 0.8%, 35.8% ± 2.1%, 19.8% ± 2.0%, and 6.0% ± 0.7%, respectively (P < .001). Moderate had a greater peak force of the anterior primary chordae (0.43 ± 0.06 N) than those of baseline (0.19 ± 0.04 N; P = .011), mild (0.23 ± 0.05 N; P = .041), and perfect repair (0.21 ± 0.03 N; P = .006). In addition, moderate had a greater peak force of the anterior secondary chordae (1.67 ± 0.17 N) than those of baseline (0.64 ± 0.13 N; P = .003), mild (0.84 ± 0.24 N; P = .019), and perfect repair (0.68 ± 0.14 N; P = .001). No significant differences in peak and average forces on both primary and secondary anterior chordae were observed between the baseline and perfect repair as well as the mild and perfect repair.Moderate residual mitral regurgitation after neochord repair was associated with increased anterior primary and secondary chordae forces in our ex vivo anterior valve prolapse model. This difference in chordal force profile may influence long-term repair durability, providing biomechanical evidence in support of obtaining minimal regurgitation when repairing mitral anterior valve prolapse.

  View details for DOI 10.1016/j.xjon.2023.04.011

  View details for PubMedID 37808060

  View details for PubMedCentralID PMC10556825

• Fractional Flow Reserve-Guided PCI or Coronary Bypass Surgery for 3-Vessel Coronary Artery Disease: 3-Year Follow-Up of the FAME 3 Trial. Circulation Zimmermann, F. M., Ding, V. Y., Pijls, N. H., Piroth, Z., van Straten, A. H., Szekely, L., Davidavicius, G., Kalinauskas, G., Mansour, S., Kharbanda, R., Östlund-Papadogeorgos, N., Aminian, A., Oldroyd, K. G., Al-Attar, N., Jagic, N., Dambrink, J. E., Kala, P., Angeras, O., MacCarthy, P., Wendler, O., Casselman, F., Witt, N., Mavromatis, K., Miner, S. E., Sarma, J., Engstrøm, T., Christiansen, E. H., Tonino, P. A., Reardon, M. J., Otsuki, H., Kobayashi, Y., Hlatky, M. A., Mahaffey, K. W., Desai, M., Woo, Y. J., Yeung, A. C., De Bruyne, B., Fearon, W. F. 2023

  Abstract

  Previous studies comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel coronary disease not involving the left main have shown significantly lower rates of death, myocardial infarction (MI), or stroke after CABG. These studies did not routinely use current-generation drug-eluting stents or fractional flow reserve (FFR) to guide PCI.FAME 3 (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) is an investigator-initiated, multicenter, international, randomized trial involving patients with 3-vessel coronary artery disease (not involving the left main coronary artery) in 48 centers worldwide. Patients were randomly assigned to receive FFR-guided PCI using zotarolimus drug-eluting stents or CABG. The prespecified key secondary end point of the trial reported here is the 3-year incidence of the composite of death, MI, or stroke.A total of 1500 patients were randomized to FFR-guided PCI or CABG. Follow-up was achieved in >96% of patients in both groups. There was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI compared with CABG (12.0% versus 9.2%; hazard ratio [HR], 1.3 [95% CI, 0.98-1.83]; P=0.07). The rates of death (4.1% versus 3.9%; HR, 1.0 [95% CI, 0.6-1.7]; P=0.88) and stroke (1.6% versus 2.0%; HR, 0.8 [95% CI, 0.4-1.7]; P=0.56) were not different. MI occurred more frequently after PCI (7.0% versus 4.2%; HR, 1.7 [95% CI, 1.1-2.7]; P=0.02).At 3-year follow-up, there was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI with current-generation drug-eluting stents compared with CABG. There was a higher incidence of MI after PCI compared with CABG, with no difference in death or stroke. These results provide contemporary data to allow improved shared decision-making between physicians and patients with 3-vessel coronary artery disease.URL: https://www.gov; Unique identifier: NCT02100722.

  View details for DOI 10.1161/CIRCULATIONAHA.123.065770

  View details for PubMedID 37602376

• Perspectives on the 2022 Joint Guidelines on the Diagnosis and Management of Aortic Disease. The Journal of thoracic and cardiovascular surgery Hui, D. S., Chen, E. P., DeAnda, A., Girardi, L. N., Kim, K. M., Woo, Y. J., Tseng, E. E., Preventza, O. 2023

  View details for DOI 10.1016/j.jtcvs.2023.07.046

  View details for PubMedID 37543165

• An analytical, mathematical annuloplasty ring curvature model for planning of valve-in-ring transcatheter mitral valve replacement. JTCVS techniques Park, M. H., Marin-Cuartas, M., Sellke, M., Pandya, P. K., Zhu, Y., Wilkerson, R. J., Holzhey, D. M., Borger, M. A., Woo, Y. J. 2023; 20: 45-54

  Abstract

  An increasing number of high-risk patients with previous mitral valve annuloplasty require transcatheter mitral valve replacement due to recurrent regurgitation. Annulus dilation with a transcatheter balloon is often performed before valve-in-ring transcatheter mitral valve replacement, which is believed to reduce misalignment and paravalvular leakage, yet little evidence exists to support this practice. Our objective was to generate intuitive annuloplasty ring analyses for improved valve-in-ring transcatheter mitral valve replacement planning.We generated a mathematical model that calculates image-tracked differential ring curvature to build quantifications for improved planning for valve-in-ring procedures. Carpentier-Edwards Physio M24 and M30 (n = 2 each), Physio II M24 and M26 (n = 3 each), LivaNova AnnuloFlex M26 (n = 2), and Edwards Geoform M28 (n = 2) rings were tested with a 30-mm Toray Inoue balloon inflated to maximum rated pressures.Curvature variance reduces with larger ring sizes, indicating that larger rings are initially more circular than smaller ones. Evaluated semi-rigid and rigid rings showed little to no difference between pre- and post-dilation states. Annuloflex rings (flexible band) showed a postdilation variance reduction of 32.83% (P < .001) followed by an increase after 10 minutes of relaxation that was still reduced by 19.62% relative to the initial state (P < .001).We discovered that balloon dilation does not significantly deform evaluated semi-rigid or rigid rings at maximum rated balloon pressures. This may mean that dilation for these conditions before valve-in-ring transcatheter mitral valve replacement is unnecessary. Our mathematical approach creates a foundation for extended classification of this practice, providing meaningful quantification of ring geometry.

  View details for DOI 10.1016/j.xjtc.2023.03.022

  View details for PubMedID 37555034

  View details for PubMedCentralID PMC10405166

• Blood transfusion in cardiac surgeries - Toward a personalized protocol. American journal of surgery Min, Y., Dalal, A. R., Pedroza, A. J., Pham, T. D., Panigrahi, A. K., Goldstone, A. B., MacArthur, J. W., Woo, Y. J., Baiocchi, M., Fischbein, M. P. 2023

  View details for DOI 10.1016/j.amjsurg.2023.07.035

  View details for PubMedID 37558518

• Biomechanics and clinical outcomes of various conduit configurations in valve sparing aortic root replacement. Annals of cardiothoracic surgery Zhu, Y., Park, M. H., Pandya, P. K., Stark, C. J., Mullis, D. M., Walsh, S. K., Kim, J. Y., Wu, C. A., Baccouche, B. M., Lee, S. H., Baraka, A. S., Joo, H., Yajima, S., Elde, S., Woo, Y. J. 2023; 12 (4): 326-337

  Abstract

  Several conduit configurations, such as straight graft (SG), Valsalva graft (VG), anticommissural plication (ACP), and the Stanford modification (SMOD) technique, have been described for the valve-sparing aortic root replacement (VSARR) procedure. Prior ex vivo studies have evaluated the impact of conduit configurations on root biomechanics, but the mock coronary artery circuits used could not replicate the physical properties of native coronary arteries. Moreover, the individual leaflet's biomechanics, including the fluttering phenomenon, were unclear.Porcine aortic roots with coronary arteries were explanted (n=5) and underwent VSARR using SG, VG, ACP, and SMOD for evaluation in an ex vivo left heart flow loop simulator. Additionally, 762 patients who underwent VSARR from 1993 through 2022 at our center were retrospectively reviewed. Analysis of variance was performed to evaluate differences between different conduit configurations, with post hoc Tukey's correction for pairwise testing.SG demonstrated lower rapid leaflet opening velocity compared with VG (P=0.001) and SMOD (P=0.045) in the left coronary cusp (LCC), lower rapid leaflet closing velocity compared with VG (P=0.04) in the right coronary cusp (RCC), and lower relative opening force compared with ACP (P=0.04) in the RCC. The flutter frequency was lower in baseline compared with VG (P=0.02) and in VG compared with ACP (P=0.03) in the LCC. Left coronary artery mean flow was higher in SG compared with SMOD (P=0.02) and ACP (P=0.05). Clinically, operations using SG compared with sinus-containing graft was associated with shorter aortic cross-clamp and cardiopulmonary bypass time (P<0.001, <0.001).SG demonstrated hemodynamics and biomechanics most closely recapitulating those from the native root with significantly shorter intraoperative times compared with repair using sinus-containing graft. Future in vivo validation studies as well as correlation with comprehensive, comparative clinical study outcomes may provide additional invaluable insights regarding strategies to further enhance repair durability.

  View details for DOI 10.21037/acs-2023-avs2-0068

  View details for PubMedID 37554719

  View details for PubMedCentralID PMC10405339

• Early clinical outcomes and molecular smooth muscle cell phenotyping using a prophylactic aortic arch replacement strategy in Loeys-Dietz syndrome. The Journal of thoracic and cardiovascular surgery Pedroza, A. J., Cheng, P., Dalal, A. R., Baeumler, K., Kino, A., Tognozzi, E., Shad, R., Yokoyama, N., Nakamura, K., Mitchel, O., Hiesinger, W., MacFarlane, E. G., Fleischmann, D., Woo, Y. J., Quertermous, T., Fischbein, M. P. 2023

  Abstract

  Loeys-Dietz syndrome (LDS) patients demonstrate heightened risk of distal thoracic aortic events after valve-sparing aortic root replacement (VSARR). This study assesses the clinical risks and hemodynamic consequences of a prophylactic aortic arch replacement strategy in LDS and characterizes smooth muscle cell (SMC) phenotype in LDS aneurysmal and normal-sized downstream aorta.Patients with genetically confirmed LDS (n=8) underwent prophylactic aortic arch replacement during VSARR. 4D flow magnetic resonance imaging (MRI) studies were performed in n=4 LDS patients (VSARR+arch) and compared with both contemporary Marfan syndrome patients (VSARR only, n=5) and control patients (without aortopathy, n=5). Aortic tissues from n=4 LDS patients and n=2 organ donors were processed for anatomically segmented single-cell RNA sequencing (scRNAseq) and histologic assessment.LDS VSARR+arch patients had no deaths, major morbidity, or aortic events in median 2.00 years follow-up. 4D-MRI demonstrated altered flow parameters in post-operative aortopathy patients relative to controls, but no clear deleterious changes attributable to arch replacement. Integrated analysis of aortic scRNAseq data (>49,000 cells) identified a continuum of abnormal SMC phenotypic modulation in LDS defined by reduced contractility and enriched extracellular matrix synthesis, adhesion receptors, and transforming growth factor-beta signaling. These 'modulated SMCs' populated the LDS tunica media with gradually reduced density from the overtly aneurysmal root to the non-dilated arch.LDS patients demonstrated excellent surgical outcomes without overt downstream flow or shear stress disturbances after concomitant VSARR+arch operations. Abnormal SMC-mediated aortic remodeling occurs within the normal diameter, clinically at-risk LDS arch segment. These initial clinical and pathophysiologic findings support concomitant arch replacement in LDS.

  View details for DOI 10.1016/j.jtcvs.2023.07.023

  View details for PubMedID 37500053

• Electrophysiological mapping of the epicardium via 3D-printed flexible arrays BIOENGINEERING & TRANSLATIONAL MEDICINE Pong, T., Cyr, K. J., Carlton, C., Aparicio-Valenzuela, J., Wang, H., Babakhanian, M., Maiuolo, A., Lucian, H., Wang, P. J., Woo, Y., Lee, A. M. 2023

  View details for DOI 10.1002/btm2.10575

  View details for Web of Science ID 001033419000001

• Advances in 3D Bioprinting: Techniques, Applications, and Future Directions for Cardiac Tissue Engineering. Bioengineering (Basel, Switzerland) Wu, C. A., Zhu, Y., Woo, Y. J. 2023; 10 (7)

  Abstract

  Cardiovascular diseases are the leading cause of morbidity and mortality in the United States. Cardiac tissue engineering is a direction in regenerative medicine that aims to repair various heart defects with the long-term goal of artificially rebuilding a full-scale organ that matches its native structure and function. Three-dimensional (3D) bioprinting offers promising applications through its layer-by-layer biomaterial deposition using different techniques and bio-inks. In this review, we will introduce cardiac tissue engineering, 3D bioprinting processes, bioprinting techniques, bio-ink materials, areas of limitation, and the latest applications of this technology, alongside its future directions for further innovation.

  View details for DOI 10.3390/bioengineering10070842

  View details for PubMedID 37508869

• Outcomes of Patients Undergoing Combined Heart-Kidney Transplantation With or Without Prior Ventricular Assist Device. Transplantation proceedings Currie, M., Leipzig, M., Kaghazchi, A., Zhu, Y., Shudo, Y., Woo, Y. J. 2023

  Abstract

  BACKGROUND: Both combined heart-kidney transplantation and ventricular assist devices (VADs) pose significant challenges, including sensitization, immunosuppressive treatment, and infrastructure demands. Despite these challenges, we hypothesized that the recipients of combined heart-kidney transplants with and without VADs would have equivalent survival. We aimed to compare the survival of heart-kidney transplant recipients with and without prior VAD placement.METHODS: We retrospectively analyzed all patients enrolled in the United Network for Organ Sharing database who underwent heart-kidney transplants. We created a matched cohort of patients undergoing heart-kidney transplantation with or without prior VAD using 1:1 nearest propensity-score matching with preoperative variables.RESULTS: In the propensity-matched cohort, 399 patients underwent heart-kidney transplantation with prior VAD, and 399 underwent heart-kidney transplantation without prior VAD. The estimated survival of heart--kidney recipients with prior VAD was 84.8% at one year, 81.2% at 3 years, and 75.3% at 5 years. The estimated survival of heart-kidney recipients without prior VAD was 86.8.7% at one year, 84.0% at 3 years, and 78.8% at 5 years. There was no statistically significant difference in the survival of heart-kidney transplant recipients with or without prior VAD at one year (P=.42; Figure 2), 3 years (P=.34), or 5 years (P=.30).CONCLUSION: Despite the increased challenge of heart-kidney transplantation in recipients with prior VAD, we demonstrated that these patients have similar survival to those who underwent heart-kidney transplantation without previous VAD placement.

  View details for DOI 10.1016/j.transproceed.2023.04.037

  View details for PubMedID 37393169

• Dedifferentiation and Proliferation of Artery Endothelial Cells Drive Coronary Collateral Development in Mice. Arteriosclerosis, thrombosis, and vascular biology Arolkar, G., Krishna Kumar, S., Wang, H., Gonzalez, K. M., Kumar, S., Bishnoi, B., Rios Coronado, P. E., Woo, Y. J., Red-Horse, K., Das, S. 2023

  Abstract

  BACKGROUND: Collateral arteries act as natural bypasses which reroute blood flow to ischemic regions and facilitate tissue regeneration. In an injured heart, neonatal artery endothelial cells orchestrate a systematic series of cellular events, which includes their outward migration, proliferation, and coalescence into fully functional collateral arteries. This process, called artery reassembly, aids complete cardiac regeneration in neonatal hearts but is absent in adults. The reason for this age-dependent disparity in artery cell response is completely unknown. In this study, we investigated if regenerative potential of coronary arteries is dictated by their ability to dedifferentiate.METHODS: Single-cell RNA sequencing of coronary endothelial cells was performed to identify differences in molecular profiles of neonatal and adult endothelial cells in mice. Findings from this in silico analyses were confirmed with in vivo experiments using genetic lineage tracing, whole organ immunostaining, confocal imaging, and cardiac functional assays in mice.RESULTS: Upon coronary occlusion, neonates showed a significant increase in actively cycling artery cells and expressed prominent dedifferentiation markers. Data from in silico pathway analyses and in vivo experiments suggested that upon myocardial infarction, cell cycle reentry of preexisting neonatal artery cells, the subsequent collateral artery formation, and recovery of cardiac function are dependent on arterial VegfR2 (vascular endothelial growth factor receptor-2). This subpopulation of dedifferentiated and proliferating artery cells was absent in nonregenerative postnatal day 7 or adult hearts.CONCLUSIONS: These data indicate that adult artery endothelial cells fail to drive collateral artery development due to their limited ability to dedifferentiate and proliferate.

  View details for DOI 10.1161/ATVBAHA.123.319319

  View details for PubMedID 37345524

• First-in-human beating-heart transplant. JTCVS techniques Krishnan, A., Kasinpila, P., Wang, H., Ruaengsri, C., Shudo, Y., Jackson, E., Woo, Y. J. 2023; 19: 80-85

  View details for DOI 10.1016/j.xjtc.2023.02.015

  View details for PubMedID 37324334

  View details for PubMedCentralID PMC10267812

• American one-cut ascending and aortic root resection technique. JTCVS techniques Zhu, Y., Paulsen, M. J., Woo, Y. J. 2023; 19: 10-11

  View details for DOI 10.1016/j.xjtc.2023.03.004

  View details for PubMedID 37324331

  View details for PubMedCentralID PMC10267861

• Biomechanical analysis of novel leaflet geometries for bioprosthetic valves. JTCVS open Pandya, P. K., Park, M. H., Zhu, Y., Woo, Y. J. 2023; 14: 77-86

  Abstract

  Objectives: Although bioprosthetic valves have excellent hemodynamic properties and can eliminate the need for lifelong anticoagulation therapy, these devices are associated with high rates of reoperation and limited durability. Although there are many distinct bioprosthesis designs, all bioprosthetic valves have historically featured a trileaflet pattern. This in silico study examines the biomechanical effect of modulating the number of leaflets in a bioprosthetic valve.Methods: Bioprosthetic valves with 2 to 6 leaflets were designed in Fusion 360 using quadratic spline geometry. Leaflets were modeled with standard mechanical parameters for fixed bovine pericardial tissue. A mesh of each design was structurally evaluated using finite element analysis software Abaqus CAE. Maximum von Mises stresses during valve closure were assessed for each leaflet geometry in both the aortic and mitral position.Results: Computational analysis demonstrated that increasing the number of leaflets is associated with reduction in leaflet stresses. Compared with the standard trileaflet design, a quadrileaflet pattern reduces leaflet maximum von Mises stresses by 36% in the aortic position and 38% in the mitral position. Maximum stress was inversely proportional to the square of the leaflet quantity. Surface area increased linearly and central leakage increased quadratically with leaflet quantity.Conclusions: A quadrileaflet pattern was found to reduce leaflet stresses while limiting increases in central leakage and surface area. These findings suggest that modulating the number of leaflets can allow for optimization of the current bioprosthetic valve design, which may translate to more durable valve replacement bioprostheses.

  View details for DOI 10.1016/j.xjon.2023.04.007

  View details for PubMedID 37425479

• Neochordal Goldilocks: Analyzing the Biomechanics of Neochord Length on Papillary Muscle Forces Suggests Higher Tolerance to Shorter Neochordae. The Journal of thoracic and cardiovascular surgery Park, M. H., van Kampen, A., Zhu, Y., Melnitchouk, S., Levine, R. A., Borger, M. A., Woo, Y. J. 2023

  Abstract

  Estimating neochord lengths during mitral valve (MV) repair is challenging, as approximation must be performed largely based on intuition and surgical experience. Little data exist on quantifying the effects of neochord length misestimation. We aimed to evaluate the impact of neochord length on papillary muscle (PM) forces and MV hemodynamics, which is especially pertinent as increased forces have been linked to aberrant MV biomechanics.Porcine MVs (n=8) were mounted in an ex vivo heart simulator, and PMs were fixed to high resolution strain gauges, while hemodynamic data were recorded. We used an adjustable system to modulate neochord lengths. Optimal length was qualitatively verified by a single experienced operator, and neochordae were randomly lengthened or shortened in 1 mm increments up to ±5 mm from the optimal length.Optimal length neochordae resulted in the lowest peak composite PM forces (6.94±0.29 N), significantly different from all lengths >±1 mm. Both longer and shorter neochordae increased forces linearly according to difference from optimal length. Both peak PM forces and MR scaled more aggressively for longer versus shorter neochordae by factors of 1.6 and 6.9, respectively.Leveraging precision ex vivo heart simulation, we found that millimeter-level neochord length differences can result in significant differences in PM forces and MR, thereby altering valvular biomechanics. Differences in lengthened versus shortened neochordae scaling of forces and MR may indicate different levels of biomechanical tolerance towards longer and shorter neochordae. Our findings highlight the need for more thorough biomechanical understanding of neochordal MV repair.

  View details for DOI 10.1016/j.jtcvs.2023.04.026

  View details for PubMedID 37160219

• Response to: Correspondence on "Has personalised surgery made another advancement in aortic root surgery?" by Zhu and Woo. Heart (British Cardiac Society) Zhu, Y., Woo, J. 2023

  View details for DOI 10.1136/heartjnl-2023-322704

  View details for PubMedID 37080763

• Remodeling valve-sparing pulmonary root replacement repair of giant pulmonary artery aneurysm. JTCVS techniques Paulsen, M. J., Aranda-Michel, E. C., Berry, G. J., Woo, Y. J. 2023; 18: 60-62

  View details for DOI 10.1016/j.xjtc.2023.01.018

  View details for PubMedID 37096108

  View details for PubMedCentralID PMC10122152

• The 170°/190° commissure positioning technique for bicuspid aortic valve repair using valve-sparing aortic root replacement. JTCVS techniques Zhu, Y., Woo, Y. J. 2023; 18: 37-39

  View details for DOI 10.1016/j.xjtc.2023.01.012

  View details for PubMedID 37096113

  View details for PubMedCentralID PMC10122148

• Ex Vivo Modeling of Atrioventricular Valve Mechanics in Single Ventricle Physiology. Annals of biomedical engineering Moye, S. C., Kidambi, S., Lee, J. Y., Cowles, T. H., Gilligan-Steinberg, S. D., Bryan, A. Y., Wilkerson, R., Woo, Y. J., Ma, M. R. 2023

  Abstract

  Single ventricle physiology (SVP) is used to describe any congenital heart lesion that is unable to support independent pulmonary and systemic circulations. Current treatment strategies rely on a series of palliation surgeries that culminate in the Fontan physiology, which relies on the single functioning ventricle to provide systemic circulation while passively routing venous return through the pulmonary circulation. Despite significant reductions in early mortality, the presence of atrioventricular valve (AVV) regurgitation is a key predictor of heart failure in these patients. We sought to evaluate the biomechanical changes associated with the AVV in SVP physiologies. Left and right ventricles were sutured onto patient-derived 3D-printed mounts and mounted into an ex vivo systemic heart simulator capable of reproducing Norwood, Glenn, Fontan and Late Fontan physiologies. We found that the tricuspid anterior leaflet experienced elevated maximum force, average force, and maximum yank compared to the posterior and septal leaflets. Between physiologies, maximum yank was greatest in the Norwood physiology relative to the Glenn, Fontan, and Late Fontan physiologies. These contrasting trends suggest that long- and short-term mechanics of AVV failure in single ventricle differ and that AVV interventions should account for asymmetries in force profiles between leaflets and physiologies.

  View details for DOI 10.1007/s10439-023-03178-1

  View details for PubMedID 36966247

  View details for PubMedCentralID 5371563

• Microfluidic encapsulation of photosynthetic cyanobacteria in hydrogel microparticles augments oxygen delivery to rescue ischemic myocardium. Journal of bioscience and bioengineering Stapleton, L. M., Farry, J. M., Zhu, Y., Lucian, H. J., Wang, H., Paulsen, M. J., Totherow, K. P., Roth, G. A., Brower, K. K., Fordyce, P. M., Appel, E. A., Woo, Y. J. 2023

  Abstract

  Cardiovascular disease, primarily caused by coronary artery disease, is the leading cause of death in the United States. While standard clinical interventions have improved patient outcomes, mortality rates associated with eventual heart failure still represent a clinical challenge. Macrorevascularization techniques inadequately address the microvascular perfusion deficits that persist beyond primary and secondary interventions. In this work, we investigate a photosynthetic oxygen delivery system that rescues the myocardium following acute ischemia. Using a simple microfluidic system, we encapsulated Synechococcus elongatus into alginate hydrogel microparticles (HMPs), which photosynthetically deliver oxygen to ischemic tissue in the absence of blood flow. We demonstrate that HMPs improve the viability of S. elongatus during the injection process and allow for simple oxygen diffusion. Adult male Wistar rats (n = 45) underwent sham surgery, acute ischemia reperfusion surgery, or a chronic ischemia reperfusion surgery, followed by injection of phosphate buffered saline (PBS), S. elongatus suspended in PBS, HMPs, or S. elongatus encapsulated in HMPs. Treatment with S. elongatus-HMPs mitigated cellular apoptosis and improved left ventricular function. Thus, delivery of S. elongatus encapsulated in HMPs improves clinical translation by utilizing a minimally invasive delivery platform that improves S. elongatus viability and enhances the therapeutic benefit of a novel photosynthetic system for the treatment of myocardial ischemia.

  View details for DOI 10.1016/j.jbiosc.2023.03.001

  View details for PubMedID 36966053

• Has personalised surgery made another advancement in aortic root surgery? Heart (British Cardiac Society) Zhu, Y., Woo, J. 2023

  View details for DOI 10.1136/heartjnl-2022-322313

  View details for PubMedID 36858806

• Blood transfusion in aortic root surgery impairs midterm survival. JTCVS open Dalal, A. R., Pedroza, A. J., Krishnan, A., Min, Y., Tognozzi, E., Yokoyama, N., Nakamura, K., Mitchel, O. R., Baiocchi, M., Woo, Y. J., MacArthur, J. W., Fischbein, M. P. 2023; 13: 9-19

  Abstract

  To evaluate the effect of perioperative allogeneic packed red blood cell (RBC) transfusion during aortic root replacement.We reviewed patients undergoing aortic root replacement at our institution between March 2014 and April 2020. In total, 760 patients underwent aortic root replacement, of whom 442 (58%) received a perioperative RBC transfusion. Propensity score matching was used to account for baseline and operative differences resulting in 159 matched pairs. All-cause mortality was assessed with Kaplan-Meier curves. Data were obtained from our institutional Society of Thoracic Surgeons database and chart review.After propensity score matching, the RBC-transfused and -nontransfused groups were similar for all preoperative characteristics. Cardiopulmonary bypass time, crossclamp time, and lowest operative temperature were similar between the transfused and nontransfused groups (standardized mean difference <0.05). RBC transfusion was associated with more frequent postoperative ventilation greater than 24 hours (36/159 [23%] vs 19/159 [12%]; P = .01), postoperative hemodialysis (9/159 [5.7%] vs 0/159 [0%]; P = .003), reoperation for mediastinal hemorrhage (9/159 [5.7%] vs 0/159 [0%]; P = .003), and longer intensive care unit and hospital length of stay (3 vs 2 days and 8 vs 6 days respectively; P < .001). Thirty-day operative mortality after propensity score matching was similar between the cohorts (1.9%; 3/159 vs 0%; P = .2), and 5-year survival was reduced in the RBC transfusion cohort (90.2% [95% confidence interval, 84.1%-96.7%] vs 97.1% [95% confidence interval, 92.3%-100%] P = .035).Aortic root replacement frequently requires RBC transfusion during and after the operation, but even after matching for observed preoperative and operative characteristics, RBC transfusion is associated with more frequent postoperative complications and reduced midterm survival.

  View details for DOI 10.1016/j.xjon.2023.01.006

  View details for PubMedID 37063152

  View details for PubMedCentralID PMC10091283

• Outcomes after concomitant arch replacement at the time of aortic root surgery. JTCVS open Krishnan, A., Dalal, A. R., Pedroza, A. J., Nakamura, K., Yokoyama, N., Tognozzi, E., Woo, Y. J., Fischbein, M., MacArthur, J. W. 2023; 13: 1-8

  Abstract

  Contemporary series of aortic arch replacement at the time of aortic root surgery are limited in number of patients and mostly address hemiarch replacement. We describe outcomes after aortic root and concomitant arch replacement, including total arch replacement.This single-institution retrospective review studied 1196 consecutive patients from May 2004 to September 2020 who underwent first-time aortic root replacement. Patients undergoing surgery for endocarditis were excluded (n = 68, 5.7%). Patients undergoing concomitant root and arch replacement were propensity matched with patients undergoing isolated root surgery based on indication, clinical and operative characteristics, demographics, medical history including connective tissue disorders, and urgency. Multivariable Cox proportional hazards and logistic regression modeling were used to assess the primary outcome of all-cause mortality and the secondary outcomes of prolonged ventilator use, postoperative blood transfusion, and debilitating stroke, adjusted for patient and operative characteristics.Among the 1128 patients who underwent aortic root intervention during the study period, 471 (41.8%) underwent concomitant aortic arch replacement. Most underwent hemiarch replacement (n = 411, 87.4%); 59 patients (12.6%) underwent total arch replacement (with elephant trunk: n = 23, 4.9%; without elephant trunk: n = 36, 7.7%). The mean follow-up time was 4.6 years postprocedure. Operative mortality was 2.2%, and total mortality over the entire study period was 9.2%. Propensity matching generated 348 matches (295 concomitant hemiarch, 53 concomitant total arch). Concomitant hemiarch (hazard ratio, 1.00; 95% confidence interval, 0.54-1.86, P = .99) and total arch replacement (hazard ratio, 1.60, 95% confidence interval, 0.72-3.57, P = .24) were not significantly associated with increased mortality. Rates of stroke were not significantly different among each group: isolated root (n = 11/348, 3.7%), root + hemiarch (n = 17/295, 5.8%), and root + total arch (n = 3/53, 5.7%) replacement (P = .50), nor was the adjusted risk of stroke. Both concomitant arch interventions were associated with prolonged ventilator use and use of postoperative blood transfusions.Hemiarch and total arch replacement are safe to perform at the time of aortic root intervention, with no significant differences in survival or stroke rates, but increased ventilator and blood product use.

  View details for DOI 10.1016/j.xjon.2022.12.014

  View details for PubMedID 37063158

  View details for PubMedCentralID PMC10091289

• Trimmed central venous catheters do not increase endothelial injury in an ovine model. The journal of vascular access Wang, H., Williams, K. M., Elde, S., Bulterys, P. L., Thakore, A. D., Lucian, H. J., Farry, J. M., Mullis, D. M., Zhu, Y., Paulsen, M. J., Woo, Y. J. 2023: 11297298231153716

  Abstract

  Central venous catheters (CVCs) are often trimmed during heart transplantation and pediatric cardiac surgery. However, the risk of endothelial injury caused by the cut tip of the CVC has not been evaluated. We hypothesized that there is no difference in the degree of endothelial injury associated with trimmed CVCs versus standard untrimmed CVCs.In four adult male sheep, the left external jugular vein was exposed in three segments, one designated for an untouched control group, one for the trimmed CVC group, and one for the untrimmed CVC group. Trimmed and untrimmed CVC tips were rotated circumferentially within their respective segments to abrade the lumen of the vein. The vein samples were explanted, and two representative sections from each sample were analyzed using hematoxylin and eosin (H&E) staining, as well as with immunohistochemistry against CD31, von Willebrand factor (vWF), endothelial nitric oxide synthase (eNOS), and caveolin. Higher immunohistochemical stain distributions and intensities are associated with normal health and function of the venous endothelium. Data are presented as counts with percentages or as means with standard error.H&E staining revealed no evidence of endothelial injury in 6/8 (75%) samples from the untouched control group, and no injury in 4/8 (50%) samples from both the trimmed and untrimmed CVC groups (p = 0.504). In all remaining samples from each group, only mild endothelial injury was observed. Immunohistochemical analysis comparing trimmed CVCs versus untrimmed CVCs revealed no difference in the percentage of endothelial cells staining positive for CD31 (57.5% ± 7.2% vs 55.0% ± 9.2%, p = 0.982), vWF (73.8% ± 8.0% vs 62.5% ± 9.6%, p = 0.579), eNOS (66.3% ± 4.2% vs 63.8% ± 7.5%, p = 0.962), and caveolin (53.8% ± 5.0% vs 51.3% ± 4.4%, p = 0.922). There were no significant differences between the groups in the distributions of stain intensity for CD31, vWF, eNOS, and caveolin.Trimmed CVCs do not increase endothelial injury compared to standard untrimmed CVCs.

  View details for DOI 10.1177/11297298231153716

  View details for PubMedID 36765464

• Outcomes of Reoperative Aortic Root Replacement After Previous Acute Type A Dissection Repair. Seminars in thoracic and cardiovascular surgery Pedroza, A. J., Dalal, A. R., Krishnan, A., Yokoyama, N., Nakamura, K., Tognozzi, E., Woo, Y. J., Macarthur, J. W., Fischbein, M. P. 2023

  Abstract

  Limited aortic root repair for acute type A dissection is associated with greater risk of proximal reoperations compared to full aortic root replacement. Surgical outcomes for patients undergoing reoperative root replacement after previous dissection repair are unknown. This study seeks to determine outcomes for these patients to further inform the debate surrounding optimal upfront management of the aortic root in acute dissection. Retrospective record review of all patients who underwent full aortic root replacement after a previous type A dissection repair operation at a tertiary academic referral center from 2004-2020 was performed. Among 57 cases of reoperative root replacement after type A repair, 35 cases included concomitant aortic arch replacements, and 21 cases involved coronary reconstruction (unilateral or bilateral modified Cabrol grafts). There were 3 acute post-operative strokes and 4 operative mortalities (composite 30-day and in-hospital deaths, 7.0%) . Mid-term outcomes were equivalent for patients who required arch replacement compared to isolated proximal repairs (81.8% vs. 80.6% estimated 5-year survival, median follow-up 5.53 years. Reoperative root replacement after index type A dissection repairs, including those with concomitant aortic arch replacement and/or coronary reconstruction is achievable with acceptable outcomes at an experienced aortic center.

  View details for DOI 10.1053/j.semtcvs.2023.02.001

  View details for PubMedID 36758660

• Beating heart pulmonary autograft harvest and modified inclusion technique with anti-commissural plication for the Ross procedure. JTCVS techniques Zhu, Y., Wang, H., Woo, Y. J. 2023; 17: 52-55

  View details for DOI 10.1016/j.xjtc.2022.10.009

  View details for PubMedID 36820349

  View details for PubMedCentralID PMC9938366

• Optimization of FRESH Microspheres for Substantially Improved 3D Bioprinting Capabilities. Tissue engineering. Part C, Methods Wu, C. A., Zhu, Y., Venkatesh, A., Stark, C. J., Lee, S. H., Woo, Y. J. 2023

  Abstract

  Three-dimensional (3D) bioprinting demonstrates technology capable of producing structures comparable to native tissues in the human body. The Freeform Reversible Embedding of Suspended Hydrogels (FRESH) technique involves hydrogel-based bio-inks printed within a thermo-reversible support bath to provide mechanical strength to the printed construct. Smaller and more uniform microsphere sizes of FRESH were reported to aid in enhancing printing resolution and construct accuracy. Therefore, we sought to optimize the FRESH generation protocol, particularly by varying stir speed and stir duration, in hopes to further improve microsphere size and uniformity. We observed optimal conditions at a stir speed of 600 rpm and stir duration for 20 hours that generated the smallest microspheres with the best uniformity. Comparison of using the optimized FRESH to the commercial FRESH LifeSupport to bioprint single filament and geometrical constructs revealed reduced single filament diameters and higher angular precision in the optimized FRESH bio-printed constructs compared to those printed in the commercial FRESH. Overall, our refinement of the FRESH manufacturing protocol represents an important step toward enhancing 3D bioprinting resolution and construct fidelity. Improving such technologies allows for the fabrication of highly accurate constructs with anatomical properties similar to native counterparts. Such work has significant implications in the field of tissue engineering for producing accurate human organ model systems.

  View details for DOI 10.1089/ten.TEC.2022.0214

  View details for PubMedID 36719778

• A newer era of heart-lung transplantation? European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Williams, K. M., Woo, Y. J. 2023

  View details for DOI 10.1093/ejcts/ezad011

  View details for PubMedID 36645242

• Revised Heart Allocation Policy Improved Waitlist Mortality and Waiting Time With Maintained Outcomes in En-Bloc Heart-Lung Transplant Candidates and Recipients. Transplant international : official journal of the European Society for Organ Transplantation Shudo, Y., He, H., Elde, S., Woo, Y. J. 2023; 36: 11956

  Abstract

  The revised United Network for Organ Sharing heart allocation policy was implemented in October 2018. Using a national transplant database, this study evaluated the transplant rate, waitlist mortality, waiting time, and other outcomes of en-bloc heart-lung transplantation recipients. Adult patients registered on the national database for heart-lung transplants before and after the policy update were selected as cohorts. Baseline characteristics, transplant rates, waitlist mortality, waiting times, and other outcomes were compared between the two periods. In total, 370 patients were registered for heart-lung transplants during the pre- and post-periods. There were significantly higher transplant rates, shorter waitlist times, and substantially reduced waitlist mortality in the post-period. Registered patients waitlisted in the post-period had significantly higher utilization of intra-aortic balloon pumps, extracorporeal membrane oxygenation, and overall life support, including ventricular assist devices. Transplant recipients had significantly longer ischemic times, increased transport distances, and shorter waiting times before transplantation in the post-policy period. Transplant recipients held similar short-term survival before and after the policy change (log-rank test, p = 0.4357). Therefore, the revised policy significantly improved access to en-bloc heart-lung allografts compared with the prior policy, with better waitlist outcomes and similar post-transplant outcomes.

  View details for DOI 10.3389/ti.2023.11956

  View details for PubMedID 38152546

• Midterm Outcomes in Type A Aortic Dissection Repair with and without Malperfusion in a Hybrid Operating Room. Seminars in thoracic and cardiovascular surgery Dalal, A. R., Dossabhoy, S., Heng, E., Yasin, A., Leipzig, M. M., Bonham, S. A., Fischbein, M. P., Lee, J. T., Woo, Y. J., Watkins, A. C. 2022

  Abstract

  Treatment approach to type A aortic dissection with malperfusion, immediate open aortic repair versus upfront endovascular treatment, remains controversial. From January 2017 to July 2021, 301 consecutive type A repairs were evaluated at our institution. Starting in 2019, all type A aortic dissections were performed in a fixed-fluoroscopy, hybrid operating room. Propensity score matching was used to control baseline patient characteristics between traditional and hybrid operating room approaches. There were 144 patients in the traditional group and 157 in the hybrid group. In the hybrid group, 41% (64/157) underwent intraoperative angiograms, and of those, 58% (37/64) received at least one endovascular intervention. Following propensity matching, 125 patients remained in each the traditional and hybrid groups. Thirty-day survival was significantly improved in the hybrid cohort at 96.7%% (122/125) as compared to the traditional cohort at 87.2% (109/125) (p=0.002). There were no significant differences in perioperative paralysis (1.6% vs. 1.6%, p>0.9), new hemodialysis (12% vs. 9.6%, p=0.5), fasciotomy (2.4% vs. 5.6%, p=0.20, and exploratory laparotomy (1.6% vs. 4.8%, p=0.3). The hybrid operating room approach to type A aortic dissection, provides the ability to immediately assess distal malperfusion and perform endovascular interventions at the time of open aortic repair, and is associated with significantly higher 30-day and 2-year survival when compared to a stepwise repair approach in a traditional operating room.

  View details for DOI 10.1053/j.semtcvs.2022.12.003

  View details for PubMedID 36567047

• Surgical management of severe mitral annular calcification. Asian cardiovascular & thoracic annals Elde, S., Zhu, Y., MacArthur, J. W., Woo, Y. J. 2022: 2184923221136935

  Abstract

  BACKGROUND: Surgical management of severe mitral annular calcification (MAC) presents a challenging problem for even the most experienced surgeons. Preoperative planning is the most effective strategy to mitigate risk in these scenarios. MAC alone should not disqualify a patient from consideration for mitral valve repair, although the presence of concurrent greater than moderate stenosis warrants consideration of mitral valve replacement.METHODS: While repair and replacement techniques for mitral regurgitation in the setting of MAC overlap with those used to repair a non-calcified mitral apparatus, there are unique considerations to the surgical conduct of these procedures. Specifically, this article describes techniques that may be employed when the severity of MAC precludes typical repair or replacement strategies.RESULTS: Between 2014 and 2021, 77 patients were operated on by a single surgeon for mitral valve disease complicated by severe MAC. Using the systematic approach described herein, 1-year mortality was 7.8% and overall mortality over a follow-up period extending 1 to 8 years was 9.1%.CONCLUSIONS: Despite the inherent challenges of mitral valve repair or replacement in the setting of severe MAC, a systematic approach beginning with preoperative planning, modification of annular suture placement, and techniques to mitigate severe complications have, in our experience, resulting in a reliable methodology for managing severe MAC with excellent outcomes.

  View details for DOI 10.1177/02184923221136935

  View details for PubMedID 36537728

• Three-Dimensional Bioprinting with Alginate by Freeform Reversible Embedding of Suspended Hydrogels with Tunable Physical Properties and Cell Proliferation. Bioengineering (Basel, Switzerland) Zhu, Y., Stark, C. J., Madira, S., Ethiraj, S., Venkatesh, A., Anilkumar, S., Jung, J., Lee, S., Wu, C. A., Walsh, S. K., Stankovich, G. A., Woo, Y. J. 2022; 9 (12)

  Abstract

  Extrusion-based three-dimensional (3D) bioprinting is an emerging technology that allows for rapid bio-fabrication of scaffolds with live cells. Alginate is a soft biomaterial that has been studied extensively as a bio-ink to support cell growth in 3D constructs. However, native alginate is a bio-inert material that requires modifications to allow for cell adhesion and cell growth. Cells grown in modified alginates with the RGD (arginine-glycine-aspartate) motif, a naturally existing tripeptide sequence that is crucial to cell adhesion and proliferation, demonstrate enhanced cell adhesion, spreading, and differentiation. Recently, the bioprinting technique using freeform reversible embedding of suspended hydrogels (FRESH) has revolutionized 3D bioprinting, enabling the use of soft bio-inks that would otherwise collapse in air. However, the printability of RGD-modified alginates using the FRESH technique has not been evaluated. The associated physical properties and bioactivity of 3D bio-printed alginates after RGD modification remains unclear. In this study, we characterized the physical properties, printability, and cellular proliferation of native and RGD-modified alginate after extrusion-based 3D bioprinting in FRESH. We demonstrated tunable physical properties of native and RGD-modified alginates after FRESH 3D bioprinting. Sodium alginate with RGD modification, especially at a high concentration, was associated with greatly improved cell viability and integrin clustering, which further enhanced cell proliferation.

  View details for DOI 10.3390/bioengineering9120807

  View details for PubMedID 36551013

• Outcomes of Heart Transplantation Using a Temperature-controlled Hypothermic Storage System. Transplantation Zhu, Y., Shudo, Y., He, H., Kim, J. Y., Elde, S., Williams, K. M., Walsh, S. K., Koyano, T. K., Guenthart, B., Woo, Y. J. 2022

  Abstract

  The SherpaPak Cardiac Transport System is a novel technology that provides stable, optimal hypothermic control during organ transport. The objectives of this study were to describe our experience using the SherpaPak system and to compare outcomes after heart transplantation after using SherpaPak versus the conventional static cold storage method (non-SherpaPak).From 2018 to June 2021, 62 SherpaPak and 186 non-SherpaPak patients underwent primary heart transplantation at Stanford University with follow-up through May 2022. The primary end point was all-cause mortality, and secondary end points were postoperative complications. Optimal variable ratio matching, cox proportional hazards regression model, and Kaplan-Meier survival analyses were performed.Before matching, the SherpaPak versus non-SherpaPak patients were older and received organs with significantly longer total allograft ischemic time. After matching, SherpaPak patients required fewer units of blood product for perioperative transfusion compared with non-SherpaPak patients but otherwise had similar postoperative outcomes such as hospital length of stay, primary graft dysfunction, inotrope score, mechanical circulatory support use, cerebral vascular accident, myocardial infarction, respiratory failure, new renal failure requiring dialysis, postoperative bleeding or tamponade requiring reoperation, infection, and survival.In conclusion, this is one of the first retrospective comparison studies that evaluated the outcomes of heart transplantation using organs preserved and transported via the SherpaPak system. Given the excellent outcomes, despite prolonged total allograft ischemic time, it may be reasonable to adopt the SherpaPak system to accept organs from a remote location to further expand the donor pool.

  View details for DOI 10.1097/TP.0000000000004416

  View details for PubMedID 36510359

• Biomechanical evaluation of aortic regurgitation from cusp prolapse using an ex vivo 3D-printed commissure geometric alignment device. Journal of cardiothoracic surgery Zhu, Y., Park, M. H., Imbrie-Moore, A., Wilkerson, R., Madira, S., Woo, Y. J. 2022; 17 (1): 303

  Abstract

  BACKGROUND: Aortic regurgitation (AR) is one of the most common cardiac valvular diseases, and it is frequently caused by cusp prolapse. However, the precise relationship of commissure position and aortic cusp prolapse with AR is not fully understood. In this study, we developed a 3D-printed commissure geometric alignment device to investigate the effect of commissure height and inter-commissure angle on AR and aortic cusp prolapse.METHODS: Three porcine aortic valves were explanted from hearts obtained from a meat abattoir and were mounted in the commissure geometric alignment device. Nine commissure configurations were tested for each specimen, exploring independent and concurrent effects of commissure height and inter-commissure angle change on AR and aortic cusp prolapse. Each commissure configuration was tested in our 3D printed ex vivo left heart simulator. Hemodynamics data, echocardiography, and high-speed videography were obtained.RESULTS: AR due to aortic cusp prolapse was successfully generated using our commissure geometric alignment device. Mean aortic regurgitation fraction measured for the baseline, high commissure, low commissure, high commissure and wide inter-commissure angle, high commissure and narrow inter-commissure angle, low commissure and wide inter-commissure angle, low commissure and narrow inter-commissure angle, wide commissure, and narrow commissure configurations from all samples were 4.6±1.4%, 9.7±3.7%, 4.2±0.5%, 11.7±5.8%, 13.0±8.5%, 4.8±0.9%, 7.3±1.7%, 5.1±1.2%, and 7.1±3.1%, respectively.CONCLUSIONS: AR was most prominent when commissure heights were changed from their native levels with concomitant reduced inter-commissure angle. Findings from this study provide important evidence demonstrating the relationship between commissure position and aortic cusp prolapse and may have a significant impact on patient outcomes after surgical repair of aortic valves.

  View details for DOI 10.1186/s13019-022-02049-5

  View details for PubMedID 36496476

• Resection of a synovial cell sarcoma by cardiac autotransplantation: A case report. JTCVS techniques Mullis, D. M., Zhu, Y., Guenthart, B. A., Bonham, S. A., Trope, W. L., Berry, G. J., Woo, Y. J., MacArthur, J. W. 2022; 16: 123-127

  View details for DOI 10.1016/j.xjtc.2022.09.009

  View details for PubMedID 36510550

  View details for PubMedCentralID PMC9735421

• Native and Post-Repair Residual Mitral Valve Prolapse Increases Forces Exerted on the Papillary Muscles: A Possible Mechanism for Localized Fibrosis? Circulation. Cardiovascular interventions Park, M. H., van Kampen, A., Melnitchouk, S., Wilkerson, R. J., Nagata, Y., Zhu, Y., Wang, H., Pandya, P. K., Morningstar, J. E., Borger, M. A., Levine, R. A., Woo, Y. J. 2022; 15 (12): e011928

  Abstract

  Recent studies have linked mitral valve prolapse to localized myocardial fibrosis, ventricular arrhythmia, and even sudden cardiac death independent of mitral regurgitation or hemodynamic dysfunction. The primary mechanistic theory is rooted in increased papillary muscle traction and forces due to prolapse, yet no biomechanical evidence exists showing increased forces. Our objective was to evaluate the biomechanical relationship between prolapse and papillary muscle forces, leveraging advances in ex vivo modeling and technologies. We hypothesized that mitral valve prolapse with limited hemodynamic dysfunction leads to significantly higher papillary muscle forces, which could be a possible trigger for cellular and electrophysiological changes in the papillary muscles and adjacent myocardium.We developed an ex vivo papillary muscle force transduction and novel neochord length adjustment system capable of modeling targeted prolapse. Using 3 unique ovine models of mitral valve prolapse (bileaflet or posterior leaflet prolapse), we directly measured hemodynamics and forces, comparing physiologic and prolapsing valves.We found that bileaflet prolapse significantly increases papillary muscle forces by 5% to 15% compared with an optimally coapting valve, which are correlated with statistically significant decreases in coaptation length. Moreover, we observed significant changes in the force profiles for prolapsing valves when compared with normal controls.We discovered that bileaflet prolapse with the absence of hemodynamic dysfunction results in significantly elevated forces and altered dynamics on the papillary muscles. Our work suggests that the sole reduction of mitral regurgitation without addressing reduced coaptation lengths and thus increased leaflet surface area exposed to ventricular pressure gradients (ie, billowing leaflets) is insufficient for an optimal repair.

  View details for DOI 10.1161/CIRCINTERVENTIONS.122.011928

  View details for PubMedID 36538583

• Force Profiles of Single Ventricle Atrioventricular Leaflets in Response to Annular Dilation and Leaflet Tethering. Seminars in thoracic and cardiovascular surgery Kidambi, S., Moye, S. C., Lee, J., Cowles, T. H., Strong, E. B., Wilkerson, R., Paulsen, M. J., Woo, Y. J., Ma, M. R. 2022

  Abstract

  We sought to understand how leaflet forces change in response to annular dilation and leaflet tethering in single ventricle physiology. Explanted fetal bovine tricuspid valves were sutured onto image-derived annuli and ventricular mounts. Control valves (CV) were secured to a size-matched HLHS-type annulus and compared to: 1) normal tricuspid valves (NTV) secured to a size-matched saddle-shaped annulus, 2) HLHS-type annulus with leaflet tethering (LT), 3) HLHS-type annulus with annular dilation (DIL), or 5) a combined disease model with both dilation and tethering (DIS). The specimens were tested in a systemic heart simulator at various SVPs. Leaflet forces were measured using optical strain sensors sutured to each leaflet edge. Average force in the anterior leaflet was 43.2% lower in CV compared to NTV (p<0.001). LT resulted in a 6.6% increase in average forces on the anterior leaflet (p=0.04), 10.7% increase on the posterior leaflet (p=0.03), and 14.1% increase on the septal leaflet (p<0.001). In DIL, average septal leaflet forces increased relative to the control valves by 42.2% (p=0.01). In DIS, average leaflet forces increased by 54.8% in the anterior leaflet (p<0.001), 37.6% in the posterior leaflet (p=0.03), and 79.9% in the septal leaflet (p<0.001). The anterior leaflet experiences the highest forces in the normal tricuspid annulus under SVP conditions. Annular dilation resulted in an increase in forces on the septal leaflet and leaflet tethering resulted in an increase in forces across all 3 leaflets. Annular dilation and leaflet tethering combined resulted in the largest increase in leaflet forces across all 3 leaflets.

  View details for DOI 10.1053/j.semtcvs.2022.09.012

  View details for PubMedID 36455710

• Coronary Artery Bypass Surgery Without Saphenous Vein Grafting: JACC Review Topic of the Week. Journal of the American College of Cardiology Royse, A., Ren, J., Royse, C., Tian, D. H., Fremes, S., Gaudino, M., Benedetto, U., Woo, Y. J., Goldstone, A. B., Davierwala, P., Borger, M., Vallely, M., Reid, C. M., Rocha, R., Glineur, D., Grau, J., Shaw, R., Paterson, H., El-Ansary, D., Boggett, S., Srivastav, N., Pawanis, Z., Canty, D., Bellomo, R. 2022; 80 (19): 1833-1843

  Abstract

  Approximately 95% of patients of any age undergoing contemporary, coronary bypass surgery will receive at least 1 saphenous vein graft (SVG). It is recognized that SVG will develop progressive and accelerated atherosclerosis, resulting in a stenosis, and in occlusion that occurs in 50% by 10 years postoperatively. For arterial conduits, there is little evidence of progressive failure as for SVG. Could avoidance of SVG (total arterial revascularization [TAR]) lead to a different late (>5 year) survival? A literature review of 23 studies (N = 100,314 matched patients) at a mean 8.8 years postoperative found reduced all-cause mortality for TAR (HR: 0.77; 95% CI: 0.71-0.84; P < 0.001). An expanded analysis with a new unpublished data set (N = 63,288 matched patients) was combined with the literature review (N = 127,565). It found reduced all-cause mortality for TAR (HR: 0.78; 95% CI: 0.72-0.85; P < 0.001). Additional Bayesian analysis found a very high probability of a TAR-associated reduction all-cause mortality.

  View details for DOI 10.1016/j.jacc.2022.08.795

  View details for PubMedID 36328694

• A novel accelerated fatigue testing system for pulsatile applications of cardiac devices using widely translatable cam and linkage-based mechanisms MEDICAL ENGINEERING & PHYSICS Park, M. H., Imbrie-Moore, A. M., Zhu, Y., Sellke, M., Marin-Cuartas, M., Wilkerson, R. J., Woo, Y. 2022; 109

  View details for DOI 10.1016/j.medengphy.2022.103896

  View details for Web of Science ID 000868472500004

• A novel accelerated fatigue testing system for pulsatile applications of cardiac devices using widely translatable cam and linkage-based mechanisms. Medical engineering & physics Park, M. H., Imbrie-Moore, A. M., Zhu, Y., Sellke, M., Marin-Cuartas, M., Wilkerson, R. J., Woo, Y. J. 2022; 109: 103896

  Abstract

  Fatigue testing of mechanical components is important for designing safe implantable medical prosthetics, and accelerated systems can be used to increase the speed of evaluation. We developed a platform for accelerated testing of linear force applications of cardiac devices, called the Fatigue Acceleration System Tester (FAST). FAST operates using a core translation mechanism, converting motor-driven rotary motion to linear actuation. The advantages of using this mechanism include 40x rate increases with largely 3D-printed components, versatility based on modular design paradigms, and accessible manufacturability with 3D-printable forms, enabling access for small and large research laboratories alike. FAST has been crucial in informing our designs for continuing device development. Over two fatigue cycle courses of 52 and 110 days, the motor cycled at rotational frequencies up to 1500 rpm, 43 times faster than those experienced in a typical heart and equating to approximate life cycles of five and ten years, respectively. In designing FAST, our goal was to accessibly bring a strong mechanical basis to study the long-term effects of repeated loading, and we present a design that can be applied across many industries to not only evaluate fatigue performance, but also generate any cycling linear motion.

  View details for DOI 10.1016/j.medengphy.2022.103896

  View details for PubMedID 36371080

• The Critical Biomechanics of Aortomitral Angle and Systolic Anterior Motion: Engineering Native Ex Vivo Simulation. Annals of biomedical engineering Park, M. H., Imbrie-Moore, A. M., Zhu, Y., Wilkerson, R. J., Wang, H., Park, G. H., Wu, C. A., Pandya, P. K., Mullis, D. M., Marin-Cuartas, M., Woo, Y. J. 2022

  Abstract

  Systolic anterior motion (SAM) of the mitral valve (MV) is a complex pathological phenomenon often occurring as an iatrogenic effect of surgical and transcatheter intervention. While the aortomitral angle has long been linked to SAM, the mechanistic relationship is not well understood. We developed the first ex vivo heart simulator capable of recreating native aortomitral biomechanics, and to generate models of SAM, we performed anterior leaflet augmentation and sequential undersized annuloplasty procedures on porcine aortomitral junctions (n=6). Hemodynamics and echocardiograms were recorded, and echocardiographic analysis revealed significantly reduced coaptation-septal distances confirming SAM (p=0.003) and effective manipulation of the aortomitral angle (p<0.001). Upon increasing the angle in our pathological models, we recorded significant increases (p<0.05) in both coaptation-septal distance and multiple hemodynamic metrics, such as aortic peak flow and effective orifice area. These results indicate that an increased aortomitral angle is correlated with more efficient hemodynamic performance of the valvular system, presenting a potential, clinically translatable treatment opportunity for reducing the risk and adverse effects of SAM. As the standard of care shifts towards surgical and transcatheter interventions, it is increasingly important to better understand SAM biomechanics, and our advances represent a significant step towards that goal.

  View details for DOI 10.1007/s10439-022-03091-z

  View details for PubMedID 36264407

• Heart transplantation with concomitant reoperative total aortic arch replacement in a patient with end-stage heart failure and chronic aortic arch dissection. JTCVS techniques Kasinpila, P., Krishnam, M., Woo, Y. J. 2022; 15: 144-146

  View details for DOI 10.1016/j.xjtc.2022.07.014

  View details for PubMedID 36276674

• A value-based approach to optimize red blood cell transfusion in patients receiving extracorporeal membrane oxygenation. Perfusion Shudo, Y., Cheng, N., He, H., Rosenberg, C., Hiesinger, W., Hadhazy, E., Shepard, J., Krishna, P., Resnik, J., Fong, R., Hill, C., Hsu, J. L., Maggio, P. M., Chang, S., Boyd, J. H., Woo, Y. J. 2022: 2676591221128138

  Abstract

  INTRODUCTION: The risk, cost, and adverse outcomes associated with packed red blood cell (RBC) transfusions in patients with cardiopulmonary failure requiring extracorporeal membrane oxygenation (ECMO) have raised concerns regarding the overutilization of RBC products. It is, therefore, necessary to establish optimal transfusion criteria and protocols for patients supported with ECMO. The goal of this study was to establish specific criteria for RBC transfusions in patients undergoing ECMO.METHODS: This was a retrospective cohort study conducted at Stanford University Hospital. Data on RBC utilization during the entire hospital stay were obtained, which included patients aged ≥18years who received ECMO support between 1 January 2017, and 30 June 2020 (n = 281). The primary outcome was in-hospital mortality.RESULTS: Hemoglobin (HGB) levels >10g/dL before transfusion did not improve in-hospital survival. Therefore, we revised the HGB threshold to ≤10g/dL to guide transfusion in patients undergoing ECMO. To validate this intervention, we prospectively compared the pre- and post-intervention cohorts for in-hospital mortality. Post-intervention analyses found 100% compliance for all eligible records and a decrease in the requirement for RBC transfusion by 1.2 units per patient without affecting the mortality.CONCLUSIONS: As an institution-driven value-based approach to guide transfusion in patients undergoing ECMO, we lowered the threshold HGB level. Validation of this revised intervention demonstrated excellent compliance and reduced the need for RBC transfusion while maintaining the clinical outcome. Our findings can help reform value-based healthcare in this cohort while maintaining the outcome.

  View details for DOI 10.1177/02676591221128138

  View details for PubMedID 36148806

• DynaRing: A Patient-Specific Mitral Annuloplasty Ring With Selective Stiffness Segments. Journal of medical devices Frishman, S., Kight, A., Pirozzi, I., Maddineni, S., Imbrie-Moore, A. M., Karachiwalla, Z., Paulsen, M. J., Kaiser, A. D., Woo, Y. J., Cutkosky, M. R. 2022; 16 (3): 031009

  Abstract

  Annuloplasty ring choice and design are critical to the long-term efficacy of mitral valve (MV) repair. DynaRing is a selectively compliant annuloplasty ring composed of varying stiffness elastomer segments, a shape-set nitinol core, and a cross diameter filament. The ring provides sufficient stiffness to stabilize a diseased annulus while allowing physiological annular dynamics. Moreover, adjusting elastomer properties provides a mechanism for effectively tuning key MV metrics to specific patients. We evaluate the ring embedded in porcine valves with an ex-vivo left heart simulator and perform a 150 million cycle fatigue test via a custom oscillatory system. We present a patient-specific design approach for determining ring parameters using a finite element model optimization and patient MRI data. Ex-vivo experiment results demonstrate that motion of DynaRing closely matches literature values for healthy annuli. Findings from the patient-specific optimization establish DynaRing's ability to adjust the anterior-posterior and intercommissural diameters and saddle height by up to 8.8%, 5.6%, 19.8%, respectively, and match a wide range of patient data.

  View details for DOI 10.1115/1.4054445

  View details for PubMedID 35646225

• A Novel Rheumatic Mitral Valve Disease Model with Ex Vivo Hemodynamic and Biomechanical Validation. Cardiovascular engineering and technology Park, M. H., Pandya, P. K., Zhu, Y., Mullis, D. M., Wang, H., Imbrie-Moore, A. M., Wilkerson, R., Marin-Cuartas, M., Woo, Y. J. 2022

  Abstract

  PURPOSE: Rheumatic heart disease is a major cause of mitral valve (MV) dysfunction, particularly in disadvantaged areas and developing countries. There lacks a critical understanding of the disease biomechanics, and as such, the purpose of this study was to generate the first ex vivo porcine model of rheumatic MV disease by simulating the human pathophysiology and hemodynamics.METHODS: Healthy porcine valves were altered with heat treatment, commissural suturing, and cyanoacrylate tissue coating, all of which approximate the pathology of leaflet stiffening and thickening as well as commissural fusion. Hemodynamic data, echocardiography, and high-speed videography were collected in a paired manner for control and model valves (n=4) in an ex vivo left heart simulator. Valve leaflets were characterized in an Instron tensile testing machine to understand the mechanical changes of the model (n=18).RESULTS: The model showed significant differences indicative of rheumatic disease: increased regurgitant fractions (p<0.001), reduced effective orifice areas (p<0.001), augmented transmitral mean gradients (p<0.001), and increased leaflet stiffness (p=0.025).CONCLUSION: This work represents the creation of the first ex vivo model of rheumatic MV disease, bearing close similarity to the human pathophysiology and hemodynamics, and it will be used to extensively study both established and new treatment techniques, benefitting the millions of affected victims.

  View details for DOI 10.1007/s13239-022-00641-3

  View details for PubMedID 35941509

• Quantitative biomechanical optimization of neochordal implantation location on mitral leaflets during valve repair. JTCVS techniques Pandya, P. K., Wilkerson, R. J., Imbrie-Moore, A. M., Zhu, Y., Marin-Cuartas, M., Park, M. H., Woo, Y. J. 2022; 14: 89-93

  Abstract

  Objective: Suture pull-out remains a significant mechanism of long-term neochordal repair failure, as demonstrated by clinical reports on recurrent mitral valve regurgitation and need for reoperation. The objective of this study was to provide a quantitative comparison of suture pull-out forces for various neochordal implantation locations.Methods: Posterior leaflets were excised from fresh porcine mitral valves (n=54) and fixed between two 3-dimensional-printed plates. Gore-Tex CV-5 sutures (WL Gore & Associates Inc) were placed with distances from the leading edge and widths between anchoring sutures with values of 2mm, 6mm, and 10mm for a total of 9 groups (n=6 per group). Mechanical testing was performed using a tensile testing machine to evaluate pull-out force of the suture through the mitral valve leaflet.Results: Increasing the suture anchoring width improved failure strength significantly across all leading-edge distances (P<.001). Additionally, increasing the leading-edge distance from 2mm to 6mm increased suture pull-out forces significantly across all suture widths (P<.001). For 6-mm and 10-mm widths, increasing the leading-edge distance from 6mm to 10mm increased suture pull-out forces by an average of 3.58±0.15N; in comparison, for leading-edge distances of 6mm and 10mm, increasing the suture anchoring width from 6mm to 10mm improves the force by an average of 7.09±0.44N.Conclusions: Increasing suture anchoring width and leading-edge distance improves the suture pull-out force through the mitral leaflet, which may optimize postrepair durability. The results suggest a comparative advantage to increasing suture anchoring width compared with leading-edge distance.

  View details for DOI 10.1016/j.xjtc.2022.05.008

  View details for PubMedID 35967240

• Combined Heart-Lung Transplantation Outcomes in Asian Populations: National Database Analysis. JACC. Asia Shudo, Y., Leipzig, M., He, H., Ingle, S. M., Bhatt, R. H., Shin, H., Woo, Y. J. 2022; 2 (4): 504-512

  Abstract

  Background: Heart-lung transplantation (HLTx) is a definitive surgical procedure for end-stage cardiopulmonary failure. Studies to understand the relationship between ethnicity and race and outcomes after HLTx are needed to uphold equitable HLTx access to the increasingly diverse U.S. population facing advanced cardiopulmonary failure.Objectives: This study sought to examine the outcomes of HLTx recipients of Asian origin, with emphasis on the ethnic and racial disparities in the outcomes.Methods: We analyzed data from the United Network for Organ Sharing (UNOS) for patients of≥18 years of age who underwent HLTx between 1987 and 2021. Propensity-score matching was performed between Asian and non-Hispanic Whites (NHWs), with a 1:3 matching ratio based on the propensity score of each patient estimated by multivariable logistic regression.Results: We identified 42 Asian and Asian American heart-lung transplant recipients and 834 NHW recipients. In the pre-matched cohort, the median survival was 1,459days (IQR: 1,080-2,692days) in Asian recipients after transplantation, whereas it was 1,521days (IQR: 1,262-1,841days) in White recipients. Of the 876 recipients, 156 transplants were successfully matched (Asian, n=36; NHW, n=108). Among the post-transplantation outcomes, there were no significant differences in morbidity and mortality between Asian and NHW cohorts.Conclusions: This large-scale analysis in Asian patients will have important implications in Asian countries that have relatively fewer HLTx surgeries. An outcome equivalent to NHW in Asian patients, as demonstrated in our study, could be the driving force for further expansion of HLTx surgeries in Asian countries.

  View details for DOI 10.1016/j.jacasi.2022.03.012

  View details for PubMedID 36339364

• Biomechanical Engineering Analysis of Pulmonary Valve Leaflet Hemodynamics and Kinematics in the Ross Procedure. Journal of biomechanical engineering Zhu, Y., Wilkerson, R., Pandya, P., Mullis, D., Wu, C., Madira, S., Marin-Cuartas, M., Park, M. H., Imbrie-Moore, A., Woo, Y. J. 2022

  Abstract

  Objectives The Ross procedure using the inclusion technique with anti-commissural plication (ACP) is associated with excellent valve hemodynamics and leaflet kinematics. The objective was to evaluate pulmonary cusp's biomechanics and fluttering by including coronary flow in the Ross procedure. Methods Ten porcine and five human pulmonary autografts were harvested from a meat abattoir and from heart transplant patients. Five porcine autografts without reinforcement served as controls. The other autografts were prepared using the inclusion technique with and without ACP (NACP). Hemodynamic and high-speed videography data were measured using the ex vivo heart simulator. Results Although porcine autografts showed similar leaflet rapid opening and closing mean velocities, human ACP compared to NACP autografts demonstrated lower leaflet rapid opening mean velocity in the right (p=.02) and left coronary cusps (p=.003). The porcine and human autograft leaflet rapid opening and closing mean velocities were similar in all cusps. Porcine autografts showed similar leaflet flutter frequencies in the left (p=.3) and non-coronary cusps (p=.4), but porcine NACP autografts vs. controls demonstrated higher leaflet flutter frequency in the right coronary cusp (p=.05). The human NACP vs. ACP autografts showed higher flutter frequency in the non-coronary cusp (p=.02). The leaflet flutter amplitudes were similar in all three cusps in both porcine and human autografts. Conclusions The ACP compared to NACP autografts in the Ross procedure was associated with more favorable leaflet kinematics. These results may translate to improved long-term durability of the pulmonary autografts.

  View details for DOI 10.1115/1.4055033

  View details for PubMedID 35864775

• A novel photosynthetic biologic topical gel for enhanced localized hyperoxygenation augments wound healing in peripheral artery disease. Scientific reports Zhu, Y., Jung, J., Anilkumar, S., Ethiraj, S., Madira, S., Tran, N. A., Mullis, D. M., Casey, K. M., Walsh, S. K., Stark, C. J., Venkatesh, A., Boakye, A., Wang, H., Woo, Y. J. 2022; 12 (1): 10028

  Abstract

  Peripheral artery disease and the associated ischemic wounds are substantial causes of global morbidity and mortality, affecting over 200 million people worldwide. Although advancements have been made in preventive, pharmacologic, and surgical strategies to treat this disease, ischemic wounds, a consequence of end-stage peripheral artery disease, remain a significant clinical and economic challenge. Synechococcus elongatus is a cyanobacterium that grows photoautotrophically and converts carbon dioxide and water into oxygen. We present a novel topical biologic gel containing S. elongatus that provides oxygen via photosynthesis to augment wound healing by rescuing ischemic tissues caused by peripheral artery disease. By using light rather than blood as a source of energy, our novel topical therapy significantly accelerated wound healing in two rodent ischemic wound models. This novel topical gel can be directly translated to clinical practice by using a localized, portable light source without interfering with patients' daily activities, demonstrating potential to generate a paradigm shift in treating ischemic wounds from peripheral artery disease. Its novelty, low production cost, and ease of clinical translatability can potentially impact the clinical care for millions of patients suffering from peripheral arterial disease.

  View details for DOI 10.1038/s41598-022-14085-1

  View details for PubMedID 35705660

• FDA Emergency Use Authorization-Approved Novel Coronavirus Disease 2019, Pressure-Regulated, Mechanical Ventilator Splitter That Enables Differential Compliance Multiplexing. ASAIO journal (American Society for Artificial Internal Organs : 1992) Paulsen, M. J., Zhu, Y., Park, M. H., Imbrie-Moore, A. M., Baker, S., Walter Edmonston, D., Dawson, T., Ly, E., Martin Bell, S., Tran, N. A., Jung, J., Cedarleaf-Pavy, J., Sridhar, K. R., Venkataraman, V., Woo, Y. J. 2022

  Abstract

  Infection with the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may cause viral pneumonia and acute respiratory distress syndrome (ARDS). Treatment of ARDS often requires mechanical ventilation and may take weeks for resolution. In areas with a large outbreaks, there may be shortages of ventilators available. While rudimentary methods for ventilator splitting have been described, given the range of independent ventilatory settings required for each patient, this solution is suboptimal. Here, we describe a device that can split a ventilator among up to four patients while allowing for individualized settings. The device has been validated in vitro and in vivo.

  View details for DOI 10.1097/MAT.0000000000001756

  View details for PubMedID 35667305

• Integration of Reinforcement Learning in a Virtual Robotic Surgical Simulation. Surgical innovation Bourdillon, A. T., Garg, A., Wang, H., Woo, Y. J., Pavone, M., Boyd, J. 2022: 15533506221095298

  Abstract

  Background. The revolutions in AI hold tremendous capacity to augment human achievements in surgery, but robust integration of deep learning algorithms with high-fidelity surgical simulation remains a challenge. We present a novel application of reinforcement learning (RL) for automating surgical maneuvers in a graphical simulation.Methods. In the Unity3D game engine, the Machine Learning-Agents package was integrated with the NVIDIA FleX particle simulator for developing autonomously behaving RL-trained scissors. Proximal Policy Optimization (PPO) was used to reward movements and desired behavior such as movement along desired trajectory and optimized cutting maneuvers along the deformable tissue-like object. Constant and proportional reward functions were tested, and TensorFlow analytics was used to informed hyperparameter tuning and evaluate performance.Results. RL-trained scissors reliably manipulated the rendered tissue that was simulated with soft-tissue properties. A desirable trajectory of the autonomously behaving scissors was achieved along 1 axis. Proportional rewards performed better compared to constant rewards. Cumulative reward and PPO metrics did not consistently improve across RL-trained scissors in the setting for movement across 2 axes (horizontal and depth).Conclusion. Game engines hold promising potential for the design and implementation of RL-based solutions to simulated surgical subtasks. Task completion was sufficiently achieved in one-dimensional movement in simulations with and without tissue-rendering. Further work is needed to optimize network architecture and parameter tuning for increasing complexity.

  View details for DOI 10.1177/15533506221095298

  View details for PubMedID 35503302

• Human Coronary Plaque T Cells Are Clonal and Cross-React to Virus and Self. Circulation research Roy Chowdhury, R., D'Addabbo, J., Huang, X., Veizades, S., Sasagawa, K., Louis, D. M., Cheng, P., Sokol, J., Jensen, A., Tso, A., Shankar, V., Wendel, B. S., Bakerman, I., Liang, G., Koyano, T., Fong, R., Nau, A., Ahmad, H., Gopakumar, J. K., Wirka, R., Lee, A., Boyd, J., Woo, Y. J., Quertermous, T., Gulati, G., Jaiswal, S., Chien, Y. H., Chan, C., Davis, M. M., Nguyen, P. K. 2022: 101161CIRCRESAHA121320090

  Abstract

  Once considered primarily a disorder of lipid deposition, coronary artery disease is an incurable, life-threatening disease that is now also characterized by chronic inflammation notable for the buildup of atherosclerotic plaques containing immune cells in various states of activation and differentiation. Understanding how these immune cells contribute to disease progression may lead to the development of novel therapeutic strategies.We used single-cell technology and in vitro assays to interrogate the immune microenvironment of human coronary atherosclerotic plaque at different stages of maturity.In addition to macrophages, we found a high proportion of αβ T cells in the coronary plaques. Most of these T cells lack high expression of CCR7 and L-selectin, indicating that they are primarily antigen-experienced, memory cells. Notably, nearly one-third of these cells express the HLA-DRA surface marker, signifying activation through their TCRs (T-cell receptors). Consistent with this, TCR repertoire analysis confirmed the presence of activated αβ T cells (CD4

  View details for DOI 10.1161/CIRCRESAHA.121.320090

  View details for PubMedID 35430876

• Quality of Life After Fractional Flow Reserve-Guided PCI Compared with Coronary Bypass Surgery. Circulation Fearon, W. F., Zimmermann, F. M., Ding, V. Y., Zelis, J. M., Piroth, Z., Davidavicius, G., Mansour, S., Kharbanda, R., Ostlund-Papadogeorgos, N., Oldroyd, K. G., Wendler, O., Reardon, M. J., Woo, Y. J., Yeung, A. C., Pijls, N. H., De Bruyne, B., Desai, M., Hlatky, M. A., FAME 3 Investigators 2022

  Abstract

  Background: Previous studies have shown quality of life improves after coronary revascularization, more so after coronary artery bypass grafting (CABG) than after percutaneous coronary intervention (PCI). This study aimed to evaluate the impact of fractional flow reserve (FFR) guidance and current generation, zotarolimus drug-eluting stents (DES) on quality of life after PCI compared with CABG. Methods: The Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) 3 trial is a multicenter, international trial including 1500 patients with three-vessel coronary artery disease (CAD) who were randomly assigned to either CABG or FFR-guided PCI. Quality of life was measured using the European Quality of Life-5 Dimensions (EQ-5D) questionnaire at baseline, 1 and 12 months. The Canadian Cardiovascular Class (CCS) angina grade and working status were assessed at the same time points and at 6 months. The primary objective was to compare EQ-5D summary index at 12 months. Secondary endpoints included angina grade and work status. Results: The EQ-5D summary index at 12 months did not differ between the PCI and CABG groups (difference=0.001, 95% confidence interval (CI) -0.016 to 0.017, p=0.946). The trajectory of EQ-5D over the 12 months differed (p<0.001) between PCI and CABG: at 1 month, EQ-5D was 0.063 (95% CI 0.047 to 0.079) higher in the PCI group. A similar trajectory was found for the EQ visual analogue scale. The proportion of patients with CCS 2 or greater angina at 12 months was 6.2% vs 3.1% (OR=2.5, 95% CI 0.96 to 6.8), respectively in the PCI group compared with the CABG group. A greater percentage of younger patients (<65 years-old) were working at 12 months in the PCI group compared with the CABG group (68% vs 57%, OR=3.9, 95% CI 1.7 to 8.8). Conclusions: In the FAME 3 trial, quality of life after FFR-guided PCI with current generation DES compared with CABG was similar at one year. The rate of significant angina was low in both groups and not significantly different. The trajectory of improvement in quality of life was significantly better after PCI, as was working status in those less than 65 years old.

  View details for DOI 10.1161/CIRCULATIONAHA.122.060049

  View details for PubMedID 35369704

• Exvivo aortic valve replacement before orthotopic heart transplantation. JTCVS techniques Elde, S. F., Guenthart, B. A., Shudo, Y., Woo, Y. J. 2022; 12: 118-120

  View details for DOI 10.1016/j.xjtc.2022.01.008

  View details for PubMedID 35403016

• Efficacy of a Novel Posterior Leaflet Repair Device to Treat Secondary Mitral Regurgitation Using an Ex Vivo Heart Model. Structural heart : the journal of the Heart Team Kapadia, S. R., Harb, S. C., Hovest, T. J., Imbrie-Moore, A. M., Wilkerson, R. J., Woo, Y. J., Navia, J. L. 2022; 6 (1): 100023

  View details for DOI 10.1016/j.shj.2022.100023

  View details for PubMedID 37273469

  View details for PubMedCentralID PMC10236895

• Efficacy of a Novel Posterior Leaflet Repair Device to Treat Secondary Mitral Regurgitation Using an Ex Vivo Heart Model STRUCTURAL HEART-THE JOURNAL OF THE HEART TEAM Kapadia, S. R., Harb, S. C., Hovest, T. J., Imbrie-Moore, A. M., Wilkerson, R. J., Woo, Y., Navia, J. L. 2022; 6 (1)

  View details for DOI 10.1016/j.shj.2022.100023

  View details for Web of Science ID 000796673400003

• Biomechanical analysis of neochordal repair error from diastolic phase inversion of static left ventricular pressurization. JTCVS techniques Park, M. H., Marin-Cuartas, M., Imbrie-Moore, A. M., Wilkerson, R. J., Pandya, P. K., Zhu, Y., Wang, H., Borger, M. A., Woo, Y. J. 2022; 12: 54-64

  Abstract

  Objective: Neochordal implantation is a common form of surgical mitral valve (MV) repair. However, neochord length is assessed using static left ventricular pressurization, leading surgeons to evaluate leaflet coaptation and valve competency when the left ventricle is dilating instead of contracting physiologically, referred to as diastolic phase inversion (DPI). We hypothesize that the difference in papillary muscle (PM) positioning between DPI and physiologic systole results in miscalculated neochord lengths, which might affect repair performance.Methods: Porcine MVs (n=6) were mounted in an exvivo heart simulator and PMs were affixed to robots that accurately simulate PM motion. Baseline hemodynamic and chordal strain data were collected, after which P2 chordae were severed to simulate posterior leaflet prolapse from chordal rupture and subsequent mitral regurgitation. Neochord implantation was performed in the physiologic and DPI static configurations.Results: Although both repairs successfully reduced mitral regurgitation, the DPI repair resulted in longer neochordae (2.19±0.4mm; P<.01). Furthermore, the hemodynamic performance was reduced for the DPI repair resulting in higher leakage volume (P=.01) and regurgitant fraction (P<.01). Peak chordal forces were reduced in the physiologic repair (0.57±0.11N) versus the DPI repair (0.68±0.12N; P<.01).Conclusions: By leveraging advanced exvivo technologies, we were able to quantify the effects of static pressurization on neochordal length determination. Our findings suggest that this post-repair assessment might slightly overestimate the neochordal length and that additional marginal shortening of neochordae might positively affect MV repair performance and durability by reducing load on surrounding native chordae.

  View details for DOI 10.1016/j.xjtc.2022.01.009

  View details for PubMedID 35403058

• Invited commentary: the choice between mechanical versus biologic mitral valves is becoming clear, what next? European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Williams, K. M., Woo, Y. J. 2022

  View details for DOI 10.1093/ejcts/ezac198

  View details for PubMedID 35349666

• American Association for Thoracic Surgery (AATS) website redesign: An update from the AATS IT Committee. The Journal of thoracic and cardiovascular surgery Woo, Y. J., Chen, F. Y., Chen, E. P. 2022

  View details for DOI 10.1016/j.jtcvs.2022.03.001

  View details for PubMedID 35307216

• Quantitative goals for research output and scholarly impact to enhance basic science R01 grant renewal for cardiothoracic surgeons. JTCVS open Wang, H., Bajaj, S. S., Heiler, J. C., Krishnan, A., Williams, K. M., Woo, Y. J., Boyd, J. H. 2022; 9: 162-175

  Abstract

  Objectives: Cardiothoracic (CT) surgeons with National Institutes of Health (NIH) R01 funding face a highly competitive renewal process. The factors that contribute to successful grant renewal for CT surgeons remain poorly defined. We hypothesized that renewed basic science grants are associated with high research output and scholarly impact during the preceding award cycle.Methods: Using a database of academic CT surgeons (n=992) at accredited training institutions in 2018, we identified basic science R01 grants awarded to CT surgeon principal investigators since 1985. Data for each award were obtained from publicly available online sources. Scholarly impact was evaluated using the NIH-validated relative citation ratio (RCR), defined as an article's citation rate divided by that of R01-funded publications in the same field. Continuous data are presented as medians and analyzed using the Mann-Whitney test.Results: We identified 102 basic science R01 award cycles, including 33 that were renewed (32.4%). Renewed and nonrenewed awards had a similar start year and funding period. Principal investigators of renewed versus nonrenewed awards were similar in surgical subspecialty, research training, attending experience, academic rank, and previous NIH funding. Renewed awards produced more publications per year over the funding cycle (3.4 vs 1.5; P=.0010) and exhibited a greater median RCR during the funding cycle (0.84 vs 0.66; P=.0183).Conclusions: CT surgery basic science R01 grants are associated with high research output and scholarly impact. At the 50th percentile among renewed grants, CT surgeons published 3.4 funded manuscripts per year with a median RCR of 0.84 during the previous award cycle.

  View details for DOI 10.1016/j.xjon.2021.10.063

  View details for PubMedID 36003453

• Ex vivo biomechanical analysis of flexible versus rigid annuloplasty rings in mitral valves using a novel annular dilation system. BMC cardiovascular disorders Zhu, Y., Imbrie-Moore, A. M., Wilkerson, R. J., Paulsen, M. J., Park, M. H., Woo, Y. J. 2022; 22 (1): 73

  Abstract

  BACKGROUND: Mitral annuloplasty rings restore annular dimensions to increase leaflet coaptation, serving a fundamental component in mitral valve repair. However, biomechanical evaluations of annuloplasty rings are lacking. We aim to biomechanically analyze flexible and rigid annuloplasty rings using an ex vivo mitral annular dilation model.METHODS: Juvenile porcine mitral valves (n=4) with intercommissural distance of 28mm were dilated to intercommissural distances of 40mm using a 3D-printed dilator and were sewn to an elastic mount. Fiber bragg grating sensors were anchored to native chordae to measure chordal forces. The valves were repaired using size 28 rigid and flexible annuloplasty rings in a random order. Hemodynamic data, echocardiography, and chordal force measurements were collected.RESULTS: Mitral annular dilation resulted in decreased leaflet coaptation height and increased mitral regurgitation fraction. Both the flexible and rigid annuloplasty rings effectively increased leaflet coaptation height compared to that post dilation. Rigid ring annuloplasty repair significantly decreased the mitral regurgitation fraction. Flexible annuloplasty ring repair reduced the chordal rate of change of force (7.1±4.4N/s versus 8.6±5.9N/s, p=0.02) and peak force (0.6±0.5N versus 0.7±0.6N, p=0.01) compared to that from post dilation. Rigid annuloplasty ring repair was associated with higher chordal rate of change of force (9.8±5.8N/s, p=0.0001) and peak force (0.7±0.5N, p=0.01) compared to that after flexible ring annuloplasty repair.CONCLUSIONS: Both rigid and flexible annuloplasty rings are effective in increasing mitral leaflet coaptation height. Although the rigid annuloplasty ring was associated with slightly higher chordal stress compared to that of the flexible annuloplasty ring, it was more effective in mitral regurgitation reduction. This study may help direct the design of an optimal annuloplasty ring to further improve patient outcomes.

  View details for DOI 10.1186/s12872-022-02515-x

  View details for PubMedID 35219298

• A Novel Device for Intraoperative Direct Visualization of a Pressurized Root in Aortic Valve Repair. The Annals of thoracic surgery Zhu, Y., Imbrie-Moore, A. M., Paulsen, M. J., Park, M. H., Tran, N. A., Woo, Y. J. 2022

  Abstract

  PURPOSE: One major challenge in generating reproducible aortic valve (AV) repair results is the inability to assess AV morphology under physiologic pressure. A transparent intraoperative aortic valve visualization device was designed and manufactured.DESCRIPTION: This device is comprised of an open proximal end, a cantilevered edge to allow attachment of the device to the aorta or graft, a distal viewing surface, and two side ports for fluid delivery and air removal.EVALUATION: The performance of the device was evaluated ex vivo using normal porcine AV in situ (n=3), AV after valve-sparing aortic root replacement (VSARR, n=3), and porcine pulmonary valve in Ross procedure (n=3), and in 3 patients who underwent VSARR. AV morphology was clearly visualized using the device in all experiments. In human, the use of this device successfully illustrated cusp prolapse after the initial VSARR and effectively guided additional cusp repair.CONCLUSIONS: This device successfully allows for direct visual assessment of the AV apparatus under physiologic pressure. The use of this device can potentially increase the adoptability of AV repair in clinical practice.

  View details for DOI 10.1016/j.athoracsur.2022.02.013

  View details for PubMedID 35216987

• Biomechanical engineering analysis of an acute papillary muscle rupture disease model using an innovative 3D-printed left heart simulator. Interactive cardiovascular and thoracic surgery Marin-Cuartas, M., Zhu, Y., Imbrie-Moore, A. M., Park, M. H., Wilkerson, R. J., Leipzig, M., Pandya, P. K., Paulsen, M. J., Borger, M. A., Woo, Y. J. 1800

  Abstract

  OBJECTIVES: The severity of acute papillary muscle (PM) rupture varies according to the extent and site of the rupture. However, the haemodynamic effects of different rupture variations are still poorly understood. Using a novel ex vivo model, we sought to study acute PM rupture to improve clinical management.METHODS: Using porcine mitral valves (n=32) mounted within an ex vivo left heart simulator, PM rupture was simulated. The mitral valve was divided into quadrants for analysis according to the PM heads. Acute PM rupture was simulated by incrementally cutting from 1/3 to the total number of chordae arising from 1 PM head of interest. Haemodynamic parameters were measured.RESULTS: Rupture >2/3 of the chordae from 1 given PM head or regurgitation fraction >60% led to markedly deteriorated haemodynamics. Rupture at the anterolateral PM had a stronger negative effect on haemodynamics than rupture at the posteromedial PM. Rupture occurring at the anterior head of the anterolateral PM led to more marked haemodynamic instability than rupture occurring at the other PM heads.CONCLUSIONS: The haemodynamic effects of acute PM rupture vary considerably according to the site and extent of the rupture. Rupture of ≤2/3 of chordae from 1 PM head or rupture at the posteromedial PM lead to less marked haemodynamics effects, suggesting a higher likelihood of tolerating surgery. Rupture at the anterolateral PM, specifically the anterior head, rupture of >2/3 of chordae from 1 PM head or regurgitation fraction >60% led to marked haemodynamic instability, suggesting the potential benefit from bridging strategies prior to surgery.

  View details for DOI 10.1093/icvts/ivab373

  View details for PubMedID 35022737

• Natural cardiac regeneration conserves native biaxial left ventricular biomechanics after myocardial infarction in neonatal rats. Journal of the mechanical behavior of biomedical materials Wang, H., Wisneski, A., Imbrie-Moore, A. M., Paulsen, M. J., Wang, Z., Xuan, Y., Lopez Hernandez, H., Hironaka, C. E., Lucian, H. J., Shin, H. S., Anilkumar, S., Thakore, A. D., Farry, J. M., Eskandari, A., Williams, K. M., Grady, F., Wu, M. A., Jung, J., Stapleton, L. M., Steele, A. N., Zhu, Y., Woo, Y. J. 1800; 126: 105074

  Abstract

  After myocardial infarction (MI), adult mammals exhibit scar formation, adverse left ventricular (LV) remodeling, LV stiffening, and impaired contractility, ultimately resulting in heart failure. Neonatal mammals, however, are capable of natural heart regeneration after MI. We hypothesized that neonatal cardiac regeneration conserves native biaxial LV mechanics after MI. Wistar rat neonates (1 day old, n=46) and adults (8-10 weeks old, n=20) underwent sham surgery or permanent left anterior descending coronary artery ligation. At 6 weeks after neonatal MI, Masson's trichrome staining revealed negligible fibrosis. Echocardiography for the neonatal MI (n=15) and sham rats (n=14) revealed no differences in LV wall thickness or chamber diameter, and both groups had normal ejection fraction (72.7% vs 77.5%, respectively, p=0.1946). Biaxial tensile testing revealed similar stress-strain curves along both the circumferential and longitudinal axes across a full range of physiologic stresses and strains. The circumferential modulus (267.9kPa vs 274.2kPa, p=0.7847), longitudinal modulus (269.3kPa vs 277.1kPa, p=0.7435), and maximum shear stress (3.30kPa vs 3.95kPa, p=0.5418) did not differ significantly between the neonatal MI and sham groups, respectively. In contrast, transmural scars were observed at 4 weeks after adult MI. Adult MI hearts (n=7) exhibited profound LV wall thinning (p<0.0001), chamber dilation (p=0.0246), and LV dysfunction (ejection fraction 45.4% vs 79.7%, p<0.0001) compared to adult sham hearts (n=7). Adult MI hearts were significantly stiffer than adult sham hearts in both the circumferential (321.5kPa vs 180.0kPa, p=0.0111) and longitudinal axes (315.4kPa vs 172.3kPa, p=0.0173), and also exhibited greater maximum shear stress (14.87kPa vs 3.23kPa, p=0.0162). Our study is the first to show that native biaxial LV mechanics are conserved after neonatal heart regeneration following MI, thus adding biomechanical support for the therapeutic potential of cardiac regeneration in the treatment of ischemic heart disease.

  View details for DOI 10.1016/j.jmbbm.2022.105074

  View details for PubMedID 35030471

• Electrophysiologic Conservation of Epicardial Conduction Dynamics After Myocardial Infarction and Natural Heart Regeneration in Newborn Piglets. Frontiers in cardiovascular medicine Wang, H., Pong, T., Obafemi, O. O., Lucian, H. J., Aparicio-Valenzuela, J., Tran, N. A., Mullis, D. M., Elde, S., Tada, Y., Baker, S. W., Wang, C. Y., Cyr, K. J., Paulsen, M. J., Zhu, Y., Lee, A. M., Woo, Y. J. 2022; 9: 829546

  Abstract

  Newborn mammals, including piglets, exhibit natural heart regeneration after myocardial infarction (MI) on postnatal day 1 (P1), but this ability is lost by postnatal day 7 (P7). The electrophysiologic properties of this naturally regenerated myocardium have not been examined. We hypothesized that epicardial conduction is preserved after P1 MI in piglets. Yorkshire-Landrace piglets underwent left anterior descending coronary artery ligation at age P1 (n = 6) or P7 (n = 7), After 7 weeks, cardiac magnetic resonance imaging was performed with late gadolinium enhancement for analysis of fibrosis. Epicardial conduction mapping was performed using custom 3D-printed high-resolution mapping arrays. Age- and weight-matched healthy pigs served as controls (n = 6). At the study endpoint, left ventricular (LV) ejection fraction was similar for controls and P1 pigs (46.4 ± 3.0% vs. 40.3 ± 4.9%, p = 0.132), but significantly depressed for P7 pigs (30.2 ± 6.6%, p < 0.001 vs. control). The percentage of LV myocardial volume consisting of fibrotic scar was 1.0 ± 0.4% in controls, 9.9 ± 4.4% in P1 pigs (p = 0.002 vs. control), and 17.3 ± 4.6% in P7 pigs (p < 0.001 vs. control, p = 0.007 vs. P1). Isochrone activation maps and apex activation time were similar between controls and P1 pigs (9.4 ± 1.6 vs. 7.8 ± 0.9 ms, p = 0.649), but significantly prolonged in P7 pigs (21.3 ± 5.1 ms, p < 0.001 vs. control, p < 0.001 vs. P1). Conduction velocity was similar between controls and P1 pigs (1.0 ± 0.2 vs. 1.1 ± 0.4 mm/ms, p = 0.852), but slower in P7 pigs (0.7 ± 0.2 mm/ms, p = 0.129 vs. control, p = 0.052 vs. P1). Overall, our data suggest that epicardial conduction dynamics are conserved in the setting of natural heart regeneration in piglets after P1 MI.

  View details for DOI 10.3389/fcvm.2022.829546

  View details for PubMedID 35355973

• Post-Transplant Extracorporeal Membrane Oxygenation for Severe Primary Graft Dysfunction to Support the Use of Marginal Donor Hearts. Transplant international : official journal of the European Society for Organ Transplantation Shudo, Y., Alassar, A., Wang, H., Lingala, B., He, H., Zhu, Y., Hiesinger, W., MacArthur, J. W., Boyd, J. H., Lee, A. M., Currie, M., Woo, Y. J. 2022; 35: 10176

  Abstract

  Severe primary graft dysfunction (PGD) is the leading cause of early postoperative mortality following orthotopic heart transplantation (OHT). Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been used as salvage therapy. This study aimed to evaluate the outcomes in adult OHT recipients who underwent VA-ECMO for severe PGD. We retrospectively reviewed 899 adult (≥18years) patients who underwent primary OHT at our institution between 1997 and 2017. Recipients treated with VA-ECMO (19, 2.1%) exhibited a higher incidence of previous cardiac surgery (p = .0220), chronic obstructive pulmonary disease (p = .0352), and treatment with a calcium channel blocker (p = .0018) and amiodarone (p = .0148). Cardiopulmonary bypass (p = .0410) and aortic cross-clamp times (p = .0477) were longer in the VA-ECMO cohort and they were more likely to have received postoperative transfusion (p = .0013); intra-aortic balloon pump (IABP, p < .0001), and reoperation for bleeding or tamponade (p < .0001). The 30-day, 1-year, and overall survival after transplantation of non-ECMO patients were 95.9, 88.8, and 67.4%, respectively, compared to 73.7, 57.9, and 47.4%, respectively in the ECMO cohort. Fourteen (73.7%) of the ECMO patients were weaned after a median of 7days following OHT (range: 1-12days). Following OHT, VA-ECMO may be a useful salvage therapy for severe PGD and can potentially support the usage of marginal donor hearts.

  View details for DOI 10.3389/ti.2022.10176

  View details for PubMedID 35340846

• Analysis of the revised heart allocation policy and the influence of increased mechanical circulatory support on survival. The Journal of thoracic and cardiovascular surgery Elde, S., He, H., Lingala, B., Baiocchi, M., Wang, H., Hiesinger, W., MacArthur, J. W., Shudo, Y., Woo, Y. J. 1800

  Abstract

  OBJECTIVES: In 2018, the new United Network for Organ Sharing heart allocation policy took effect. This study evaluated waitlist mortality, mechanical circulatory support utilization, and its influence on posttransplant survival.METHODS: Two 12-month cohorts matched for time of year before and after the policy change were defined by inclusion criteria of first-time transplant recipients aged 18years or older who were listed and underwent transplant during the same era. Student t test and Wilcoxon rank-sum test were used for mean and median differences, respectively. Categorical variables were compared using chi2 or Fisher exact test. Kaplan-Meier curves were used to characterize survival, including time-to-event analysis with the log-rank test. Fine-Gray modeling was used to characterize waitlist mortality. Cox proportional-hazard models were used for multivariate analysis.RESULTS: Waitlist mortality in the new era is significantly improved based on a competing-risks model (Gray test P=.0064). Unadjusted 180-day posttransplant mortality increased from 5.8% during the old era to 8.0% during the new (P=.0134). However, time-to-event analysis showed similar 180-day survival in both eras. After risk adjustment, the hazard ratio for posttransplant 180-day mortality during the new era was 1.18 (95% CI, 0.85-1.64; P=.333). The posttransplant 180-day mortality of the extracorporeal membrane oxygenation bridge-to-transplant subgroup improved from 28.6% in the old era to 8.4% in the new era (P=.0103; log-rank P=.0021). Patients with an intra-aortic balloon pump at the time of transplant had similar 180-day posttransplant mortality between eras (5.4% vs 7.0%; P=.4831).CONCLUSIONS: The United Network for Organ Sharing policy change is associated with reduced waitlist mortality and similar risk adjusted posttransplant 180-day mortality. The new era is also associated with improved 180-day survival in patientsundergoing bridge to transplant with extracorporeal membrane oxygenation.

  View details for DOI 10.1016/j.jtcvs.2021.11.076

  View details for PubMedID 35027214

• Biomechanical engineering comparison of four leaflet repair techniques for mitral regurgitation using a novel 3-dimensional-printed left heart simulator. JTCVS techniques Paulsen, M. J., Cuartas, M. M., Imbrie-Moore, A., Wang, H., Wilkerson, R., Farry, J., Zhu, Y., Ma, M., MacArthur, J. W., Woo, Y. J. 2021; 10: 244-251

  Abstract

  Mitral valve repair is the gold standard treatment for degenerative mitral regurgitation; however, a multitude of repair techniques exist with little quantitative data comparing these approaches. Using a novel ex vivo model, we sought to evaluate biomechanical differences between repair techniques.Using porcine mitral valves mounted within a custom 3-dimensional-printed left heart simulator, we induced mitral regurgitation using an isolated P2 prolapse model by cutting primary chordae. Next, we repaired the valves in series using the edge-to-edge technique, neochordoplasty, nonresectional remodeling, and classic leaflet resection. Hemodynamic data and chordae forces were measured and analyzed using an incomplete counterbalanced repeated measures design with the healthy pre-prolapse valve as a control.With the exception of the edge-to-edge technique, all repair methods effectively corrected mitral regurgitation, returning regurgitant fraction to baseline levels (baseline 11.9% ± 3.7%, edge-to-edge 22.5% ± 6.9%, nonresectional remodeling 12.3% ± 3.0%, neochordal 13.4% ± 4.8%, resection 14.7% ± 5.5%, P < 0.01). Forces on the primary chordae were minimized using the neochordal and nonresectional techniques whereas the edge-to-edge and resectional techniques resulted in significantly elevated primary forces. Secondary chordae forces also followed this pattern, with edge-to-edge repair generating significantly higher secondary forces and leaflet resection trending higher than the nonresectional and neochord repairs.Although multiple methods of degenerative mitral valve repair are used clinically, their biomechanical properties vary significantly. Nonresectional techniques, including leaflet remodeling and neochordal techniques, appear to result in lower chordal forces in this ex vivo technical engineering model.

  View details for DOI 10.1016/j.xjtc.2021.09.040

  View details for PubMedID 34977730

  View details for PubMedCentralID PMC8691825

• Valve-sparing reoperations for failed pulmonary autografts JTCVS TECHNIQUES Goldstone, A. B., Woo, Y. 2021; 10: 408-412

  View details for DOI 10.1016/j.xjtc.2021.01.041

  View details for Web of Science ID 000732665100052

• Biomechanical engineering comparison of four leaflet repair techniques for mitral regurgitation using a novel 3-dimensional-printed left heart simulator JTCVS TECHNIQUES Paulsen, M. J., Cuartas, M., Imbrie-Moore, A., Wang, H., Wilkerson, R., Farry, J., Zhu, Y., Ma, M., MacArthur, J. W., Woo, Y. 2021; 10: 244-251

  View details for DOI 10.1016/j.xjtc.2021.09.040

  View details for Web of Science ID 000732665100001

• Valve-sparing reoperations for failed pulmonary autografts. JTCVS techniques Goldstone, A. B., Woo, Y. J. 2021; 10: 408-412

  View details for DOI 10.1016/j.xjtc.2021.01.041

  View details for PubMedID 34977766

  View details for PubMedCentralID PMC8689671

• Biomechanical engineering analysis of commonly utilized mitral neochordae. JTCVS open Marin-Cuartas, M., Imbrie-Moore, A. M., Zhu, Y., Park, M. H., Wilkerson, R., Leipzig, M., Borger, M. A., Woo, Y. J. 2021; 8: 263-275

  Abstract

  Objective: To evaluate the suture rupture forces of commonly clinically utilized neochord repair techniques to identify the most biomechanically resistant most biomechanically resistant technique.Methods: Several types of neochord techniques (standard interrupted neochordae, continuous running neochordae, and loop technique), numbers of neochordae, and suture calibers (polytetrafluoroethylene CV-3 to CV-6) were compared. To perform the tests, both ends of the neochordae were loaded in a tensile force analysis machine. During the test, the machine applied tension to the neochord until rupture was achieved. The tests were performed 3 times for each variation, and the rupture forces were averaged for statistical analysis.Results: Rupture force was significantly higher for running neochordae relative to interrupted neochordae (P<.01). However, a single rupture in the running technique resulted in failure of the complete neochord system. For both running and interrupted neochordae, a greater number of neochordae as well as a thicker suture caliber significantly increased the neochord rupture force (P<.01). The loop technique ruptured at significantly lower forces compared with the other 2 techniques (P<.01). A greater number of loops did not significantly increase the rupture force of loop neochordae. Observed rupture forces for all techniques were higher than those normally observed in physiologic conditions.Conclusions: Under experimental conditions, the running neochord technique has the best mechanical performance due to an increased rupture force. If using running neochordae, more than 1 independent set of multiple running neochordae are advised (ie, >2 independent sets of multiple running neochordae in each set).

  View details for DOI 10.1016/j.xjon.2021.07.040

  View details for PubMedID 36004068

• Association of Volume and Outcomes in 234,556 Patients Undergoing Surgical Aortic Valve Replacement. The Annals of thoracic surgery Thourani, V. H., Brennan, J. M., Edelman, J. J., Thibault, D., Jawitz, O. K., Bavaria, J. E., Higgins, R. S., Sabik, J. F., Prager, R. L., Dearani, J. A., MacGillivray, T. E., Badhwar, V., Svensson, L. G., Reardon, M. J., Shahian, D. M., Jacobs, J. P., Ailawadi, G., Szeto, W. Y., Desai, N., Roselli, E. E., Woo, Y. J., Vemulapalli, S., Carroll, J. D., Yadav, P., Malaisrie, S. C., Russo, M., Nguyen, T. C., Kaneko, T., Tang, G., Ruel, M., Chikwe, J., Lee, R., Habib, R. H., George, I., Leon, M. B., Mack, M. J. 2021

  Abstract

  BACKGROUND: The relationship between institutional volume and operative mortality following SAVR remains unclear.METHODS: From 1/2013 to 6/2018, 234,556 patients underwent isolated SAVR (n=144,177) or SAVR+CABG (n=90,379) within the STS ACSD. The association between annualized SAVR volume [Group 1 (1-25 SAVR), Group 2 (26-50 SAVR), Group 3 (51-100 SAVR), and Group 4 (>100 SAVR)] and operative mortality and composite major morbidity/mortality was assessed. Random effects models were used to evaluate whether historic (2013-2015) SAVR volume or risk-adjusted outcomes explained future (2016-2018) risk-adjusted outcomes.RESULTS: The annualized median number of SAVRs per site was 35 [IQR: 22-59, isolated AVR: 20, AVR+CABG: 13]. Among isolated SAVR cases, the mean operative mortality and composite morbidity/mortality were 1.5% and 9.7%, respectively, at the highest volume sites (Group 4); with significantly higher rates among progressively lower volume groups (p-trend<0.001). After adjustment, lower volume centers experienced increased odds of operative mortality [Group 1 vs. 4 (Ref): AOR (SAVR), 2.24 (1.91-2.64); AOR (SAVR+CABG), 1.96 (1.67-2.30)] and major morbidity/mortality [AOR (SAVR), 1.53 (1.39-1.69); AOR (SAVR+CABG), 1.46 (1.32-1.61)] compared to the highest volume institutions. Substantial variation in outcomes was observed across hospitals within each volume category and prior outcomes explained a greater proportion of hospital operative outcomes than prior volume.CONCLUSIONS: Operative outcomes following SAVR±CABG is inversely associated with institutional procedure volumes; however, prior outcomes are more predictive than prior volume of future outcomes. Given excellent outcomes observed at many lower volume hospitals, procedural outcomes may be preferable to procedural volumes as a quality metric.

  View details for DOI 10.1016/j.athoracsur.2021.06.095

  View details for PubMedID 34785247

• Fractional Flow Reserve-Guided PCI as Compared with Coronary Bypass Surgery. The New England journal of medicine Fearon, W. F., Zimmermann, F. M., De Bruyne, B., Piroth, Z., van Straten, A. H., Szekely, L., Davidavicius, G., Kalinauskas, G., Mansour, S., Kharbanda, R., Ostlund-Papadogeorgos, N., Aminian, A., Oldroyd, K. G., Al-Attar, N., Jagic, N., Dambrink, J. E., Kala, P., Angeras, O., MacCarthy, P., Wendler, O., Casselman, F., Witt, N., Mavromatis, K., Miner, S. E., Sarma, J., Engstrom, T., Christiansen, E. H., Tonino, P. A., Reardon, M. J., Lu, D., Ding, V. Y., Kobayashi, Y., Hlatky, M. A., Mahaffey, K. W., Desai, M., Woo, Y. J., Yeung, A. C., Pijls, N. H., FAME 3 Investigators 2021

  Abstract

  BACKGROUND: Patients with three-vessel coronary artery disease have been found to have better outcomes with coronary-artery bypass grafting (CABG) than with percutaneous coronary intervention (PCI), but studies in which PCI is guided by measurement of fractional flow reserve (FFR) have been lacking.METHODS: In this multicenter, international, noninferiority trial, patients with three-vessel coronary artery disease were randomly assigned to undergo CABG or FFR-guided PCI with current-generation zotarolimus-eluting stents. The primary end point was the occurrence within 1 year of a major adverse cardiac or cerebrovascular event, defined as death from any cause, myocardial infarction, stroke, or repeat revascularization. Noninferiority of FFR-guided PCI to CABG was prespecified as an upper boundary of less than 1.65 for the 95% confidence interval of the hazard ratio. Secondary end points included a composite of death, myocardial infarction, or stroke; safety was also assessed.RESULTS: A total of 1500 patients underwent randomization at 48 centers. Patients assigned to undergo PCI received a mean (±SD) of 3.7±1.9 stents, and those assigned to undergo CABG received 3.4±1.0 distal anastomoses. The 1-year incidence of the composite primary end point was 10.6% among patients randomly assigned to undergo FFR-guided PCI and 6.9% among those assigned to undergo CABG (hazard ratio, 1.5; 95% confidence interval [CI], 1.1 to 2.2), findings that were not consistent with noninferiority of FFR-guided PCI (P=0.35 for noninferiority). The incidence of death, myocardial infarction, or stroke was 7.3% in the FFR-guided PCI group and 5.2% in the CABG group (hazard ratio, 1.4; 95% CI, 0.9 to 2.1). The incidences of major bleeding, arrhythmia, and acute kidney injury were higher in the CABG group than in the FFR-guided PCI group.CONCLUSIONS: In patients with three-vessel coronary artery disease, FFR-guided PCI was not found to be noninferior to CABG with respect to the incidence of a composite of death, myocardial infarction, stroke, or repeat revascularization at 1 year. (Funded by Medtronic and Abbott Vascular; FAME 3 ClinicalTrials.gov number, NCT02100722.).

  View details for DOI 10.1056/NEJMoa2112299

  View details for PubMedID 34735046

• Ex Vivo Model of Ischemic Mitral Regurgitation and Analysis of Adjunctive Papillary Muscle Repair. Annals of biomedical engineering Imbrie-Moore, A. M., Zhu, Y., Bandy-Vizcaino, T., Park, M. H., Wilkerson, R. J., Woo, Y. J. 2021

  Abstract

  Ischemic mitral regurgitation (IMR) is particularly challenging to repair with lasting durability due to the complex valvular and subvalvular pathologies resulting from left ventricular dysfunction. Ex vivo simulation is uniquely suited to quantitatively analyze the repair biomechanics, but advancements are needed to model the nuanced IMR disease state. Here we present a novel IMR model featuring a dilation device with precise dilatation control that preserves annular elasticity to enable accurate ex vivo analysis of surgical repair. Coupled with augmented papillary muscle head positioning, the enhanced heart simulator system successfully modeled IMR pre- and post-surgical intervention and enabled the analysis of adjunctive subvalvular papillary muscle repair to alleviate regurgitation recurrence. The model resulted in an increase in regurgitant fraction: 11.6 ± 1.7% to 36.1 ± 4.4% (p<0.001). Adjunctive papillary muscle head fusion was analyzed relative to a simple restrictive ring annuloplasty repair and, while both repairs successfully eliminated regurgitation initially, the addition of the adjunctive subvalvular repair reduced regurgitation recurrence: 30.4 ± 5.7% vs. 12.5 ± 2.6% (p=0.002). Ultimately, this system demonstrates the success of adjunctive papillary muscle head fusion in repairing IMR as well as provides a platform to optimize surgical techniques for increased repair durability.

  View details for DOI 10.1007/s10439-021-02879-9

  View details for PubMedID 34734363

• The impact of the American Association for Thoracic Surgery on National Institutes of Health grant funding for cardiothoracic surgeons. The Journal of thoracic and cardiovascular surgery Mehaffey, J. H., Wang, H., Narahari, A. K., Bajaj, S. S., Chandrabhatla, A. S., Krupnick, A. S., Sellke, F. W., Rosengart, T. K., Woo, Y. J. 2021

  Abstract

  OBJECTIVES: The American Association for Thoracic Surgery, through its annual meeting, pilot grant funding, Scientific Affairs and Government Relations Committee activity, and academic development programs (Grant Writing Workshop, Clinical Trials Course, Innovation Summit), has aimed to develop the research careers of cardiothoracic surgeons. We hypothesized that American Association for Thoracic Surgery activities have helped increase National Institutes of Health grants awarded to cardiothoracic surgeons.METHODS: A database of 1869 academic cardiothoracic surgeons in the United States was created in December 2020. National Institutes of Health grant records from 1985 to 2020 were obtained for each surgeon using National Institutes of Health Research Portfolio Online Reporting Tools Expenditures and Results. Analyses were normalized to the number of active surgeons per year, based on the year of each surgeon's earliest research publication on Scopus.RESULTS: A total of 346 cardiothoracic surgeons have received 696 National Institutes of Health grants totaling more than $1.5 billion in funding, with 48 surgeons actively serving as principal investigator of 66 R01 grants in 2020. The prevalence of research grants (7.4 vs 5.6 grants per 100 active surgeons, P<.0001), percentage of surgeons with a research grant (5.3% vs 4.7%, P=.0342), and number of research grants per funded surgeon (1.4 vs 1.2 grants, P<.0001) were significantly greater during the Scientific Affairs and Government Relations era (2003-2020) than the pre-Scientific Affairs and Government Relations era (1985-2002). The incidence of new research grants after surgeon participation in an American Association for Thoracic Surgery academic development program was significantly greater than that in the absence of participation (3.5 vs 1.1 new grants per 100 surgeons per year, P<.0001).CONCLUSIONS: Through dedicated efforts and programs, the American Association for Thoracic Surgery has provided effective support to help increase National Institutes of Health grant funding awarded to cardiothoracic surgeons.

  View details for DOI 10.1016/j.jtcvs.2021.10.031

  View details for PubMedID 34809972

• Altered Cardiac Energetics and Mitochondrial Dysfunction in Hypertrophic Cardiomyopathy. Circulation Ranjbarvaziri, S., Kooiker, K. B., Ellenberger, M., Fajardo, G., Zhao, M., Vander Roest, A. S., Woldeyes, R. A., Koyano, T. T., Fong, R., Ma, N., Tian, L., Traber, G. M., Chan, F., Perrino, J., Reddy, S., Chiu, W., Wu, J. C., Woo, J. Y., Ruppel, K. M., Spudich, J. A., Snyder, M. P., Contrepois, K., Bernstein, D. 2021

  Abstract

  Background: Hypertrophic cardiomyopathy (HCM) is a complex disease partly explained by the effects of individual gene variants on sarcomeric protein biomechanics. At the cellular level, HCM mutations most commonly enhance force production, leading to higher energy demands. Despite significant advances in elucidating sarcomeric structure-function relationships, there is still much to be learned about the mechanisms that link altered cardiac energetics to HCM phenotypes. In this work, we test the hypothesis that changes in cardiac energetics represent a common pathophysiologic pathway in HCM. Methods: We performed a comprehensive multi-omics profile of the molecular (transcripts, metabolites, and complex lipids), ultrastructural, and functional components of HCM energetics using myocardial samples from 27 HCM patients and 13 normal controls (donor hearts). Results: Integrated omics analysis revealed alterations in a wide array of biochemical pathways with major dysregulation in fatty acid metabolism, reduction of acylcarnitines, and accumulation of free fatty acids. HCM hearts showed evidence of global energetic decompensation manifested by a decrease in high energy phosphate metabolites [ATP, ADP, and phosphocreatine (PCr)] and a reduction in mitochondrial genes involved in creatine kinase and ATP synthesis. Accompanying these metabolic derangements, electron microscopy showed an increased fraction of severely damaged mitochondria with reduced cristae density, coinciding with reduced citrate synthase (CS) activity and mitochondrial oxidative respiration. These mitochondrial abnormalities were associated with elevated reactive oxygen species (ROS) and reduced antioxidant defenses. However, despite significant mitochondrial injury, HCM hearts failed to upregulate mitophagic clearance. Conclusions: Overall, our findings suggest that perturbed metabolic signaling and mitochondrial dysfunction are common pathogenic mechanisms in patients with HCM. These results highlight potential new drug targets for attenuation of the clinical disease through improving metabolic function and reducing mitochondrial injury.

  View details for DOI 10.1161/CIRCULATIONAHA.121.053575

  View details for PubMedID 34672721

• Videographic conceptual dynamic representation of bicuspid aortic valve anatomic configurations and structural inter-relationships. JTCVS techniques Woo, Y. J., Paulsen, M. J., de Kerchove, L., Zhu, Y. 2021; 9: 44-45

  View details for DOI 10.1016/j.xjtc.2021.06.019

  View details for PubMedID 34647056

• From hardware store to hospital: a COVID-19-inspired, cost-effective, open-source, in vivo-validated ventilator for use in resource-scarce regions. Bio-design and manufacturing Park, M. H., Zhu, Y., Wang, H., Tran, N. A., Jung, J., Paulsen, M. J., Imbrie-Moore, A. M., Baker, S., Wilkerson, R., Marin-Cuartas, M., Mullis, D. M., Woo, Y. J. 2021: 1-8

  Abstract

  Resource-scarce regions with serious COVID-19 outbreaks do not have enough ventilators to support critically ill patients, and these shortages are especially devastating in developing countries. To help alleviate this strain, we have designed and tested the accessible low-barrier in vivo-validated economical ventilator (ALIVE Vent), a COVID-19-inspired, cost-effective, open-source, in vivo-validated solution made from commercially available components. The ALIVE Vent operates using compressed oxygen and air to drive inspiration, while two solenoid valves ensure one-way flow and precise cycle timing. The device was functionally tested and profiled using a variable resistance and compliance artificial lung and validated in anesthetized large animals. Our functional test results revealed its effective operation under a wide variety of ventilation conditions defined by the American Association of Respiratory Care guidelines for ventilator stockpiling. The large animal test showed that our ventilator performed similarly if not better than a standard ventilator in maintaining optimal ventilation status. The FiO2, respiratory rate, inspiratory to expiratory time ratio, positive-end expiratory pressure, and peak inspiratory pressure were successfully maintained within normal, clinically validated ranges, and the animals were recovered without any complications. In regions with limited access to ventilators, the ALIVE Vent can help alleviate shortages, and we have ensured that all used materials are publicly available. While this pandemic has elucidated enormous global inequalities in healthcare, innovative, cost-effective solutions aimed at reducing socio-economic barriers, such as the ALIVE Vent, can help enable access to prompt healthcare and life saving technology on a global scale and beyond COVID-19.Supplementary Information: The online version contains supplementary material available at 10.1007/s42242-021-00164-1.

  View details for DOI 10.1007/s42242-021-00164-1

  View details for PubMedID 34567825

• Exvivo biomechanical analysis of the Ross procedure using the modified inclusion technique in a 3-dimensionally printed left heart simulator. The Journal of thoracic and cardiovascular surgery Zhu, Y., Marin-Cuartas, M., Park, M. H., Imbrie-Moore, A. M., Wilkerson, R. J., Madira, S., Mullis, D. M., Woo, Y. J. 2021

  Abstract

  OBJECTIVE: The inclusion technique was developed to reinforce the pulmonary autograft to prevent dilation after the Ross procedure. Anticommissural plication (ACP), a modification technique, can reduce graft size and create neosinuses. The objective was to evaluate pulmonary valve biomechanics using the inclusion technique in the Ross procedure with and without ACP.METHODS: Seven porcine and 5 human pulmonary autografts were harvested from hearts obtained from a meat abattoir and from heart transplant recipients and donors, respectively. Five additional porcine autografts without reinforcement were used as controls. The Ross procedure was performed using the inclusion technique with a straight polyethylene terephthalate graft. The same specimens were tested both with and without ACP. Hemodynamic parameter data, echocardiography, and high-speed videography were collected via the exvivo heart simulator.RESULTS: Porcine autograft regurgitation was significantly lower after the use of inclusion technique compared with controls (P<.01). ACP compared with non-ACP in both porcine and human pulmonary autografts was associated with lower leaflet rapid opening velocity (3.9±2.4cm/sec vs 5.9±2.4cm/sec; P=.03; 3.5±0.9cm/sec vs 4.4±1.0cm/sec; P=.01), rapid closing velocity (1.9±1.6cm/sec vs 3.1±2.0cm/sec; P=.01; 1.8±0.7cm/sec vs 2.2±0.3cm/sec; P=.13), relative rapid opening force (4.6±3.0 vs 7.7±5.2; P=.03; 3.0±0.6 vs 4.0±2.1; P=.30), and relative rapid closing force (2.5±3.4 vs 5.9±2.3; P=.17; 1.4±1.3 vs 2.3±0.6; P=.25).CONCLUSIONS: The Ross procedure using the inclusion technique demonstrated excellent hemodynamic parameter results. The ACP technique was associated with more favorable leaflet biomechanics. Invivo validation should be performed to allow direct translation to clinical practice.

  View details for DOI 10.1016/j.jtcvs.2021.06.070

  View details for PubMedID 34625236

• Extended Static Hypothermic Preservation In Cardiac Transplantation: A Case Report. Transplantation proceedings Guenthart, B. A., Krishnan, A., Koyano, T., La Francessca, S., Chan, J., Alassar, A., Macarthur, J. W., Shudo, Y., Hiesinger, W., Woo, Y. J. 2021

  Abstract

  BACKGROUND: The donor shortage poses a major limitation to use of heart transplantation. Novel strategies such as use of expanded-criteria donors with prolonged ischemia times are being employed to address this need. Recent developments in static hypothermia have allowed for the safe use of cardiac allografts with prolonged ischemic times.CASE REPORT: We present the case of a 68-year-old woman with valvular cardiomyopathy refractory to medical therapy who underwent orthotopic heart transplantation with a cardiac allograft exposed to elevated ischemic times. This was achieved through use of the federally approved SherpaPak Cardiac Transport System for transportation of the allograft. This method of static hypothermic organ preservation allowed for a 330-minute total ischemic time, including 283 minutes of storage within the preservation system. The patient tolerated the procedure well and was discharged on postoperative day 10, with excellent graft function and no evidence of rejection 3 months postoperatively.CONCLUSIONS: Though traditionally ischemic times of 240 minutes or less are recommended for cardiac allografts, we demonstrate, to our knowledge, the longest reported ischemic time of 330 minutes via use of a novel method of static hypothermia for organ preservation. The recipient had an excellent outcome postoperatively, demonstrating the potential for this new organ preservation system to expand the donor pool and improve access and use of heart transplantation.

  View details for DOI 10.1016/j.transproceed.2021.08.021

  View details for PubMedID 34521542

• A neonatal leporine model of age-dependent natural heart regeneration after myocardial infarction. The Journal of thoracic and cardiovascular surgery Wang, H., Hironaka, C. E., Mullis, D. M., Lucian, H. J., Shin, H. S., Tran, N. A., Thakore, A. D., Anilkumar, S., Wu, M. A., Paulsen, M. J., Zhu, Y., Baker, S. W., Woo, Y. J. 2021

  Abstract

  OBJECTIVES: Neonatal rodents and piglets naturally regenerate the injured heart after myocardial infarction. We hypothesized that neonatal rabbits also exhibit natural heart regeneration after myocardial infarction.METHODS: New Zealand white rabbit kits underwent sham surgery or left coronary ligation on postnatal day 1 (n=94), postnatal day 4 (n=11), or postnatal day 7 (n=52). Hearts were explanted 1day postsurgery to confirm ischemic injury, at 1week postsurgery to assess cardiomyocyte proliferation, and at 3weeks postsurgery to assess left ventricular ejection fraction and scar size. Data are presented as mean±standard deviation.RESULTS: Size of ischemic injury as a percentage of left ventricular area was similar after myocardial infarction on postnatal day 1 versus on postnatal day 7 (42.3%±5.4% vs 42.3%±4.7%, P=.9984). Echocardiography confirmed severely reduced ejection fraction at 1day after postnatal day 1 myocardial infarction (33.7%±5.3% vs 65.2%±5.5% for postnatal day 1 sham, P=.0001), but no difference at 3weeks after postnatal day 1 myocardial infarction (56.0%±4.0% vs 58.0%±3.3% for postnatal day 1 sham, P=.2198). Ejection fraction failed to recover after postnatal day 4 myocardial infarction (49.2%±1.8% vs 58.5%±5.8% for postnatal day 4 sham, P=.0109) and postnatal day 7 myocardial infarction (39.0%±7.8% vs 60.2%±5.0% for postnatal day 7 sham, P<.0001). At 3weeks after infarction, fibrotic scar represented 5.3%±1.9%, 14.3%±4.9%, and 25.4%±13.3% of the left ventricle area in the postnatal day 1, postnatal day 4, and postnatal day 7 groups, respectively. An increased proportion of peri-infarct cardiomyocytes expressed Ki67 (15.9%±1.8% vs 10.2%±0.8%, P=.0039) and aurora B kinase (4.0%±0.9% vs 1.5%±0.6%, P=.0088) after postnatal day 1 myocardial infarction compared with sham, but no increase was observed after postnatal day 7 myocardial infarction.CONCLUSIONS: A neonatal leporine myocardial infarction model reveals that newborn rabbits are capable of age-dependent natural heart regeneration.

  View details for DOI 10.1016/j.jtcvs.2021.08.013

  View details for PubMedID 34649718

• The Stanford experience of heart transplantation over five decades. European heart journal Zhu, Y., Lingala, B., Baiocchi, M., Toro Arana, V., Williams, K. M., Shudo, Y., Oyer, P. E., Woo, Y. J. 2021

  Abstract

  AIMS: Since 1968, heart transplantation has become the definitive treatment for patients with end-stage heart failure. We aimed to summarize our experience in heart transplantation at Stanford University since the first transplantation performed over 50years ago.METHODS AND RESULTS: From 6 January 1968 to 30 November 2020, 2671 patients presented to Stanford University for heart transplantation, of which 1958 were adult heart transplantations. Descriptive analyses were performed for patients in 1968-95 (n=639). Stabilized inverse probability weighting was applied to compare patients in 1996-2006 (n=356) vs. 2007-19 (n=515). Follow-up data were updated through 2020. The primary endpoint was all-cause mortality. Prior to weighting, recipients in 2007-19 vs. those in 1996-2006 were older and had heavier burden of chronic diseases. After the application of stabilized inverse probability weighting, the distance organ travelled increased from 84.2±111.1 miles to 159.3±169.9 miles from 1996-2006 to 2007-19. Total allograft ischaemia time also increased over time (199.6±52.7 vs. 225.3±50.0min). Patients in 2007-19 showed superior survival than those in 1996-2006 with a median survival of 12.1 vs. 11.1years.CONCLUSION: In this half-century retrospective descriptive study from one of the largest heart transplant programmes in the USA, long-term survival after heart transplantation has improved over time despite increased recipient and donor age, worsening comorbidities, increased technical complexity, and prolonged total allograft ischaemia time. Further investigation is warranted to delineate factors associated with the excellent outcomes observed in this study.

  View details for DOI 10.1093/eurheartj/ehab416

  View details for PubMedID 34333595

• Patient-Specific Computational Fluid Dynamics Reveal Localized Flow Patterns Predictive of Post-Left Ventricular Assist Device Aortic Incompetence. Circulation. Heart failure Shad, R., Kaiser, A. D., Kong, S., Fong, R., Quach, N., Bowles, C., Kasinpila, P., Shudo, Y., Teuteberg, J., Woo, Y. J., Marsden, A. L., Hiesinger, W. 2021: CIRCHEARTFAILURE120008034

  Abstract

  BACKGROUND: Progressive aortic valve disease has remained a persistent cause of concern in patients with left ventricular assist devices. Aortic incompetence (AI) is a known predictor of both mortality and readmissions in this patient population and remains a challenging clinical problem.METHODS: Ten left ventricular assist device patients with de novo aortic regurgitation and 19 control left ventricular assist device patients were identified. Three-dimensional models of patients' aortas were created from their computed tomography scans, following which large-scale patient-specific computational fluid dynamics simulations were performed with physiologically accurate boundary conditions using the SimVascular flow solver.RESULTS: The spatial distributions of time-averaged wall shear stress and oscillatory shear index show no significant differences in the aortic root in patients with and without AI (mean difference, 0.67 dyne/cm2 [95% CI, -0.51 to 1.85]; P=0.23). Oscillatory shear index was also not significantly different between both groups of patients (mean difference, 0.03 [95% CI, -0.07 to 0.019]; P=0.22). The localized wall shear stress on the leaflet tips was significantly higher in the AI group than the non-AI group (1.62 versus 1.35 dyne/cm2; mean difference [95% CI, 0.15-0.39]; P<0.001), whereas oscillatory shear index was not significantly different between both groups (95% CI, -0.009 to 0.001; P=0.17).CONCLUSIONS: Computational fluid dynamics serves a unique role in studying the hemodynamic features in left ventricular assist device patients where 4-dimensional magnetic resonance imaging remains unfeasible. Contrary to the widely accepted notions of highly disturbed flow, in this study, we demonstrate that the aortic root is a region of relatively stagnant flow. We further identified localized hemodynamic features in the aortic root that challenge our understanding of how AI develops in this patient population.

  View details for DOI 10.1161/CIRCHEARTFAILURE.120.008034

  View details for PubMedID 34139862

• Impact of thoracotomy approach on right ventricular failure and length of stay in left ventricular assist device implants: an intermacs registry analysis. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Lampert, B. C., Teuteberg, J. J., Cowger, J., Mokadam, N. A., Cantor, R. S., Benza, R. L., Ganapathi, A. M., Myers, S. L., Hiesinger, W., Woo, J., Pagani, F., Kirklin, J. K., Whitson, B. A. 2021

  Abstract

  INTRODUCTION: Traditionally, implantation of Left Ventricular Assist Devices (LVADs) is performed via median sternotomy. Recently, less invasive thoracotomy approaches are growing in popularity as they involve less surgical trauma, potentially less bleeding, and may preserve right ventricular function. We hypothesized implantation of LVADs via thoracotomy has less perioperative right ventricular failure (RVF) and shorter postoperative length of stay (LOS).METHODS: Continuous flow LVAD implants from Intermacs between February 6, 2014 - December 31, 2018 were identified. Patients implanted via thoracotomy were propensity matched in a 1:1 ratio with patients implanted via sternotomy. Outcomes were compared between sternotomy and thoracotomy approach and by device type (axial, centrifugal-flow with hybrid levitation (CF-HL), centrifugal-flow with full magnetic levitation devices (CF-FML)). The primary outcome was time to first moderate or severe RVF. Secondary outcomes included survival and LOS.RESULTS: Overall 978 thoracotomy patients were matched with 978 sternotomy patients. Over the study period, 242 thoracotomy patients and 219 sternotomy patients developed RVF with no significant difference in time to first moderate to severe RVF by surgical approach overall (p=0.27) or within CF-HL (p=0.36) or CF-FML devices (p=0.25). Survival did not differ by implant technique (150 deaths in thoracotomy group, 154 deaths in sternotomy group; p=0.58). However, sternotomy approach was associated with a significantly shorter LOS (17 Vs 18 days, p=0.009).CONCLUSION: As compared to sternotomy, implantation of continuous flow LVADs via thoracotomy approach does not reduce moderate to severe RVF or improve survival but does reduce post-operative LOS. Device type did not influence outcomes and most centers did a small volume of thoracotomy implants.

  View details for DOI 10.1016/j.healun.2021.05.022

  View details for PubMedID 34229917

• Cusp repair techniques in bicuspid and tricuspid aortic valves. JTCVS techniques Zhu, Y., Woo, Y. J. 2021; 7: 109-116

  View details for DOI 10.1016/j.xjtc.2021.01.029

  View details for PubMedID 34318219

  View details for PubMedCentralID PMC8311607

• stratamatch: Prognostic Score Stratification Using a Pilot Design R JOURNAL Aikens, R. C., Rigdon, J., Lee, J., Baiocchi, M., Goldstone, A. B., Chiu, P., Woo, Y., Chen, J. H. 2021; 13 (1): 614-630

  View details for Web of Science ID 000684952200037

• Cusp repair techniques in bicuspid and tricuspid aortic valves JTCVS TECHNIQUES Zhu, Y., Woo, Y. 2021; 7: 109-116

  View details for DOI 10.1016/j.xjtc.2021.01.029

  View details for Web of Science ID 000656818000033

• New horizons in aortic valve repair JTCVS TECHNIQUES Woo, Y. 2021; 7: 71

  View details for DOI 10.1016/j.xjtc.2021.04.018

  View details for Web of Science ID 000656818000022

• New horizons in aortic valve repair. JTCVS techniques Woo, Y. J. 2021; 7: 71

  View details for DOI 10.1016/j.xjtc.2021.04.018

  View details for PubMedID 34471910

  View details for PubMedCentralID PMC8312231

• stratamatch: Prognostic Score Stratification Using a Pilot Design. The R journal Aikens, R. C., Rigdon, J., Lee, J., Baiocchi, M., Goldstone, A. B., Chiu, P., Woo, Y. J., Chen, J. H. 2021; 13 (1): 614-630

  Abstract

  In a block-randomized controlled trial, individuals are subdivided by prognostically important baseline characteristics (e.g., age group, sex, or smoking status), prior to randomization. This step reduces the heterogeneity between the treatment groups with respect to the baseline factors most important to determining the outcome, thus enabling more precise estimation of treatment effect. The stratamatch package extends this approach to the observational setting by implementing functions to separate an observational data set into strata and interrogate the quality of different stratification schemes. Once an acceptable stratification is found, treated and control individuals can be matched by propensity score within strata, thereby recapitulating the block-randomized trial design for the observational study. The stratification scheme implemented by stratamatch applies a "pilot design" approach (Aikens, Greaves, and Baiocchi 2019) to estimate a quantity called the prognostic score (Hansen 2008), which is used to divide individuals into strata. The potential benefits of such an approach are twofold. First, stratifying the data enables more computationally efficient matching of large data sets. Second, methodological studies suggest that using a prognostic score to inform the matching process increases the precision of the effect estimate and reduces sensitivity to bias from unmeasured confounding factors (Aikens et al. 2019; Leacy and Stuart 2014; Antonelli, Cefalu, Palmer, and Agniel 2018). A common mistake is to believe reserving more data for the analysis phase of a study is always better. Instead, the stratamatch approach suggests how clever use of data in the design phase of large studies can lead to major benefits in the robustness of the study conclusions.

  View details for DOI 10.32614/RJ-2021-063

  View details for PubMedID 35821911

  View details for PubMedCentralID PMC9273035

• Extracorporeal Membrane Oxygenation Bridge to Heart-Lung Transplantation. ASAIO journal (American Society for Artificial Internal Organs : 1992) Shudo, Y., Elde, S., Lingala, B., He, H., Casselman, K. G., Zhu, Y., Kasinpila, P., Woo, Y. J. 2021

  View details for DOI 10.1097/MAT.0000000000001457

  View details for PubMedID 34843181

• Navigating the Crossroads of Cell Therapy and Natural Heart Regeneration. Frontiers in cell and developmental biology Elde, S., Wang, H., Woo, Y. J. 2021; 9: 674180

  Abstract

  Cardiovascular disease remains the leading cause of death worldwide despite significant advances in our understanding of the disease and its treatment. Consequently, the therapeutic potential of cell therapy and induction of natural myocardial regeneration have stimulated a recent surge of research and clinical trials aimed at addressing this challenge. Recent developments in the field have shed new light on the intricate relationship between inflammation and natural regeneration, an intersection that warrants further investigation.

  View details for DOI 10.3389/fcell.2021.674180

  View details for PubMedID 34046410

  View details for PubMedCentralID PMC8148343

• The impact of donor sex on heart transplantation outcomes-a study of over 60,000 patients in the United States. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Zhu, Y., Shudo, Y., Lingala, B., Joseph Woo, Y. 2021

  Abstract

  BACKGROUND: The impact of donor sex on heart transplantation outcomes irrespective of recipient sex remains unclear. The objective of this study was to evaluate the impact of donor sex on heart transplantation outcomes in the United States.METHODS: From 1987 to March 2019, 63,775 adult patients who underwent heart transplantation were matched to 27,509 male and 11,474 female donors in the United States. Data were prospectively collected by the United Network for Organ Sharing (UNOS). Patients without missing data were stratified by donor sex and donor menopause status. The groups were matched 1:1 using the propensity score of each patient. Kaplan-Meier survival and cox proportional hazards regression analyses were performed. The primary endpoint was all-cause mortality. Secondary endpoints were postoperative complications.RESULTS: Propensity matching generated 15,506 and 1,094 patients based on donor sex and menopause status, respectively. Recipients who received female donor allografts were more likely to have acute rejection episodes requiring anti-rejection medical treatment (11.9% vs 10.1%, p=.007) and require post-transplant dialysis (10.9% vs 9.3%, p = .001) than those who received male donor allografts. Overall survival using female vs male donor allografts was similar (p=.34). Recipients who received pre- vs post-menopausal female donor hearts had similar postoperative outcomes and overall survival (p=.23).CONCLUSIONS: Analysis of the UNOS database showed similar median survival using female vs male donor hearts in adult heart transplantation, irrespective of donor menopause status. Female donor allografts are used far less frequently, thus these results represent an opportunity to maximize usage by better utilization of suitable female donor organs.

  View details for DOI 10.1016/j.healun.2021.04.016

  View details for PubMedID 34083118

• STratification risk analysis in OPerative management (STOP score) for drug-induced endocarditis. Journal of cardiac surgery Habertheuer, A., Geirsson, A., Gleason, T., Woo, J., Whitson, B., Arnaoutakis, G. J., Atluri, P., Jassar, A., Kaneko, T., Kilic, A., Tang, P. C., Schranz, A. J., Bin Mahmood, S. U., Mori, M., Sultan, I. 2021

  Abstract

  BACKGROUND: The opioid epidemic has seen a drastic increase in the incidence of drug-associated infective endocarditis (IE). No clinical tool exists to predict operative morbidity and mortality in patients undergoing surgery.METHODS: A multi-institutional database was reviewed between 2011 and 2018. Multivariate logistic regression was fitted in an automated stepwise fashion. The STratification risk analysis in OPerative management of drug-associated IE (STOP) score was constructed. Morbidity was defined as reintubation, prolonged ventilation, pneumonia, renal failure, dialysis, stroke, reoperation for bleeding, and a permanent pacemaker. Cross-validation provided an unbiased estimate of out-of-sample performance.RESULTS: A total of 1181 patients underwent surgery for drug-associated IE (median age, 39; interquartile range [IQR], 30-54, 386 women [32.7%], 341 reoperations for prosthetic valve endocarditis [28.9%], 316 patients with multivalve disease [26.8%]). Operative morbidity and mortality were 41.1% and 5.9%, respectively. Predictors of morbidity were dialysis (95% confidence interval [CI], 1.16-2.82), emergent intervention (1.83-4.73), multivalve procedure (1.01-1.98), causative organisms other than Streptococcus (1.09-2.02), and type of valve procedure performed [aortic valve procedure (1.07-2.15), mitral valve replacement (1.03-2.05), tricuspid valve replacement (1.21-2.60)]. Predictors of mortality were dialysis (1.29-5.74), active endocarditis (1.32-83), lung disease (1.25-5.43), emergent intervention (1.69-6.60), prosthetic valve endocarditis (1.24-3.69), aortic valve procedure (1.49-5.92) and multivalve disease (1.00-2.95). Variables maximizing explanatory power were translated into a scoring system. Each point increased odds of morbidity and mortality by 22.0% and 22.4% with an accuracy of 94.0% and 94.1%, respectively.CONCLUSION: Drug-related IE is associated with significant morbidity and mortality. An easily-applied risk stratification score may aid in clinical decision-making.

  View details for DOI 10.1111/jocs.15570

  View details for PubMedID 33896038

• Expert contributions enhance knowledge of valvular heart disease. The Journal of thoracic and cardiovascular surgery Badhwar, V., Smith, C. R., Woo, J. 2021

  View details for DOI 10.1016/j.jtcvs.2021.03.113

  View details for PubMedID 33985813

• Dynamic Hydrogels for Prevention of Post-Operative Peritoneal Adhesions ADVANCED THERAPEUTICS Stapleton, L. M., Lucian, H. J., Grosskopf, A. K., Smith, A. A., Totherow, K. P., Woo, Y., Appel, E. A. 2021

  View details for DOI 10.1002/adtp.202000242

  View details for Web of Science ID 000606949300001

• Heart Valve Biomechanics: The Frontiers of Modeling Modalities and the Expansive Capabilities of Ex Vivo Heart Simulation. Frontiers in cardiovascular medicine Park, M. H., Zhu, Y., Imbrie-Moore, A. M., Wang, H., Marin-Cuartas, M., Paulsen, M. J., Woo, Y. J. 2021; 8: 673689

  Abstract

  The field of heart valve biomechanics is a rapidly expanding, highly clinically relevant area of research. While most valvular pathologies are rooted in biomechanical changes, the technologies for studying these pathologies and identifying treatments have largely been limited. Nonetheless, significant advancements are underway to better understand the biomechanics of heart valves, pathologies, and interventional therapeutics, and these advancements have largely been driven by crucial in silico, ex vivo, and in vivo modeling technologies. These modalities represent cutting-edge abilities for generating novel insights regarding native, disease, and repair physiologies, and each has unique advantages and limitations for advancing study in this field. In particular, novel ex vivo modeling technologies represent an especially promising class of translatable research that leverages the advantages from both in silico and in vivo modeling to provide deep quantitative and qualitative insights on valvular biomechanics. The frontiers of this work are being discovered by innovative research groups that have used creative, interdisciplinary approaches toward recapitulating in vivo physiology, changing the landscape of clinical understanding and practice for cardiovascular surgery and medicine.

  View details for DOI 10.3389/fcvm.2021.673689

  View details for PubMedID 34307492

• Predicting post-operative right ventricular failure using video-based deep learning. Nature communications Shad, R., Quach, N., Fong, R., Kasinpila, P., Bowles, C., Castro, M., Guha, A., Suarez, E. E., Jovinge, S., Lee, S., Boeve, T., Amsallem, M., Tang, X., Haddad, F., Shudo, Y., Woo, Y. J., Teuteberg, J., Cunningham, J. P., Langlotz, C. P., Hiesinger, W. 2021; 12 (1): 5192

  Abstract

  Despite progressive improvements over the decades, the rich temporally resolved data in an echocardiogram remain underutilized. Human assessments reduce the complex patterns of cardiac wall motion, to a small list of measurements of heart function. All modern echocardiography artificial intelligence (AI) systems are similarly limited by design - automating measurements of the same reductionist metrics rather than utilizing the embedded wealth of data. This underutilization is most evident where clinical decision making is guided by subjective assessments of disease acuity. Predicting the likelihood of developing post-operative right ventricular failure (RV failure) in the setting of mechanical circulatory support is one such example. Here we describe a video AI system trained to predict post-operative RV failure using the full spatiotemporal density of information in pre-operative echocardiography. We achieve an AUC of 0.729, and show that this ML system significantly outperforms a team of human experts at the same task on independent evaluation.

  View details for DOI 10.1038/s41467-021-25503-9

  View details for PubMedID 34465780

• miR-106a-363 cluster in extracellular vesicles promotes endogenous myocardial repair via Notch3 pathway in ischemic heart injury. Basic research in cardiology Jung, J. H., Ikeda, G. n., Tada, Y. n., von Bornstädt, D. n., Santoso, M. R., Wahlquist, C. n., Rhee, S. n., Jeon, Y. J., Yu, A. C., O'brien, C. G., Red-Horse, K. n., Appel, E. A., Mercola, M. n., Woo, J. n., Yang, P. C. 2021; 116 (1): 19

  Abstract

  Endogenous capability of the post-mitotic human heart holds great promise to restore the injured myocardium. Recent evidence indicates that the extracellular vesicles (EVs) regulate cardiac homeostasis and regeneration. Here, we investigated the molecular mechanism of EVs for self-repair. We isolated EVs from human iPSC-derived cardiomyocytes (iCMs), which were exposed to hypoxic (hEVs) and normoxic conditions (nEVs), and examined their roles in in vitro and in vivo models of cardiac injury. hEV treatment significantly improved the viability of hypoxic iCMs in vitro and cardiac function of severely injured murine myocardium in vivo. Microarray analysis of the EVs revealed significantly enriched expression of the miR-106a-363 cluster (miR cluster) in hEVs vs. nEVs. This miR cluster preserved survival and contractility of hypoxia-injured iCMs and maintained murine left-ventricular (LV) chamber size, improved LV ejection fraction, and reduced myocardial fibrosis of the injured myocardium. RNA-Seq analysis identified Jag1-Notch3-Hes1 as a target intracellular pathway of the miR cluster. Moreover, the study found that the cell cycle activator and cytokinesis genes were significantly up-regulated in the iCMs treated with miR cluster and Notch3 siRNA. Together, these results suggested that the miR cluster in the EVs stimulated cardiomyocyte cell cycle re-entry by repressing Notch3 to induce cell proliferation and augment myocardial self-repair. The miR cluster may represent an effective therapeutic approach for ischemic cardiomyopathy.

  View details for DOI 10.1007/s00395-021-00858-8

  View details for PubMedID 33742276

• Operative Technique of Donor Organ Procurement for En Bloc Heart-Liver Transplantation. Transplantation Elde, S. n., Brubaker, A. L., Than, P. A., Rinewalt, D. n., MacArthur, J. W., Alassar, A. n., Bonham, C. A., Esquivel, C. O., Shudo, Y. n., Concepcion, W. n., Woo, Y. J. 2021

  Abstract

  Combined heart-liver transplant is an emerging option for patients with indications for heart transplantation and otherwise prohibitive hepatic dysfunction. Heart-liver transplantation is particularly relevant for patients with single ventricle physiology who often develop Fontan-associated liver disease and fibrosis. While only performed at a limited number of centers, several approaches to combined heart-liver transplantation have been described. The en bloc technique offers several potential advantages over the traditional sequential technique. Specifically, en bloc heart-liver transplantation may allow improved hemodynamics, decreased bleeding, reduced liver allograft ischemic time, and may result in reduced rates of graft dysfunction. Here we describe our center's en bloc heart-liver procurement technique in detail, with the aim of allowing broader use and standardization of this technique. Supplemental Visual Abstract; http://links.lww.com/TP/C147.

  View details for DOI 10.1097/TP.0000000000003697

  View details for PubMedID 33606485

• Navigating the Crossroads of Cell Therapy and Natural Heart Regeneration Frontiers in Cell and Developmental Biology Elde, S., Wang, H., Woo, Y. 2021: 674180

  Abstract

  Cardiovascular disease remains the leading cause of death worldwide despite significant advances in our understanding of the disease and its treatment. Consequently, the therapeutic potential of cell therapy and induction of natural myocardial regeneration have stimulated a recent surge of research and clinical trials aimed at addressing this challenge. Recent developments in the field have shed new light on the intricate relationship between inflammation and natural regeneration, an intersection that warrants further investigation.

  View details for DOI 10.3389/fcell.2021.674180

  View details for PubMedCentralID PMC8148343

• Photosynthetic symbiotic therapeutics - An innovative, effective treatment for ischemic cardiovascular diseases. Journal of molecular and cellular cardiology Zhu, Y., Woo, Y. J. 2021

  Abstract

  Ischemic heart disease is a major cause of global morbidity and mortality, affecting over 15 million patients in the United States. Recent advances in research and innovation have greatly broadened clinicians' ability to treatment ischemic heart disease and associated heart failure using various preventive, pharmacologic, and surgical strategies. Specifically, innovative photosynthetic symbiotic systems using Synechococcus elongatus has gained significant attention. S. elongatus is a unicellular cyanobacterium that can carry out oxygenic photosynthesis. Photosynthetic therapies have been developed to rescue ischemic tissue by taking up tissue-derived carbon dioxide and in turn releasing oxygen for sustained aerobic metabolism during ischemia. In this article, we review the application of cyanobacteria, specifically S. elongatus, in the field of biotechnology, ischemic heart disease, and other clinical applications in ischemic diseases. We also address the motivation for innovation and current limitations in the field of S. elongatus photosynthetic therapeutics for ischemic cardiovascular disease interventions.

  View details for DOI 10.1016/j.yjmcc.2021.11.007

  View details for PubMedID 34813842

• First lung and kidney multi-organ transplant following COVID-19 Infection. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Guenthart, B. A., Krishnan, A., Alassar, A., Madhok, J., Kakol, M., Miller, S., Cole, S. P., Rao, V. K., Acero, N. M., Hill, C. C., Cheung, C., Jackson, E. C., Feinstein, I., Tsai, A. H., Mooney, J. J., Pham, T., Elliott, I. A., Liou, D. Z., La Francesca, S., Shudo, Y., Hiesinger, W., MacArthur, J. W., Brar, N., Berry, G. J., McCarra, M. B., Desai, T. J., Dhillon, G. S., Woo, Y. J. 2021

  Abstract

  As the world responds to the global crisis of the COVID-19 pandemic an increasing number of patients are experiencing increased morbidity as a result of multi-organ involvement. Of these, a small proportion will progress to end-stage lung disease, become dialysis dependent, or both. Herein, we describe the first reported case of a successful combined lung and kidney transplantation in a patient with COVID-19. Lung transplantation, isolated or combined with other organs, is feasible and should be considered for select patients impacted by this deadly disease.

  View details for DOI 10.1016/j.healun.2021.02.015

  View details for PubMedID 34059432

• The Expanding Armamentarium of Innovative Bioengineered Strategies to Augment Cardiovascular Repair and Regeneration Frontiers in Bioengineering and Biotechnology Elde, S., Wang, H., Woo, Y. 2021: 674172

  Abstract

  Cardiovascular disease remains the leading cause of death worldwide. While clinical trials of cell therapy have demonstrated largely neutral results, recent investigations into the mechanisms of natural myocardial regeneration have demonstrated promising new intersections between molecular, cellular, tissue, biomaterial, and biomechanical engineering solutions. New insight into the crucial role of inflammation in natural regenerative processes may explain why previous efforts have yielded only modest degrees of regeneration. Furthermore, the new understanding of the interdependent relationship of inflammation and myocardial regeneration have catalyzed the emergence of promising new areas of investigation at the intersection of many fields.

  View details for DOI 10.3389/fbioe.2021.674172

  View details for PubMedCentralID PMC8205517

• Intracardiac paragangliomas: surgical approach and perioperative management. General thoracic and cardiovascular surgery Guenthart, B. A., Trope, W., Keeyapaj, W., Weiel, J. J., Edmonson, A., MacArthur, J. W., Annes, J. P., Woo, Y. J., Lui, N. S. 2020

  Abstract

  Intracardiac paragangliomas most commonly arise from the left atrium and are often infiltrative and densely adherent to surrounding structures. Given their rarity, only scattered reports exist in the literature and standardized perioperative and surgical management is not well established. We describe a case of a 60-year-old woman with a mildly functioning intracardiac paraganglioma in which division of the superior vena cava improved exposure and enabled a complex limited resection. Further, we provide an overview of the diagnostic workup, perioperative medical management, surgical approach, and surveillance strategy in patients with these challenging tumors.

  View details for DOI 10.1007/s11748-020-01503-2

  View details for PubMedID 33074472

• The role and significance of sensitivity analyses in enhancing the statistical validity of clinical studies. The Journal of thoracic and cardiovascular surgery Baiocchi, M., Woo, Y. J., Chiu, P., Goldstone, A. B. 2020

  View details for DOI 10.1016/j.jtcvs.2020.09.134

  View details for PubMedID 33229182

• A Novel Alternative to The Commando Procedure: Constructing a Neo-Aortic Root by Anchoring to the Sewing Ring of the Replaced Mitral Valve. JTCVS techniques Elde, S., de Biasi, A., Woo, Y. J., Burton, E. 2020

  View details for DOI 10.1016/j.xjtc.2020.08.037

  View details for PubMedID 32875308

• Hypertrophic Cardiomyopathy, a Disease of Altered Cardiac Energetics Ranjbarvaziri, S., Ellenberger, M., Kooiker, K., Fajardo, G., Zhao, M., Schroer, A., Woo, Y. Y., Ruppel, K. M., Spudich, J. A., Snyder, M., Contrepois, K., Bernstein, D. LIPPINCOTT WILLIAMS & WILKINS. 2020

  View details for DOI 10.1161/res.127.suppl_1.235

  View details for Web of Science ID 000606541500028

• Electrophysiologic Conservation of Epicardial Conduction Dynamics After Myocardial Infarction in Newborn Piglets Wang, H., Pong, T., Lucian, H., Aparicio-Valenzuela, J., Tada, Y., Sakhamuri, S., Baker, S. W., Tran, N. A., Paulsen, M. J., Zhu, Y., Lee, A. M., Woo, Y. LIPPINCOTT WILLIAMS & WILKINS. 2020

  View details for DOI 10.1161/res.127.suppl_1.MP164

  View details for Web of Science ID 000606541500318

• Clinical trial in a dish using iPSCs shows lovastatin improves endothelial dysfunction and cellular cross-talk in LMNA cardiomyopathy. Science translational medicine Sayed, N., Liu, C., Ameen, M., Himmati, F., Zhang, J. Z., Khanamiri, S., Moonen, J., Wnorowski, A., Cheng, L., Rhee, J., Gaddam, S., Wang, K. C., Sallam, K., Boyd, J. H., Woo, Y. J., Rabinovitch, M., Wu, J. C. 2020; 12 (554)

  Abstract

  Mutations in LMNA, the gene that encodes lamin A and C, causes LMNA-related dilated cardiomyopathy (DCM) or cardiolaminopathy. LMNA is expressed in endothelial cells (ECs); however, little is known about the EC-specific phenotype of LMNA-related DCM. Here, we studied a family affected by DCM due to a frameshift variant in LMNA Human induced pluripotent stem cell (iPSC)-derived ECs were generated from patients with LMNA-related DCM and phenotypically characterized. Patients with LMNA-related DCM exhibited clinical endothelial dysfunction, and their iPSC-ECs showed decreased functionality as seen by impaired angiogenesis and nitric oxide (NO) production. Moreover, genome-edited isogenic iPSC lines recapitulated the EC disease phenotype in which LMNA-corrected iPSC-ECs showed restoration of EC function. Simultaneous profiling of chromatin accessibility and gene expression dynamics by combining assay for transposase-accessible chromatin using sequencing (ATAC-seq) and RNA sequencing (RNA-seq) as well as loss-of-function studies identified Kruppel-like factor 2 (KLF2) as a potential transcription factor responsible for the EC dysfunction. Gain-of-function studies showed that treatment of LMNA iPSC-ECs with KLF2 agonists, including lovastatin, rescued the EC dysfunction. Patients with LMNA-related DCM treated with lovastatin showed improvements in clinical endothelial dysfunction as indicated by increased reactive hyperemia index. Furthermore, iPSC-derived cardiomyocytes (iPSC-CMs) from patients exhibiting the DCM phenotype showed improvement in CM function when cocultured with iPSC-ECs and lovastatin. These results suggest that impaired cross-talk between ECs and CMs can contribute to the pathogenesis of LMNA-related DCM, and statin may be an effective therapy for vascular dysfunction in patients with cardiolaminopathy.

  View details for DOI 10.1126/scitranslmed.aax9276

  View details for PubMedID 32727917

• Collagen-Supplemented Incubation Rapidly Augments Mechanical Property of Fibroblast Cell Sheets. Tissue engineering. Part A Zhu, Y., Thakore, A. D., Farry, J. M., Jung, J., Anilkumar, S., Wang, H., Imbrie-Moore, A. M., Park, M. H., Tran, N. A., Woo, Y. J. 2020

  Abstract

  Cell sheet technology using UpCell plates is a modern tool that enables the rapid creation of a single-layered cells without using extracellular matrix enzymatic digestion. Although this technique has the advantage of maintaining a sheet of cells without needing artificial scaffolds, these cell sheets remain extremely fragile. Collagen, the most abundant extracellular matrix component, is an attractive candidate for modulating tissue mechanical properties given its tunable property. In this study, we demonstrated rapid mechanical property augmentation of human dermal fibroblast cell sheets after incubation with bovine type I collagen for 24 hours on UpCell plates. We showed that treatment with collagen resulted in increased collagen I incorporation within the cell sheet without affecting cell morphology, cell type, or cell sheet quality. Atomic force microscopy measurements for controls, and cell sheets that received 50g/mL and 100g/mL collagen I treatments revealed an average Young's modulus of their respective intercellular regions: 6.6±1.0, 14.4±6.6, and 19.8±3.8 kPa during the loading condition, and 10.3±4.7, 11.7±2.2, and 18.1±3.4 kPa during the unloading condition. This methodology of rapid mechanical property augmentation of a cell sheet has a potential impact on cell sheet technology by improving the ease of construct manipulation, enabling new translational tissue engineering applications.

  View details for DOI 10.1089/ten.TEA.2020.0128

  View details for PubMedID 32703108

• Transcriptional Profiling of Normal, Stenotic, and Regurgitant Human Aortic Valves. Genes Greene, C. L., Jaatinen, K. J., Wang, H., Koyano, T. K., Bilbao, M. S., Woo, Y. J. 2020; 11 (7)

  Abstract

  The genetic mechanisms underlying aortic stenosis (AS) and aortic insufficiency (AI) disease progression remain unclear. We hypothesized that normal aortic valves and those with AS or AI all exhibit unique transcriptional profiles. Normal control (NC) aortic valves were collected from non-matched donor hearts that were otherwise acceptable for transplantation (n = 5). Valves with AS or AI (n = 5, each) were collected from patients undergoing surgical aortic valve replacement. High-throughput sequencing of total RNA revealed 6438 differentially expressed genes (DEGs) for AS vs. NC, 4994 DEGs for AI vs. NC, and 2771 DEGs for AS vs. AI. Among 21 DEGs of interest, APCDD1L, CDH6, COL10A1, HBB, IBSP, KRT14, PLEKHS1, PRSS35, and TDO2 were upregulated in both AS and AI compared to NC, whereas ALDH1L1, EPHB1, GPX3, HIF3A, and KCNT1 were downregulated in both AS and AI (p < 0.05). COL11A1, H19, HIF1A, KCNJ6, PRND, and SPP1 were upregulated only in AS, and NPY was downregulated only in AS (p < 0.05). The functional network for AS clustered around ion regulation, immune regulation, and lipid homeostasis, and that for AI clustered around ERK1/2 regulation. Overall, we report transcriptional profiling data for normal human aortic valves from non-matched donor hearts that were acceptable for transplantation and demonstrated that valves with AS and AI possess unique genetic signatures. These data create a roadmap for the development of novel therapeutics to treat AS and AI.

  View details for DOI 10.3390/genes11070789

  View details for PubMedID 32674273

• Ex Vivo Analysis of a Porcine Bicuspid Aortic Valve and Aneurysm Disease Model. The Annals of thoracic surgery Zhu, Y., Imbrie-Moore, A. M., Park, M. H., Paulsen, M. J., Wang, H., MacArthur, J. W., Woo, Y. J. 2020

  Abstract

  We identified an extremely rare congenital porcine type 0 lateral bicuspid aortic valve (BAV) from a fresh porcine heart. Using a 3D-printed ex vivo left heart simulator, we analyzed valvular hemodynamics at baseline, in an aortic aneurysm disease model, and after valve-sparing root replacement (VSRR). We showed that BAV regurgitation due to aortic aneurysm can be successfully repaired without significant hemodynamic impairment with the VSRR technique in an individualized approach. Our results provide direct hemodynamic evidence supporting the use of VSRR for patients with BAV regurgitation.

  View details for DOI 10.1016/j.athoracsur.2020.05.086

  View details for PubMedID 32663472

• 2019 AATS/ACC/SCAI/STS Expert Consensus Systems of Care Document: Operator and Institutional Recommendations and Requirements for Transcatheter Mitral Valve Intervention A Joint Report of the American Association for Thoracic Surgery, the American College of Cardiology, the Society for Cardiovascular Angiography and Interventions, and The Society of Thoracic Surgeons JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Bonow, R. O., O'Gara, P. T., Adams, D. H., Badhwar, V., Bavaria, J. E., Elmariah, S., Hung, J. W., Lindenfeld, J., Morris, A., Satpathy, R., Whisenant, B., Woo, Y. 2020; 76 (1): 96–117

  View details for DOI 10.1016/j.jacc.2019.12.002

  View details for Web of Science ID 000552380300014

  View details for PubMedID 31857196

• Donors after circulatory death heart trial. Future cardiology Shudo, Y., Benjamin-Addy, R., Koyano, T. K., Hiesinger, W., MacArthur, J. W., Woo, Y. J. 2020

  Abstract

  Orthotopic heart transplantation is the gold standard treatment for end-stage heart failure. However, the persistent shortage of available donor organs has resulted in an ever-increasing waitlist and longer waiting periods for transplantation. On the contrary, increasing the number of heart transplants by preserving extended criteria donors and donation after circulatory deathhearts with the Organ Care System (OCS) Heart System has the potential to provide the goldstandard, life-saving treatment to patients with end-stage heart failure. The objective of the Donation After Circulatory Death Heart Trial is to evaluate the effectiveness of the OCS Heart System to preserve and assess hearts donated after circulatory death for transplantation to increase the pool of donor hearts available for transplantation, which can potentially provide patients with end-stage heart failure with the life-saving treatment. Clinical Trial Registration: NCT03831048 (ClinicalTrials.gov).

  View details for DOI 10.2217/fca-2020-0070

  View details for PubMedID 32628044

• Relation of Length of Survival After Orthotopic Heart Transplantation to Age of the Donor. The American journal of cardiology Shudo, Y., Guenther, S. P., Lingala, B., He, H., Hiesinger, W., MacArthur, J. W., Currie, M. E., Lee, A. M., Boyd, J. H., Woo, Y. J. 2020

  Abstract

  We aim to evaluate the impact of donor age on the outcomes in orthotropic heart transplantation recipients. The United Network for Organ Sharing database was queried for adult patients (age; ≥60) underwent first-time orthotropic heart transplantation between 1987 and 2019 (n = 18,447). We stratified the cohort by donor age; 1,702 patients (9.2%) received a heart from a donor age of <17 years; 11,307 patients (61.3%) from a donor age of 17 ≥, < 40; 3,525 patients (19.1%) from a donor age of 40 ≥, < 50); and 1,913 patients (10.4%) from a donor age of ≥50. There was a significant difference in the survival likelihood (p < 0.0001) based on donor's age-based categorized cohort, however, the median survival was 10.5 years in the cohort in whom the donor was <17, 10.3 years in whom the donor was 17 ≥, < 40, 9.4 years in whom the donor was 40 ≥, < 50, and 9.0 years in whom the donor was ≥ 50. Additionally, there was no significant difference in the episode of acute rejection (p = 0.19) nor primary graft failure (p = 0.24). In conclusion, this study demonstrated that patients receiving hearts from the donor age of ≥50 years old showed slight inferior survival likelihood, but appeared to be equivalent median survival.

  View details for DOI 10.1016/j.amjcard.2020.06.036

  View details for PubMedID 32736794

• Novel bicuspid aortic valve model with aortic regurgitation for hemodynamic status analysis using an exvivo simulator. The Journal of thoracic and cardiovascular surgery Zhu, Y., Imbrie-Moore, A. M., Paulsen, M. J., Priromprintr, B., Wang, H., Lucian, H. J., Farry, J. M., Woo, Y. J. 2020

  Abstract

  OBJECTIVE: The objective was to design and evaluate a clinically relevant, novel exvivo bicuspid aortic valve model that mimics the most common human phenotype with associated aortic regurgitation.METHODS: Three bovine aortic valves were mounted asymmetrically in a previously validated 3-dimensional-printed left heart simulator. The non-right commissure and the non-left commissure were both shifted slightly toward the left-right commissure, and the left and right coronary cusps were sewn together. The left-right commissure was then detached and reimplanted 10mm lower than its native height. Free margin shortening was used for valve repair. Hemodynamic status, high-speed videography, and echocardiography data were collected before and after the repair.RESULTS: The bicuspid aortic valve model was successfully produced and repaired. High-speed videography confirmed prolapse of the fused cusp of the baseline bicuspid aortic valve models in diastole. Hemodynamic and pressure data confirmed accurate simulation of diseased conditions with aortic regurgitation and the subsequent repair. Regurgitant fraction postrepair was significantly reduced compared with that at baseline (14.5 ± 4.4% vs 28.6%±3.4%; P=.037). There was no change in peak velocity, peak gradient, or mean gradient across the valve pre- versus postrepair: 293.3±18.3cm/sec versus 325.3±58.2cm/sec (P=.29), 34.3±4.2mm Hg versus 43.3±15.4mm Hg (P=.30), and 11±1mm Hg versus 9.3±2.5mm Hg (P=.34), respectively.CONCLUSIONS: An exvivo bicuspid aortic valve model was designed that recapitulated the most common human phenotype with aortic regurgitation. These valves were successfully repaired, validating its potential for evaluating valve hemodynamics and optimizing surgical repair for bicuspid aortic valves.

  View details for DOI 10.1016/j.jtcvs.2020.06.028

  View details for PubMedID 32747120

• Bilateral vs. Single Internal Mammary Artery Grafts for Coronary Artery Bypass in the United States. The Annals of thoracic surgery Zhu, Y., Lingala, B., Wang, H., Woo, Y. J. 2020

  Abstract

  BACKGROUND: The use of bilateral internal mammary arteries (BIMA) in coronary artery bypass grafting remains controversial. The objective of this study was to investigate the long-term outcomes using BIMA versus single internal mammary artery (SIMA) in the United States.METHODS: Medicare beneficiaries who underwent primary isolated coronary artery bypass surgery using SIMA or BIMA from 1999 to 2010 were included in this retrospective study, with follow up through 2014. Greedy matching algorithms were used for 1:4 matching on propensity score based on age, gender, year of surgery, and comorbidities. Kaplan-Meier survival analyses were performed. The primary outcome was death from any cause.RESULTS: A total of 1,156,339 and 25,005 patients aged 72±7.6 and 70.3±7.9 years-old underwent primary isolated coronary artery bypass surgery using SIMA and BIMA, respectively. Matching created comparable groups with 95,780 SIMA and 24,160 BIMA patients. Matched median survival using SIMA was 11.8 versus 12.4 years using BIMA (p<.0001). At ten years of follow up, the respective survival rates of using SIMA versus BIMA were 58.3% versus 61.1%, respectively. The stratified matched median survival using SIMA versus BIMA with one, two, three, and four or more aortocoronary bypasses were 11.8 versus 12.3 years (p=.005), 11.7 versus 12.5 years (p<.0001), 11.9 versus 12.3 years (p=.01), and 11.4 versus 12 years (p=.02), respectively.CONCLUSIONS: Primary isolated coronary artery bypass surgery using BIMA rather than SIMA was associated with improved long-term survival. This survival advantage was independent of aortocoronary bypass grafts or patient diabetes status.

  View details for DOI 10.1016/j.athoracsur.2020.05.049

  View details for PubMedID 32599051

• Safety of photosynthetic Synechococcus elongatus for in vivo cyanobacteria-mammalian symbiotic therapeutics. Microbial biotechnology Williams, K. M., Wang, H., Paulsen, M. J., Thakore, A. D., Rieck, M., Lucian, H. J., Grady, F., Hironaka, C. E., Chien, A. J., Farry, J. M., Shin, H. S., Jaatinen, K. J., Eskandari, A., Stapleton, L. M., Steele, A. N., Cohen, J. E., Woo, Y. J. 2020

  Abstract

  The cyanobacterium Synechococcus elongatus (SE) has been shown to rescue ischaemic heart muscle after myocardial infarction by photosynthetic oxygen production. Here, we investigated SE toxicity and hypothesized that systemic SE exposure does not elicit a significant immune response in rats. Wistar rats intravenously received SE (n=12), sterile saline (n=12) or E. coli lipopolysaccharide (LPS, n=4), and a subset (8 SE, 8 saline) received a repeat injection 4weeks later. At baseline, 4h, 24h, 48h, 8days and 4weeks after injection, clinical assessments, blood cultures, blood counts, lymphocyte phenotypes, liver function tests, proinflammatory cytokines and immunoglobulins were assessed. Across all metrics, SE rats responded comparably to saline controls, displaying no clinically significant immune response. As expected, LPS rats exhibited severe immunological responses. Systemic SE administration does not induce sepsis or toxicity in rats, thereby supporting the safety of cyanobacteria-mammalian symbiotic therapeutics using this organism.

  View details for DOI 10.1111/1751-7915.13596

  View details for PubMedID 32476224

• Cardiac transplantation for cancer involving the heart. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Wingo, M., de Biasi, A. R., Shudo, Y., Bharathi, V., Blackburn, A., Gaudino, M., Girardi, L. N., Woo, Y. J. 2020

  View details for DOI 10.1016/j.healun.2020.05.010

  View details for PubMedID 32532569

• Multiaxial Lenticular Stress-Strain Relationship of Native Myocardium is Preserved by Infarct-Induced Natural Heart Regeneration in Neonatal Mice. Scientific reports Wang, H., Bennett-Kennett, R., Paulsen, M. J., Hironaka, C. E., Thakore, A. D., Farry, J. M., Eskandari, A., Lucian, H. J., Shin, H. S., Wu, M. A., Imbrie-Moore, A. M., Steele, A. N., Stapleton, L. M., Zhu, Y., Dauskardt, R. H., Woo, Y. J. 2020; 10 (1): 7319

  Abstract

  Neonatal mice exhibit natural heart regeneration after myocardial infarction (MI) on postnatal day 1 (P1), but this ability is lost by postnatal day 7 (P7). Cardiac biomechanics intricately affect long-term heart function, but whether regenerated cardiac muscle is biomechanically similar to native myocardium remains unknown. We hypothesized that neonatal heart regeneration preserves native left ventricular (LV) biomechanical properties after MI. C57BL/6J mice underwent sham surgery or left anterior descending coronary artery ligation at age P1 or P7. Echocardiography performed 4 weeks post-MI showed that P1 MI and sham mice (n=22, each) had similar LV wall thickness, diameter, and ejection fraction (59.6% vs 60.7%, p=0.6514). Compared to P7 shams (n=20), P7 MI mice (n=20) had significant LV wall thinning, chamber enlargement, and depressed ejection fraction (32.6% vs 61.8%, p<0.0001). Afterward, the LV was explanted and pressurized ex vivo, and the multiaxial lenticular stress-strain relationship was tracked. While LV tissue modulus for P1 MI and sham mice were similar (341.9 kPa vs 363.4 kPa, p=0.6140), the modulus for P7 MI mice was significantly greater than that for P7 shams (691.6 kPa vs 429.2 kPa, p=0.0194). We conclude that, in neonatal mice, regenerated LV muscle has similar biomechanical properties as native LV myocardium.

  View details for DOI 10.1038/s41598-020-63324-w

  View details for PubMedID 32355240

• Screening and Prophylactic Amiodarone Reduces Post-Operative Atrial Fibrillation in At-Risk Patients JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Pong, T., Cyr, K., Niesen, J., Aparicio-Valenzuela, J., Carlton, C., Fischbein, M. P., Woo, Y., Boyd, J. H., Lee, A. M. 2020; 75 (11): 1361–63

  View details for DOI 10.1016/j.jacc.2020.01.016

  View details for Web of Science ID 000520057100016

  View details for PubMedID 32192666

• Exosomes From Induced Pluripotent Stem Cell-Derived Cardiomyocytes Promote Autophagy for Myocardial Repair. Journal of the American Heart Association Santoso, M. R., Ikeda, G., Tada, Y., Jung, J., Vaskova, E., Sierra, R. G., Gati, C., Goldstone, A. B., von Bornstaedt, D., Shukla, P., Wu, J. C., Wakatsuki, S., Woo, Y. J., Yang, P. C. 2020; 9 (6): e014345

  Abstract

  Background Induced pluripotent stem cells and their differentiated cardiomyocytes (iCMs) have tremendous potential as patient-specific therapy for ischemic cardiomyopathy following myocardial infarctions, but difficulties in viable transplantation limit clinical translation. Exosomes secreted from iCMs (iCM-Ex) can be robustly collected in vitro and injected in lieu of live iCMs as a cell-free therapy for myocardial infarction. Methods and Results iCM-Ex were precipitated from iCM supernatant and characterized by protein marker expression, nanoparticle tracking analysis, and functionalized nanogold transmission electron microscopy. iCM-Ex were then used in in vitro and in vivo models of ischemic injuries. Cardiac function in vivo was evaluated by left ventricular ejection fraction and myocardial viability measurements by magnetic resonance imaging. Cardioprotective mechanisms were studied by JC-1 (tetraethylbenzimidazolylcarbocyanine iodide) assay, immunohistochemistry, quantitative real-time polymerase chain reaction, transmission electron microscopy, and immunoblotting. iCM-Ex measured 140nm and expressed CD63 and CD9. iCM and iCM-Ex microRNA profiles had significant overlap, indicating that exosomal content was reflective of the parent cell. Mice treated with iCM-Ex demonstrated significant cardiac improvement post-myocardial infarction, with significantly reduced apoptosis and fibrosis. In vitro iCM apoptosis was significantly reduced by hypoxia and exosome biogenesis inhibition and restored by treatment with iCM-Ex or rapamycin. Autophagosome production and autophagy flux was upregulated in iCM-Ex groups in vivo and in vitro. Conclusions iCM-Ex improve post-myocardial infarction cardiac function by regulating autophagy in hypoxic cardiomyoytes, enabling a cell-free, patient-specific therapy for ischemic cardiomyopathy.

  View details for DOI 10.1161/JAHA.119.014345

  View details for PubMedID 32131688

• A novel cross-species model of Barlow's disease to biomechanically analyze repair techniques in an exvivo left heart simulator. The Journal of thoracic and cardiovascular surgery Imbrie-Moore, A. M., Paulsen, M. J., Zhu, Y., Wang, H., Lucian, H. J., Farry, J. M., MacArthur, J. W., Ma, M., Woo, Y. J. 2020

  Abstract

  OBJECTIVE: Barlow's disease remains challenging to repair, given the complex valvular morphology and lack of quantitative data to compare techniques. Although there have been recent strides in exvivo evaluation of cardiac mechanics, to our knowledge, there is no disease model that accurately simulates the morphology and pathophysiology of Barlow's disease. The purpose of this study was to design such a model.METHODS: To simulate Barlow's disease, a cross-species exvivo model was developed. Bovine mitral valves (n=4) were sewn into a porcine annulus mount to create excess leaflet tissue and elongated chordae. A heart simulator generated physiologic conditions while hemodynamic data, high-speed videography, and chordal force measurements were collected. The regurgitant valves were repaired using nonresectional repair techniques such as neochord placement.RESULTS: The model successfully imitated the complexities of Barlow's disease, including redundant, billowing bileaflet tissues with notable regurgitation. After repair, hemodynamic data confirmed reduction of mitral leakage volume (25.9±2.9 vs 2.1±1.8mL, P<.001) and strain gauge analysis revealed lower primary chordae forces (0.51±0.17 vs 0.10±0.05N, P<.001). In addition, the maximum rate of change of force was significantly lower postrepair for both primary (30.80±11.38 vs 8.59±4.83N/s, P<.001) and secondary chordae (33.52±10.59 vs 19.07±7.00N/s, P=.006).CONCLUSIONS: This study provides insight into the biomechanics of Barlow's disease, including sharply fluctuating force profiles experienced by elongated chordae prerepair, as well as restoration of primary chordae forces postrepair. Our disease model facilitates further in-depth analyses to optimize the repair of Barlow's disease.

  View details for DOI 10.1016/j.jtcvs.2020.01.086

  View details for PubMedID 32249088

• A novel 3D-Printed preferential posterior mitral annular dilation device delineates regurgitation onset threshold in an ex vivo heart simulator. Medical engineering & physics Imbrie-Moore, A. M., Paullin, C. C., Paulsen, M. J., Grady, F., Wang, H., Hironaka, C. E., Farry, J. M., Lucian, H. J., Woo, Y. J. 2020

  Abstract

  Mitral regurgitation (MR) due to annular dilation occurs in a variety of mitral valve diseases and is observed in many patients with heart failure due to mitral regurgitation. To understand the biomechanics of MR and ultimately design an optimized annuloplasty ring, a representative disease model with asymmetric dilation of the mitral annulus is needed. This work shows the design and implementation of a 3D-printed valve dilation device to preferentially dilate the posterior mitral valve annulus. Porcine mitral valves (n=3) were sewn into the device and mounted within a left heart simulator that generates physiologic pressures and flows through the valves, while chordal forces were measured. The valves were incrementally dilated, inducing MR, while hemodynamic and force data were collected. Flow analysis demonstrated that MR increased linearly with respect to percent annular dilation when dilation was greater than a 25.6% dilation threshold (p<0.01). Pre-threshold, dilation did not cause significant increases in regurgitant fraction. Forces on the chordae tendineae increased as dilation increased prior to the identified threshold (p < 0.01); post-threshold, the MR resulted in highly variable forces. Ultimately, this novel dilation device can be used to more accurately model a wide range of MR disease states and their corresponding repair techniques using ex vivo experimentation. In particular, this annular dilation device provides the means to investigate the design and optimization of novel annuloplasty rings.

  View details for DOI 10.1016/j.medengphy.2020.01.005

  View details for PubMedID 32008935

• Natural Heart Regeneration in a Neonatal Rat Myocardial Infarction Model. Cells Wang, H., Paulsen, M. J., Hironaka, C. E., Shin, H. S., Farry, J. M., Thakore, A. D., Jung, J., Lucian, H. J., Eskandari, A., Anilkumar, S., Wu, M. A., Cabatu, M. C., Steele, A. N., Stapleton, L. M., Zhu, Y., Woo, Y. J. 2020; 9 (1)

  Abstract

  Newborn mice and piglets exhibit natural heart regeneration after myocardial infarction (MI). Discovering other mammals with this ability would provide evidence that neonatal cardiac regeneration after MI may be a conserved phenotype, which if activated in adults could open new options for treating ischemic cardiomyopathy in humans. Here, we hypothesized that newborn rats undergo natural heart regeneration after MI. Using a neonatal rat MI model, we performed left anterior descending coronary artery ligation or sham surgery in one-day-old rats under hypothermic circulatory arrest (n = 74). Operative survival was 97.3%. At 1 day post-surgery, rats in the MI group exhibited significantly reduced ejection fraction (EF) compared to shams (87.1% vs. 53.0%, p < 0.0001). At 3 weeks post-surgery, rats in the sham and MI groups demonstrated no difference in EF (71.1% vs. 69.2%, respectively, p = 0.2511), left ventricular wall thickness (p = 0.9458), or chamber diameter (p = 0.7801). Masson's trichome and picrosirius red staining revealed minimal collagen scar after MI. Increased numbers of cardiomyocytes positive for 5-ethynyl-2'-deoxyuridine (p = 0.0072), Ki-67 (p = 0.0340), and aurora B kinase (p = 0.0430) were observed within the peri-infarct region after MI, indicating ischemia-induced cardiomyocyte proliferation. Overall, we present a neonatal rat MI model and demonstrate that newborn rats are capable of endogenous neocardiomyogenesis after MI.

  View details for DOI 10.3390/cells9010229

  View details for PubMedID 31963369

• Multi-phase catheter-injectable hydrogel enables dual-stage protein-engineered cytokine release to mitigate adverse left ventricular remodeling following myocardial infarction in a small animal model and a large animal model. Cytokine Steele, A. N., Paulsen, M. J., Wang, H. n., Stapleton, L. M., Lucian, H. J., Eskandari, A. n., Hironaka, C. E., Farry, J. M., Baker, S. W., Thakore, A. D., Jaatinen, K. J., Tada, Y. n., Hollander, M. J., Williams, K. M., Seymour, A. J., Totherow, K. P., Yu, A. C., Cochran, J. R., Appel, E. A., Woo, Y. J. 2020; 127: 154974

  Abstract

  Although ischemic heart disease is the leading cause of death worldwide, mainstay treatments ultimately fail because they do not adequately address disease pathophysiology. Restoring the microvascular perfusion deficit remains a significant unmet need and may be addressed via delivery of pro-angiogenic cytokines. The therapeutic effect of cytokines can be enhanced by encapsulation within hydrogels, but current hydrogels do not offer sufficient clinical translatability due to unfavorable viscoelastic mechanical behavior which directly impacts the ability for minimally-invasive catheter delivery. In this report, we examine the therapeutic implications of dual-stage cytokine release from a novel, highly shear-thinning biocompatible catheter-deliverable hydrogel. We chose to encapsulate two protein-engineered cytokines, namely dimeric fragment of hepatocyte growth factor (HGFdf) and engineered stromal cell-derived factor 1α (ESA), which target distinct disease pathways. The controlled release of HGFdf and ESA from separate phases of the hyaluronic acid-based hydrogel allows extended and pronounced beneficial effects due to the precise timing of release. We evaluated the therapeutic efficacy of this treatment strategy in a small animal model of myocardial ischemia and observed a significant benefit in biological and functional parameters. Given the encouraging results from the small animal experiment, we translated this treatment to a large animal preclinical model and observed a reduction in scar size, indicating this strategy could serve as a potential adjunct therapy for the millions of people suffering from ischemic heart disease.

  View details for DOI 10.1016/j.cyto.2019.154974

  View details for PubMedID 31978642

• Engineered biomaterials for heart disease. Current opinion in biotechnology Stapleton, L. n., Zhu, Y. n., Woo, Y. J., Appel, E. n. 2020; 66: 246–54

  Abstract

  Ischemic heart disease is the most common type of heart disease, responsible for roughly 10 million deaths worldwide annually. While standard clinical interventions have resulted in improved patient outcomes, access to small diameter vessels required for cardiovascular interventions, and long-term patient mortality rates associated with eventual heart failure, remain critical challenges. In this current opinion piece we discuss novel methodologies for the advancement of vascular grafts, cardiac patches, and injectable drug delivery depot technologies as they relate to treatment of ischemic heart disease, including bilayered conduits, acellular bioactive extracellular matrix (ECM) scaffolds, and protease-responsive hydrogel delivery platforms. We address the motivation for innovation and current limitations in the field of engineered biomaterials for myocardial ischemia therapeutics and interventions.

  View details for DOI 10.1016/j.copbio.2020.08.008

  View details for PubMedID 33011453

• Operative Techniques and Pitfalls in Donor Bilateral Lung Procurement. Transplantation proceedings Dalal, A. R., Rinewalt, D. E., MacArthur, J. W., Shudo, Y. n., Woo, Y. J. 2020

  Abstract

  Demand for lung transplant continues to grow nationally, and the number of donation after brain death and donation after circulatory death lung procurements increases each year.We describe the Stanford technique for bilateral lung procurement for donation after brain death and donation after circulatory death and highlight the pitfalls and common mistakes to standardize the procurement process and ensure proper harvesting to prevent organ loss.Damage to the lung graft during bilateral en bloc procurement most commonly results from either poor preservation or injury to a pulmonary vein during division of the left atrial cuff.En bloc bilateral lung procurement should be standardized to ensure reproducible graft harvesting and preservation while teaching new generations of transplant surgeons.

  View details for DOI 10.1016/j.transproceed.2020.01.023

  View details for PubMedID 32139275

• Three-Dimensional Multi-layered Microstructure using Laser Direct-Writing System. Tissue engineering. Part A Shudo, Y. n., MacArthur, J. W., Kunitomi, Y. n., Joubert, L. M., Kawamura, M. n., Ono, J. n., Thakore, A. D., Jaatinen, K. J., Eskandari, A. n., Hironaka, C. E., Shin, H. S., Woo, Y. J. 2020

  Abstract

  Tissue engineering is an essential component of developing effective regenerative therapies. Here, we introduce a promising method to create scaffold-free three dimensional (3D) tissue engineered multi-layered microstructures from cultured cells using the "3D tissue fabrication system" (Regenova®, Cyfuse, Japan). This technique utilizes the adhesive nature of cells. When cells are cultured in non-adhesive wells, they tend to aggregateand form a spheroidal structure. The advantage of this approach is that cellular components can be mixed into one spheroid, thereby promoting the formation of extracellular matrices, such as collagen and elastin. This system enables one to create a pre-designed 3D structure composed of cultured cells. We found the advantages of this system to be: (1) the length, size, and shape of the structure were designable and highly reproducible because of the computer controlled robotics system, (2) the graftable structure could be created within a reasonable period (8 days), and (3) the constructed tissue did not contain any foreign material, which may avoid the potential issues ofcontamination, biotoxicity, and allergy. The utilization of this robotic system enabled thecreation of a 3D multi-layered microstructure made of cell based spheres with a satisfactory mechanical properties and abundant extracellular matrix during a short period of time. These results suggest that this new technology will represent a promising, attractive, and practical strategy in the field of tissue engineering.

  View details for DOI 10.1089/ten.TEA.2019.0313

  View details for PubMedID 32085692

• Racial and Sex Disparities Persist in Modern Cardiac Surgical Outcomes. Annals of surgery Elde, S. F., Woo, Y. J. 2020; 272 (4): 668

  View details for DOI 10.1097/SLA.0000000000004333

  View details for PubMedID 32932323

• Signalosome-Regulated SRF Phosphorylation Determining Myocyte Growth in Width versus Length as a Therapeutic Target for Heart Failure. Circulation Li, J. n., Tan, Y. n., Passariello, C. L., Martinez, E. C., Kritzer, M. D., Li, X. n., Li, X. n., Li, Y. n., Yu, Q. n., Ohgi, K. n., Thakur, H. n., MacArthur, J. W., Ivey, J. R., Woo, Y. J., Emter, C. A., Dodge-Kafka, K. n., Rosenfeld, M. G., Kapiloff, M. S. 2020

  Abstract

  Background: Concentric and eccentric cardiac hypertrophy are associated with pressure and volume overload, respectively, in cardiovascular disease both conferring an increased risk of heart failure. These contrasting forms of hypertrophy are characterized by asymmetric growth of the cardiac myocyte in mainly width or length, respectively. The molecular mechanisms determining myocyte preferential growth in width versus length remain poorly understood. Identification of the mechanisms governing asymmetric myocyte growth could provide new therapeutic targets for the prevention or treatment of heart failure. Methods: Primary adult rat ventricular myocytes, adeno-associated virus (AAV)-mediated gene delivery in mice, and human tissue samples are used to define a regulatory pathway controlling pathological myocyte hypertrophy. Chromatin Immunoprecipitation Assays with Sequencing (ChIP-seq) and Precision Nuclear Run-On Sequencing (PRO-seq) are used to define a transcriptional mechanism. Results: Here we report that asymmetric cardiac myocyte hypertrophy is modulated by serum response factor (SRF) phosphorylation, constituting an epigenomic switch balancing the growth in width versus length of adult ventricular myocytes in vitro and in vivo. SRF Ser103 phosphorylation is bidirectionally regulated by p90 ribosomal S6 kinase type 3 (RSK3) and protein phosphatase 2A (PP2A) at signalosomes organized by the scaffold protein muscle A-kinase anchoring protein β (mAKAPβ), such that increased SRF phosphorylation activates Activator Protein 1 (AP1)-dependent enhancers that direct myocyte growth in width. AAV are used to express in vivo mAKAPβ-derived RSK3 and PP2A anchoring disruptor peptides that block the association of the enzymes with the mAKAPβ scaffold. Inhibition of RSK3 signaling prevents concentric cardiac remodeling due to pressure overload, while inhibition of PP2A signaling prevents eccentric cardiac remodeling induced by myocardial infarction, in each case improving cardiac function. SRF Ser103 phosphorylation is significantly decreased in dilated human hearts, supporting the notion that modulation of the mAKAPβ-SRF signalosome could be a new therapeutic approach for human heart failure. Conclusions: We have identified a new molecular switch, namely mAKAPβ signalosome-regulated SRF phosphorylation, that controls a transcriptional program responsible for modulating changes in cardiac myocyte morphology that occur secondary to pathological stressors. Complementary AAV-based gene therapies constitute rationally-designed strategies for a new translational modality for heart failure.

  View details for DOI 10.1161/CIRCULATIONAHA.119.044805

  View details for PubMedID 32933333

• Outcomes after heart retransplantation: A 50-year single-center experience. The Journal of thoracic and cardiovascular surgery Zhu, Y. n., Shudo, Y. n., Lingala, B. n., Baiocchi, M. n., Oyer, P. E., Woo, Y. J. 2020

  Abstract

  To evaluate outcomes after heart retransplantation.From January 6, 1968, to June 2019, 123 patients (112 adult and 11 pediatric patients) underwent heart retransplantation, and 2092 received primary transplantation at our institution. Propensity-score matching was used to account for baseline differences between the retransplantation and the primary transplantation-only groups. Kaplan-Meier survival analyses were performed. The primary end point was all-cause mortality, and secondary end points were postoperative complications.Retransplantation recipient age was 39.6 ± 16.4 years, and donor age was 26.4 ± 11.2 years. Ninety-two recipients (74.8%) were male. Compared with recipients who only underwent primary heart transplantation, retransplantation recipients were more likely to have hypertension (44/73.3% vs 774/53.3%, P = .0022), hyperlipidemia (40/66.7% vs 447/30.7%, P < .0001), and require dialysis (7/11.7% vs 42/2.9%, P = .0025). The indications for heart retransplantation were cardiac allograft vasculopathy (32/80%), primary graft dysfunction (6/15%), and refractory acute rejection (2/5%). After matching, postoperative outcomes such as hospital length of stay, severe primary graft dysfunction requiring intra-aortic balloon pump or extracorporeal membrane oxygenation, cerebral vascular accident, respiratory failure, renal failure requiring dialysis, and infection were similar between the 2 groups. Matched median survival after retransplantation was 4.6 years compared with 6.5 years after primary heart transplantation (log-rank P = .36, stratified log-rank P = .0063).In this single-center cohort, the unadjusted long-term survival after heart retransplantation was inferior to that after primary heart transplantation, and short-term survival difference persisted after propensity-score matching. Heart retransplantation should be considered for select patients for optimal donor organ usage.

  View details for DOI 10.1016/j.jtcvs.2020.06.121

  View details for PubMedID 32798029

• SELECTIVELY COMPLIANT ANNULOPLASTY RING TO ENABLE ANNULAR DYNAMICS IN MITRAL VALVE REPAIR EVALUATED BY IN-VITRO STEREOVISION Frishman, S., Imbrie-Moore, A. M., Cutkosky, M. R., Kight, A., Pirozzi, I., Paulsen, M. J., Woo, J. Y., Am Soc Mech Eng AMER SOC MECHANICAL ENGINEERS. 2020

  View details for Web of Science ID 000624287000005

• Less Invasive Mitral Surgery versus Conventional Sternotomy Stratified by Mitral Pathology. The Annals of thoracic surgery Nissen, A. P., Miller, C. C., Thourani, V. H., Woo, Y. J., Gammie, J. S., Ailawadi, G. n., Nguyen, T. C. 2020

  Abstract

  Our objective was to compare national mitral repair rates and outcomes after less invasive mitral surgery (LIMS) versus conventional sternotomy across the spectrum of mitral pathologies and repair techniques.Patients undergoing isolated primary mitral valve surgery in the Society of Thoracic Surgeons Adult Cardiac Surgery Database from July 2014 - December 2018 were evaluated. Propensity score models were constructed non-parsimoniously, and prediction models used to compute adjusted effects of surgical approach. Hypothesis tests were adjusted for propensity score with inverse-probability weighting.A total of 41,082 patients met inclusion criteria; including 10,238 (24.9%) LIMS and 30,844 (75.1%) conventional sternotomy, with increased LIMS adoption annually. Surgeons reporting LIMS cases had higher annual median mitral case volumes than those who did not (23 vs. 8, p<0.0001). Groups were well-balanced after propensity adjustment including mitral pathology. Propensity score-adjusted outcomes showed increased procedural volume (OR 1.030 [95% CI 1.028 - 1.031]), and LIMS (OR 2.139, [95% CI 2.032 - 2.251]) were independently associated with higher mitral repair rates. Propensity-adjusted outcomes included reduced stroke (p<0.0007), atrial fibrillation (p<0.0001), pacemaker (p<0.0001), renal failure (p<0.0001), and lengths of stay (p<0.0001) for LIMS vs. sternotomy, without differences in mortality. Operative volume influenced outcomes in both groups.LIMS was associated with higher mitral repair rates, and lower morbidity. Further studies regarding the impact of surgeon volume on choice of operative approach are necessary.

  View details for DOI 10.1016/j.athoracsur.2020.05.145

  View details for PubMedID 32717233

• In Vivo Validation of Restored Chordal Biomechanics After Mitral Ring Annuloplasty in a Rare Ovine Case of Natural Chronic Functional Mitral Regurgitation. Journal of cardiovascular development and disease Wang, H. n., Paulsen, M. J., Imbrie-Moore, A. M., Tada, Y. n., Bergamasco, H. n., Baker, S. W., Shudo, Y. n., Ma, M. n., Woo, J. Y. 2020; 7 (2)

  Abstract

  Mitral valve chordae tendineae forces are elevated in the setting of mitral regurgitation (MR). Ring annuloplasty is an essential component of surgical repair for MR, but whether chordal forces are reduced after mitral annuloplasty has never been validated in vivo. Here, we present an extremely rare ovine case of natural, severe chronic functional MR, in which we used force-sensing fiber Bragg grating neochordae to directly measure chordal forces in the baseline setting of severe MR, as well as after successful mitral ring annuloplasty repair. Overall, our report is the first to confirm in vivo that mitral ring annuloplasty reduces elevated chordae tendineae forces associated with chronic functional MR.

  View details for DOI 10.3390/jcdd7020017

  View details for PubMedID 32429298

• Long-term outcome of orthotopic heart transplantation in Asians: An analysis of the United Network of Organ Sharing database. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Kohsaka, S. n., Shudo, Y. n., Wang, H. n., Lingala, B. n., Kawana, M. n., Woo, Y. J. 2020

  View details for DOI 10.1016/j.healun.2020.07.016

  View details for PubMedID 32948416

• A Novel Aortic Regurgitation Model from Cusp Prolapse with Hemodynamic Validation Using an Ex Vivo Left Heart Simulator. Journal of cardiovascular translational research Zhu, Y. n., Imbrie-Moore, A. M., Paulsen, M. J., Priromprintr, B. n., Park, M. H., Wang, H. n., Lucian, H. J., Farry, J. M., Woo, Y. J. 2020

  Abstract

  Although ex vivo simulation is a valuable tool for surgical optimization, a disease model that mimics human aortic regurgitation (AR) from cusp prolapse is needed to accurately examine valve biomechanics. To simulate AR, four porcine aortic valves were explanted, and the commissure between the two largest leaflets was detached and re-implanted 5 mm lower to induce cusp prolapse. Four additional valves were tested in their native state as controls. All valves were tested in a heart simulator while hemodynamics, high-speed videography, and echocardiography data were collected. Our AR model successfully reproduced cusp prolapse with significant increase in regurgitant volume compared with that of the controls (23.2 ± 8.9 versus 2.8 ± 1.6 ml, p = 0.017). Hemodynamics data confirmed the simulation of physiologic disease conditions. Echocardiography and color flow mapping demonstrated the presence of mild to moderate eccentric regurgitation in our AR model. This novel AR model has enormous potential in the evaluation of valve biomechanics and surgical repair techniques. Graphical Abstract.

  View details for DOI 10.1007/s12265-020-10038-z

  View details for PubMedID 32495264

• Heart Transplant Using Hepatitis C-Seropositive and Viremic Organs in Seronegative Recipients. Annals of transplantation Zhu, Y. n., Shudo, Y. n., Lee, R. n., Woo, Y. J. 2020; 25: e922723

  Abstract

  BACKGROUND Hepatitis C virus (HCV)-seropositive donor hearts are underutilized for orthotopic heart transplantation (OHT). The advancement of direct-acting antiviral agent (DAA) treatment for HCV makes utilizing HCV-seropositive and viremic donor organs in HCV-seronegative recipients a possibility. MATERIAL AND METHODS From 1997 to 2019, adult patients who underwent OHT at our institution were retrospectively reviewed. Ten HCV-seronegative patients received HCV-seropositive donor hearts, 3 of which tested nucleic acid-positive. Kaplan-Meier curves were performed for survival analyses. This study was approved by the Institutional Review Board. RESULTS Recipient median age was 57.5 years old, and 2 (20%) were female. Donor median age was 42 years old, and 3 (30%) were female. One donor was cured from HCV with DAA prior to OHT. Four recipients developed hepatitis C viremia immediately after OHT. DAA treatment was completed in 3 recipients who demonstrated cure. Thirty-day and 1-year survival rates were both 80%. CONCLUSIONS We describe 10 HCV-seronegative patients who received HCV-seropositive donor hearts at our institution, with excellent short-term outcomes, even in those who received nucleic acid testing positive organs. DAA can be effective in treating hepatitis C viremia before and after OHT, with excellent recipient survival. Large clinical studies are needed to further evaluate the long-term outcomes of DAA therapy in patients after heart transplantation.

  View details for DOI 10.12659/AOT.922723

  View details for PubMedID 32527989

• Biomimetic six-axis robots replicate human cardiac papillary muscle motion: pioneering the next generation of biomechanical heart simulator technology. Journal of the Royal Society, Interface Imbrie-Moore, A. M., Park, M. H., Paulsen, M. J., Sellke, M. n., Kulkami, R. n., Wang, H. n., Zhu, Y. n., Farry, J. M., Bourdillon, A. T., Callinan, C. n., Lucian, H. J., Hironaka, C. E., Deschamps, D. n., Joseph Woo, Y. n. 2020; 17 (173): 20200614

  Abstract

  Papillary muscles serve as attachment points for chordae tendineae which anchor and position mitral valve leaflets for proper coaptation. As the ventricle contracts, the papillary muscles translate and rotate, impacting chordae and leaflet kinematics; this motion can be significantly affected in a diseased heart. In ex vivo heart simulation, an explanted valve is subjected to physiologic conditions and can be adapted to mimic a disease state, thus providing a valuable tool to quantitatively analyse biomechanics and optimize surgical valve repair. However, without the inclusion of papillary muscle motion, current simulators are limited in their ability to accurately replicate cardiac biomechanics. We developed and implemented image-guided papillary muscle (IPM) robots to mimic the precise motion of papillary muscles. The IPM robotic system was designed with six degrees of freedom to fully capture the native motion. Mathematical analysis was used to avoid singularity conditions, and a supercomputing cluster enabled the calculation of the system's reachable workspace. The IPM robots were implemented in our heart simulator with motion prescribed by high-resolution human computed tomography images, revealing that papillary muscle motion significantly impacts the chordae force profile. Our IPM robotic system represents a significant advancement for ex vivo simulation, enabling more reliable cardiac simulations and repair optimizations.

  View details for DOI 10.1098/rsif.2020.0614

  View details for PubMedID 33259750

• Comprehensive Ex Vivo Comparison of 5 Clinically Used Conduit Configurations for Valve-Sparing Aortic Root Replacement Using a 3-Dimensional-Printed Heart Simulator. Circulation Paulsen, M. J., Imbrie-Moore, A. M., Baiocchi, M. n., Wang, H. n., Hironaka, C. E., Lucian, H. J., Farry, J. M., Thakore, A. D., Zhu, Y. n., Ma, M. n., MacArthur, J. W., Woo, Y. J. 2020; 142 (14): 1361–73

  Abstract

  Many graft configurations are clinically used for valve-sparing aortic root replacement, some specifically focused on recapitulating neosinus geometry. However, the specific impact of such neosinuses on valvular and root biomechanics and the potential influence on long-term durability are unknown.Using a custom 3-dimenstional-printed heart simulator with porcine aortic roots (n=5), the anticommissural plication, Stanford modification, straight graft (SG), Uni-Graft, and Valsalva graft configurations were tested in series using an incomplete counterbalanced measures design, with the native root as a control, to mitigate ordering effects. Hemodynamic and videometric data were analyzed using linear models with conduit as the fixed effect of interest and valve as a fixed nuisance effect with post hoc pairwise testing using Tukey's correction.Hemodynamics were clinically similar between grafts and control aortic roots. Regurgitant fraction varied between grafts, with SG and Uni-Graft groups having the lowest regurgitant fractions and anticommissural plication having the highest. Root distensibility was significantly lower in SG versus both control roots and all other grafts aside from the Stanford modification (P≤0.01 for each). All grafts except SG had significantly higher cusp opening velocities versus native roots (P<0.01 for each). Relative cusp opening forces were similar between SG, Uni-Graft, and control groups, whereas anticommissural plication, Stanford modification, and Valsalva grafts had significantly higher opening forces versus controls (P<0.01). Cusp closing velocities were similar between native roots and the SG group, and were significantly lower than observed in the other conduits (P≤0.01 for each). Only SG and Uni-Graft groups experienced relative cusp closing forces approaching that of the native root, whereas relative forces were >5-fold higher in the anticommissural plication, Stanford modification, and Valsalva graft groups.In this ex vivo modeling system, clinically used valve-sparing aortic root replacement conduit configurations have comparable hemodynamics but differ in biomechanical performance, with the straight graft most closely recapitulating native aortic root biomechanics.

  View details for DOI 10.1161/CIRCULATIONAHA.120.046612

  View details for PubMedID 33017215

• A Bioengineered Neuregulin-Hydrogel Therapy Reduces Scar Size and Enhances Post-Infarct Ventricular Contractility in an Ovine Large Animal Model. Journal of cardiovascular development and disease Cohen, J. E., Goldstone, A. B., Wang, H. n., Purcell, B. P., Shudo, Y. n., MacArthur, J. W., Steele, A. N., Paulsen, M. J., Edwards, B. B., Aribeana, C. N., Cheung, N. C., Burdick, J. A., Woo, Y. J. 2020; 7 (4)

  Abstract

  The clinical efficacy of neuregulin (NRG) in the treatment of heart failure is hindered by off-target exposure due to systemic delivery. We previously encapsulated neuregulin in a hydrogel (HG) for targeted and sustained myocardial delivery, demonstrating significant induction of cardiomyocyte proliferation and preservation of post-infarct cardiac function in a murine myocardial infarction (MI) model. Here, we performed a focused evaluation of our hydrogel-encapsulated neuregulin (NRG-HG) therapy's potential to enhance cardiac function in an ovine large animal MI model. Adult male Dorset sheep (n = 21) underwent surgical induction of MI by coronary artery ligation. The sheep were randomized to receive an intramyocardial injection of saline, HG only, NRG only, or NRG-HG circumferentially around the infarct borderzone. Eight weeks after MI, closed-chest intracardiac pressure-volume hemodynamics were assessed, followed by heart explant for infarct size analysis. Compared to each of the control groups, NRG-HG significantly augmented left ventricular ejection fraction (p = 0.006) and contractility based on the slope of the end-systolic pressure-volume relationship (p = 0.006). NRG-HG also significantly reduced infarct scar size (p = 0.002). Overall, using a bioengineered hydrogel delivery system, a one-time dose of NRG delivered intramyocardially to the infarct borderzone at the time of MI in adult sheep significantly reduces scar size and enhances ventricular contractility at 8 weeks after MI.

  View details for DOI 10.3390/jcdd7040053

  View details for PubMedID 33212844

• Quadrupling the N95 Supply during the COVID-19 Crisis with an Innovative 3D-Printed Mask Adaptor. Healthcare (Basel, Switzerland) Imbrie-Moore, A. M., Park, M. H., Zhu, Y. n., Paulsen, M. J., Wang, H. n., Woo, Y. J. 2020; 8 (3)

  Abstract

  The need for personal protective equipment during the COVID-19 pandemic is far outstripping our ability to manufacture and distribute these supplies to hospitals. In particular, the medical N95 mask shortage is resulting in healthcare providers reusing masks or utilizing masks with filtration properties that do not meet medical N95 standards. We developed a solution for immediate use: a mask adaptor, outfitted with a quarter section of an N95 respirator that maintains the N95 seal standard, thereby quadrupling the N95 supply. A variety of designs were 3D-printed and optimized based on the following criteria: seal efficacy, filter surface area and N95 respirator multiplicity. The final design is reusable and features a 3D-printed soft silicone base as well as a rigid 3D-printed cartridge to seal one-quarter of a 3M 1860 N95 mask. Our mask passed the computerized N95 fit test for six individuals. All files are publicly available with this publication. Our design can provide immediate support for healthcare professionals in dire need of medical N95 masks by extending the current supply by a factor of four.

  View details for DOI 10.3390/healthcare8030225

  View details for PubMedID 32717841

• Use of patient-specific computational models for optimization of aortic insufficiency after implantation of left ventricular assist device. The Journal of thoracic and cardiovascular surgery Kasinpila, P. n., Kong, S. n., Fong, R. n., Shad, R. n., Kaiser, A. D., Marsden, A. L., Woo, Y. J., Hiesinger, W. n. 2020

  Abstract

  Aortic incompetence (AI) is observed to be accelerated in the continuous-flow left ventricular assist device (LVAD) population and is related to increased mortality. Using computational fluid dynamics (CFD), we investigated the hemodynamic conditions related to the orientation of the LVAD outflow in these patients.We identified 10 patients with new aortic regurgitation, and 20 who did not, after LVAD implantation between 2009 and 2018. Three-dimensional models of patients' aortas were created from their computed tomography scans. The geometry of the LVAD outflow graft in relation to the aorta was quantified using azimuth angles (AA), polar angles (PAs), and distance from aortic root. The models were used to run CFD simulations, which calculated the pressures and wall shear stress (rWSS) exerted on the aortic root.The AA and PA were found to be similar. However, for combinations of high values of AA and low values of PA, there were no patients with AI. The distance from aortic root to the outflow graft was also smaller in patients who developed AI (3.39 ± 0.7 vs 4.07 ± 0.77 cm, P = .04). There was no significant difference in aortic root pressures in the 2 groups. The rWSS was greater in AI patients (4.60 ± 5.70 vs 2.37 ± 1.20 dyne/cm2, P < .001). Qualitatively, we observed a trend of greater perturbations, regions of high rWSS, and flow eddies in the AI group.Using CFD simulations, we demonstrated that patients who developed de novo AI have greater rWSS at the aortic root, and their outflow grafts were placed closer to the aortic roots than those patients without de novo AI.

  View details for DOI 10.1016/j.jtcvs.2020.04.164

  View details for PubMedID 32653292

• 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

• Artificial papillary muscle device for off-pump transapical mitral valve repair. The Journal of thoracic and cardiovascular surgery Imbrie-Moore, A. M., Zhu, Y. n., Park, M. H., Paulsen, M. J., Wang, H. n., Woo, Y. J. 2020

  Abstract

  New transapical minimally invasive artificial chordae implantation devices are a promising alternative to traditional open-heart repair, with the potential for decreased postoperative morbidity and reduced recovery time. However, these devices can place increased stress on the artificial chordae. We designed an artificial papillary muscle to alleviate artificial chordae stresses and thus increase repair durability.The artificial papillary muscle device is a narrow elastic column with an inner core that can be implanted during the minimally invasive transapical procedure via the same ventricular incision site. The device was 3-dimensionally printed in biocompatible silicone for this study. To test efficacy, porcine mitral valves (n = 6) were mounted in a heart simulator, and isolated regurgitation was induced. Each valve was repaired with a polytetrafluoroethylene suture with apical anchoring followed by artificial papillary muscle anchoring. In each case, a high-resolution Fiber Bragg Grating sensor recorded forces on the suture.Hemodynamic data confirmed that both repairs-with and without the artificial papillary muscle device-were successful in eliminating mitral regurgitation. Both the peak artificial chordae force and the rate of change of force at the onset of systole were significantly lower with the device compared with apical anchoring without the device (P < .001 and P < .001, respectively).Our novel artificial papillary muscle could integrate with minimally invasive repairs to shorten the artificial chordae and behave as an elastic damper, thus reducing sharp increases in force. With our device, we have the potential to improve the durability of off-pump transapical mitral valve repair procedures.

  View details for DOI 10.1016/j.jtcvs.2020.11.105

  View details for PubMedID 33451843

• Impact of Surgical Approach in Double Lung Transplantation: Median Sternotomy vs Clamshell Thoracotomy. Transplantation proceedings Shudo, Y. n., Rinewalt, D. n., Lingala, B. n., Kim, F. Y., He, H. n., Boyd, J. H., Lee, A. M., Hiesinger, W. n., Currie, M. E., MacArthur, J. W., Woo, Y. J. 2020

  Abstract

  Double lung transplantation (DLT) remains the gold standard for end-stage lung disease. Although DLT was historically performed via clamshell thoracotomy, recently the median sternotomy has emerged as a viable alternative. As the ideal surgical approach remains unclear, the aim of our study was to compare the short- and long-term outcomes of these 2 surgical approaches in DLT.We retrospectively reviewed 192 consecutive adult patients who underwent primary DLT at our institution between 2012 and 2017 (sternotomy, n = 147; clamshell, n = 45). The impact of each surgical approach on post-transplant morbidity was investigated, and the overall survival probability analyses were performed.There were no significant differences in recipients' baseline and donors' characteristics and bilateral allograft ischemic time. Freedom from primary graft dysfunction, acute rejection episodes, postoperative prolonged ventilator support, tracheostomy, postoperative stroke, and airway dehiscence were comparable between these 2 groups. The duration of cardiopulmonary bypass and operative time were significantly longer in the clamshell thoracotomy group. Postoperative extracorporeal membrane oxygenation usage tended to be more frequent in the clamshell thoracotomy group than the median sternotomy group, despite no statistical significance. Length of hospital and intensive care unit stay were not influenced by the type of incision. There was no significant difference in overall survival between these 2 procedure groups (P = .61, log-rank test).The median sternotomy approach in DLT decreases operative time and more importantly leads to a shorter duration of cardiopulmonary bypass. The type of surgical approach did not show any statistically significant impact on adult DLT recipients' morbidity and survival.

  View details for DOI 10.1016/j.transproceed.2019.10.018

  View details for PubMedID 31911057

• Improved midterm outcomes after endovascular repair of nontraumatic descending thoracic aortic rupture compared with open surgery. The Journal of thoracic and cardiovascular surgery Ogawa, Y., Watkins, A. C., Lingala, B., Nathan, I., Chiu, P., Iwakoshi, S., He, H., Lee, J. T., Fischbein, M., Woo, Y. J., Dake, M. D. 2019

  Abstract

  BACKGROUND: Thoracic endovascular aortic repair (TEVAR) has become first-line treatment for descending thoracic aortic rupture (DTAR), but its midterm and long-term outcomes remain undescribed. This study evaluated whether TEVAR would improve midterm outcomes of nontraumatic DTAR relative to open surgical repair (OSR).METHODS: Between December 1999 and October 2018, 118 patients with DTAR were treated with either OSR (n=39) or TEVAR (n=79) at a single center. Primary end points were 30-day and long-term all-cause mortalities. Secondary end points included stroke, permanent spinal cord ischemia (SCI), prolonged ventilation support or tracheostomy, permanent hemodialysis, and aortic reintervention.RESULTS: Thirty-day mortality was significantly lower with TEVAR (OSR, 38.5%; TEVAR, 16.5%; P=.01). Stroke (15.6% vs 3.8%; P=.03), permanent SCI (15.6% vs 2.5%; P=.02), prolonged ventilation (30.8% vs 8.9%; P=.002), and tracheostomy (12.8% vs 2.5%; P=.04) were significantly lower after TEVAR than OSR. Need for hemodialysis trended higher after OSR (12.8% vs 5.1%; P=.2). Mean follow ups were 1048±1591days for OSR group and 828±1258days for TEVAR. All-cause mortality at last follow-up was significantly lower after TEVAR than OSR (35.4% vs 66.7%; P=.001). Aortic reintervention was required more frequently within 30days after TEVAR (15.2% vs 2.6%; P=.06). By multivariate analysis, TAAA was an independent predictor for mortality.CONCLUSIONS: TEVAR improves both early and midterm outcomes of DTAR relative to OSR. TAAA was a predictor of mortality. Endovascular approach to DTAR may provide the greatest chance at survival.

  View details for DOI 10.1016/j.jtcvs.2019.10.156

  View details for PubMedID 31926735

• Redo Valve-Sparing Root Replacement for Delayed Cusp Derangement From Ventricular Septal Defect ANNALS OF THORACIC SURGERY Zhu, Y., Cohen, J. E., Ma, M., Woo, Y. 2019; 108 (5): E295–E296

  View details for DOI 10.1016/j.athoracsur.2019.03.040

  View details for Web of Science ID 000492187300005

• Mitral chordae tendineae force profile characterization using a posterior ventricular anchoring neochordal repair model for mitral regurgitation in a three-dimensional-printed ex vivo left heart simulator. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Paulsen, M. J., Imbrie-Moore, A. M., Wang, H., Bae, J. H., Hironaka, C. E., Farry, J. M., Lucian, H. J., Thakore, A. D., MacArthur, J. W., Cutkosky, M. R., Woo, Y. J. 2019

  Abstract

  OBJECTIVES: Posterior ventricular anchoring neochordal (PVAN) repair is a non-resectional technique for correcting mitral regurgitation (MR) due to posterior leaflet prolapse, utilizing a single suture anchored in the myocardium behind the leaflet. This technique has demonstrated clinical efficacy, although a theoretical limitation is stability of the anchoring suture. We hypothesize that the PVAN suture positions the leaflet for coaptation, after which forces are distributed evenly with low repair suture forces.METHODS: Porcine mitral valves were mounted in a 3-dimensional-printed heart simulator and chordal forces, haemodynamics and echocardiography were collected at baseline, after inducing MR by severing chordae, and after PVAN repair. Repair suture forces were measured with a force-sensing post positioned to mimic in vivo suture placement. Forces required to pull the myocardial suture free were also determined.RESULTS: Relative primary and secondary chordae forces on both leaflets were elevated during prolapse (P<0.05). PVAN repair eliminated MR in all valves and normalized chordae forces to baseline levels on anterior primary (0.37±0.23 to 0.22±0.09 N, P<0.05), posterior primary (0.62±0.37 to 0.14±0.05 N, P=0.001), anterior secondary (1.48±0.52 to 0.85±0.43 N, P<0.001) and posterior secondary chordae (1.42±0.69 to 0.59±0.17 N, P=0.005). Repair suture forces were minimal, even compared to normal primary chordae forces (0.08±0.04 vs 0.19±0.08 N, P=0.002), and were 90 times smaller than maximum forces tolerated by the myocardium (0.08±0.04 vs 6.9±1.3 N, P<0.001).DISCUSSION: PVAN repair eliminates MR by positioning the posterior leaflet for coaptation, distributing forces throughout the valve. Given extremely low measured forces, the strength of the repair suture and the myocardium is not a limitation.

  View details for DOI 10.1093/ejcts/ezz258

  View details for PubMedID 31638697

• Multidisciplinary approach utilizing early, intensive physical rehabilitation to accelerate recovery from veno-venous extracorporeal membrane oxygenation EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Zhu, Y., Bankar, D., Shudo, Y., Woo, Y. 2019; 56 (4): 811–12

  View details for DOI 10.1093/ejcts/ezz042

  View details for Web of Science ID 000491248300025

• Heart-lung transplantation with concomitant aortic arch reconstruction for Eisenmenger syndrome and type B interrupted aortic arch. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Wang, H., Shudo, Y., MacArthur, J. W., Woo, Y. J. 2019

  View details for DOI 10.1016/j.healun.2019.09.002

  View details for PubMedID 31570290

• Vascularization of Engineered Spatially Patterned Myocardial Tissue Derived From Human Pluripotent Stem Cells in vivo. Frontiers in bioengineering and biotechnology Wanjare, M., Kawamura, M., Hu, C., Alcazar, C., Wang, H., Woo, Y. J., Huang, N. F. 2019; 7: 208

  Abstract

  Tissue engineering approaches to regenerate myocardial tissue after disease or injury is promising. Integration with the host vasculature is critical to the survival and therapeutic efficacy of engineered myocardial tissues. To create more physiologically oriented engineered myocardial tissue with organized cellular arrangements and endothelial interactions, randomly oriented or parallel-aligned microfibrous polycaprolactone scaffolds were seeded with human pluripotent stem cell-derived cardiomyocytes (iCMs) and/or endothelial cells (iECs). The resultant engineered myocardial tissues were assessed in a subcutaneous transplantation model and in a myocardial injury model to evaluate the effect of scaffold anisotropy and endothelial interactions on vascular integration of the engineered myocardial tissue. Here we demonstrated that engineered myocardial tissue composed of randomly oriented scaffolds seeded with iECs promoted the survival of iECs for up to 14 days. However, engineered myocardial tissue composed of aligned scaffolds preferentially guided the organization of host capillaries along the direction of the microfibers. In a myocardial injury model, epicardially transplanted engineered myocardial tissues composed of randomly oriented scaffolds seeded with iCMs augmented microvessel formation leading to a significantly higher arteriole density after 4 weeks, compared to engineered tissues derived from aligned scaffolds. These findings that the scaffold microtopography imparts differential effect on revascularization, in which randomly oriented scaffolds promote pro-survival and pro-angiogenic effects, and aligned scaffolds direct the formation of anisotropic vessels. These findings suggest a dominant role of scaffold topography over endothelial co-culture in modulating cellular survival, vascularization, and microvessel architecture.

  View details for DOI 10.3389/fbioe.2019.00208

  View details for PubMedID 31552234

  View details for PubMedCentralID PMC6733921

• Vascularization of Engineered Spatially Patterned Myocardial Tissue Derived From Human Pluripotent Stem Cells in vivo FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY Wanjare, M., Kawamura, M., Hu, C., Alcazar, C., Wang, H., Woo, Y., Huang, N. F. 2019; 7

  View details for DOI 10.3389/fbioe.2019.00208

  View details for Web of Science ID 000483596200001

• Time-to-operation does not predict outcome in acute type A aortic dissection complicated by neurologic injury at presentation JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Chiu, P., Rotto, T. J., Goldstone, A. B., Whisenant, J. B., Woo, Y., Fischbein, M. P. 2019; 158 (3): 665–72

  View details for DOI 10.1016/j.jtcvs.2018.12.023

  View details for Web of Science ID 000481621000026

• Integrated Thoracic Surgery Residency: Current Status and Future Evolution SEMINARS IN THORACIC AND CARDIOVASCULAR SURGERY Zhu, Y., Goldstone, A. B., Woo, Y. 2019; 31 (3): 345–49

  View details for DOI 10.1053/j.semtcvs.2019.04.002

  View details for Web of Science ID 000484387200003

• Cardioaortic replacement for a ruptured root pseudoaneurysm with pulsatile subcutaneous extension EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Wang, H., Shudo, Y., Hittinger, S. A., Woo, Y. 2019; 56 (3): 615–17

  View details for DOI 10.1093/ejcts/ezy447

  View details for Web of Science ID 000493091000028

• Custom Patient-Specific Three-Dimensional Printed Mitral Valve Models for Pre-Operative Patient Education Enhance Patient Satisfaction and Understanding JOURNAL OF MEDICAL DEVICES-TRANSACTIONS OF THE ASME Hung, K. S., Paulsen, M. J., Wang, H., Hironaka, C., Woo, Y. 2019; 13 (3)

  View details for DOI 10.1115/1.4043737

  View details for Web of Science ID 000483046800013

• A modified implantation technique for temporary right ventricular assist device: Enabling ambulation and less invasive decannulation. Journal of cardiac surgery Rinewalt, D., Shudo, Y., MacArthur, J. W., Woo, Y. J., Hiesinger, W. 2019

  Abstract

  This report describes our unique temporary right ventricular assist device (RVAD) implantation technique, which enables early mobilization even during biventricular support and subsequent less invasive RVAD removal without needing resternotomy upon recovery.

  View details for DOI 10.1111/jocs.14193

  View details for PubMedID 31389624

• Neonatal Heart Regeneration Preserves Native Ventricular Biomechanical Properties After Myocardial Infarction Wang, H., Bennett-Kennett, R., Paulsen, M. J., Hironaka, C. E., Thakore, A. D., Farry, J. M., Eskandari, A., Lucian, H. J., Wu, M. A., Imbrie-Moore, A., Steele, A. N., Stapleton, L. M., Dauskardt, R. H., Woo, Y. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000511467800427

• Modeling conduit choice for valve-sparing aortic root replacement on biomechanics with a 3-dimensional-printed heart simulator JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Paulsen, M. J., Kasinpila, P., Imbrie-Moore, A. M., Wang, H., Hironaka, C. E., Koyano, T. K., Fong, R., Chiu, P., Goldstone, A. B., Steele, A. N., Stapleton, L. M., Ma, M., Woo, Y. 2019; 158 (2): 392–403

  View details for DOI 10.1016/j.jtcvs.2018.10.145

  View details for Web of Science ID 000475496900041

• Bioengineered analog of stromal cell-derived factor 1 alpha preserves the biaxial mechanical properties of native myocardium after infarction JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS Wang, H., Wisneski, A., Paulsen, M. J., Imbrie-Moore, A., Wang, Z., Xuan, Y., Hernandez, H., Lucian, H. J., Eskandari, A., Thakore, A. D., Parry, J. M., Hironaka, C. E., von Bornstaedt, D., Steele, A. N., Stapleton, L. M., Williams, K. M., Wu, M. A., MacArthur, J. W., Woo, Y. 2019; 96: 165–71

  View details for DOI 10.1016/j.jmbbm.2019.04.014

  View details for Web of Science ID 000472243400018

• Atheroprotective roles of smooth muscle cell phenotypic modulation and the TCF21 disease gene as revealed by single-cell analysis. Nature medicine Wirka, R. C., Wagh, D., Paik, D. T., Pjanic, M., Nguyen, T., Miller, C. L., Kundu, R., Nagao, M., Coller, J., Koyano, T. K., Fong, R., Woo, Y. J., Liu, B., Montgomery, S. B., Wu, J. C., Zhu, K., Chang, R., Alamprese, M., Tallquist, M. D., Kim, J. B., Quertermous, T. 2019

  Abstract

  In response to various stimuli, vascular smooth muscle cells (SMCs) can de-differentiate, proliferate and migrate in a process known as phenotypic modulation. However, the phenotype of modulated SMCs in vivo during atherosclerosis and the influence of this process on coronary artery disease (CAD) risk have not been clearly established. Using single-cell RNA sequencing, we comprehensively characterized the transcriptomic phenotype of modulated SMCs in vivo in atherosclerotic lesions of both mouse and human arteries and found that these cells transform into unique fibroblast-like cells, termed 'fibromyocytes', rather than into a classical macrophage phenotype. SMC-specific knockout of TCF21-a causal CAD gene-markedly inhibited SMC phenotypic modulation in mice, leading to the presence of fewer fibromyocytes within lesions as well as within the protective fibrous cap of the lesions. Moreover, TCF21 expression was strongly associated with SMC phenotypic modulation in diseased human coronary arteries, and higher levels of TCF21 expression were associated with decreased CAD risk in human CAD-relevant tissues. These results establish a protective role for both TCF21 and SMC phenotypic modulation in this disease.

  View details for DOI 10.1038/s41591-019-0512-5

  View details for PubMedID 31359001

• Risk of reoperative valve surgery for endocarditis associated with drug use. The Journal of thoracic and cardiovascular surgery Mori, M., Bin Mahmood, S. U., Schranz, A. J., Sultan, I., Axtell, A. L., Sarsour, N., Hiesinger, W., Boskovski, M. T., Hirji, S., Kaneko, T., Woo, J., Tang, P., Jassar, A. S., Atluri, P., Whitson, B. A., Gleason, T., Geirsson, A. 2019

  Abstract

  BACKGROUND: We aimed to quantify incidence and operative risks associated with reoperative valve surgeries (RVS) in patients with drug-associated infective endocarditis in a multi-center setting.METHODS: We formed a registry of patients with drug-associated infective endocarditis who underwent valve surgeries at 8 US centers between 2011 and 2017. Outcomes of first-time valve surgery (FVS) and RVS were compared. Multivariable logistic regression models related RVS to 30-day mortality. Poisson regression models were fitted to evaluate temporal trends in overall case volume and proportions of patients undergoing RVS.RESULTS: The cohort consisted of 925 patients with drug-associated infective endocarditis who underwent a valve surgery, of which 652 were FVS and 273 were RVS. Patients undergoing FVS had fewer comorbidities than those undergoing RVS. Overall case volume increased from 108 in 2012 to 229 cases in 2017 (P<.001). The proportion of redo valve cases increased from 19% in 2012 to 28% in 2017 (P<.001). The 30-day mortality in RVS was higher compared with FVS (8.1% vs 4.8%; P=.049). An increase in unadjusted mortality rates were observed as the number of prior cardiac surgeries increased, from 4.8% in FVS to 11.8% in ≥3 RVS. Multivariable model demonstrated that RVS was associated with an increased risk of 30-day mortality (odds ratio, 2.22; 95% confidence interval, 1.22-4.06; P=.010).CONCLUSIONS: An increasing proportion of valve surgery for drug-associated infective endocarditis is for RVS. Despite being young and harboring few comorbidities, the RVS cohort is still susceptible to increased risk of 30-day mortality compared with those undergoing FVS.

  View details for DOI 10.1016/j.jtcvs.2019.06.055

  View details for PubMedID 31420136

• Ex Vivo Biomechanical Study of Apical Versus Papillary Neochord Anchoring for Mitral Regurgitation Imbrie-Moore, A. M., Paulsen, M. J., Thakore, A. D., Wang, H., Hironaka, C. E., Lucian, H. J., Farry, J. M., Edwards, B. B., Bae, J., Cutkosky, M. R., Woo, Y. ELSEVIER SCIENCE INC. 2019: 90–97

  View details for DOI 10.1016/j.athoracsur.2019.01.053

  View details for Web of Science ID 000472226100037

• Short-term outcomes of en bloc combined heart and liver transplantation in the failing Fontan CLINICAL TRANSPLANTATION Vaikunth, S. S., Concepcion, W., Daugherty, T., Fowler, M., Lutchman, G., Maeda, K., Rosenthal, D. N., Teuteberg, J., Woo, Y., Lui, G. K. 2019; 33 (6)

  View details for DOI 10.1111/ctr.13540

  View details for Web of Science ID 000473087200014

• Stanford Cardiovascular Institute At the Forefront of Cardiovascular Research CIRCULATION RESEARCH Wu, J. C., Woo, Y., Mayerle, M., Harrington, R. A., Quertermous, T. 2019; 124 (10): 1420–24

  View details for DOI 10.1161/CIRCRESAHA.119.310761

  View details for Web of Science ID 000469344600007

• Attrition of the Cardiothoracic Surgeon-Scientist: Definition of the Problem and Remedial Strategies. The Annals of thoracic surgery Ikonomidis, J. S., Menasche, P., Kreisel, D., Sellke, F. W., Woo, Y. J., Colson, Y. L. 2019

  View details for DOI 10.1016/j.athoracsur.2019.04.002

  View details for PubMedID 31208650

• First in line for robotic surgery: Would you want to know? JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Woo, Y., Handy, J. R., Sade, R. M. 2019; 157 (5): 1934–40

  View details for DOI 10.1016/j.jtcvs.2018.11.025

  View details for Web of Science ID 000464437100084

• A protocol update of the Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) 3 trial: A comparison of fractional flow reserve-guided percutaneous coronary intervention and coronary artery bypass graft surgery in patients with multivessel coronary artery disease. American heart journal Zimmermann, F. M., De Bruyne, B., Pijls, N. H., Desai, M., Oldroyd, K. G., Reardon, M. J., Wendler, O., Woo, J., Yeung, A. C., Fearon, W. F. 2019; 214: 156–57

  View details for DOI 10.1016/j.ahj.2019.04.012

  View details for PubMedID 31207442

• Redo Valve-Sparing Root Replacement for Delayed Cusp Derangement from Ventricular Septal Defect. The Annals of thoracic surgery Zhu, Y., Cohen, J. E., Ma, M., Woo, Y. J. 2019

  Abstract

  A 28-year-old gentleman with ventricular septal defect (VSD), double-chambered right ventricle (DCRV) with associated right ventricular outflow tract obstruction, and anomalous right coronary artery (RCA) underwent resection of the DCRV, trans-aortic VSD repair, and unroofing of anomalous RCA. Two years later, he returned with delayed presentation of VSD flow funnel related aortic cusp prolapse and symptomatic severe aortic regurgitation. He underwent reoperative valve-sparing aortic root replacement and aortic cusp repair with an excellent outcome.

  View details for PubMedID 30986415

• Integrated Thoracic Surgery Residency: Current Status and Future Evolution. Seminars in thoracic and cardiovascular surgery Zhu, Y., Goldstone, A. B., Woo, Y. J. 2019

  Abstract

  There are 28 integrated thoracic surgery residency programs. Program growth has plateaued, and training evolutions are anticipated.

  View details for PubMedID 30954666

• Attrition of the cardiothoracic surgeon-scientist: Definition of the problem and remedial strategies. The Journal of thoracic and cardiovascular surgery Ikonomidis, J. S., Menasche, P., Kreisel, D., Sellke, F. W., Woo, Y. J., Colson, Y. L. 2019

  View details for DOI 10.1016/j.jtcvs.2019.03.057

  View details for PubMedID 31208802

• Intramyocardial Injection of Mesenchymal Precursor Cells and Successful TemporaryWeaning From Left Ventricular Assist Device Support in Patients With Advanced Heart Failure A Randomized Clinical Trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Yau, T. M., Pagani, F. D., Mancini, D. M., Chang, H. L., Lala, A., Woo, Y., Acker, M. A., Selzman, C. H., Soltesz, E. G., Kern, J. A., Maltais, S., Charbonneau, E., Pan, S., Marks, M. E., Moquete, E. G., O'Sullivan, K. L., Taddei-Peters, W. C., McGowan, L. K., Green, C., Rose, E. A., Jeffries, N., Parides, M. K., Weisel, R. D., Miller, M. A., Hung, J., O'Gara, P. T., Moskowitz, A. J., Gelijns, A. C., Bagiella, E., Milano, C. A., Buxton, D., Geller, N. L., Gordon, D., Burke, C., Lee, A., Smith, T., Moy, C. S., Weisel, R., Cardiothoracic Surg Trials Network 2019; 321 (12): 1176–86

  View details for DOI 10.1001/jama.2019.2341

  View details for Web of Science ID 000463074900013

• Intramyocardial Injection of Mesenchymal Precursor Cells and Successful Temporary Weaning From Left Ventricular Assist Device Support in Patients With Advanced Heart Failure: A Randomized Clinical Trial. JAMA Yau, T. M., Pagani, F. D., Mancini, D. M., Chang, H. L., Lala, A., Woo, Y. J., Acker, M. A., Selzman, C. H., Soltesz, E. G., Kern, J. A., Maltais, S., Charbonneau, E., Pan, S., Marks, M. E., Moquete, E. G., O'Sullivan, K. L., Taddei-Peters, W. C., McGowan, L. K., Green, C., Rose, E. A., Jeffries, N., Parides, M. K., Weisel, R. D., Miller, M. A., Hung, J., O'Gara, P. T., Moskowitz, A. J., Gelijns, A. C., Bagiella, E., Milano, C. A., Cardiothoracic Surgical Trials Network 2019; 321 (12): 1176–86

  Abstract

  Importance: Left ventricular assist device (LVAD) therapy improves myocardial function, but few patients recover sufficiently for explant, which has focused attention on stem cells to augment cardiac recovery.Objective: To assess efficacy and adverse effects of intramyocardial injections of mesenchymal precursor cells (MPCs) during LVAD implant.Design, Setting, and Participants: A randomized phase 2 clinical trial involving patients with advanced heart failure, undergoing LVAD implant, at 19 North American centers (July 2015-August 2017). The 1-year follow-up ended August 2018.Interventions: Intramyocardial injections of 150 million allogeneic MPCs or cryoprotective medium as a sham treatment in a 2:1 ratio (n=106 vs n=53).Main Outcomes and Measures: The primary efficacy end point was the proportion of successful temporary weans (of 3 planned assessments) from LVAD support within 6 months of randomization. This end point was assessed using a Bayesian analysis with a predefined threshold of a posterior probability of 80% to indicate success. The 1-year primary safety end point was the incidence of intervention-related adverse events (myocarditis, myocardial rupture, neoplasm, hypersensitivity reactions, and immune sensitization). Secondary end points included readmissions and adverse events at 6 months and 1-year survival.Results: Of 159 patients (mean age, 56 years; 11.3% women), 155 (97.5%) completed 1-year of follow-up. The posterior probability that MPCs increased the likelihood of successful weaning was 69%; below the predefined threshold for success. The mean proportion of successful temporary weaning from LVAD support over 6 months was 61% in the MPC group and 58% in the control group (rate ratio [RR], 1.08; 95% CI, 0.83-1.41; P=.55). No patient experienced a primary safety end point. Of 10 prespecified secondary end points reported, 9 did not reach statistical significance. One-year mortality was not significantly different between the MPC group and the control group (14.2% vs 15.1%; hazard ratio [HR], 0.89; 95%, CI, 0.38-2.11; P=.80). The rate of serious adverse events was not significantly different between groups (70.9 vs 78.7 per 100 patient-months; difference, -7.89; 95% CI, -39.95 to 24.17; P=.63) nor was the rate of readmissions (0.68 vs 0.75 per 100 patient-months; difference, -0.07; 95% CI, -0.41 to 0.27; P=.68).Conclusions and Relevance: Among patients with advanced heart failure, intramyocardial injections of mesenchymal precursor cells, compared with injections of a cryoprotective medium as sham treatment, did not improve successful temporary weaning from left ventricular assist device support at 6 months. The findings do not support the use of intramyocardial mesenchymal stem cells to promote cardiac recovery as measured by temporary weaning from device support.Trial Registration: clinicaltrials.gov Identifier: NCT02362646.

  View details for PubMedID 30912838

• Short-Term Outcomes of en bloc Combined Heart and Liver Transplantation in the Failing Fontan. Clinical transplantation Vaikunth, S. S., Concepcion, W., Daugherty, T., Fowler, M., Lutchman, G., Maeda, K., Rosenthal, D. N., Teuteberg, J., Joseph Woo, Y., Lui, G. K. 2019: e13540

  Abstract

  Patients with failing Fontan physiology and liver cirrhosis are being considered for combined heart and liver transplantation. We performed a retrospective review of our experience with en bloc combined heart and liver transplantation in Fontan patients > 10 years old from 2006-18 per Institutional Review Board approval. Six females and 3 males (median age 20.7, range 14.2-41.3 years) underwent en bloc combined heart and liver transplantation. Indications for heart transplant included ventricular dysfunction, atrioventricular valve regurgitation, arrhythmia and/or lymphatic abnormalities. Indication for liver transplant included portal hypertension and cirrhosis. Median Fontan/single ventricular end diastolic pressure was 18/12 mm Hg, respectively. Median Model for End-Stage Liver Disease excluding International Normalized Ratio score was 10 (7-26), eight patients had a Varices, Ascites, Splenomegaly, Thrombocytopenia score of>2, and all patients had cirrhosis. Median cardiopulmonary bypass and donor ischemic times were 262 (178-307) and 287 (227-396) minutes, respectively. Median intensive care and hospital stay were 19 (5-96) and 29 (13-197) days, respectively. Survival was 100% and rejection was 0% at 30 days and 1 year post-transplant. En bloc combined heart and liver transplantation is an acceptable treatment in the failing Fontan patient with liver cirrhosis. This article is protected by copyright. All rights reserved.

  View details for PubMedID 30891780

• Ex vivo biomechanical study of apical versus papillary neochord anchoring for mitral regurgitation. The Annals of thoracic surgery Imbrie-Moore, A. M., Paulsen, M. J., Thakore, A. D., Wang, H., Hironaka, C. E., Lucian, H. J., Farry, J. M., Edwards, B. B., Bae, J. H., Cutkosky, M. R., Woo, Y. J. 2019

  Abstract

  BACKGROUND: Neochordoplasty is an important repair technique, though optimal anchoring position is unknown. While typically anchored at papillary muscles, new percutaneous devices anchor the chordae at or near the ventricular apex, which may have an effect on chordal forces and the long-term durability of the repair.METHODS: Porcine mitral valves (n=6) were mounted in a left heart simulator that generates physiological pressure and flow through the valves while chordal forces were measured using Fiber Bragg Grating strain gauge sensors. Isolated mitral regurgitation was induced by cutting P2 primary chordae and the regurgitant valve was repaired using PTFE neochord with apical anchoring, followed by papillary muscle fixation for comparison. In both cases, the neochord was anchored to a customized force-sensing post positioned to mimic the relevant in vivo placement.RESULTS: Echocardiographic and hemodynamic data confirmed that the repairs restored physiologic hemodynamics. Forces on the chordae and neochord were lower for papillary fixation than the apical (p=0.003). Additionally, the maximum rate of change of force was higher for the chordae and neochord for apical fixation when compared to papillary (p=0.028).CONCLUSIONS: Apical point of anchoring results in higher forces on the chordae and neochord stitch as well as an increased rate of loading on the neochord when compared to the papillary muscle fixation. These results suggest the papillary fixation repair may have superior durability.

  View details for PubMedID 30836099

• The bicaval Wythenshawe technique in 2018-Reply to Dimarakis and Venkateswaran EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Shudo, Y., Wang, H., Woo, Y. 2019; 55 (3): 596

  View details for DOI 10.1093/ejcts/ezy280

  View details for Web of Science ID 000462721200038

• Multidisciplinary approach utilizing early, intensive physical rehabilitation to accelerate recovery from veno-venous extracorporeal membrane oxygenation. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Zhu, Y., Bankar, D., Shudo, Y., Woo, Y. J. 2019

  Abstract

  This case demonstrates the benefits of our early, intensive physical rehabilitation intervention to prevent the natural sequelae occurring from prolonged bed rest. This minimizes neuromuscular weakness and optimizes strength, endurance and cardiorespiratory function, thus accelerating recovery from a long duration of femorally cannulated veno-venous extracorporeal membrane oxygenation.

  View details for PubMedID 30796438

• A Unique Collateral Artery Development Program Promotes Neonatal Heart Regeneration CELL Das, S., Goldstone, A. B., Wang, H., Farry, J., D'Amato, G., Paulsen, M. J., Eskandari, A., Hironaka, C. E., Phansalkar, R., Sharma, B., Rhee, S., Shamskhou, E., Agalliu, D., Perez, V., Woo, Y., Red-Horse, K. 2019; 176 (5): 1128-+

  View details for DOI 10.1016/j.cell.2018.12.023

  View details for Web of Science ID 000459257500015

• Photosynthetic symbiotic therapy AGING-US Wang, H., Wu, M. A., Woo, Y. 2019; 11 (3): 843–44

  View details for DOI 10.18632/aging.101796

  View details for Web of Science ID 000459482200004

• A Biocompatible Therapeutic Catheter-Deliverable Hydrogel for In Situ Tissue Engineering. Advanced healthcare materials Steele, A. N., Stapleton, L. M., Farry, J. M., Lucian, H. J., Paulsen, M. J., Eskandari, A., Hironaka, C. E., Thakore, A. D., Wang, H., Yu, A. C., Chan, D., Appel, E. A., Woo, Y. J. 2019: e1801147

  Abstract

  Hydrogels have emerged as a diverse class of biomaterials offering a broad range of biomedical applications. Specifically, injectable hydrogels are advantageous for minimally invasive delivery of various therapeutics and have great potential to treat a number of diseases. However, most current injectable hydrogels are limited by difficult and time-consuming fabrication techniques and are unable to be delivered through long, narrow catheters, preventing extensive clinical translation. Here, the development of an easily-scaled, catheter-injectable hydrogel utilizing a polymer-nanoparticle crosslinking mechanism is reported, which exhibits notable shear-thinning and self-healing behavior. Gelation of the hydrogel occurs immediately upon mixing the biochemically modified hyaluronic acid polymer with biodegradable nanoparticles and can be easily injected through a high-gauge syringe due to the dynamic nature of the strong, yet reversible crosslinks. Furthermore, the ability to deliver this novel hydrogel through a long, narrow, physiologically-relevant catheter affixed with a 28-G needle is highlighted, with hydrogel mechanics unchanged after delivery. Due to the composition of the gel, it is demonstrated that therapeutics can be differentially released with distinct elution profiles, allowing precise control over drug delivery. Finally, the cell-signaling and biocompatibility properties of this innovative hydrogel are demonstrated, revealing its wide range of therapeutic applications.

  View details for PubMedID 30714355

• Successful heart-lung-kidney and domino heart transplantation following veno-venous extracorporeal membrane oxygenation support INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY Zhu, Y., Shudo, Y., Lee, A. M., Woo, Y. 2019; 28 (2): 316–17

  View details for DOI 10.1093/icvts/ivy251

  View details for Web of Science ID 000467955400022

• Impact of "increased-risk" donor hearts on transplant outcomes: A propensity-matched analysis. The Journal of thoracic and cardiovascular surgery Shudo, Y., Cohen, J. E., Lingala, B., He, H., Zhu, Y., Woo, Y. J. 2019; 157 (2): 603–10

  Abstract

  OBJECTIVES: Orthotopic heart transplantation (OHT) remains the gold standard for advanced heart failure. Increased risk (IR) donors were categorized by the United Network for Organ Sharing Database (UNOS) according to the Centers for Disease Control and Prevention (CDC) criteria. However, the impact of CDC IR donor hearts on the outcome of adult OHT recipients remains unclear. The aim of this study was to compare the outcome of adult OHT recipients between CDC IR and non-CDC IR donor grafts.METHODS: Data were obtained from the United Network for Organ Sharing Databas. All adult patients (age ≥18years) undergoing OHT from 2004 through 2016 were included (n=24,751). Propensity scores for CDC IR donors were calculated by estimating probabilities of CDC IR donor graft use using a nonparsimonious multivariable logistic regression model. Patients were matched 1:1 using a greedy matching algorithm based on the propensity score of each patient. The impact of CDC IR donors on the post-transplant outcomes, such as 30-day and overall mortalities, was investigated using Cox-proportional hazards. Overall survival probability analyses were performed.RESULTS: Of 24,751 primary heart transplants from 2004 to 2016 with 3584 (14.5%) as IR donors, 6304 transplants were successfully matched (n=3152 in CDC IR group and non-IR group). There were no significant differences in baseline characteristics in recipients and donors. In the Cox-proportional hazards model for matched subjects, the use of CDC IR grafts was not associated with 30-day (hazard ratio of IR group vs non-IR group 0.97; 95% confidence interval, 0.87-1.08; P=.57) and overall mortalities (hazard ratio, 0.94; 95% confidence interval, 0.73-1.21; P=.62). Interestingly, post-transplant acute myocardial rejection episodes during hospital stays were found more often in the CDC-IR group, compared with the non-CDC IR group (CDC IR, n=358 [11.4%]; non-CDC IR, n=304 [9.6%] P = .03), whereas post-transplant pacemaker placements were performed less frequently in the CDC IR group (CDC IR, n=80 [2.6%]; non-CDC IR, n=111 [3.5%] P = .020). Importantly, there was no significant difference in the overall survival probability between CDC IR and non-IR groups in both unadjusted and adjusted survival analyses.CONCLUSIONS: CDC IR status does not have a significant impact on adult OHT recipient survival probability. Increased use of CDC IR donor grafts can potentially alleviate the persistent and worsening shortage of available donor organs and shorten the waitlist time for heart transplantation.

  View details for PubMedID 30669225

• 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

• Impact of "increased-risk'' donor hearts on transplant outcomes: A propensity-matched analysis JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Shudo, Y., Cohen, J. E., Lingala, B., He, H., Zhu, Y., Woo, Y. 2019; 157 (2): 603–10

  View details for DOI 10.1016/j.jtcvs.2018.08.120

  View details for Web of Science ID 000456169700056

• Heart-lung transplantation over the past 10 years: an up-to-date concept EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Shudo, Y., Kasinpila, P., Lingala, B., Kim, F. Y., Woo, Y. 2019; 55 (2): 304–8

  View details for DOI 10.1093/ejcts/ezy253

  View details for Web of Science ID 000462711700020

• Photosynthetic symbiotic therapy. Aging Wang, H., Wu, M. A., Woo, Y. J. 2019

  View details for PubMedID 30683833

• A Unique Collateral Artery Development Program Promotes Neonatal Heart Regeneration. Cell Das, S., Goldstone, A. B., Wang, H., Farry, J., D'Amato, G., Paulsen, M. J., Eskandari, A., Hironaka, C. E., Phansalkar, R., Sharma, B., Rhee, S., Shamskhou, E. A., Agalliu, D., de Jesus Perez, V., Woo, Y. J., Red-Horse, K. 2019

  Abstract

  Collateral arteries are an uncommon vessel subtype that can provide alternate blood flow to preserve tissue following vascular occlusion. Some patients with heart disease develop collateral coronary arteries, and this correlates with increased survival. However, it is not known how these collaterals develop or how to stimulate them. We demonstrate that neonatal mouse hearts use a novel mechanism to build collateral arteries in response to injury. Arterial endothelial cells (ECs) migrated away from arteries along existing capillaries and reassembled into collateral arteries, which we termed "artery reassembly". Artery ECs expressed CXCR4, and following injury, capillary ECs induced its ligand, CXCL12. CXCL12 or CXCR4 deletion impaired collateral artery formation and neonatal heart regeneration. Artery reassembly was nearly absent in adults but was induced by exogenous CXCL12. Thus, understanding neonatal regenerative mechanisms can identify pathways that restore these processes in adults and identify potentially translatable therapeutic strategies for ischemic heart disease.

  View details for PubMedID 30686582

• Ageism in cardiac surgery: is less really more? AGING-US Goldstone, A. B., Woo, Y. 2019; 11 (1): 1–2

  View details for DOI 10.18632/aging.101701

  View details for Web of Science ID 000457388700001

• Cardioaortic replacement for a ruptured root pseudoaneurysm with pulsatile subcutaneous extension. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Wang, H., Shudo, Y., Hittinger, S. A., Woo, Y. J. 2019

  Abstract

  Orthotopic heart transplantation with concomitant aortic surgery is rarely performed. Herein, we describe the successful management of a patient with an otherwise inoperable, ruptured aortic root pseudoaneurysm using combined cardioaortic replacement under hypothermic circulatory arrest.

  View details for PubMedID 30608529

• Ageism in cardiac surgery: is less really more? Aging Goldstone, A. B., Woo, Y. J. 2019

  View details for PubMedID 30606889

• Stanford Cardiovascular Institute. Circulation research Wu, J. C., Woo, Y. J., Mayerle, M. n., Harrington, R. A., Quertermous, T. n. 2019; 124 (10): 1420–24

  View details for PubMedID 31070998

• Successful orthotopic heart transplantation in a patient with Marfan syndrome. Journal of cardiac surgery Ogawa, Y. n., Choi, C. W., Shudo, Y. n., Woo, Y. J. 2019

  Abstract

  Cardiovascular diseases represent the leading cause of mortality in patients with Marfan syndrome. Many treatments have been developed for patients with end-stage heart failure, among which orthotopic heart transplantation remains the gold standard. We report a successful orthotopic heart transplantation for a Marfan syndrome patient in end-stage heart failure.

  View details for DOI 10.1111/jocs.14129

  View details for PubMedID 31233233

• Physical therapy in successful venoarterial extracorporeal membrane oxygenation bridge to orthotopic heart transplantation. Journal of cardiac surgery Rinewalt, D. n., Shudo, Y. n., Kawana, M. n., Woo, Y. J. 2019

  Abstract

  Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a temporary mechanical circulatory support system that may be used as a lifesaving therapy for patients in acute heart failure and as a bridge to definitive management. Physical therapy in these patients remains challenging, with limited protocols to guide practitioners.We describe a case of a 37-year-old gentleman who presented with familial cardiomyopathy and cardiogenic shock.Our patient underwent urgent peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) followed by successful heart transplantation. While on ECMO support he was enrolled in a physical therapy program that included the VitalGo Tilt Bed to improve lower body weight bearing while avoiding hip flexion and damage to the peripheral ECMO cannulae. The patient was discharged home expeditiously after heart transplant due to aggressive physical rehabilitation while on full VA-ECMO support.Early intensive physical rehabilitation is feasible and safe and may result in improved outcomes and expeditious discharge in VA ECMO patients. Protocol driven multidisciplinary physical therapy with a patient on femorally cannulated VA-ECMO retains the advantages of lower extremity peripheral cannulation while eliminating the risks of immobility. The new UNOS allocation system may result in a successful bridge to transplantation in patients on VA-ECMO due to the increased prioritization of this population to receive donor organs.

  View details for DOI 10.1111/jocs.14220

  View details for PubMedID 31441558

• Optimizing the Use of Heart Transplant in the United States. JAMA Sandhu, A. T., Woo, Y. J., Khush, K. K. 2019; 322 (18): 1772–74

  View details for DOI 10.1001/jama.2019.16002

  View details for PubMedID 31714972

• Use of a supramolecular polymeric hydrogel as an effective post-operative pericardial adhesion barrier. Nature biomedical engineering Stapleton, L. M., Steele, A. N., Wang, H. n., Lopez Hernandez, H. n., Yu, A. C., Paulsen, M. J., Smith, A. A., Roth, G. A., Thakore, A. D., Lucian, H. J., Totherow, K. P., Baker, S. W., Tada, Y. n., Farry, J. M., Eskandari, A. n., Hironaka, C. E., Jaatinen, K. J., Williams, K. M., Bergamasco, H. n., Marschel, C. n., Chadwick, B. n., Grady, F. n., Ma, M. n., Appel, E. A., Woo, Y. J. 2019; 3 (8): 611–20

  Abstract

  Post-operative adhesions form as a result of normal wound healing processes following any type of surgery. In cardiac surgery, pericardial adhesions are particularly problematic during reoperations, as surgeons must release the adhesions from the surface of the heart before the intended procedure can begin, thereby substantially lengthening operation times and introducing risks of haemorrhage and injury to the heart and lungs during sternal re-entry and cardiac dissection. Here we show that a dynamically crosslinked supramolecular polymer-nanoparticle hydrogel, with viscoelastic and flow properties that enable spraying onto tissue as well as robust tissue adherence and local retention in vivo for two weeks, reduces the formation of pericardial adhesions. In a rat model of severe pericardial adhesions, the hydrogel markedly reduced the severity of the adhesions, whereas commercial adhesion barriers (including Seprafilm and Interceed) did not. The hydrogels also reduced the severity of cardiac adhesions (relative to untreated animals) in a clinically relevant cardiopulmonary-bypass model in sheep. This viscoelastic supramolecular polymeric hydrogel represents a promising clinical solution for the prevention of post-operative pericardial adhesions.

  View details for DOI 10.1038/s41551-019-0442-z

  View details for PubMedID 31391596

• Transatlantic Editorial: Attrition of the cardiothoracic surgeon-scientist: definition of the problem and remedial strategies. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Ikonomidis, J. S., Menasche, P. n., Kreisel, D. n., Sellke, F. W., Woo, Y. J., Colson, Y. L. 2019

  View details for DOI 10.1093/ejcts/ezz188

  View details for PubMedID 31199476

• Interfacility Transfer of Medicare Beneficiaries With Acute Type A Aortic Dissection and Regionalization of Care in the United States. Circulation Goldstone, A. B., Chiu, P. n., Baiocchi, M. n., Lingala, B. n., Lee, J. n., Rigdon, J. n., Fischbein, M. P., Woo, Y. J. 2019; 140 (15): 1239–50

  Abstract

  The feasibility and effectiveness of delaying surgery to transfer patients with acute type A aortic dissection-a catastrophic disease that requires prompt intervention-to higher-volume aortic surgery hospitals is unknown. We investigated the hypothesis that regionalizing care at high-volume hospitals for acute type A aortic dissections will lower mortality. We further decomposed this hypothesis into subparts, investigating the isolated effect of transfer and the isolated effect of receiving care at a high-volume versus a low-volume facility.We compared the operative mortality and long-term survival between 16 886 Medicare beneficiaries diagnosed with an acute type A aortic dissection between 1999 and 2014 who (1) were transferred versus not transferred, (2) underwent surgery at high-volume versus low-volume hospitals, and (3) were rerouted versus not rerouted to a high-volume hospital for treatment. We used a preference-based instrumental variable design to address unmeasured confounding and matching to separate the effect of transfer from volume.Between 1999 and 2014, 40.5% of patients with an acute type A aortic dissection were transferred, and 51.9% received surgery at a high-volume hospital. Interfacility transfer was not associated with a change in operative mortality (risk difference, -0.69%; 95% CI, -2.7% to 1.35%) or long-term mortality. Despite delaying surgery, a regionalization policy that transfers patients to high-volume hospitals was associated with a 7.2% (95% CI, 4.1%-10.3%) absolute risk reduction in operative mortality; this association persisted in the long term (hazard ratio, 0.81; 95% CI, 0.75-0.87). The median distance needed to reroute each patient to a high-volume hospital was 50.1 miles (interquartile range, 12.4-105.4 miles).Operative and long-term mortality were substantially reduced in patients with acute type A aortic dissection who were rerouted to high-volume hospitals. Policy makers should evaluate the feasibility and benefits of regionalizing the surgical treatment of acute type A aortic dissection in the United States.

  View details for DOI 10.1161/CIRCULATIONAHA.118.038867

  View details for PubMedID 31589488

• Current evidence for prosthesis selection: What can we really say? The Journal of thoracic and cardiovascular surgery Chiu, P. n., Goldstone, A. B., Fischbein, M. P., Woo, Y. J. 2019

  View details for DOI 10.1016/j.jtcvs.2019.03.094

  View details for PubMedID 31200938

• Transplantation Outcomes in Adults With Congenital Heart Disease Have Room to Grow. The Canadian journal of cardiology Elde, S. n., Woo, Y. J. 2019

  View details for DOI 10.1016/j.cjca.2019.11.016

  View details for PubMedID 32046908

• Bioengineered analog of stromal cell-derived factor 1α preserves the biaxial mechanical properties of native myocardium after infarction. Journal of the mechanical behavior of biomedical materials Wang, H. n., Wisneski, A. n., Paulsen, M. J., Imbrie-Moore, A. n., Wang, Z. n., Xuan, Y. n., Hernandez, H. L., Lucian, H. J., Eskandari, A. n., Thakore, A. D., Farry, J. M., Hironaka, C. E., von Bornstaedt, D. n., Steele, A. N., Stapleton, L. M., Williams, K. M., Wu, M. A., MacArthur, J. W., Woo, Y. J. 2019; 96: 165–71

  Abstract

  Adverse remodeling of the left ventricle (LV) after myocardial infarction (MI) results in abnormal tissue biomechanics and impaired cardiac function, often leading to heart failure. We hypothesized that intramyocardial delivery of engineered stromal cell-derived factor 1α analog (ESA), our previously-developed supra-efficient pro-angiogenic chemokine, preserves biaxial LV mechanical properties after MI. Male Wistar rats (n = 45) underwent sham surgery (n = 15) or permanent left anterior descending coronary artery ligation. Rats sustaining MI were randomized for intramyocardial injections of either saline (100 μL, n = 15) or ESA (6 μg/kg, n = 15), delivered at four standardized borderzone sites. After 4 weeks, echocardiography was performed, and the hearts were explanted. Tensile testing of the anterolateral LV wall was performed using a displacement-controlled biaxial load frame, and modulus was determined after constitutive modeling. At 4 weeks post-MI, compared to saline controls, ESA-treated hearts had greater wall thickness (1.68 ± 0.05 mm vs 1.42 ± 0.08 mm, p = 0.008), smaller end-diastolic LV internal dimension (6.88 ± 0.29 mm vs 7.69 ± 0.22 mm, p = 0.044), and improved ejection fraction (62.8 ± 3.0% vs 49.4 ± 4.5%, p = 0.014). Histologic analysis revealed significantly reduced infarct size for ESA-treated hearts compared to saline controls (29.4 ± 2.9% vs 41.6 ± 3.1%, p = 0.021). Infarcted hearts treated with ESA exhibited decreased modulus compared to those treated with saline in both the circumferential (211.5 ± 6.9 kPa vs 264.3 ± 12.5 kPa, p = 0.001) and longitudinal axes (194.5 ± 6.5 kPa vs 258.1 ± 14.4 kPa, p < 0.001). In both principal directions, ESA-treated infarcted hearts possessed similar tissue compliance as sham non-infarcted hearts. Overall, intramyocardial ESA therapy improves post-MI ventricular remodeling and function, reduces infarct size, and preserves native LV biaxial mechanical properties.

  View details for PubMedID 31035067

• Evaluation of Risk Factors for Heart-Lung Transplant Recipient Outcome: An Analysis of the United Network for Organ Sharing Database. Circulation Shudo, Y. n., Wang, H. n., Lingala, B. n., He, H. n., Kim, F. Y., Hiesinger, W. n., Lee, A. M., Boyd, J. H., Currie, M. n., Woo, Y. J. 2019; 140 (15): 1261–72

  Abstract

  Heart-lung transplantation (HLTx) is an effective treatment for patients with advanced cardiopulmonary failure. However, no large multicenter study has focused on the relationship between donor and recipient risk factors and post-HLTx outcomes. Thus, we investigated this issue using data from the United Network for Organ Sharing database.All adult patients (age ≥18 years) registered in the United Network for Organ Sharing database who underwent HLTx between 1987 and 2017 were included (n=997). We stratified the cohort by patients who were alive without retransplant at 1 year (n=664) and patients who died or underwent retransplant within 1 year of HLTx (n=333). The primary outcome was the influence of donor and recipient characteristics on 1-year post-HLTx recipient death or retransplant. Kaplan-Meier curves were created to assess overall freedom from death or retransplant. To obtain a better effect estimation on hazard and survival time, the parametric Accelerated Failure Time model was chosen to perform time-to-event modeling analyses.Overall graft survival at 1-year post-HLTx was 66.6%. Of donors, 53% were male, and the mean age was 28.2 years. Univariable analysis showed advanced donor age, recipient male sex, recipient creatinine, recipient history of prior cardiac or lung surgery, recipient extracorporeal membrane oxygenation support, transplant year, and transplant center volume were associated with 1-year post-HLTx death or retransplant. On multivariable analysis, advanced donor age (hazard ratio [HR], 1.017; P=0.0007), recipient male sex (HR, 1.701; P=0.0002), recipient extracorporeal membrane oxygenation support (HR, 4.854; P<0.0001), transplant year (HR, 0.962; P<0.0001), and transplantation at low-volume (HR, 1.694) and medium-volume centers (HR, 1.455) in comparison with high-volume centers (P=0.0007) remained as significant predictors of death or retransplant. These predictors were incorporated into an equation capable of estimating the preliminary probability of graft survival at 1-year post-HLTx on the basis of preoperative factors alone.HLTx outcomes may be improved by considering the strong influence of donor age, recipient sex, recipient hemodynamic status, and transplant center volume. Marginal donors and recipients without significant factors contributing to poor post-HLTx outcomes may still be considered for transplantation, potentially with less impact on the risk of early postoperative death or retransplant.

  View details for DOI 10.1161/CIRCULATIONAHA.119.040682

  View details for PubMedID 31589491

• Development and ex vivo validation of novel force-sensing neochordae for measuring chordae tendineae tension in the mitral valve apparatus using optical fibers with embedded Bragg gratings. Journal of biomechanical engineering Paulsen, M. J., Bae, J. H., Imbrie-Moore, A. n., Wang, H. n., Hironaka, C. n., Farry, J. M., Lucian, H. n., Thakore, A. n., Cutkosky, M. R., Woo, Y. J. 2019

  Abstract

  Few technologies exist that can provide quantitative data on forces within the mitral valve apparatus. Marker-based strain measurements can be performed, but chordal geometry and restricted optical access are limitations. Foil-based strain sensors have been described and work well, but the sensor footprint limits the number of chordae that can be measured. We instead utilized Fiber Bragg Grating (FBG) sensors-optical strain gauges made of 125µm diameter silica fibers- to overcome some limitations of previous methods of measuring chordae tendineae forces. Using FBG sensors, we created a force-sensing neochord that mimics the natural shape and movement of native chordae. FBG sensors reflect a specific wavelength of light depending on the spatial period of gratings. When force is applied, the gratings move relative to one another, shifting the wavelength of reflected light. This shift is directly proportional to force applied. The FBG sensors were housed in a protective sheath fashioned from a 0.025" flat coil, and attached to the chordae using polytetrafluoroethylene suture. The function of the force-sensing neochordae was validated in a 3D-printed left heart simulator, which demonstrated that FBG sensors provide highly sensitive force measurements of mitral valve chordae at a temporal resolution of 1000 Hz. As ventricular pressures increased, such as in hypertension, chordae forces also increased. Overall, FBG sensors are a viable, durable, and high-fidelity sensing technology that can be effectively used to measure mitral valve chordae forces and overcome some limitations of other such technologies.

  View details for DOI 10.1115/1.4044142

  View details for PubMedID 31253992

• Time-to-operation does not predict outcome in acute type A aortic dissection complicated by neurologic injury at presentation. The Journal of thoracic and cardiovascular surgery Chiu, P., Rotto, T. J., Goldstone, A. B., Whisenant, J. B., Woo, Y. J., Fischbein, M. P. 2018

  Abstract

  OBJECTIVE: Neurologic injury complicating the presentation of acute type A aortic dissection remains a challenge for cardiac surgeons.METHODS: This was a retrospective review of patients undergoing open repair of acute type A aortic dissection at our institution between January 2005 and December 2015. Evidence of neurologic injury at the time of presentation was abstracted from the medical record. Propensity-score matching was used to account for baseline differences between groups, and outcome analysis was performed using logistic regression and Kaplan-Meier analysis. Among patients with persistent neurologic deficits, a threshold for time-to-operation was evaluated using receiver operating characteristic curves.RESULTS: There were 345 patients who underwent open repair for acute type A aortic dissection; 50 patients presented with neurologic injury. In the matched analysis, in-hospital mortality was greater among patients who presented with neurologic deficits (odds ratio, 4.42; 95% confidence interval, 1.15-16.97; P=.03). Among patients with persistent neurologic deficits at presentation, receiver operating characteristic curve analysis with cross-validation suggested that time-to-operation was a poor predictor of both neurologic outcome (area under the curve, 0.40) and death (area under the curve, 0.49).CONCLUSIONS: Neurologic injury at the time of presentation with acute type A aortic dissection was associated with an increased risk of in-hospital mortality. Among patients with persistent neurological deficits, time-to-operation failed to predict either neurologic outcome or perioperative mortality suggesting that longer time from onset of symptoms of neurologic injury should not act as a contraindication to proceeding to the operating room for expedient repair.

  View details for PubMedID 30712911

• Intramyocardial Injection of Mesenchymal Precursor Cells in Left Ventricular Assist Device Recipients: Impact on Myocardial Recovery and Morbidity Pagani, F. D., Milano, C. A., Mancini, D. M., Lala, A., Woo, Y., Chang, H. L., Acker, M. A., Selzman, C. H., Moskowtiz, A. J., Soltesz, E. G., Kern, J. A., Maltais, S., Charbonneau, E., Marks, M. E., Moquete, E. G., O'Sullivan, K., Parides, M. K., Weisel, R. D., Taddei-Peters, W. C., McGowan, L. K., Green, C., O'Gara, P. T., Hung, J., Jeffries, N., Miller, M. A., Gelijns, A. C., Bagiella, E., Yau, T. M., CTSN Investigators LIPPINCOTT WILLIAMS & WILKINS. 2018: E765–E766

  View details for Web of Science ID 000453713500028

• mpact of Donor Obesity on Outcomes After Orthotopic Heart Transplantation JOURNAL OF THE AMERICAN HEART ASSOCIATION Shudo, Y., Cohen, J. E., Lingala, B., He, H., Woo, Y. 2018; 7 (23)

  View details for DOI 10.1161/JAHA.118.010253

  View details for Web of Science ID 000452891400021

• Impact of Donor Obesity on Outcomes After Orthotopic Heart Transplantation. Journal of the American Heart Association Shudo, Y., Cohen, J. E., Lingala, B., He, H., Woo, Y. J. 2018; 7 (23): e010253

  Abstract

  Background The impact of donor obesity on the outcome of orthotopic heart transplantation has not been studied. The aim of this study was to investigate the impact of donor obesity on the outcomes of adult orthotopic heart transplantation recipients. Methods and Results Data were obtained from the United Network for Organ Sharing database. All adult (age ≥18 years) patients undergoing orthotopic heart transplantation from 2000 through 2016 were included (n=31920). We stratified the cohort by donor body mass index ( BMI ); 13015 patients (40.8%) received a heart from a normal-weight donor ( BMI 18.5-24.9), 11271 patients (35.3%) received a heart from an overweight donor ( BMI 25.0-29.9), 4910 patients (15.4%) received a heart from an obese donor ( BMI 30.0-34.9), and 2724 patients (8.5%) received a heart from an extremely obese donor ( BMI ≥35). The cohort of obese donors was older, included a higher incidence of diabetes mellitus, and had a higher creatinine. Our data also showed that the recipients of obese donor grafts were older, had a higher BMI , creatinine, percentage of diabetes mellitus, and longer total waiting period. There was no significant difference detected in the survival likelihood ( P=0.08) of patients based on a donor's BMI-based categorized cohort. There were no significant differences found in the overall survival probability among 4 groups in the adjusted survival analyses ( P=0.25). Conclusions This study demonstrated that patients receiving higher BMI donor hearts might not be subjected to an increased risk of death, at least during the short term after transplant, compared with those using the normal-weight donors.

  View details for PubMedID 30511896

• The Incremental Value of Right Ventricular Size and Strain in the Risk Assessment of Right Heart Failure Post - Left Ventricular Assist Device Implantation JOURNAL OF CARDIAC FAILURE Aymami, M., Amsallem, M., Adams, J., Sallam, K., Moneghetti, K., Wheeler, M., Hiesinger, W., Teuteberg, J., Weisshaar, D., Verhoye, J., Woo, Y., Ha, R., Haddad, F., Banerjee, D. 2018; 24 (12): 823–32

  View details for DOI 10.1016/j.cardfail.2018.10.012

  View details for Web of Science ID 000454671800003

• Operative Techniques and Pitfalls in Donor Heart-Lung Procurement. Transplantation proceedings Salna, M., Shudo, Y., Woo, Y. J. 2018; 50 (10): 3111–12

  Abstract

  BACKGROUND: Heart-lung transplantation is a well-established therapeutic modality for concomitant end-stage heart and lung failure. With growing organ scarcity, the rates of these transplants are declining, and center experience is waning.METHODS: With over 35 years of experience performing heart-lung transplantation, we describe our procurement protocol herein, as well as offer suggestions to avoid potential pitfalls in order to ensure technical excellence in harvesting these valuable grafts.RESULTS: Procurement issues most commonly arise with organ preservation and inadvertent damage to structures that are difficult to fully visualize.CONCLUSIONS: En-bloc heart-lung procurement can be taught effectively and safely to trainees with an emphasis on avoiding common pitfalls that may compromise graft function.

  View details for PubMedID 30577175

• The Incremental Value of Right Ventricular Size and Strain in the Risk Assessment of Right Heart Failure Post - Left Ventricular Assist Device Implantation. Journal of cardiac failure Aymami, M., Amsallem, M., Adams, J., Sallam, K., Moneghetti, K., Wheeler, M., Hiesinger, W., Teuteberg, J., Weisshaar, D., Verhoye, J., Woo, Y. J., Ha, R., Haddad, F., Banerjee, D. 2018; 24 (12): 823–32

  Abstract

  BACKGROUND: Right heart failure (RHF) after left ventricular assist device (LVAD) implantation is associated with high morbidity and mortality. Existing risk scores include semiquantitative evaluation of right ventricular (RV) dysfunction. This study aimed to determine whether quantitative evaluation of both RV size and function improve risk stratification for RHF after LVAD implantation beyond validated scores.METHODS AND RESULTS: From 2009 to 2015, 158 patients who underwent implantation of continuous-flow devices who had complete echocardiographic and hemodynamic data were included. Quantitative RV parameters included RV end-diastolic (RVEDAI) and end-systolic area index, RV free-wall longitudinal strain (RVLS), fractional area change, tricuspid annular plane systolic excursion, and right atrial area and pressure. Independent correlates of early RHF (<30 days) were determined with the use of logistic regression analysis. Mean age was 56 ± 13 years, with 79% male; 49% had INTERMACS profiles ≤2. RHF occurred in 60 patients (38%), with 20 (13%) requiring right ventricular assist device. On multivariate analysis, INTERMACS profiles (adjusted odds ratio 2.38 [95% confidence interval [CI] 1.47-3.85]), RVEDAI (1.61 [1.08-2.32]), and RVLS (2.72 [1.65-4.51]) were independent correlates of RHF (all P < .05). Both RVLS and RVEDAI were incremental to validated risk scores (including the EUROMACS score) for early RHF after LVAD (all P < .01).CONCLUSIONS: RV end-diastolic and strain are complementary prognostic markers of RHF after LVAD implantation.

  View details for PubMedID 30539717

• First in line for robotic surgery: Would you want to know? The Journal of thoracic and cardiovascular surgery Woo, Y. J., Handy, J. R., Sade, R. M. 2018

  View details for PubMedID 30578065

• Modeling conduit choice for valve-sparing aortic root replacement on biomechanics with a 3-dimensional-printed heart simulator. The Journal of thoracic and cardiovascular surgery Paulsen, M. J., Kasinpila, P., Imbrie-Moore, A. M., Wang, H., Hironaka, C. E., Koyano, T. K., Fong, R., Chiu, P., Goldstone, A. B., Steele, A. N., Stapleton, L. M., Ma, M., Woo, Y. J. 2018

  Abstract

  OBJECTIVE: The optimal conduit for valve-sparing aortic root replacement is still debated, with several conduit variations available, ranging from straight tubular grafts to Valsalva grafts. Benefits of neosinus reconstruction include enhanced flow profiles and improved hemodynamics. Curiously, however, some clinical data suggest that straight grafts may have greater long-term durability. In this study, we hypothesized that straight tubular grafts may help maintain the native cylindrical position of the aortic valve commissures radially, resulting in preserved leaflet coaptation, reduced stresses, and potentially improved valve performance.METHODS: Using 3D printing, a left heart simulator with a valve-sparing root replacement model and a physiologic coronary circulation was constructed. Aortic valves were dissected from fresh porcine hearts and reimplanted into either straight tubular grafts (n=6) or Valsalva grafts (n=6). Conduits were mounted into the heart simulator and hemodynamic, echocardiographic, and high-speed videometric data were collected.RESULTS: Hemodynamic parameters and coronary blood flow were similar between straight and Valsalva grafts, although the former were associated with lower regurgitant fractions, less peak intercommissural radial separation, preserved leaflet coaptation, decreased leaflet velocities, and lower relative leaflet forces compared with Valsalva grafts.CONCLUSIONS: Valsalva grafts and straight grafts perform equally well in terms of gross hemodyanics and coronary blood flow. Interestingly, however, the biomechanics of these 2 conduits differ considerably, with straight grafts providing increased radial commissural stability and leaflet coaptation. Further investigation into how these parameters influence clinical outcomes is warranted.

  View details for PubMedID 30745047

• Rapid Self-Assembly of Bioengineered Cardiovascular Bypass Grafts From Scaffold-Stabilized, Tubular Bilevel Cell Sheets. Circulation von Bornstädt, D., Wang, H., Paulsen, M. J., Goldstone, A. B., Eskandari, A., Thakore, A., Stapleton, L., Steele, A. N., Truong, V. N., Jaatinen, K., Hironaka, C., Woo, Y. J. 2018; 138 (19): 2130-2144

  Abstract

  Cardiovascular bypass grafting is an essential treatment for complex cases of atherosclerotic disease. Because the availability of autologous arterial and venous conduits is patient-limited, self-assembled cell-only grafts have been developed to serve as functional conduits with off-the-shelf availability. The unacceptably long production time required to generate these conduits, however, currently limits their clinical utility. Here, we introduce a novel technique to significantly accelerate the production process of self-assembled engineered vascular conduits.Human aortic smooth muscle cells and skin fibroblasts were used to construct bilevel cell sheets. Cell sheets were wrapped around a 22.5-gauge Angiocath needle to form tubular vessel constructs. A thin, flexible membrane of clinically approved biodegradable tissue glue (Dermabond Advanced) served as a temporary, external scaffold, allowing immediate perfusion and endothelialization of the vessel construct in a bioreactor. Subsequently, the matured vascular conduits were used as femoral artery interposition grafts in rats (n=20). Burst pressure, vasoreactivity, flow dynamics, perfusion, graft patency, and histological structure were assessed.Compared with engineered vascular conduits formed without external stabilization, glue membrane-stabilized conduits reached maturity in the bioreactor in one-fifth the time. After only 2 weeks of perfusion, the matured conduits exhibited flow dynamics similar to that of control arteries, as well as physiological responses to vasoconstricting and vasodilating drugs. The matured conduits had burst pressures exceeding 500 mm Hg and had sufficient mechanical stability for surgical anastomoses. The patency rate of implanted conduits at 8 weeks was 100%, with flow rate and hind-limb perfusion similar to those of sham controls. Grafts explanted after 8 weeks showed a histological structure resembling that of typical arteries, including intima, media, adventitia, and internal and external elastic membrane layers.Our technique reduces the production time of self-assembled, cell sheet-derived engineered vascular conduits to 2 weeks, thereby permitting their use as bypass grafts within the clinical time window for elective cardiovascular surgery. Furthermore, our method uses only clinically approved materials and can be adapted to various cell sources, simplifying the path toward future clinical translation.

  View details for DOI 10.1161/CIRCULATIONAHA.118.035231

  View details for PubMedID 30474423

  View details for PubMedCentralID PMC6261325

• Single Cell Characterization of Smooth Muscle Cell Phenotypic Modulation in vivo Reveals a Critical Role for the Coronary Disease Gene Tcf21 in Mice and Humans Wirka, R., Kim, J. B., Wagh, D., Paik, D. T., Pjanic, M., Nguyen, T., Miller, C., Kundu, R. K., Coller, J., Zhu Kuixi, Chang, R., Koyano, T. K., Fong, R., Woo, J., Liu Boxiang, Montgomery, S. B., Quertermous, T. LIPPINCOTT WILLIAMS & WILKINS. 2018

  View details for Web of Science ID 000528619403025

• Computationally-Engineered Analog of Stromal Cell-Derived Factor 1[alpha] Preserves the Mechanical Properties of Infarcted Myocardium Under Planar Biaxial Tension Wang, H., Wisneski, A., Paulsen, M. J., Wang, Z., Hernandez, L., Xuan, Y., von Bornstaedt, D., Steele, A. N., Stapleton, L. M., Lucian, H. J., Anahita, E., Thakore, A. D., Farry, J. M., Hironaka, C. E., Williams, K. M., Wu, M., MacArthur, J. W., Woo, Y. LIPPINCOTT WILLIAMS & WILKINS. 2018

  View details for Web of Science ID 000528619407263

• A 3D Printed Ex Vivo Left Heart Simulator Quantifies and Validates Posterior Ventricular Anchoring Neochordoplasty Paulsen, M. J., Bae, J., Imbrie-Moore, A. M., Wang, H., Farry, J. M., Lin, M. A., Hironaka, C. E., Lucian, H. J., Edwards, B. B., Thankore, A. D., MacArthur, J. W., Steele, A. N., Stapleton, L., Williams, K. M., Deschamps, D., Kulkarni, R., Cutkosky, M. R., Woo, Y. LIPPINCOTT WILLIAMS & WILKINS. 2018

  View details for Web of Science ID 000528619407215

• Development and Ex Vivo Validation of Novel Force-Sensing Neo-Tendons for Measuring Chordae Tendineae Tension in the Mitral Valve Apparatus Using Optical Fibers With Embedded Bragg Gratings Paulsen, M. J., Bae, J., Imbrie-Moore, A. M., Wang, H., Hironaka, C. E., Lucian, H. J., Edwards, B. B., Farry, J. M., Deschamps, D., Kulkarni, R., Thakore, A. D., Williams, K. M., Cutkosky, M. R., Woo, Y. LIPPINCOTT WILLIAMS & WILKINS. 2018

  View details for Web of Science ID 000528619407353

• Exosomes From Induced Pluripotent Stem Cell-Derived Cardiomyocytes Salvage the Injured Myocardium by Modulation of Autophagy Santoso, M. R., Tada, Y., Ikeda, G., Jung, J., Vaskova, E., Sierra, R. G., Gati, C., Goldstone, A. B., Bornstaedt, D., Shukla, P., Wu, J. C., Wakatsuki, S., Woo, J., Yang, P. C. LIPPINCOTT WILLIAMS & WILKINS. 2018

  View details for Web of Science ID 000528619407290

• Exosomal miR-106a-363 Cluster Repairs the Injured Myocardium Jung, J., Tada, Y., Wahlquist, C., Bornstadt, D., Santoso, M., Woo, J., Mercola, M., Yang, P. LIPPINCOTT WILLIAMS & WILKINS. 2018

  View details for Web of Science ID 000528619403162

• Rapid Self-Assembly of Bioengineered Cardiovascular Bypass Grafts From Scaffold-Stabilized, Tubular Bilevel Cell Sheets CIRCULATION von Bornstadt, D., Wang, H., Paulsen, M. J., Goldstone, A. B., Eskandari, A., Thakore, A., Stapleton, L., Steele, A. N., Truong, V. N., Jaatinen, K., Hironaka, C., Woo, Y. 2018; 138 (19): 2130–44

  View details for DOI 10.1161/CIRCULATIONAHA.118.035231

  View details for Web of Science ID 000449158500010

• Would evolving recommendations for mechanical mitral valve replacement further raise the bar for successful mitral valve repair? EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Chiu, P., Goldstone, A. B., Woo, Y. 2018; 54 (4): 622–26

  View details for DOI 10.1093/ejcts/ezy284

  View details for Web of Science ID 000446093800002

• Planned Concomitant Left and Right Ventricular Assist Device Insertion to Avoid Long-term Biventricular Mechanical Support: Bridge to Right Ventricular Recovery. The heart surgery forum Salna, M., Shudo, Y., Teuteberg, J. J., Banerjee, D., Ha, R. V., Woo, Y. J., Hiesinger, W. 2018; 21 (5): E412–E414

  Abstract

  INTRODUCTION: The planned use of a temporary right ventricular assist device (RVAD) at the time of left ventricular assist device (LVAD) implantation may prevent the need for a permanent biventricular assist device (BiVAD). Herein we describe our RVAD weaning protocol that was effectively employed in 4 patients to prevent the need for permanent BiVAD.METHODS: Four patients in refractory cardiogenic shock underwent planned RVAD insertion during LVAD implantation due to severely depressed right ventricular function with dilation preoperatively. A standardized RVAD weaning protocol was employed in these 4 patients in preparation for decannulation.RESULTS: Temporary RVADs were successfully placed in all 4 patients at the time of LVAD implantation. All patients survived to RVAD decannulation and discharge and were alive at the time of most recent follow-up (range, 528-742 days post-RVAD decannulation).CONCLUSION: Planned implantation of a temporary RVAD in high risk patients may avoid the need for biventricular mechanical support in the future.

  View details for PubMedID 30311895

• Mechanical Versus Bioprosthetic Aortic Valve Replacement in Patients Aged 50 Years and Younger Hirji, S. A., Kolkailah, A. A., Ramirez-Del Val, F., Lee, J., McGurk, S., Pelletier, M., Singh, S., Mallidi, H. R., Aranki, S., Shekar, P., Kaneko, T., Goldstone, A. B., Woo, Y. ELSEVIER SCIENCE INC. 2018: 1113–21

  Abstract

  This study evaluated outcomes in younger patients, specifically aged 50 years and younger, after mechanical aortic valve replacement (mAVR) and bioprosthetic AVR (bAVR).From 1994 to 2016, 643 patients underwent AVR (411 mAVR and 232 bAVR) at age 50 or younger. Concomitant coronary artery bypass grafting and mitral valve procedures were also included. Propensity score-matching methods resulted in 170 evenly matched patient pairs. Primary end points were operative mortality and long-term survival. Secondary end points were stroke, major bleeding, and redo AVR. Median observation time was 8.1 years (range, 0 to 23.6 years).Overall, mean age was 41.9 years, and 29.3% were women, with an increasing trend toward use of bAVR. Mean age in the matched patients was 43.3 years for both cohorts (p = 0.68). Operative mortality, stroke, atrial fibrillation, reoperation for bleeding, and readmission rates within 30 days were all similar between the two groups. bAVR patients were at higher risk for redo AVR (13% vs 1.6%, p < 0.001), and mAVR patients were at higher risk for major bleeding events (8.5% vs 2.2%, p = 0.006). However, when adjusted, there were no differences in midterm and long-term survival between unmatched and matched cohorts.The increased risk of reoperation for bAVR and major bleeding incidents for mAVR was not reflected in midterm and long-term survival differences between the two groups. Our results suggest that bAVR may be an acceptable prosthesis choice for some patients aged 50 years and younger, although the results should be taken with caution.

  View details for DOI 10.1016/j.athoracsur.2018.05.073

  View details for Web of Science ID 000445116100044

  View details for PubMedID 29966596

• POSTPARTUM DIAGNOSIS OF CARDIAC PARAGANGLIOMA: A CASE REPORT JOURNAL OF EMERGENCY MEDICINE Berona, K., Joshi, R., Woo, Y., Shrager, J. 2018; 55 (4): E101–E105

  Abstract

  Extra-adrenal pheochromocytomas, or paragangliomas, originate from neural crest chromaffin cells and can be found anywhere along the sympathetic chain from head to toe.A 34-year-old female presented 4 days postpartum with episodes of palpitations, hypertension, and shortness of breath. Two episodes in the emergency department confirmed hypertension and supraventricular tachycardia (SVT). A mediastinal mass was noted during workup for pulmonary embolus and was subsequently diagnosed as a cardiac paraganglioma. Our patient underwent surgical resection and was doing well 3 months postoperatively. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case represents a rare presentation of mediastinal paraganglioma with episodic SVT and hypertension postpartum, diagnosed during workup for pulmonary embolus. Although exceedingly rare, emergency physicians should consider paragangliomas in the differential of pregnant or postpartum women who present with episodic hypertension, palpitations, headache, and sweating.

  View details for PubMedID 30037518

• Heart-lung transplantation over the past 10 years: an up-to-date concept. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Shudo, Y., Kasinpila, P., Lingala, B., Kim, F. Y., Woo, Y. J. 2018

  Abstract

  OBJECTIVES: Heart-lung transplantation has been established as an effective treatment for patients with advanced cardiopulmonary failure. Over the years, the number of operations performed has declined. In 2015, only 38 adult heart-lung transplants were reported worldwide. Since then, we have performed 16 operations in high-acuity patients with excellent postoperative outcomes. Herein, we review our single-centre experience with heart-lung transplantation over the past 10 years.METHODS: We retrospectively reviewed 49 heart-lung transplant recipients between 2008 and 2018 to investigate the patient characteristics and outcomes while comparing those results across 2 cohorts (2008-2015, Era I, n=30 and 2016-2018, Era II, n=19).RESULTS: Our patient demographics and waitlist time did not significantly change over time. However, the lung allocation score was significantly higher in Era II compared to Era I (51.1±19.8 in Era II and 41.6±19.5 in Era I; P=0.006). We also observed a higher rate-while not statistically significant-of preoperative and postoperative use of mechanical circulatory support in the present era. Although there is a trend of higher acuity in the present era, we continue to have excellent outcomes with 100% 30-day and 1-year survival.CONCLUSIONS: These results suggest that in a high-volume heart-lung transplant programme, excellent postoperative outcomes can be achieved even in patients with rapid and severe cardiopulmonary decline and that, to this day, heart-lung transplantation remains a viable option for patients with advanced cardiopulmonary disease.

  View details for PubMedID 30260389

• Small Molecule Derived From Carboxyethylpyrrole Protein Adducts Promotes Angiogenesis in a Mouse Model of Peripheral Arterial Disease JOURNAL OF THE AMERICAN HEART ASSOCIATION Hou, L., Yang, G., Tang, S., Alcazar, C., Joshi, P., Strassberg, Z., Kim, M., Kawamura, M., Woo, Y., Shrager, J., Ding, S., Huang, N. F. 2018; 7 (18)

  View details for DOI 10.1161/JAHA.118.009234

  View details for Web of Science ID 000452805400014

• Small Molecule Derived From Carboxyethylpyrrole Protein Adducts Promotes Angiogenesis in a Mouse Model of Peripheral Arterial Disease. Journal of the American Heart Association Hou, L., Yang, G., Tang, S., Alcazar, C., Joshi, P., Strassberg, Z., Kim, M., Kawamura, M., Woo, Y. J., Shrager, J., Ding, S., Huang, N. F. 2018; 7 (18): e009234

  Abstract

  Background CEP (omega-[2-carboxyethyl]pyrrole) protein adducts are the end products of lipid oxidation associated with inflammation and have been implicated in the induction of angiogenesis in pathological conditions such as tissue ischemia. We synthesized small molecules derived from CEP protein adducts and evaluated the angiogenic effect of the CEP analog CEP 03 in the setting of peripheral arterial disease. Methods and Results The angiogenic effect of CEP 03 was assessed by invitro analysis of primary human microvascular endothelial cell proliferation and tubelike formation in Matrigel (Corning). In the presence of CEP 03, proliferation of endothelial cells invitro increased by 27±18% under hypoxic (1% O2) conditions, reaching similar levels to that of VEGF A (vascular endothelial growth factor A) stimulation (22±10%), relative to the vehicle control treatment. A similar effect of CEP 03 was demonstrated in the increased number of tubelike branches in Matrigel, reaching >70% induction in hypoxia, compared with the vehicle control. The therapeutic potential of CEP 03 was further evaluated in a mouse model of peripheral arterial disease by quantification of blood perfusion recovery and capillary density. In the ischemic hind limb, treatment of CEP 03 encapsulated within Matrigel significantly enhanced blood perfusion by 2-fold after 14days compared with those treated with Matrigel alone. Moreover, these results concurred with histological finding that treatment of CEP 03 in Matrigel resulted in a significant increase in microvessel density compared with Matrigel alone. Conclusions Our data suggest that CEP 03 has a profound positive effect on angiogenesis and neovessel formation and thus has therapeutic potential for treatment of peripheral arterial disease.

  View details for PubMedID 30371212

• Lessons Learned: A Roundtable Discussion on Succeeding in Cardiothoracic Surgical Residency and Practice SEMINARS IN THORACIC AND CARDIOVASCULAR SURGERY Woo, Y., Baker, C., Colson, Y., Cooke, D., Fann, J., Goldstone, A. 2018; 30 (3): 293–303

  View details for DOI 10.1053/j.semtcvs.2018.09.005

  View details for Web of Science ID 000450371100009

  View details for PubMedID 30219543

• Ambulating femoral venoarterial extracorporeal membrane oxygenation bridge to heart-lung transplant JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Shudo, Y., Kasinpila, P., Lee, A. M., Rao, V. K., Woo, Y. 2018; 156 (3): E135–E137

  View details for DOI 10.1016/j.jtcvs.2018.03.002

  View details for Web of Science ID 000441556000001

• Would evolving recommendations for mechanical mitral valve replacement further raise the bar for successful mitral valve repair? European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Chiu, P., Goldstone, A. B., Woo, Y. J. 2018

  View details for PubMedID 30165483

• Reply to Dimarakis and Venkateswaran. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Shudo, Y., Wang, H., Woo, Y. J. 2018

  View details for PubMedID 30113629

• Successful heart-lung-kidney and domino heart transplantation following veno-venous extracorporeal membrane oxygenation support. Interactive cardiovascular and thoracic surgery Zhu, Y., Shudo, Y., Lee, A. M., Woo, Y. J. 2018

  Abstract

  A 60-year-old man with cystic fibrosis, mediastinal shift and end-stage kidney disease underwent a heart-lung-kidney transplantation. His explanted heart was used for a domino heart transplantation. This case showed an excellent outcome, even with high preoperative acuity requiring veno-venous extracorporeal membrane oxygenation and continuous veno-venous haemodialysis.

  View details for PubMedID 30113636

• SDF 1-alpha Attenuates Myocardial Injury Without Altering the Direct Contribution of Circulating Cells JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH Goldstone, A. B., Burnett, C. E., Cohen, J. E., Paulsen, M. J., Eskandari, A., Edwards, B. E., Ingason, A. B., Steele, A. N., Patel, J. B., MacArthur, J. W., Shizuru, J. A., Woo, Y. 2018; 11 (4): 274–84

  View details for DOI 10.1007/s12265-017-9772-y

  View details for Web of Science ID 000443418700002

• Mechanical versus Bioprosthetic Aortic Valve Replacement in Patients Aged 50 Years and Younger (Commentary). The Annals of thoracic surgery Goldstone, A. B., Woo, Y. J. 2018

  View details for PubMedID 30055140

• Immediate operation for acute type A aortic dissection complicated by visceral or peripheral malperfusion JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Chiu, P., Tsou, S., Goldstone, A. B., Louie, M., Woo, Y., Fischbein, M. P. 2018; 156 (1): 18-+

  View details for DOI 10.1016/j.jtcvs.2018.01.096

  View details for Web of Science ID 000436592600021

• Heart transplant after profoundly extended ambulatory central venoarterial extracorporeal membrane oxygenation JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Shudo, Y., Wang, H., Ha, R. V., Hayes, A. D., Woo, Y. 2018; 156 (1): E7–E9

  View details for DOI 10.1016/j.jtcvs.2018.02.001

  View details for Web of Science ID 000436592600003

• The Wheat sprouts new life JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Woo, Y., Edmonson, A. 2018; 156 (1): 1–2

  View details for DOI 10.1016/j.jtcvs.2018.03.054

  View details for Web of Science ID 000436592600015

• To repair or to replace: four decades in the making ANNALS OF TRANSLATIONAL MEDICINE Kasinpila, P., Woo, Y. 2018; 6 (7)

  View details for DOI 10.21037/atm.2017.05.22

  View details for Web of Science ID 000430714000015

• To repair or to replace: four decades in the making. Annals of translational medicine Kasinpila, P., Woo, Y. J. 2018; 6 (7): 125

  View details for DOI 10.21037/atm.2017.05.22

  View details for PubMedID 29955585

  View details for PubMedCentralID PMC6015943

• The Wheat sprouts new life. The Journal of thoracic and cardiovascular surgery Woo, Y. J., Edmonson, A. 2018

  View details for PubMedID 29754798

• OUTCOME OF EN-BLOC COMBINED HEART AND LIVER TRANSPLANTATION IN THE ADULT FAILING FONTAN Vaikunth, S., Concepcion, W., Daugherty, T., Fowler, M., Lutchman, G., Maeda, K., Rosenthal, D., Teuteberg, J., Woo, Y., Lui, G. K. ELSEVIER SCIENCE INC. 2018: 539

  View details for DOI 10.1016/S0735-1097(18)31080-5

  View details for Web of Science ID 000429659701389

• Ambulating femoral venoarterial extracorporeal membrane oxygenation bridge to heart-lung transplant. The Journal of thoracic and cardiovascular surgery Shudo, Y., Kasinpila, P., Lee, A. M., Rao, V. K., Woo, Y. J. 2018

  View details for PubMedID 29628344

• Angiogenesis precedes cardiomyocyte migration in regenerating mammalian hearts JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Ingason, A. B., Goldstone, A. B., Paulsen, M. J., Thakore, A. D., Truong, V. N., Edwards, B. B., Eskandari, A., Bollig, T., Steele, A. N., Woo, Y. 2018; 155 (3): 1118-+

  Abstract

  Although the mammalian heart's ability to fully regenerate is debated, its potential to extensively repair itself is gaining support. We hypothesized that heart regeneration relies on rapid angiogenesis to support myocardial regrowth and sought to characterize the timeline for angiogenesis and cell proliferation in regeneration.One-day-old CD-1 mice (P1, N = 60) underwent apical resection or sham surgery. Hearts were explanted at serial time points from 0 to 30 days postresection and analyzed with immunohistochemistry to visualize vessel ingrowth and cardiomyocyte migration into the resected region. Proliferating cells were labeled with 5-ethynyl-2'-deoxyuridine injections 12 hours before explant. 5-Ethynyl-2'-deoxyuridine-positive cells were counted in both the apex and remote areas of the heart. Masson's trichrome was used to assess fibrosis.By 30 days postresection, hearts regenerated with minimal fibrosis. Compared with sham surgery, apical resection stimulated a significant increase in proliferation of preexisting cardiomyocytes between 3 and 11 days after injury. Capillary migration into the apical thrombus was detected as early as 2 days postresection, with development of mature arteries by 5 days postresection. New vessels became perfused by 5 days postresection as evidenced by lectin injection. Vessel density and diameter significantly increased within the resected area over 21 days, and vessel ingrowth always preceded cardiomyocyte migration, with coalignment of most migrating cardiomyocytes with ingrowing vessels.Endothelial cells migrate into the apical thrombus early after resection, develop into functional arteries, and precede cardiomyocyte ingrowth during mammalian heart regeneration. This endogenous neonatal response emphasizes the importance of expeditious angiogenesis required for neomyogenesis.

  View details for PubMedID 29452461

• Prosthesis Type for Aortic- and Mitral-Valve Replacement REPLY NEW ENGLAND JOURNAL OF MEDICINE Goldstone, A. B., Chiu, P., Woo, Y. 2018; 378 (8): 778–79

  View details for Web of Science ID 000425613900027

• Prosthesis Type for Aortic- and Mitral-Valve Replacement NEW ENGLAND JOURNAL OF MEDICINE Chikwe, J., Blackstone, E. H., Adams, D. H. 2018; 378 (8): 778

  View details for Web of Science ID 000425613900026

  View details for PubMedID 29469559

• SDF 1-alpha Attenuates Myocardial Injury Without Altering the Direct Contribution of Circulating Cells. Journal of cardiovascular translational research Goldstone, A. B., Burnett, C. E., Cohen, J. E., Paulsen, M. J., Eskandari, A., Edwards, B. E., Ingason, A. B., Steele, A. N., Patel, J. B., MacArthur, J. W., Shizuru, J. A., Woo, Y. J. 2018

  Abstract

  Stromal cell-derived factor 1-alpha (SDF) is a potent bone marrow chemokine capable of recruiting circulating progenitor populations to injured tissue. SDF has known angiogenic capabilities, but bone marrow-derived cellular contributions to tissue regeneration remain controversial. Bone marrow from DsRed-transgenic donors was transplanted into recipients to lineage-trace circulating cells after myocardial infarction (MI). SDF was delivered post-MI, and hearts were evaluated for recruitment and plasticity of bone marrow-derived populations. SDF treatment improved ventricular function, border zone vessel density, and CD31+ cell frequency post-MI. Bone marrow-derived endothelial cells were observed; these cells arose through both cell fusion and transdifferentiation. Circulating cells also adopted cardiomyocyte fates, but such events were exceedingly rare and almost exclusively resulted from cell fusion. SDF did not significantly alter the proportion of circulating cells that adopted non-hematopoietic fates. Mechanistic insight into the governance of circulating cells is essential to realizing the full potential of cytokine therapies.

  View details for PubMedID 29468554

• Heart transplant after profoundly extended ambulatory central venoarterial extracorporeal membrane oxygenation. The Journal of thoracic and cardiovascular surgery Shudo, Y., Wang, H., Ha, R. V., Hayes, A. D., Woo, Y. J. 2018

  View details for PubMedID 29576264

• Second Arterial Versus Venous Conduits for Multivessel Coronary Artery Bypass Surgery in California. Circulation Goldstone, A. B., Chiu, P. n., Baiocchi, M. n., Wang, H. n., Lingala, B. n., Boyd, J. H., Woo, Y. J. 2018; 137 (16): 1698–1707

  Abstract

  Whether a second arterial conduit improves outcomes after multivessel coronary artery bypass grafting remains unclear. Consequently, arterial conduits other than the left internal thoracic artery are seldom used in the United States.Using a state-maintained clinical registry including all 126 nonfederal hospitals in California, we compared all-cause mortality and rates of stroke, myocardial infarction, repeat revascularization, and sternal wound infection between propensity score-matched cohorts who underwent primary, isolated multivessel coronary artery bypass grafting with the left internal thoracic artery, and who received a second arterial conduit (right internal thoracic artery or radial artery, n=5866) or a venous conduit (n=53 566) between 2006 and 2011. Propensity score matching using 34 preoperative characteristics yielded 5813 matched sets. A subgroup analysis compared outcomes between propensity score-matched recipients of a right internal thoracic artery (n=1576) or a radial artery (n=4290).Second arterial conduit use decreased from 10.7% in 2006 to 9.1% in 2011 (P<0.0001). However, receipt of a second arterial conduit was associated with significantly lower mortality (13.1% versus 10.6% at 7 years; hazard ratio, 0.79; 95% confidence interval [CI], 0.72-0.87), and lower risks of myocardial infarction (hazard ratio, 0.78; 95% CI, 0.70-0.87) and repeat revascularization (hazard ratio, 0.82; 95% CI, 0.76-0.88). In comparison with radial artery grafts, right internal thoracic artery grafts were associated with similar mortality rates (right internal thoracic artery 10.3% versus radial artery 10.7% at 7 years; hazard ratio, 1.10; 95% CI, 0.89-1.37) and individual risks of cardiovascular events, but the risk of sternal wound infection was increased (risk difference, 1.07%; 95% CI, 0.15-2.07).Second arterial conduit use in California is low and declining, but arterial grafts were associated with significantly lower mortality and fewer cardiovascular events. A right internal thoracic artery graft offered no benefit over that of a radial artery, but did increase risk of sternal wound infection. These findings suggest surgeons should consider lowering their threshold for using arterial grafts, and the radial artery may be the preferred second conduit.

  View details for PubMedID 29242351

• Limited root repair in acute type A aortic dissection is safe but results in increased risk of reoperation JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Chiu, P., Trojan, J., Tsou, S., Goldstone, A. B., Woo, Y., Fischbein, M. P. 2018; 155 (1): 1-+

  View details for DOI 10.1016/j.jtcvs.2017.08.137

  View details for Web of Science ID 000422751300024

• Planned Concomitant Left and Right Ventricular Assist Device Insertion to Avoid Long-term Biventricular Mechanical Support: Bridge to Right Ventricular Recovery HEART SURGERY FORUM Salna, M., Shudo, Y., Teuteberg, J. J., Banerjee, D., Ha, R. V., Woo, Y., Hiesinger, W. 2018; 21 (5): E412–E414

  View details for DOI 10.1532/hsf.2035

  View details for Web of Science ID 000457932600016

• Aligned Nanofibrillar Scaffolds for Controlled Delivery of Modified mRNA. Tissue engineering. Part A Zaitseva, T. n., Alcazar, C. n., Zamani, M. n., Hou, L. n., Sawamura, S. n., Yakubov, E. n., Hopkins, M. n., Woo, Y. J., Paukshto, M. n., Huang, N. F. 2018

  Abstract

  RNA-based vector delivery is a promising gene therapy approach. Recent advances in chemical modification of mRNA structure to form modified mRNA (mmRNA or cmRNA or modRNA) have substantially improved their stability and translational efficiency within cells. However, mmRNA conventionally delivered in solution can be taken up non-specifically or become cleared away prematurely, which markedly limits the potential benefit of mmRNA therapy. To address this limitation, we developed mmRNA-incorporated nanofibrillar scaffolds that could target spatially localized delivery and temporally controlled release of the mmRNA both in vitro and in vivo. To establish the efficacy of mmRNA therapy, mmRNA encoding reporter proteins such as green fluorescence protein (GFP) or firefly luciferase (Fluc) was loaded into aligned nanofibrillar collagen scaffolds. The mmRNA was released from mmRNA-loaded scaffolds in a transient and temporally controlled fashion and induced transfection in human fibroblasts in a dose-dependent manner. In vitro transfection was further verified using mmRNA encoding the angiogenic growth factor, hepatocyte growth factor (HGF). Finally, scaffold-based delivery of HGF mmRNA to the site of surgically induced muscle injury in mice resulted in significantly higher vascular regeneration after 14 days, compared to implantation of Fluc mmRNA-releasing scaffolds. After transfection with Fluc mmRNA-releasing scaffold in vivo, Fluc activity was detectable and localized to the muscle region, based on non-invasive bioluminescence imaging. Scaffold-based local mmRNA delivery as an off-the-shelf form of gene therapy has broad translatability for treating a broad range of diseases or injuries.

  View details for PubMedID 29717619

• Immediate operation for acute type A aortic dissection complicated by visceral or peripheral malperfusion. The Journal of thoracic and cardiovascular surgery Chiu, P. n., Tsou, S. n., Goldstone, A. B., Louie, M. n., Woo, Y. J., Fischbein, M. P. 2018

  Abstract

  To evaluate the effect of visceral, renal, or peripheral malperfusion on the outcome of acute type A aortic dissection.We performed a retrospective review of the acute type A aortic dissection experience at Stanford Hospital between January 2005 and December 2015. Inverse probability weighting was used to account for differences between patients who experienced malperfusion syndromes and those who did not. Weighted logistic regression was used to evaluate in-hospital mortality, and midterm survival was assessed with the restricted mean survival time and weighted Cox regression. Reintervention was assessed with death as a competing risk.There were 305 patients with type A dissection extending beyond the ascending aorta, and 82 (26.9%) presented with a malperfusion syndrome. In-hospital mortality in the malperfusion subgroup was no different compared with patients without malperfusion in weighted logistic regression, odds ratio, 1.50 (95% confidence interval, 0.65-3.47; P = .3). There was no difference in midterm survival using restricted mean survival time, -50.2 days (95% CI, -366.8 to 266.4; P = .8) in patients with malperfusion compared with patients without malperfusion at 8 years. Patients with malperfusion had an increased risk of interventions (12.5%) on aortic branches compared with patients without (5.7%) in weighted analysis at 10-years, hazard ratio, 3.06 (95% CI, 1.24-7.56; P = .02). The median time to reintervention on aortic branches was 2 days for patients with malperfusion compared with 230 days without malperfusion, P = .01.Immediate operation for acute type A aortic dissection complicated by malperfusion is associated with good results.

  View details for PubMedID 29615333

• Prosthesis Type for Aortic- and Mitral-Valve Replacement. The New England journal of medicine Goldstone, A. B., Chiu, P. n., Woo, Y. J. 2018; 378 (8): 778–79

  View details for PubMedID 29466153

• 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

• Paracrine Effects of the Pluripotent Stem Cell-Derived Cardiac Myocytes Salvage the Injured Myocardium CIRCULATION RESEARCH Tachibana, A., Santoso, M. R., Mahmoudi, M., Shukla, P., Wang, L., Bennett, M., Goldstone, A. B., Wang, M., Fukushi, M., Ebert, A. D., Woo, Y., Rulifson, E., Yang, P. C. 2017; 121 (6): E22-+

  Abstract

  Cardiac myocytes derived from pluripotent stem cells have demonstrated the potential to mitigate damage of the infarcted myocardium and improve left ventricular ejection fraction. However, the mechanism underlying the functional benefit is unclear.To evaluate whether the transplantation of cardiac-lineage differentiated derivatives enhance myocardial viability and restore left ventricular ejection fraction more effectively than undifferentiated pluripotent stem cells after a myocardial injury. Herein, we utilize novel multimodality evaluation of human embryonic stem cells (hESCs), hESC-derived cardiac myocytes (hCMs), human induced pluripotent stem cells (iPSCs), and iPSC-derived cardiac myocytes (iCMs) in a murine myocardial injury model.Permanent ligation of the left anterior descending coronary artery was induced in immunosuppressed mice. Intramyocardial injection was performed with (1) hESCs (n=9), (2) iPSCs (n=8), (3) hCMs (n=9), (4) iCMs (n=14), and (5) PBS control (n=10). Left ventricular ejection fraction and myocardial viability, measured by cardiac magnetic resonance imaging and manganese-enhanced magnetic resonance imaging, respectively, was significantly improved in hCM- and iCM-treated mice compared with pluripotent stem cell- or control-treated mice. Bioluminescence imaging revealed limited cell engraftment in all treated groups, suggesting that the cell secretions may underlie the repair mechanism. To determine the paracrine effects of the transplanted cells, cytokines from supernatants from all groups were assessed in vitro. Gene expression and immunohistochemistry analyses of the murine myocardium demonstrated significant upregulation of the promigratory, proangiogenic, and antiapoptotic targets in groups treated with cardiac lineage cells compared with pluripotent stem cell and control groups.This study demonstrates that the cardiac phenotype of hCMs and iCMs salvages the injured myocardium effectively than undifferentiated stem cells through their differential paracrine effects.

  View details for PubMedID 28743804

• DACH1 stimulates shear stress-guided endothelial cell migration and coronary artery growth through the CXCL12-CXCR4 signaling axis GENES & DEVELOPMENT Chang, A. H., Raftrey, B. C., D'Amato, G., Surya, V. N., Poduri, A., Chen, H. I., Goldstone, A. B., Woo, J., Fuller, G. G., Dunn, A. R., Red-Horse, K. 2017; 31 (13): 1308–24

  Abstract

  Sufficient blood flow to tissues relies on arterial blood vessels, but the mechanisms regulating their development are poorly understood. Many arteries, including coronary arteries of the heart, form through remodeling of an immature vascular plexus in a process triggered and shaped by blood flow. However, little is known about how cues from fluid shear stress are translated into responses that pattern artery development. Here, we show that mice lacking endothelial Dach1 had small coronary arteries, decreased endothelial cell polarization, and reduced expression of the chemokine Cxcl12 Under shear stress in culture, Dach1 overexpression stimulated endothelial cell polarization and migration against flow, which was reversed upon CXCL12/CXCR4 inhibition. In vivo, DACH1 was expressed during early arteriogenesis but was down in mature arteries. Mature artery-type shear stress (high, uniform laminar) specifically down-regulated DACH1, while the remodeling artery-type flow (low, variable) maintained DACH1 expression. Together, our data support a model in which DACH1 stimulates coronary artery growth by activating Cxcl12 expression and endothelial cell migration against blood flow into developing arteries. This activity is suppressed once arteries reach a mature morphology and acquire high, laminar flow that down-regulates DACH1. Thus, we identified a mechanism by which blood flow quality balances artery growth and maturation.

  View details for PubMedID 28779009

• Stem Cell Therapy: Healing or Hype? Why Stem Cell Delivery Doesn't Work CIRCULATION RESEARCH Steele, A. N., MacArthur, J. W., Woo, Y. 2017; 120 (12): 1868–70

  View details for PubMedID 28596172

• A novel protein-engineered hepatocyte growth factor analog released via a shear-thinning injectable hydrogel enhances post-infarction ventricular function. Biotechnology and bioengineering Steele, A. N., Cai, L., Truong, V. N., Edwards, B. B., Goldstone, A. B., Eskandari, A., Mitchell, A. C., Marquardt, L. M., Foster, A. A., Cochran, J. R., Heilshorn, S. C., Woo, Y. J. 2017

  Abstract

  In the last decade, numerous growth factors and biomaterials have been explored for the treatment of myocardial infarction (MI). While pre-clinical studies have demonstrated promising results, clinical trials have been disappointing and inconsistent, likely due to poor translatability. In the present study, we investigate a potential myocardial regenerative therapy consisting of a protein-engineered dimeric fragment of hepatocyte growth factor (HGFdf) encapsulated in a shear-thinning, self-healing, bioengineered hydrogel (SHIELD). We hypothesized that SHIELD would facilitate targeted, sustained intramyocardial delivery of HGFdf thereby attenuating myocardial injury and post-infarction remodeling. Adult male Wistar rats (n = 45) underwent sham surgery or induction of MI followed by injection of phosphate buffered saline (PBS), 10 μg HGFdf alone, SHIELD alone, or SHIELD encapsulating 10 μg HGFdf. Ventricular function, infarct size, and angiogenic response were assessed 4 weeks post-infarction. Treatment with SHIELD + HGFdf significantly reduced infarct size and increased both ejection fraction and borderzone arteriole density compared to the controls. Thus, sustained delivery of HGFdf via SHIELD limits post-infarction adverse ventricular remodeling by increasing angiogenesis and reducing fibrosis. Encapsulation of HGFdf in SHIELD improves clinical translatability by enabling minimally-invasive delivery and subsequent retention and sustained administration of this novel, potent angiogenic protein analog. Biotechnol. Bioeng. 2017;9999: 1-11. © 2017 Wiley Periodicals, Inc.

  View details for DOI 10.1002/bit.26345

  View details for PubMedID 28574594

• Pneumonia after cardiac surgery: Experience of the National Institutes of Health/Canadian Institutes of Health Research Cardiothoracic Surgical Trials Network. journal of thoracic and cardiovascular surgery Ailawadi, G., Chang, H. L., O'Gara, P. T., O'Sullivan, K., Woo, Y. J., DeRose, J. J., Parides, M. K., Thourani, V. H., Robichaud, S., Gillinov, A. M., Taddei-Peters, W. C., Miller, M. A., Perrault, L. P., Smith, R. L., Goldsmith, L., Horvath, K. A., Doud, K., Baio, K., Gelijns, A. C., Moskowitz, A. J., Bagiella, E., Alexander, J. H., Iribarne, A. 2017; 153 (6): 1384-1391 e3

  Abstract

  Pneumonia remains the most common major infection after cardiac surgery despite numerous preventive measures.To prospectively examine the timing, pathogens, and risk factors, including modifiable management practices, for postoperative pneumonia and estimate its impact on clinical outcomes.A total of 5158 adult cardiac surgery patients were enrolled prospectively in a cohort study across 10 centers. All infections were adjudicated by an independent committee. Competing risk models were used to assess the association of patient characteristics and management practices with pneumonia within 65 days of surgery. Mortality was assessed by Cox proportional hazards model and length of stay by a multistate model.The cumulative incidence of pneumonia was 2.4%, 33% of which occurred after discharge. Older age, lower hemoglobin level, chronic obstructive pulmonary disease, steroid use, operative time, and left ventricular assist device/heart transplant were risk factors. Ventilation time (24-48 vs ≤24 hours; hazard ratio [HR], 2.83; 95% confidence interval [95% CI], 1.72-4.66; >48 hours HR, 4.67; 95% CI, 2.70-8.08), nasogastric tubes (HR, 1.80; 95% CI, 1.10-2.94), and each unit of blood cells transfused (HR, 1.16; 95% CI, 1.08-1.26) increased the risk of pneumonia. Prophylactic use of second-generation cephalosporins (HR, 0.66; 95% CI, 0.45-0.97) and platelet transfusions (HR, 0.49, 95% CI, 0.30-0.79) were protective. Pneumonia was associated with a marked increase in mortality (HR, 8.89; 95% CI, 5.02-15.75) and longer length of stay of 13.55 ± 1.95 days (bootstrap 95% CI, 10.31-16.58).Pneumonia continues to impose a major impact on the health of patients after cardiac surgery. After we adjusted for baseline risk, several specific management practices were associated with pneumonia, which offer targets for quality improvement and further research.

  View details for DOI 10.1016/j.jtcvs.2016.12.055

  View details for PubMedID 28341473

• Tricuspid leaflet repair: innovative solutions ANNALS OF CARDIOTHORACIC SURGERY Boyd, J. H., Edelman, J. B., Scoville, D. H., Woo, Y. 2017; 6 (3): 248–54

  Abstract

  Tricuspid regurgitation (TR) represents a significant disease process and when severe, is associated with increased mortality. Recent guidelines support a more aggressive approach to tricuspid valve (TV) surgery, especially when encountered with left-sided valvular pathology. While annuloplasty has been the standard treatment for TR, it may not provide as effective or durable a repair compared to annuloplasty combined with TV repair techniques. Several of these approaches are discussed including bicuspidalization, anterior leaflet augmentation, edge to edge repair, neochords, leaflet resection and combined approaches. Although patient cohorts in most of the studies examining these techniques are small, the long-term durability of TV repair is significant.

  View details for PubMedID 28706867

• Injectable Bioengineered Hydrogel Therapy in the Treatment of Ischemic Cardiomyopathy. Current treatment options in cardiovascular medicine MacArthur, J. W., Steele, A. N., Goldstone, A. B., Cohen, J. E., Hiesinger, W., Woo, Y. J. 2017; 19 (4): 30-?

  Abstract

  Over the past two decades, the field of cardiovascular medicine has seen the rapid development of multiple different modalities for the treatment of ischemic myocardial disease. Most research efforts have focused on strategies aimed at coronary revascularization, with significant technological advances made in percutaneous coronary interventions as well as coronary artery bypass graft surgery. However, recent research efforts have shifted towards ways to address the downstream effects of myocardial infarction on both cellular and molecular levels. To this end, the broad application of injectable hydrogel therapy after myocardial infarction has stimulated tremendous interest. In this article, we will review what hydrogels are, how they can be bioengineered in unique ways to optimize therapeutic potential, and how they can be used as part of a treatment strategy after myocardial infarction.

  View details for DOI 10.1007/s11936-017-0530-x

  View details for PubMedID 28337717

• EFFECTIVENESS OF A SECOND ARTERIAL CONDUIT FOR MULTI VESSEL CORONARY BYPASS: A STATE-WIDE ANALYSIS OF 60,897 PATIENTS Goldstone, A. B., Chiu, P., Baiocchi, M., Ligala, B., Boyd, J., Woo, Y. ELSEVIER SCIENCE INC. 2017: 26

  View details for Web of Science ID 000397342300027

• Current status of domino heart transplantation. Journal of cardiac surgery Shudo, Y., Ma, M., Boyd, J. H., Woo, Y. J. 2017; 32 (3): 229-232

  Abstract

  Domino heart transplant, wherein the explanted heart from the recipient of an en-bloc heart-lung is utilized for a second recipient, represents a unique surgical strategy for patients with end-stage heart failure. With a better understanding of the potential advantages and disadvantages of this procedure, its selective use in the current era can improve and maximize organ allocation in the United States. In this report, we reviewed the current status of domino heart transplantation.

  View details for DOI 10.1111/jocs.13104

  View details for PubMedID 28219115

• TRANSFORM (Multicenter Experience With Rapid Deployment Edwards INTUITY Valve System for Aortic Valve Replacement) US clinical trial: Performance of a rapid deployment aortic valve JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Barnhart, G. R., Accola, K. D., Grossi, E. A., Woo, Y. J., Mumtaz, M. A., Sabik, J. F., Slachman, F. N., Patel, H. J., Borger, M. A., Garrett, H. E., Rodriguez, E., McCarthy, P. M., Ryan, W. H., Duhay, F. G., Mack, M. J., Chitwood, W. R. 2017; 153 (2): 241-?

  Abstract

  The TRANSFORM (Multicenter Experience With Rapid Deployment Edwards INTUITY Valve System for Aortic Valve Replacement) trial (NCT01700439) evaluated the performance of the INTUITY rapid deployment aortic valve replacement (RDAVR) system in patients with severe aortic stenosis.TRANSFORM was a prospective, nonrandomized, multicenter (n = 29), single-arm trial. INTUITY is comprised of a cloth-covered balloon-expandable frame attached to a Carpentier-Edwards PERIMOUNT Magna Ease aortic valve. Primary and effectiveness endpoints were evaluated at 1 year.Between 2012 and 2015, 839 patients underwent RDAVR. Mean age was 73.5 ± 8.3 years. Full sternotomy (FS) was used in 59% and minimally invasive surgical incisions in 41%. Technical success rate was 95%. For isolated RDAVR, mean crossclamp and cardiopulmonary bypass times for FS were 49.3 ± 26.9 minutes and 69.2 ± 34.7 minutes, respectively, and for minimally invasive surgical 63.1 ± 25.4 minutes and 84.6 ± 33.5 minutes, respectively. These times were favorable compared with Society of Thoracic Surgeons database comparators for FS: 76.3 minutes and 104.2 minutes, respectively, and for minimally invasive surgical, 82.9 minutes and 111.4 minutes, respectively (P < .001). At 30 days, all-cause mortality was 0.8%; valve explant, 0.1%; thromboembolism, 3.5%; and major bleeding, 1.3%. In patients with isolated aortic valve replacement, the rate of permanent pacemaker implantation was 11.9%. At 1 year, mean effective orifice area was 1.7 cm2; mean gradient, 10.3 mm Hg; and moderate and severe paravalvular leak, 1.2% and 0.4%, respectively.INTUITY RDAVR performed effectively in this North American trial. It may lead to a relative reduction in aortic crossclamp time and cardiopulmonary bypass time and has excellent hemodynamic performance. Pacemaker implantation rate observed was somewhat greater than European trials and requires further investigation.

  View details for DOI 10.1016/j.jtcvs.2016.09.062

  View details for Web of Science ID 000396894200023

• TRANSFORM (Multicenter Experience With Rapid Deployment Edwards INTUITY Valve System for Aortic Valve Replacement) US clinical trial: Performance of a rapid deployment aortic valve. The Journal of thoracic and cardiovascular surgery Barnhart, G. R., Accola, K. D., Grossi, E. A., Woo, Y. J., Mumtaz, M. A., Sabik, J. F., Slachman, F. N., Patel, H. J., Borger, M. A., Garrett, H. E., Rodriguez, E., McCarthy, P. M., Ryan, W. H., Duhay, F. G., Mack, M. J., Chitwood, W. R. 2017; 153 (2): 241-251.e2

  Abstract

  The TRANSFORM (Multicenter Experience With Rapid Deployment Edwards INTUITY Valve System for Aortic Valve Replacement) trial (NCT01700439) evaluated the performance of the INTUITY rapid deployment aortic valve replacement (RDAVR) system in patients with severe aortic stenosis.TRANSFORM was a prospective, nonrandomized, multicenter (n = 29), single-arm trial. INTUITY is comprised of a cloth-covered balloon-expandable frame attached to a Carpentier-Edwards PERIMOUNT Magna Ease aortic valve. Primary and effectiveness endpoints were evaluated at 1 year.Between 2012 and 2015, 839 patients underwent RDAVR. Mean age was 73.5 ± 8.3 years. Full sternotomy (FS) was used in 59% and minimally invasive surgical incisions in 41%. Technical success rate was 95%. For isolated RDAVR, mean crossclamp and cardiopulmonary bypass times for FS were 49.3 ± 26.9 minutes and 69.2 ± 34.7 minutes, respectively, and for minimally invasive surgical 63.1 ± 25.4 minutes and 84.6 ± 33.5 minutes, respectively. These times were favorable compared with Society of Thoracic Surgeons database comparators for FS: 76.3 minutes and 104.2 minutes, respectively, and for minimally invasive surgical, 82.9 minutes and 111.4 minutes, respectively (P < .001). At 30 days, all-cause mortality was 0.8%; valve explant, 0.1%; thromboembolism, 3.5%; and major bleeding, 1.3%. In patients with isolated aortic valve replacement, the rate of permanent pacemaker implantation was 11.9%. At 1 year, mean effective orifice area was 1.7 cm2; mean gradient, 10.3 mm Hg; and moderate and severe paravalvular leak, 1.2% and 0.4%, respectively.INTUITY RDAVR performed effectively in this North American trial. It may lead to a relative reduction in aortic crossclamp time and cardiopulmonary bypass time and has excellent hemodynamic performance. Pacemaker implantation rate observed was somewhat greater than European trials and requires further investigation.

  View details for DOI 10.1016/j.jtcvs.2016.09.062

  View details for PubMedID 27817951

• Tissue-engineered smooth muscle cell and endothelial progenitor cell bi-level cell sheets prevent progression of cardiac dysfunction, microvascular dysfunction, and interstitial fibrosis in a rodent model of type 1 diabetes-induced cardiomyopathy. Cardiovascular diabetology Kawamura, M. n., Paulsen, M. J., Goldstone, A. B., Shudo, Y. n., Wang, H. n., Steele, A. N., Stapleton, L. M., Edwards, B. B., Eskandari, A. n., Truong, V. N., Jaatinen, K. J., Ingason, A. B., Miyagawa, S. n., Sawa, Y. n., Woo, Y. J. 2017; 16 (1): 142

  Abstract

  Diabetes mellitus is a risk factor for coronary artery disease and diabetic cardiomyopathy, and adversely impacts outcomes following coronary artery bypass grafting. Current treatments focus on macro-revascularization and neglect the microvascular disease typical of diabetes mellitus-induced cardiomyopathy (DMCM). We hypothesized that engineered smooth muscle cell (SMC)-endothelial progenitor cell (EPC) bi-level cell sheets could improve ventricular dysfunction in DMCM.Primary mesenchymal stem cells (MSCs) and EPCs were isolated from the bone marrow of Wistar rats, and MSCs were differentiated into SMCs by culturing on a fibronectin-coated dish. SMCs topped with EPCs were detached from a temperature-responsive culture dish to create an SMC-EPC bi-level cell sheet. A DMCM model was induced by intraperitoneal streptozotocin injection. Four weeks after induction, rats were randomized into 3 groups: control (no DMCM induction), untreated DMCM, and treated DMCM (cell sheet transplant covering the anterior surface of the left ventricle).SMC-EPC cell sheet therapy preserved cardiac function and halted adverse ventricular remodeling, as demonstrated by echocardiography and cardiac magnetic resonance imaging at 8 weeks after DMCM induction. Myocardial contrast echocardiography demonstrated that myocardial perfusion and microvascular function were preserved in the treatment group compared with untreated animals. Histological analysis demonstrated decreased interstitial fibrosis and increased microvascular density in the SMC-EPC cell sheet-treated group.Treatment of DMCM with tissue-engineered SMC-EPC bi-level cell sheets prevented cardiac dysfunction and microvascular disease associated with DMCM. This multi-lineage cellular therapy is a novel, translatable approach to improve microvascular disease and prevent heart failure in diabetic patients.

  View details for PubMedID 29096622

• An innovative biologic system for photon-powered myocardium in the ischemic heart. Science advances Cohen, J. E., Goldstone, A. B., Paulsen, M. J., Shudo, Y. n., Steele, A. N., Edwards, B. B., Patel, J. B., MacArthur, J. W., Hopkins, M. S., Burnett, C. E., Jaatinen, K. J., Thakore, A. D., Farry, J. M., Truong, V. N., Bourdillon, A. T., Stapleton, L. M., Eskandari, A. n., Fairman, A. S., Hiesinger, W. n., Esipova, T. V., Patrick, W. L., Ji, K. n., Shizuru, J. A., Woo, Y. J. 2017; 3 (6): e1603078

  Abstract

  Coronary artery disease is one of the most common causes of death and disability, afflicting more than 15 million Americans. Although pharmacological advances and revascularization techniques have decreased mortality, many survivors will eventually succumb to heart failure secondary to the residual microvascular perfusion deficit that remains after revascularization. We present a novel system that rescues the myocardium from acute ischemia, using photosynthesis through intramyocardial delivery of the cyanobacterium Synechococcus elongatus. By using light rather than blood flow as a source of energy, photosynthetic therapy increases tissue oxygenation, maintains myocardial metabolism, and yields durable improvements in cardiac function during and after induction of ischemia. By circumventing blood flow entirely to provide tissue with oxygen and nutrients, this system has the potential to create a paradigm shift in the way ischemic heart disease is treated.

  View details for PubMedID 28630913

• A modified explant technique of HeartWare ventricular assist device for bridge to recovery. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Shudo, Y. n., Choi, C. W., Woo, Y. J., Ha, R. V. 2017

  Abstract

  The HeartWare left ventricular assist device is a miniaturized, continuous centrifugal-flow pump. The implantation technique is well described and relatively standardized across different institutions. However, there still exists a technical concern about handling the inflow cannula at the time of device explant. Specifically, the removal of the sewing ring and plicating the apical defect en masse may distort the geometry of the left ventricle and impart myocardial dysfunction. Additionally, a prefabricated repair mechanism by the manufacturer is not readily available in all countries (i.e. USA). Here, we describe a technique to address the apical core defect, using a tailor-made plug and leaving the sewing ring in situ, at the time of the HeartWare left ventricular assist device explant.

  View details for PubMedID 28950296

• Resection of a Giant Cardiac Lymphovenous Malformation Involving the Right Atrioventricular Groove. The Annals of thoracic surgery Chiu, P. n., Edmonson, A. n., Brewer, Z. E., Woo, Y. J. 2017; 104 (3): e257–e259

  Abstract

  Lymphovenous malformations of the heart are rare, and optimal management is uncertain. We present a case of a 39-year-old gentleman with a giant symptomatic lymphovenous malformation involving the right atrium, ventricle, and coronary artery. Radical resection was performed with replacement of the tricuspid valve and bovine pericardial reconstruction of the atrium and ventricle. Additional coronary artery bypass grafting was performed to the acute marginal and distal right coronary artery. Radical resection for this benign process is feasible and may be considered given the possibility of recurrence seen with lymphatic malformations of other parts of the body.

  View details for PubMedID 28838522

• Layered smooth muscle cell-endothelial progenitor cell sheets derived from the bone marrow augment postinfarction ventricular function. The Journal of thoracic and cardiovascular surgery Shudo, Y. n., Goldstone, A. B., Cohen, J. E., Patel, J. B., Hopkins, M. S., Steele, A. N., Edwards, B. B., Kawamura, M. n., Miyagawa, S. n., Sawa, Y. n., Woo, Y. J. 2017; 154 (3): 955–63

  Abstract

  The angiogenic potential of endothelial progenitor cells (EPCs) may be limited by the absence of their natural biologic foundation, namely smooth muscle pericytes. We hypothesized that joint delivery of EPCs and smooth muscle cells (SMCs) in a novel, totally bone marrow-derived cell sheet will mimic the native architecture of a mature blood vessel and act as an angiogenic construct to limit post infarction ventricular remodeling.Primary EPCs and mesenchymal stem cells were isolated from bone marrow of Wistar rats. Mesenchymal stem cells were transdifferentiated into SMCs by culture on fibronectin-coated culture dishes. Confluent SMCs topped with confluent EPCs were detached from an Upcell dish to create a SMC-EPC bi-level cell sheet. A rodent model of ischemic cardiomyopathy was then created by ligating the left anterior descending artery. Rats were randomized into 3 groups: cell sheet transplantation (n = 9), no treatment (n = 12), or sham surgery control (n = 7).Four weeks postinfarction, mature vessel density tended to increase in cell sheet-treated animals compared with controls. Cell sheet therapy significantly attenuated the extent of cardiac fibrosis compared with that of the untreated group (untreated vs cell sheet, 198 degrees [interquartile range (IQR), 151-246 degrees] vs 103 degrees [IQR, 92-113 degrees], P = .04). Furthermore, EPC-SMC cell sheet transplantation attenuated myocardial dysfunction, as evidenced by an increase in left ventricular ejection fraction (untreated vs cell sheet vs sham, 33.5% [IQR, 27.8%-35.7%] vs 45.9% [IQR, 43.6%-48.4%] vs 59.3% [IQR, 58.8%-63.5%], P = .001) and decreases in left ventricular dimensions.The bone marrow-derived, spatially arranged SMC-EPC bi-level cell sheet is a novel, multilineage cellular therapy obtained from a translationally practical source. Interactions between SMCs and EPCs augment mature neovascularization, limit adverse remodeling, and improve ventricular function after myocardial infarction.

  View details for PubMedID 28651946

• Autograft Valve-Sparing Root Replacement for Late Ross Failure during Quadruple-Valve Surgery ANNALS OF THORACIC AND CARDIOVASCULAR SURGERY Goldstone, A. B., Jensen, C. W., Bilbao, M., Woo, Y. 2017; 23 (6): 313–15

  Abstract

  Approximately 25% of patients require reoperation within 15 yrs of a Ross procedure. Increasing experience with valve-sparing root replacement (VSRR) has led some surgeons to spare the autograft valve. Here, we demonstrate that all valves can be surgically repaired or replaced safely during autograft VSRR. As more patients are considered for this operation, coexistent mitral, tricuspid, and pulmonic valve dysfunction should not preclude salvage of the autograft valve, nor should autograft leaflet prolapse.

  View details for PubMedID 29046487

• Limited root repair in acute type A aortic dissection is safe but results in increased risk of reoperation. The Journal of thoracic and cardiovascular surgery Chiu, P. n., Trojan, J. n., Tsou, S. n., Goldstone, A. B., Woo, Y. J., Fischbein, M. P. 2017

  Abstract

  Management of the aortic root is a challenge for surgeons treating acute type A aortic dissection.We performed a retrospective review of the acute type A aortic dissection experience at Stanford Hospital between 2005 and 2015 and identified patients who underwent either limited root repair or aortic root replacement. Differences in baseline characteristics were balanced with inverse probability weighting to estimate the average treatment effect on the controls. Weighted logistic regression was used to evaluate in-hospital mortality. Weighted Cox proportional hazards regression was used to evaluate differences in the hazard for mid-term death. Reoperation was evaluated with death as a competing risk with the Fine-Gray subdistribution hazard.After we excluded patients managed either nonoperatively or with definitive endovascular repair, there were 293 patients without connective tissue disease who underwent either limited root repair or aortic root replacement. There was no difference in weighted perioperative mortality, odds ratio 0.89 (95% confidence interval [CI], 0.44-1.76, P = .7), and there was no difference in weighted survival, hazard ratio 1.12 (95% CI, 0.54-2.31, P = .8). Risk of reoperation was greater in limited root repair (11.8%, 95% CI, 0.0%-23.8%) than for root replacement (0%), P < .001.Limited root repair was associated with increased risk of late reoperation after repair of acute type A aortic dissection. Surgeons with adequate experience may consider aortic root replacement in well-selected patients. However, given good outcomes after limited root repair, surgeons should not feel compelled to perform this more-complex operation.

  View details for PubMedID 29042100

• Mechanical or Biologic Prostheses for Aortic-Valve and Mitral-Valve Replacement. The New England journal of medicine Goldstone, A. B., Chiu, P. n., Baiocchi, M. n., Lingala, B. n., Patrick, W. L., Fischbein, M. P., Woo, Y. J. 2017; 377 (19): 1847–57

  Abstract

  In patients undergoing aortic-valve or mitral-valve replacement, either a mechanical or biologic prosthesis is used. Biologic prostheses have been increasingly favored despite limited evidence supporting this practice.We compared long-term mortality and rates of reoperation, stroke, and bleeding between inverse-probability-weighted cohorts of patients who underwent primary aortic-valve replacement or mitral-valve replacement with a mechanical or biologic prosthesis in California in the period from 1996 through 2013. Patients were stratified into different age groups on the basis of valve position (aortic vs. mitral valve).From 1996 through 2013, the use of biologic prostheses increased substantially for aortic-valve and mitral-valve replacement, from 11.5% to 51.6% for aortic-valve replacement and from 16.8% to 53.7% for mitral-valve replacement. Among patients who underwent aortic-valve replacement, receipt of a biologic prosthesis was associated with significantly higher 15-year mortality than receipt of a mechanical prosthesis among patients 45 to 54 years of age (30.6% vs. 26.4% at 15 years; hazard ratio, 1.23; 95% confidence interval [CI], 1.02 to 1.48; P=0.03) but not among patients 55 to 64 years of age. Among patients who underwent mitral-valve replacement, receipt of a biologic prosthesis was associated with significantly higher mortality than receipt of a mechanical prosthesis among patients 40 to 49 years of age (44.1% vs. 27.1%; hazard ratio, 1.88; 95% CI, 1.35 to 2.63; P<0.001) and among those 50 to 69 years of age (50.0% vs. 45.3%; hazard ratio, 1.16; 95% CI, 1.04 to 1.30; P=0.01). The incidence of reoperation was significantly higher among recipients of a biologic prosthesis than among recipients of a mechanical prosthesis. Patients who received mechanical valves had a higher cumulative incidence of bleeding and, in some age groups, stroke than did recipients of a biologic prosthesis.The long-term mortality benefit that was associated with a mechanical prosthesis, as compared with a biologic prosthesis, persisted until 70 years of age among patients undergoing mitral-valve replacement and until 55 years of age among those undergoing aortic-valve replacement. (Funded by the National Institutes of Health and the Agency for Healthcare Research and Quality.).

  View details for PubMedID 29117490

• Percutaneous, minimally invasive approach to implantable left ventricular assist device deactivation. The Journal of thoracic and cardiovascular surgery Kidambi, S. n., Shudo, Y. n., Dake, M. D., Woo, Y. J., Ha, R. V. 2017

  View details for PubMedID 29102456

• Alternative Progenitor Cells Compensate to Rebuild the Coronary Vasculature in Elabela- and Apj-Deficient Hearts. Developmental cell Sharma, B. n., Ho, L. n., Ford, G. H., Chen, H. I., Goldstone, A. B., Woo, Y. J., Quertermous, T. n., Reversade, B. n., Red-Horse, K. n. 2017

  Abstract

  Organogenesis during embryonic development occurs through the differentiation of progenitor cells. This process is extraordinarily accurate, but the mechanisms ensuring high fidelity are poorly understood. Coronary vessels of the mouse heart derive from at least two progenitor pools, the sinus venosus and endocardium. We find that the ELABELA (ELA)-APJ signaling axis is only required for sinus venosus-derived progenitors. Because they do not depend on ELA-APJ, endocardial progenitors are able to expand and compensate for faulty sinus venosus development in Apj mutants, leading to normal adult heart function. An upregulation of endocardial SOX17 accompanied compensation in Apj mutants, which was also seen in Ccbe1 knockouts, indicating that the endocardium is activated in multiple cases where sinus venosus angiogenesis is stunted. Our data demonstrate that by diversifying their responsivity to growth cues, distinct coronary progenitor pools are able to compensate for each other during coronary development, thereby providing robustness to organ development.

  View details for PubMedID 28890073

• Operative technique and pitfalls in donor heart procurement. Asian cardiovascular & thoracic annals Shudo, Y., Hiesinger, W., Oyer, P. E., Woo, Y. J. 2017; 25 (1): 80-82

  Abstract

  We describe a simple and reproducible donor heart procurement technique in sequential steps. A detailed understanding of procurement and organ preservation techniques should be an essential part of a heart transplant training program.

  View details for DOI 10.1177/0218492316678716

  View details for PubMedID 28074702

• A modified technique for orthotopic heart transplantation to minimize warm ischaemic time. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Shudo, Y. n., Wang, H. n., Woo, Y. J. 2017

  Abstract

  Prolonged allograft ischaemic time in heart transplantation adversely impacts the performance of the donor heart in the immediate postoperative period and ultimately results in decreased post-transplant survival. Therefore, optimal surgical technique for heart transplantation should aim to minimize allograft ischaemic time. Here, we report a case of successful orthotopic heart transplantation using a modified technique to reduce allograft ischaemic time and warm ischaemic time.

  View details for PubMedID 29186382

• Successful use of donor lungs after repairing severely injured pulmonary vein of donor lungs. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Shudo, Y. n., Miller, S. L., Boyd, J. H., Woo, Y. J. 2017

  View details for PubMedID 29186381

• Minimally invasive mitral valve repair in situs inversus totalis JOURNAL OF CARDIAC SURGERY Goldstone, A. B., Patrick, W. L., Bilbao, M. S., Woo, Y. J. 2016; 31 (12): 718-720

  Abstract

  We describe the surgical technique for mitral and tricuspid valve repair using a minimally invasive approach in a patient with situs inversus totalis.

  View details for DOI 10.1111/jocs.12859

  View details for PubMedID 27862312

• A modified implantation technique of left ventricular assist device: optimal outflow tract positioning. International journal of cardiology Shudo, Y., Choi, C. W., Woo, Y. J., Ha, R. V. 2016; 223: 776-778

  View details for DOI 10.1016/j.ijcard.2016.08.209

  View details for PubMedID 27573606

• Is minimally invasive thoracoscopic surgery the new benchmark for treating mitral valve disease? Annals of cardiothoracic surgery Goldstone, A. B., Woo, Y. J. 2016; 5 (6): 567-572

  Abstract

  The treatment of mitral valve disease remains dynamic; surgeons and patients must now choose between many different surgical options when addressing mitral regurgitation and mitral stenosis. Notably, advances in imaging and surgical instrumentation allow surgeons to perform less invasive mitral valve surgery that spares the sternum. With favorable long-term data now emerging, we compare the benefits and risks of thoracoscopic mitral valve surgery with that through conventional sternotomy or surgery that is robot-assisted.

  View details for PubMedID 27942489

• Regulating Stem Cell Secretome Using Injectable Hydrogels with In Situ Network Formation. Advanced healthcare materials Cai, L., Dewi, R. E., Goldstone, A. B., Cohen, J. E., Steele, A. N., Woo, Y. J., Heilshorn, S. C. 2016

  Abstract

  A family of shear-thinning hydrogels for injectable encapsulation and long-term delivery (SHIELD) has been designed and synthesized with controlled in situ stiffening properties to regulate the stem cell secretome. The authors demonstrate that SHIELD with an intermediate stiffness (200-400 Pa) could significantly promote the angiogenic potential of human adipose-derived stem cells.

  View details for DOI 10.1002/adhm.201600497

  View details for PubMedID 27709809

• Biochemically engineered stromal cell-derived factor 1-alpha analog increases perfusion in the ischemic hind limb. Journal of vascular surgery Edwards, B. B., Fairman, A. S., Cohen, J. E., Macarthur, J. W., Goldstone, A. B., Woo, J. B., Hiesinger, W., Woo, Y. J. 2016; 64 (4): 1093-1099

  Abstract

  Despite promising therapeutic innovation over the last decade, peripheral arterial disease remains a prevalent morbidity, as many patients are still challenged with peripheral ischemia. We hypothesized that delivery of engineered stromal cell-derived factor 1-alpha (ESA) in an ischemic hind limb will yield significant improvement in perfusion.Male rats underwent right femoral artery ligation, and animals were randomized to receive a 100 μL injection of saline (n = 9) or 6 μg/kg dosage of equal volume of ESA (n = 12) into the ipsilateral quadriceps muscle. Both groups of animals were also given an intraperitoneal injection of 40 μg/kg of granulocyte macrophage colony-stimulating factor (GMCSF). Perfusion was quantified using a laser Doppler imaging device preoperatively, and on postoperative days 0, 7, and 14. Immunohistochemistry was performed to quantify angiogenesis on day 14, and an mRNA profile was evaluated for angiogenic and inflammatory markers.Compared with the saline/GMCSF group at day 14, the ESA/GMCSF-injected animals had greater reperfusion ratios (Saline/GMCSF, 0.600 ± 0.140 vs ESA/GMCSF, 0.900 ± 0.181; group effect P = .006; time effect P < .0001; group×time effect P < .0001), elevated capillary density (10×; Saline/GMCSF, 6.40 ± 2.01 vs ESA/GMCSF, 18.55 ± 5.30; P < .01), and increased mRNA levels of vascular endothelial growth factor-A (Saline/GMCSF [n = 6], 0.298 ± 0.205 vs ESA/GMCSF [n = 8], 0.456 ± 0.139; P = .03).Delivery of ESA significantly improves perfusion in a rat model of peripheral arterial disease via improved neovasculogenesis, a finding which may prove beneficial in the treatment strategy for this debilitating disease.

  View details for DOI 10.1016/j.jvs.2015.06.140

  View details for PubMedID 26372192

• The value of preoperative 3-dimensional over 2-dimensional valve analysis in predicting recurrent ischemic mitral regurgitation after mitral annuloplasty. journal of thoracic and cardiovascular surgery Wijdh-den Hamer, I. J., Bouma, W., Lai, E. K., Levack, M. M., Shang, E. K., Pouch, A. M., Eperjesi, T. J., Plappert, T. J., Yushkevich, P. A., Hung, J., Mariani, M. A., Khabbaz, K. R., Gleason, T. G., Mahmood, F., Acker, M. A., Woo, Y. J., Cheung, A. T., Gillespie, M. J., Jackson, B. M., Gorman, J. H., Gorman, R. C. 2016; 152 (3): 847-859

  Abstract

  Repair for ischemic mitral regurgitation with undersized annuloplasty is characterized by high recurrence rates. We sought to determine the value of pre-repair 3-dimensional echocardiography over 2-dimensional echocardiography in predicting recurrence at 6 months.Intraoperative transesophageal 2-dimensional echocardiography and 3-dimensional echocardiography were performed in 50 patients undergoing undersized annuloplasty for ischemic mitral regurgitation. Two-dimensional echocardiography annular diameter and tethering parameters were measured in the apical 2- and 4-chamber views. A customized protocol was used to assess 3-dimensional annular geometry and regional leaflet tethering. Recurrence (grade ≥2) was assessed with 2-dimensional transthoracic echocardiography at 6 months.Preoperative 2- and 3-dimensional annular geometry were similar in all patients with ischemic mitral regurgitation. Preoperative 2- and 3-dimensional leaflet tethering were significantly higher in patients with recurrence (n = 13) when compared with patients without recurrence (n = 37). Multivariate logistic regression revealed preoperative 2-dimensional echocardiography posterior tethering angle as an independent predictor of recurrence with an optimal cutoff value of 32.0° (area under the curve, 0.81; 95% confidence interval, 0.68-0.95; P = .002) and preoperative 3-dimensional echocardiography P3 tethering angle as an independent predictor of recurrence with an optimal cutoff value of 29.9° (area under the curve, 0.92; 95% confidence interval, 0.84-1.00; P < .001). The predictive value of the 3-dimensional geometric multivariate model can be augmented by adding basal aneurysm/dyskinesis (area under the curve, 0.94; 95% confidence interval, 0.87-1.00; P < .001).Preoperative 3-dimensional echocardiography P3 tethering angle is a stronger predictor of ischemic mitral regurgitation recurrence after annuloplasty than preoperative 2-dimensional echocardiography posterior tethering angle, which is highly influenced by viewing plane. In patients with a preoperative P3 tethering angle of 29.9° or larger (especially when combined with basal aneurysm/dyskinesis), chordal-sparing valve replacement should be strongly considered.

  View details for DOI 10.1016/j.jtcvs.2016.06.040

  View details for PubMedID 27530639

• Cell transplantation in heart failure: where do we stand in 2016? EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY MacArthur, J. W., Goldstone, A. B., Cohen, J. E., Hiesinger, W., Woo, Y. 2016; 50 (3): 396–99

  View details for PubMedID 27587719

• Modeling the Myxomatous Mitral Valve With Three-Dimensional Echocardiography. Annals of thoracic surgery Pouch, A. M., Jackson, B. M., Lai, E., Takebe, M., Tian, S., Cheung, A. T., Woo, Y. J., Patel, P. A., Wang, H., Yushkevich, P. A., Gorman, R. C., Gorman, J. H. 2016; 102 (3): 703-710

  Abstract

  Degenerative mitral valve disease is associated with variable and complex defects in valve morphology. Three-dimensional echocardiography (3DE) has shown promise in aiding preoperative planning for patients with this disease but to date has not been as transformative as initially predicted. The clinical usefulness of 3DE has been limited by the laborious methods currently required to extract quantitative data from the images.To maximize the utility of 3DE for preoperative valve evaluation, this work describes an automated 3DE image analysis method for generating models of the mitral valve that are well suited for both qualitative and quantitative assessment. The method is unique in that it captures detailed alterations in mitral leaflet and annular morphology and produces image-derived models with locally varying leaflet thickness. The method is evaluated on midsystolic transesophageal 3DE images acquired from 22 subjects with myxomatous degeneration and from 22 subjects with normal mitral valve morphology.Relative to manual image analysis, the automated method accurately represents both normal and complex leaflet geometries with a mean boundary displacement error on the order of one image voxel. A detailed quantitative analysis of the valves is presented and reveals statistically significant differences between normal and myxomatous valves with respect to numerous aspects of annular and leaflet geometry.This work demonstrates a successful methodology for the relatively rapid quantitative description of the complex mitral valve distortions associated with myxomatous degeneration. The methodology has the potential to significantly improve surgical planning for patients with complex mitral valve disease.

  View details for DOI 10.1016/j.athoracsur.2016.05.087

  View details for PubMedID 27492671

• Novel MRI Contrast Agent from Magnetotactic Bacteria Enables In Vivo Tracking of iPSC-derived Cardiomyocytes SCIENTIFIC REPORTS Mahmoudi, M., Tachibana, A., Goldstone, A. B., Woo, Y. J., Chakraborty, P., Lee, K. R., Foote, C. S., Piecewicz, S., Barrozo, J. C., Wakeel, A., Rice, B. W., Bell, C. B., Yang, P. C. 2016; 6

  Abstract

  Therapeutic delivery of human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs) represents a novel clinical approach to regenerate the injured myocardium. However, methods for robust and accurate in vivo monitoring of the iCMs are still lacking. Although superparamagnetic iron oxide nanoparticles (SPIOs) are recognized as a promising tool for in vivo tracking of stem cells using magnetic resonance imaging (MRI), their signal persists in the heart even weeks after the disappearance of the injected cells. This limitation highlights the inability of SPIOs to distinguish stem cell viability. In order to overcome this shortcoming, we demonstrate the use of a living contrast agent, magneto-endosymbionts (MEs) derived from magnetotactic bacteria for the labeling of iCMs. The ME-labeled iCMs were injected into the infarcted area of murine heart and probed by MRI and bioluminescence imaging (BLI). Our findings demonstrate that the MEs are robust and effective biological contrast agents to track iCMs in an in vivo murine model. We show that the MEs clear within one week of cell death whereas the SPIOs remain over 2 weeks after cell death. These findings will accelerate the clinical translation of in vivo MRI monitoring of transplanted stem cell at high spatial resolution and sensitivity.

  View details for DOI 10.1038/srep26960

  View details for Web of Science ID 000377072000001

  View details for PubMedCentralID PMC4893600

• Influence of durable mechanical circulatory support and allosensitization on mortality after heart transplantation. journal of heart and lung transplantation Chiu, P., Schaffer, J. M., Oyer, P. E., Pham, M., Banerjee, D., Joseph Woo, Y., Ha, R. 2016; 35 (6): 731-742

  Abstract

  Allosensitization has been shown to negatively affect post-heart transplant (HTx) survival even with a negative crossmatch. Whether allosensitization related to mechanical circulatory support (MCS) is associated with worse post-HTx survival remains controversial.Adult HTx recipients listed in the United Network for Organ Sharing database (July 2006-December 2012) were identified. Multivariate Cox regression assessed the effect of allosensitization on survival. Propensity matching was performed to compare patients who were and were not allosensitized. Kaplan-Meier survival analysis compared matched and unmatched patients in the MCS and medically managed cohorts.We identified 11,840 HTx recipients, of whom 4,167 had MCS. MCS was associated with allosensitization in multivariate logistic regression. Each different MCS device was associated with worse post-HTx survival in multivariate Cox regression. Allosensitization did not predict post-HTx mortality in MCS patients (hazard ratio, 1.07; 95% confidence interval, 0.89-1.28; p = 0.48. Among patients without MCS, allosensitization was associated with post-HTx mortality (hazard ratio, 1.19; 95% confidence interval, 1.03-1.39; p = 0.02). Kaplan-Meier analysis revealed equivalent survival in unmatched and matched cohorts when MCS patients who were allosensitized were compared with non-allosensitized MCS patients. Among non-MCS patients, allosensitization was associated with worse survival in unmatched and matched analysis.MCS was associated with allosensitization. For MCS patients, allosensitization did not independently predict worse post-HTx outcome. Among non-MCS patients, allosensitization was associated with worse post-HTx survival. Allosensitization appears to be a heterogeneous process influenced by presence of MCS.

  View details for DOI 10.1016/j.healun.2015.12.023

  View details for PubMedID 26856669

• Treatment and Prognosis of Pulmonary Hypertension in the Left Ventricular Assist Device Patient. Current heart failure reports Jensen, C. W., Goldstone, A. B., Woo, Y. J. 2016; 13 (3): 140-150

  Abstract

  This review will discuss the medical management of pulmonary hypertension in patients with left ventricular assist devices. Although much has been written on the management of primary pulmonary hypertension, also called pulmonary arterial hypertension, this review will instead focus on the treatment of pulmonary hypertension secondary to left heart disease. The relevant pharmacotherapy can be divided into medications for treating heart failure, such as diuretics and β-blockers, and medications for treating pulmonary hypertension. We also discuss important preoperative considerations in patients with pulmonary hypertension; the relationships between left ventricular assist devices, pulmonary hemodynamics, and right heart failure; as well as optimal perioperative and long-term postoperative medical management of pulmonary hypertension.

  View details for DOI 10.1007/s11897-016-0288-6

  View details for PubMedID 27241336

• Influence of durable mechanical circulatory support and allosensitization on mortality after heart transplantation JOURNAL OF HEART AND LUNG TRANSPLANTATION Chiu, P., Schaffer, J. M., Oyer, P. E., Pham, M., Banerjee, D., Woo, Y. J., Ha, R. 2016; 35 (6): 731-742

  Abstract

  Allosensitization has been shown to negatively affect post-heart transplant (HTx) survival even with a negative crossmatch. Whether allosensitization related to mechanical circulatory support (MCS) is associated with worse post-HTx survival remains controversial.Adult HTx recipients listed in the United Network for Organ Sharing database (July 2006-December 2012) were identified. Multivariate Cox regression assessed the effect of allosensitization on survival. Propensity matching was performed to compare patients who were and were not allosensitized. Kaplan-Meier survival analysis compared matched and unmatched patients in the MCS and medically managed cohorts.We identified 11,840 HTx recipients, of whom 4,167 had MCS. MCS was associated with allosensitization in multivariate logistic regression. Each different MCS device was associated with worse post-HTx survival in multivariate Cox regression. Allosensitization did not predict post-HTx mortality in MCS patients (hazard ratio, 1.07; 95% confidence interval, 0.89-1.28; p = 0.48. Among patients without MCS, allosensitization was associated with post-HTx mortality (hazard ratio, 1.19; 95% confidence interval, 1.03-1.39; p = 0.02). Kaplan-Meier analysis revealed equivalent survival in unmatched and matched cohorts when MCS patients who were allosensitized were compared with non-allosensitized MCS patients. Among non-MCS patients, allosensitization was associated with worse survival in unmatched and matched analysis.MCS was associated with allosensitization. For MCS patients, allosensitization did not independently predict worse post-HTx outcome. Among non-MCS patients, allosensitization was associated with worse post-HTx survival. Allosensitization appears to be a heterogeneous process influenced by presence of MCS.

  View details for DOI 10.1016/j.healun.2015.12.023

  View details for Web of Science ID 000379367700006

• Prosthetic valve choice in middle-aged patients: guidelines and other guiding principles EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Woo, Y., Greene, C. L. 2016; 49 (5): 1468–69

  View details for PubMedID 26758044

• 2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention and the 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Levine, G. N., Bates, E. R., Blankenship, J. C., Bailey, S. R., Bittl, J. A., Cercek, B., Chambers, C. E., Ellis, S. G., Guyton, R. A., Hollenberg, S. M., Khot, U. N., Lange, R. A., Mauri, L., Mehran, R., Moussa, I. D., Mukherjee, D., Ting, H. H., O'Gara, P. T., Kushner, F. G., Ascheim, D. D., Brindis, R. G., Casey, D. E., Chung, M. K., de Lemos, J. A., Diercks, D. B., Fang, J. C., Franklin, B. A., Granger, C. B., Krumholz, H. M., Linderbaum, J. A., Morrow, D. A., Newby, L. K., Ornato, J. P., Ou, N., Radford, M. J., Tamis-Holland, J. E., Tommaso, C. L., Tracy, C. M., Woo, Y. J., Zhao, D. X. 2016; 87 (6): 1001-1019

  View details for DOI 10.1002/ccd.26325

  View details for Web of Science ID 000375896800007

• TARGETED SUPERPARAMAGNETIC IRON OXIDE NANOPARTICLES FACILITATE ENGRAFTMENT OF THE IPSC-DERIVED CARDIOMYOCYTES INTO THE INJURED MURINE MYOCARDIUM Mahmoudi, M., Tachibana, A., Cohen, J., Goldstone, A., Edwards, B., Rulifson, E., Woo, Y., Yang, P. ELSEVIER SCIENCE INC. 2016: 2126

  View details for DOI 10.1016/S0735-1097(16)32127-1

  View details for Web of Science ID 000375188702972

• EXOSOMES FROM THE HUMAN PLACENTA-DERIVED AMNIOTIC MESENCHYMAL STEM CELLS RESTORE THE INJURED MURINE MYOCARDIUM Santoso, M., Mahmoudi, M., Tachibana, A., Sierra, R. G., Matsui, T., Goldstone, A., Edwards, B., Wakatsuki, S., Woo, J., Yang, P. ELSEVIER SCIENCE INC. 2016: 1393

  View details for DOI 10.1016/S0735-1097(16)31394-8

  View details for Web of Science ID 000375188702239

• Isolation and trans-differentiation of mesenchymal stromal cells into smooth muscle cells: Utility and applicability for cell-sheet engineering. Cytotherapy Shudo, Y., Cohen, J. E., Goldstone, A. B., MacArthur, J. W., Patel, J., Edwards, B. B., Hopkins, M. S., Steele, A. N., Joubert, L., Miyagawa, S., Sawa, Y., Woo, Y. J. 2016; 18 (4): 510-517

  Abstract

  Bone marrow (BM)-derived mesenchymal stromal cells (MSCs) have shown potential to differentiate into various cell types, including smooth muscle cells (SMCs). The extracellular matrix (ECM) represents an appealing and readily available source of SMCs for use in tissue engineering. In this study, we hypothesized that the ECM could be used to induce MSC differentiation to SMCs for engineered cell-sheet construction.Primary MSCs were isolated from the BM of Wistar rats, transferred and cultured on dishes coated with 3 different types of ECM: collagen type IV (Col IV), fibronectin (FN), and laminin (LM). Primary MSCs were also included as a control. The proportions of SMC (a smooth muscle actin [aSMA] and SM22a) and MSC markers were examined with flow cytometry and Western blotting, and cell proliferation rates were also quantified.Both FN and LM groups were able to induce differentiation of MSCs toward smooth muscle-like cell types, as evidenced by an increase in the proportion of SMC markers (aSMA; Col IV 42.3 ± 6.9%, FN 65.1 ± 6.5%, LM 59.3 ± 7.0%, Control 39.9 ± 3.1%; P = 0.02, SM22; Col IV 56.0 ± 7.7%, FN 74.2 ± 6.7%, LM 60.4 ± 8.7%, Control 44.9 ± 3.6%) and a decrease in that of MSC markers (CD105: Col IV 64.0 ± 5.2%, FN 57.6 ± 4.0%, LM 60.3 ± 7.0%, Control 85.3 ± 4.2%; P = 0.03). The LM group showed a decrease in overall cell proliferation, whereas FN and Col IV groups remained similar to control MSCs (Col IV, 9.0 ± 2.3%; FN, 9.8 ± 2.5%; LM, 4.3 ± 1.3%; Control, 9.8 ± 2.8%).Our findings indicate that ECM selection can guide differentiation of MSCs into the SMC lineage. Fibronectin preserved cellular proliferative capacity while yielding the highest proportion of differentiated SMCs, suggesting that FN-coated materials may be facilitate smooth muscle tissue engineering.

  View details for DOI 10.1016/j.jcyt.2016.01.012

  View details for PubMedID 26971679

• 2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention and the 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction. Journal of the American College of Cardiology Levine, G. N., Bates, E. R., Blankenship, J. C., Bailey, S. R., Bittl, J. A., Cercek, B., Chambers, C. E., Ellis, S. G., Guyton, R. A., Hollenberg, S. M., Khot, U. N., Lange, R. A., Mauri, L., Mehran, R., Moussa, I. D., Mukherjee, D., Ting, H. H., O'Gara, P. T., Kushner, F. G., Ascheim, D. D., Brindis, R. G., Casey, D. E., Chung, M. K., de Lemos, J. A., Diercks, D. B., Fang, J. C., Franklin, B. A., Granger, C. B., Krumholz, H. M., Linderbaum, J. A., Morrow, D. A., Newby, L. K., Ornato, J. P., Ou, N., Radford, M. J., Tamis-Holland, J. E., Tommaso, C. L., Tracy, C. M., Woo, Y. J., Zhao, D. X. 2016; 67 (10): 1235-1250

  View details for DOI 10.1016/j.jacc.2015.10.005

  View details for PubMedID 26498666

• 2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention and the 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation Levine, G. N., Bates, E. R., Blankenship, J. C., Bailey, S. R., Bittl, J. A., Cercek, B., Chambers, C. E., Ellis, S. G., Guyton, R. A., Hollenberg, S. M., Khot, U. N., Lange, R. A., Mauri, L., Mehran, R., Moussa, I. D., Mukherjee, D., Ting, H. H., O'Gara, P. T., Kushner, F. G., Ascheim, D. D., Brindis, R. G., Casey, D. E., Chung, M. K., de Lemos, J. A., Diercks, D. B., Fang, J. C., Franklin, B. A., Granger, C. B., Krumholz, H. M., Linderbaum, J. A., Morrow, D. A., Newby, L. K., Ornato, J. P., Ou, N., Radford, M. J., Tamis-Holland, J. E., Tommaso, C. L., Tracy, C. M., Woo, Y. J., Zhao, D. X. 2016; 133 (11): 1135-1147

  View details for DOI 10.1161/CIR.0000000000000336

  View details for PubMedID 26490017

• Stem cell-based therapies to promote angiogenesis in ischemic cardiovascular disease AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Hou, L., Kim, J. J., Woo, Y. J., Huang, N. F. 2016; 310 (4): H455-H465

  Abstract

  Stem cell therapy is a promising approach for treatment of tissue ischemia associated with myocardial infarction and peripheral arterial disease. Stem and progenitor cells derived from bone marrow or from pluripotent stem cells have shown therapeutic benefit in boosting angiogenesis as well as restoring tissue function. Notably, adult stem and progenitor cells including mononuclear cells, endothelial progenitor cells, and mesenchymal stem cells have progressed into clinical trials and have shown positive benefits. In this review, we overview the major classes of stem and progenitor cells, including pluripotent stem cells, and summarize the state-of-the-art in applying these cell types for treating myocardial infarction and peripheral arterial disease.

  View details for DOI 10.1152/ajpheart.00726.2015

  View details for PubMedID 26683902

• Preoperative Three-Dimensional Valve Analysis Predicts Recurrent Ischemic Mitral Regurgitation After Mitral Annuloplasty ANNALS OF THORACIC SURGERY Bouma, W., Lai, E. K., Levack, M. M., Shang, E. K., Pouch, A. M., Eperjesi, T. J., Plappert, T. J., Yushkevich, P. A., Mariani, M. A., Khabbaz, K. R., Gleason, T. G., Mahmood, F., Acker, M. A., Woo, Y. J., Cheung, A. T., Jackson, B. M., Gorman, J. H., Gorman, R. C. 2016; 101 (2): 567-575

  Abstract

  Valve repair for ischemic mitral regurgitation (IMR) with undersized annuloplasty rings is characterized by high IMR recurrence rates. Patient-specific preoperative imaging-based risk stratification for recurrent IMR would optimize results. We sought to determine if prerepair three-dimensional (3D) echocardiography combined with a novel valve-modeling algorithm would be predictive of IMR recurrence 6 months after repair.Intraoperative transesophageal real-time 3D echocardiography was performed in 50 patients undergoing undersized ring annuloplasty for IMR and in 21 patients with normal mitral valves. A customized image analysis protocol was used to assess 3D annular geometry and regional leaflet tethering. IMR recurrence (≥ grade 2) was assessed with two-dimensional transthoracic echocardiography 6 months after repair.Preoperative annular geometry was similar in all IMR patients, and preoperative leaflet tethering was significantly higher in patients with recurrent IMR (n=13) than in patients in whom IMR did not recur (n=37) (tethering index: 3.91 ± 1.01 vs 2.90 ± 1.17, p = 0.008; tethering angles of A3: 23.5° ± 8.9° vs 14.4° ± 11.4°, p = 0.012; P2: 44.4° ± 8.8° vs 28.2° ± 17.0°, p = 0.002; and P3: 35.2° ± 6.0° vs. 18.6° ± 12.7°, p < 0.001). Multivariate logistic regression analysis revealed the preoperative P3 tethering angle as an independent predictor of IMR recurrence with an optimal cutoff value of 29.9° (area under the curve, 0.92; 95% confidence interval, 0.84 to 1.00; p < 0.001).3D echocardiography combined with valve modeling is predictive of recurrent IMR. Preoperative regional leaflet tethering of segment P3 is a strong independent predictor of IMR recurrence after undersized ring annuloplasty. In patients with a preoperative P3 tethering angle of 29.9° or larger, chordal-sparing valve replacement rather than valve repair should be strongly considered.

  View details for DOI 10.1016/j.athoracsur.2015.09.076

  View details for Web of Science ID 000368189700039

  View details for PubMedCentralID PMC4718840

• Preoperative Three-Dimensional Valve Analysis Predicts Recurrent Ischemic Mitral Regurgitation After Mitral Annuloplasty. The Annals of thoracic surgery Bouma, W., Lai, E. K., Levack, M. M., Shang, E. K., Pouch, A. M., Eperjesi, T. J., Plappert, T. J., Yushkevich, P. A., Mariani, M. A., Khabbaz, K. R., Gleason, T. G., Mahmood, F., Acker, M. A., Woo, Y. J., Cheung, A. T., Jackson, B. M., Gorman, J. H., Gorman, R. C. 2016; 101 (2): 567-75; discussion 575

  Abstract

  Valve repair for ischemic mitral regurgitation (IMR) with undersized annuloplasty rings is characterized by high IMR recurrence rates. Patient-specific preoperative imaging-based risk stratification for recurrent IMR would optimize results. We sought to determine if prerepair three-dimensional (3D) echocardiography combined with a novel valve-modeling algorithm would be predictive of IMR recurrence 6 months after repair.Intraoperative transesophageal real-time 3D echocardiography was performed in 50 patients undergoing undersized ring annuloplasty for IMR and in 21 patients with normal mitral valves. A customized image analysis protocol was used to assess 3D annular geometry and regional leaflet tethering. IMR recurrence (≥ grade 2) was assessed with two-dimensional transthoracic echocardiography 6 months after repair.Preoperative annular geometry was similar in all IMR patients, and preoperative leaflet tethering was significantly higher in patients with recurrent IMR (n=13) than in patients in whom IMR did not recur (n=37) (tethering index: 3.91 ± 1.01 vs 2.90 ± 1.17, p = 0.008; tethering angles of A3: 23.5° ± 8.9° vs 14.4° ± 11.4°, p = 0.012; P2: 44.4° ± 8.8° vs 28.2° ± 17.0°, p = 0.002; and P3: 35.2° ± 6.0° vs. 18.6° ± 12.7°, p < 0.001). Multivariate logistic regression analysis revealed the preoperative P3 tethering angle as an independent predictor of IMR recurrence with an optimal cutoff value of 29.9° (area under the curve, 0.92; 95% confidence interval, 0.84 to 1.00; p < 0.001).3D echocardiography combined with valve modeling is predictive of recurrent IMR. Preoperative regional leaflet tethering of segment P3 is a strong independent predictor of IMR recurrence after undersized ring annuloplasty. In patients with a preoperative P3 tethering angle of 29.9° or larger, chordal-sparing valve replacement rather than valve repair should be strongly considered.

  View details for DOI 10.1016/j.athoracsur.2015.09.076

  View details for PubMedID 26688087

  View details for PubMedCentralID PMC4718840

• The contemporary evolution of mitral valve surgery JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Woo, Y., Goldstone, A. B. 2016; 151 (1): 7–9

  View details for PubMedID 26520009

• Novel MRI Contrast Agent from Magnetotactic Bacteria Enables In Vivo Tracking of iPSC-derived Cardiomyocytes. Scientific reports Mahmoudi, M., Tachibana, A., Goldstone, A. B., Woo, Y. J., Chakraborty, P., Lee, K. R., Foote, C. S., Piecewicz, S., Barrozo, J. C., Wakeel, A., Rice, B. W., Bell Iii, C. B., Yang, P. C. 2016; 6: 26960-?

  Abstract

  Therapeutic delivery of human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs) represents a novel clinical approach to regenerate the injured myocardium. However, methods for robust and accurate in vivo monitoring of the iCMs are still lacking. Although superparamagnetic iron oxide nanoparticles (SPIOs) are recognized as a promising tool for in vivo tracking of stem cells using magnetic resonance imaging (MRI), their signal persists in the heart even weeks after the disappearance of the injected cells. This limitation highlights the inability of SPIOs to distinguish stem cell viability. In order to overcome this shortcoming, we demonstrate the use of a living contrast agent, magneto-endosymbionts (MEs) derived from magnetotactic bacteria for the labeling of iCMs. The ME-labeled iCMs were injected into the infarcted area of murine heart and probed by MRI and bioluminescence imaging (BLI). Our findings demonstrate that the MEs are robust and effective biological contrast agents to track iCMs in an in vivo murine model. We show that the MEs clear within one week of cell death whereas the SPIOs remain over 2 weeks after cell death. These findings will accelerate the clinical translation of in vivo MRI monitoring of transplanted stem cell at high spatial resolution and sensitivity.

  View details for DOI 10.1038/srep26960

  View details for PubMedID 27264636

  View details for PubMedCentralID PMC4893600

• 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

• Valve-sparing root replacement for failed pulmonary autografts: Should a David repair a Ross? JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Goldstone, A. B., Woo, Y. 2015; 150 (5): 1138–39

  View details for PubMedID 26546201

• A Tissue-Engineered Chondrocyte Cell Sheet Induces Extracellular Matrix Modification to Enhance Ventricular Biomechanics and Attenuate Myocardial Stiffness in Ischemic Cardiomyopathy TISSUE ENGINEERING PART A Shudo, Y., Cohen, J. E., MacArthur, J. W., Goldstone, A. B., Otsuru, S., Trubelja, A., Patel, J., Edwards, B. B., Hung, G., Fairman, A. S., Brusalis, C., Hiesinger, W., Atluri, P., Hiraoka, A., Miyagawa, S., Sawa, Y., Woo, Y. J. 2015; 21 (19-20): 2515-2525

  Abstract

  There exists a substantial body of work describing cardiac support devices to mechanically support the left ventricle (LV); however, these devices lack biological effects. To remedy this, we implemented a cell sheet engineering approach utilizing chondrocytes, which in their natural environment produce a relatively elastic extracellular matrix (ECM) for a cushioning effect. Therefore, we hypothesized that a chondrocyte cell sheet applied to infarcted and borderzone myocardium will biologically enhance the ventricular ECM and increase elasticity to augment cardiac function in a model of ischemic cardiomyopathy (ICM). Primary articular cartilage chondrocytes of Wistar rats were isolated and cultured on temperature-responsive culture dishes to generate cell sheets. A rodent ICM model was created by ligating the left anterior descending coronary artery. Rats were divided into two groups: cell sheet transplantation (1.0 × 10(7) cells/dish) and no treatment. The cell sheet was placed onto the surface of the heart covering the infarct and borderzone areas. At 4 weeks following treatment, the decreased fibrotic extension and increased elastic microfiber networks in the infarct and borderzone areas correlated with this technology's potential to stimulate ECM formation. The enhanced ventricular elasticity was further confirmed by the axial stretch test, which revealed that the cell sheet tended to attenuate tensile modulus, a parameter of stiffness. This translated to increased wall thickness in the infarct area, decreased LV volume, wall stress, mass, and improvement of LV function. Thus, the chondrocyte cell sheet strengthens the ventricular biomechanical properties by inducing the formation of elastic microfiber networks in ICM, resulting in attenuated myocardial stiffness and improved myocardial function.

  View details for DOI 10.1089/ten.tea.2014.0155

  View details for PubMedID 26154752

• Rationale and design of the Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) 3 Trial: A comparison of fractional flow reserve-guided percutaneous coronary intervention and coronary artery bypass graft surgery in patients with multivessel coronary artery disease. American heart journal Zimmermann, F. M., De Bruyne, B., Pijls, N. H., Desai, M., Oldroyd, K. G., Park, S., Reardon, M. J., Wendler, O., Woo, J., Yeung, A. C., Fearon, W. F. 2015; 170 (4): 619-626 e2

  Abstract

  Guidelines recommend coronary artery bypass graft (CABG) surgery over percutaneous coronary intervention (PCI) for the treatment of 3-vessel coronary artery disease (3-VD). The inferior results of PCI demonstrated by previous large randomized trials comparing PCI and CABG might be explained by the use of suboptimal stent technology and by the lack of fractional flow reserve (FFR) guidance of PCI.The objective of this investigator-initiated, multicenter, randomized clinical trial is to investigate whether FFR-guided PCI with new-generation stents is noninferior to CABG in patients with 3-VD, not including the left main coronary artery. Eligible patients must have ≥50% coronary stenoses in all 3 major epicardial vessels or major side branches. Patients with a nondominant right coronary artery may be included only if the left anterior descending artery and left circumflex have ≥50% stenoses. Consecutive patients who meet all of the inclusion criteria and none of the exclusion criteria will be randomized in a 1:1 fashion to either CABG or FFR-guided PCI. Coronary artery bypass graft will be performed based on the angiogram as per clinical routine. Patients assigned to FFR-guided PCI will have FFR measured in each diseased vessel and only undergo stenting if the FFR is ≤0.80. The primary end point of the study is a composite of major adverse cardiac and cerebrovascular events, including death, myocardial infarction, repeat coronary revascularization, and stroke at 1 year. Key secondary end point will be a composite of death, myocardial infarction, and stroke at 3-year follow-up. Other secondary end points include the individual adverse events, cost-effectiveness, and quality of life at 2-year, 3-year, with up to 5-year follow-up.The FAME 3 study will compare in a multicenter, randomized fashion FFR-guided PCI with contemporary drug-eluting stents to CABG in patients with 3-VD.

  View details for DOI 10.1016/j.ahj.2015.06.024

  View details for PubMedID 26386784

• Obstructive Sleep Apnea Is an Independent Predictor of Postoperative Atrial Fibrillation in Cardiac Surgery JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA Wong, J. K., Maxwell, B. G., Kushida, C. A., Sainani, K. L., Lobato, R. L., Woo, J., Pearl, R. G. 2015; 29 (5): 1140-1147

  Abstract

  To test the hypothesis that obstructive sleep apnea (OSA) is a risk factor for development of postoperative atrial fibrillation (POAF) after cardiac surgery.Retrospective analysis.Single-center university hospital.Five hundred forty-five patients in sinus rhythm preoperatively undergoing coronary artery bypass grafting (CABG), aortic valve replacement, mitral valve replacement/repair, or combined valve/CABG surgery from January 2008 to April 2011.Retrospective review of medical records.Postoperative atrial fibrillation was defined as atrial fibrillation requiring therapeutic intervention. Of 545 cardiac surgical patients, 226 (41%) patients developed POAF. The risk was higher in 72 OSA patients than 473 patients without OSA (67% v 38%, adjusted hazard ratio 1.83 [95% CI: 1.30-2.58], p<0.001). Of the 32 OSA patients who used home positive airway pressure (PAP) therapy, 18 (56%) developed POAF compared with 29 of 38 (76%) patients who did not use PAP at home (unadjusted hazard ratio 0.63 [95% CI: 0.35-1.15], p = 0.13).OSA is significantly associated with POAF in cardiac surgery patients. Further investigation is needed to determine whether or not use of positive airway pressure in OSA patients reduces the risk of POAF.

  View details for DOI 10.1053/j.jvca.2015.03.024

  View details for PubMedID 26154572

• Evaluation of late aortic insufficiency with continuous flow left ventricular assist device†. European journal of cardio-thoracic surgery Hiraoka, A., Cohen, J. E., Shudo, Y., Macarthur, J. W., Howard, J. L., Fairman, A. S., Atluri, P., Kirkpatrick, J. N., Woo, Y. J. 2015; 48 (3): 400-406

  Abstract

  The aim of this study was to evaluate late development of aortic insufficiency (AI) with continuous flow left ventricular assist device (CLVAD). Development of AI is an increasingly recognized important complication in CLVAD therapy, but there are still few reports about this topic.We analysed data from 99 patients who underwent CLVAD implantation. De novo AI was defined as the development of mild or greater AI in patients with none or trace preoperative AI. Anatomic and functional correlates of de novo AI were investigated.Among the 17 patients with preoperative mild AI, no improvements were observed in mitral regurgitation or LV end-systolic dimension. Of the remaining 82 patients, de novo AI was identified in 43 patients (52%), on the most recent follow-up echocardiography, and did not influence survival nor improvement of LV geometry. Rate of freedom from de novo AI at 1 year after CLVAD implantation was 35.9%. Development of significantly greater AI was observed in patients without valve opening (AI grade 1.3 ± 1.0 vs 0.7 ± 0.9; P = 0.005). By multivariate Cox hazard model, smaller body surface area (BSA) [hazard ratio: 0.83 [95% confidence interval (CI): 0.72-0.97], P = 0.018], larger aortic root diameter (AOD) [hazard ratio: 1.11 (95% CI: 1.02-1.22), P = 0.012] and higher pulmonary artery systolic pressure (PASP) [hazard ratio: 1.24 (95% CI: 1.10-1.41), P < 0.001] were identified as the independent preoperative risk factors for de novo AI. In a subset of patients with speed adjustments, increase of CLVAD speed worsened AI and led to insufficient LV unloading in patients with aortic dilatation (AOD ≥ 3.5 cm).Any significant mortality difference related to preoperative or development of postimplant AI was not found. AI was associated with changes in LV size, and there appears to be an interaction between BSA, preoperative PASP, time since implant, aortic valve opening, aortic size and development of AI. Longitudinal clinical management in CLVAD patients, particularly in terms of CLVAD speed optimization, should include careful assessment.

  View details for DOI 10.1093/ejcts/ezu507

  View details for PubMedID 25653250

• Alternative approaches for mitral valve repair. Annals of cardiothoracic surgery Goldstone, A. B., Woo, Y. J. 2015; 4 (5): 469-473

  Abstract

  Unique situations arise in which alternative exposures for mitral valve surgery offer distinct advantages over traditional approaches. Each exposure facilitates both mitral valve repair and replacement, although the standard repair procedures must be modified to accommodate these non-traditional exposures. Here, we detail the technical considerations required to perform transventricular and transaortic mitral valve repair as well as discuss the advantages for employing these less conventional approaches.

  View details for DOI 10.3978/j.issn.2225-319X.2015.08.10

  View details for PubMedID 26539353

• Prior Sternotomy and Ventricular Assist Device Implantation Do Not Adversely Impact Survival or Allograft Function After Heart Transplantation ANNALS OF THORACIC SURGERY Gaffey, A. C., Phillips, E. C., Howard, J., Hung, G., Han, J., Emery, R., Goldberg, L., Acker, M. A., Woo, Y. J., Atluri, P. 2015; 100 (2): 542-549

  Abstract

  Orthotopic heart transplantation (OHT) remains the gold standard for end-stage heart failure. However, donor availability is severely limited. With a median wait time of 6.6 months and more than 12% of patients waiting 5 or more years, the decision is often made to implant a left ventricular assist device (LVAD) as a bridge to transplantation for medical stabilization. Furthermore, the number of patients who have had at least one prior sternotomy while awaiting transplantation is increasing. Previous studies have indicated reoperative sternotomy as a risk factor for compromised survival. Concerns are specifically focused on perioperative, short-term, and long-term outcomes after LVAD explantation or redo sternotomy before OHT because of increasing operative complexity. We hypothesize that despite the greater technical difficulty caused by LVAD explantation or redo sternotomy, outcomes would not be compromised.We retrospectively analyzed patients who underwent OHT at the University of Pennsylvania during a 5-year period (2008-2013; n = 253). All patients who underwent a bridge to transplantation LVAD (n = 72) or prior sternotomy (n = 65) were compared with those undergoing OHT with a virgin chest (n = 116). Preoperative, intraoperative, and postoperative variables were analyzed. Short- and long-term survival were studied (minimum follow-up, 6 months).Comorbidities were similar among the groups. There was no difference in donor allograft ischemic time (p = 0.6). However, cardiopulmonary bypass time was longer in both bridge to transplantation and prior sternotomy cohorts (p < 0.00001). The blood transfusion requirement was higher in bridge to transplantation (12.5 ± 13.7 units; p = 0.0007) and prior sternotomy groups (11.7 ± 12.9 units; p = 0.02) as compared with the virgin chest cohort (7.1 ± 10.7 units). For bridge to transplantation, both time to extubation (1.0 ± 1.6 versus 0.9 ± 1.0 days; p = 0.03) and intensive care unit length of stay (7.0 ± 7.0 versus 6.0 ± 7.0 days; p = 0.06) were longer compared with the virgin chest cohort. The same was true for prior sternotomy (extubation time, 1.9 ± 4.4 days; p = 0.005; intensive care unit length of stay, 8.0 ± 12.0 days; p = 0.06). There was no difference in hospital length of stay (p = 0.2). Overall, there was no difference in short- or long-term survival.Implantation of an LVAD as a bridge to transplantation or prior sternotomy does not adversely impact allograft function, hospital length of stay, or long-term outcomes after OHT. The decision to manage a patient medically while awaiting transplantation versus an LVAD bridge strategy should not be limited by concerns of subsequent poor outcomes after transplantation.

  View details for DOI 10.1016/j.athoracsur.2015.02.093

  View details for PubMedID 26070597

• Aligned-Braided Nanofibrillar Scaffold with Endothelial Cells Enhances Arteriogenesis. ACS nano Nakayama, K. H., Hong, G., Lee, J. C., Patel, J., Edwards, B., Zaitseva, T. S., Paukshto, M. V., Dai, H., Cooke, J. P., Woo, Y. J., Huang, N. F. 2015; 9 (7): 6900-6908

  Abstract

  The objective of this study was to enhance the angiogenic capacity of endothelial cells (ECs) using nanoscale signaling cues from aligned nanofibrillar scaffolds in the setting of tissue ischemia. Thread-like nanofibrillar scaffolds with porous structure were fabricated from aligned-braided membranes generated under shear from liquid crystal collagen solution. Human ECs showed greater outgrowth from aligned scaffolds than from nonpatterned scaffolds. Integrin α1 was in part responsible for the enhanced cellular outgrowth on aligned nanofibrillar scaffolds, as the effect was abrogated by integrin α1 inhibition. To test the efficacy of EC-seeded aligned nanofibrillar scaffolds in improving neovascularization in vivo, the ischemic limbs of mice were treated with EC-seeded aligned nanofibrillar scaffold; EC-seeded nonpatterned scaffold; ECs in saline; aligned nanofibrillar scaffold alone; or no treatment. After 14 days, laser Doppler blood spectroscopy demonstrated significant improvement in blood perfusion recovery when treated with EC-seeded aligned nanofibrillar scaffolds, in comparison to ECs in saline or no treatment. In ischemic hindlimbs treated with scaffolds seeded with human ECs derived from induced pluripotent stem cells (iPSC-ECs), single-walled carbon nanotube (SWNT) fluorophores were systemically delivered to quantify microvascular density after 28 days. Near infrared-II (NIR-II, 1000-1700 nm) imaging of SWNT fluorophores demonstrated that iPSC-EC-seeded aligned scaffolds group showed significantly higher microvascular density than the saline or cells groups. These data suggest that treatment with EC-seeded aligned nanofibrillar scaffolds improved blood perfusion and arteriogenesis, when compared to treatment with cells alone or scaffold alone, and have important implications in the design of therapeutic cell delivery strategies.

  View details for DOI 10.1021/acsnano.5b00545

  View details for PubMedID 26061869

• Protein Corona Influences Cell-Biomaterial Interactions in Nanostructured Tissue Engineering Scaffolds ADVANCED FUNCTIONAL MATERIALS Serpooshan, V., Mahmoudi, M., Zhao, M., Wei, K., Sivanesan, S., Motamedchaboki, K., Malkovskiy, A. V., Goldstone, A. B., Cohen, J. E., Yang, P. C., Rajadas, J., Bernstein, D., Woo, Y. J., Ruiz-Lozano, P. 2015; 25 (28): 4379-4389

  Abstract

  Biomaterials are extensively used to restore damaged tissues, in the forms of implants (e.g. tissue engineered scaffolds) or biomedical devices (e.g. pacemakers). Once in contact with the physiological environment, nanostructured biomaterials undergo modifications as a result of endogenous proteins binding to their surface. The formation of this macromolecular coating complex, known as 'protein corona', onto the surface of nanoparticles and its effect on cell-particle interactions are currently under intense investigation. In striking contrast, protein corona constructs within nanostructured porous tissue engineering scaffolds remain poorly characterized. As organismal systems are highly dynamic, it is conceivable that the formation of distinct protein corona on implanted scaffolds might itself modulate cell-extracellular matrix interactions. Here, we report that corona complexes formed onto the fibrils of engineered collagen scaffolds display specific, distinct, and reproducible compositions that are a signature of the tissue microenvironment as well as being indicative of the subject's health condition. Protein corona formed on collagen matrices modulated cellular secretome in a context-specific manner ex-vivo, demonstrating their role in regulating scaffold-cellular interactions. Together, these findings underscore the importance of custom-designing personalized nanostructured biomaterials, according to the biological milieu and disease state. We propose the use of protein corona as in situ biosensor of temporal and local biomarkers.

  View details for DOI 10.1002/adfm.201500875

  View details for Web of Science ID 000358504000001

  View details for PubMedCentralID PMC4978190

• Protein Corona Influences Cell-Biomaterial Interactions in Nanostructured Tissue Engineering Scaffolds. Advanced functional materials Serpooshan, V., Mahmoudi, M., Zhao, M., Wei, K., Sivanesan, S., Motamedchaboki, K., Malkovskiy, A. V., Gladstone, A. B., Cohen, J. E., Yang, P. C., Rajadas, J., Bernstein, D., Woo, Y. J., Ruiz-Lozano, P. 2015; 25 (28): 4379-4389

  Abstract

  Biomaterials are extensively used to restore damaged tissues, in the forms of implants (e.g. tissue engineered scaffolds) or biomedical devices (e.g. pacemakers). Once in contact with the physiological environment, nanostructured biomaterials undergo modifications as a result of endogenous proteins binding to their surface. The formation of this macromolecular coating complex, known as 'protein corona', onto the surface of nanoparticles and its effect on cell-particle interactions are currently under intense investigation. In striking contrast, protein corona constructs within nanostructured porous tissue engineering scaffolds remain poorly characterized. As organismal systems are highly dynamic, it is conceivable that the formation of distinct protein corona on implanted scaffolds might itself modulate cell-extracellular matrix interactions. Here, we report that corona complexes formed onto the fibrils of engineered collagen scaffolds display specific, distinct, and reproducible compositions that are a signature of the tissue microenvironment as well as being indicative of the subject's health condition. Protein corona formed on collagen matrices modulated cellular secretome in a context-specific manner ex-vivo, demonstrating their role in regulating scaffold-cellular interactions. Together, these findings underscore the importance of custom-designing personalized nanostructured biomaterials, according to the biological milieu and disease state. We propose the use of protein corona as in situ biosensor of temporal and local biomarkers.

  View details for DOI 10.1002/adfm.201500875

  View details for PubMedID 27516731

  View details for PubMedCentralID PMC4978190

• Aligned-Braided Nanofibrillar Scaffold with Endothelial Cells Enhances Arteriogenesis ACS NANO Nakayarna, K. H., Hong, G., Lee, J. C., Patel, J., Edwards, B., Zaitseva, T. S., Paukshto, M. V., Dai, H., Cooke, J. P., Woo, Y. J., Huang, N. F. 2015; 9 (7): 6900-6908

  Abstract

  The objective of this study was to enhance the angiogenic capacity of endothelial cells (ECs) using nanoscale signaling cues from aligned nanofibrillar scaffolds in the setting of tissue ischemia. Thread-like nanofibrillar scaffolds with porous structure were fabricated from aligned-braided membranes generated under shear from liquid crystal collagen solution. Human ECs showed greater outgrowth from aligned scaffolds than from nonpatterned scaffolds. Integrin α1 was in part responsible for the enhanced cellular outgrowth on aligned nanofibrillar scaffolds, as the effect was abrogated by integrin α1 inhibition. To test the efficacy of EC-seeded aligned nanofibrillar scaffolds in improving neovascularization in vivo, the ischemic limbs of mice were treated with EC-seeded aligned nanofibrillar scaffold; EC-seeded nonpatterned scaffold; ECs in saline; aligned nanofibrillar scaffold alone; or no treatment. After 14 days, laser Doppler blood spectroscopy demonstrated significant improvement in blood perfusion recovery when treated with EC-seeded aligned nanofibrillar scaffolds, in comparison to ECs in saline or no treatment. In ischemic hindlimbs treated with scaffolds seeded with human ECs derived from induced pluripotent stem cells (iPSC-ECs), single-walled carbon nanotube (SWNT) fluorophores were systemically delivered to quantify microvascular density after 28 days. Near infrared-II (NIR-II, 1000-1700 nm) imaging of SWNT fluorophores demonstrated that iPSC-EC-seeded aligned scaffolds group showed significantly higher microvascular density than the saline or cells groups. These data suggest that treatment with EC-seeded aligned nanofibrillar scaffolds improved blood perfusion and arteriogenesis, when compared to treatment with cells alone or scaffold alone, and have important implications in the design of therapeutic cell delivery strategies.

  View details for DOI 10.1021/acsnano.5b00545

  View details for Web of Science ID 000358823200027

• Long-term outcomes of septal reduction for obstructive hypertrophic cardiomyopathy JOURNAL OF CARDIOLOGY Sedehi, D., Finocchiaro, G., Tibayan, Y., Chi, J., Pavlovic, A., Kim, Y. M., Tibayan, F. A., Reitz, B. A., Robbins, R. C., Woo, J., Ha, R., Lee, D. P., Ashley, E. A. 2015; 66 (1-2): 57-62

  Abstract

  Surgical myectomy and alcohol septal ablation (ASA) aim to decrease left ventricular outflow tract (LVOT) gradient in hypertrophic cardiomyopathy (HCM). Outcome of myectomy beyond 10 years has rarely been described. We describe 20 years of follow-up of surgical myectomy and 5 years of follow-up for ASA performed for obstructive HCM.We studied 171 patients who underwent myectomy for symptomatic LVOT obstruction between 1972 and 2006. In addition, we studied 52 patients who underwent ASA for the same indication and who declined surgery. Follow-up of New York Heart Association (NYHA) functional class, echocardiographic data, and vital status were obtained from patient records. Mortality rates were compared with expected mortality rates of age- and sex-matched populations.Surgical myectomy improved NYHA class (2.74±0.65 to 1.54±0.74, p<0.001), reduced resting gradient (67.4±43.4mmHg to 11.2±16.4mmHg, p<0.001), and inducible LVOT gradient (98.1±34.7mmHg to 33.6±34.9mmHg, p<0.001). Similarly, ASA improved functional class (2.99±0.35 to 1.5±0.74, p<0.001), resting gradient (67.1±26.9mmHg to 23.9±29.4mmHg, p<0.001) and provoked gradient (104.4±34.9mmHg to 35.5±38.6mmHg, p<0.001). Survival after myectomy at 5, 10, 15, and 20 years of follow-up was 92.9%, 81.1%, 68.9%, and 47.5%, respectively. Of note, long-term survival after myectomy was lower than for the general population [standardized mortality ratio (SMR)=1.40, p<0.005], but still compared favorably with historical data from non-operated HCM patients. Survival after ASA at 2 and 5 years was 97.8% and 94.7%, respectively. Short-term (5 year) survival after ASA (SMR=0.61, p=0.48) was comparable to that of the general population.Long-term follow-up of septal reduction strategies in obstructive HCM reveals that surgical myectomy and ASA are effective for symptom relief and LVOT gradient reduction and are associated with favorable survival. While overall prognosis for the community HCM population is similar to the general population, the need for surgical myectomy may identify a sub-group with poorer long-term prognosis. We await long-term outcomes of more extensive myectomy approaches adopted in the past 10 years at major institutions.

  View details for DOI 10.1016/j.jjcc.2014.08.010

  View details for Web of Science ID 000359684600010

• Long-term outcomes of septal reduction for obstructive hypertrophic cardiomyopathy. Journal of cardiology Sedehi, D., Finocchiaro, G., Tibayan, Y., Chi, J., Pavlovic, A., Kim, Y. M., Tibayan, F. A., Reitz, B. A., Robbins, R. C., Woo, J., Ha, R., Lee, D. P., Ashley, E. A. 2015; 66 (1): 57-62

  Abstract

  Surgical myectomy and alcohol septal ablation (ASA) aim to decrease left ventricular outflow tract (LVOT) gradient in hypertrophic cardiomyopathy (HCM). Outcome of myectomy beyond 10 years has rarely been described. We describe 20 years of follow-up of surgical myectomy and 5 years of follow-up for ASA performed for obstructive HCM.We studied 171 patients who underwent myectomy for symptomatic LVOT obstruction between 1972 and 2006. In addition, we studied 52 patients who underwent ASA for the same indication and who declined surgery. Follow-up of New York Heart Association (NYHA) functional class, echocardiographic data, and vital status were obtained from patient records. Mortality rates were compared with expected mortality rates of age- and sex-matched populations.Surgical myectomy improved NYHA class (2.74±0.65 to 1.54±0.74, p<0.001), reduced resting gradient (67.4±43.4mmHg to 11.2±16.4mmHg, p<0.001), and inducible LVOT gradient (98.1±34.7mmHg to 33.6±34.9mmHg, p<0.001). Similarly, ASA improved functional class (2.99±0.35 to 1.5±0.74, p<0.001), resting gradient (67.1±26.9mmHg to 23.9±29.4mmHg, p<0.001) and provoked gradient (104.4±34.9mmHg to 35.5±38.6mmHg, p<0.001). Survival after myectomy at 5, 10, 15, and 20 years of follow-up was 92.9%, 81.1%, 68.9%, and 47.5%, respectively. Of note, long-term survival after myectomy was lower than for the general population [standardized mortality ratio (SMR)=1.40, p<0.005], but still compared favorably with historical data from non-operated HCM patients. Survival after ASA at 2 and 5 years was 97.8% and 94.7%, respectively. Short-term (5 year) survival after ASA (SMR=0.61, p=0.48) was comparable to that of the general population.Long-term follow-up of septal reduction strategies in obstructive HCM reveals that surgical myectomy and ASA are effective for symptom relief and LVOT gradient reduction and are associated with favorable survival. While overall prognosis for the community HCM population is similar to the general population, the need for surgical myectomy may identify a sub-group with poorer long-term prognosis. We await long-term outcomes of more extensive myectomy approaches adopted in the past 10 years at major institutions.

  View details for DOI 10.1016/j.jjcc.2014.08.010

  View details for PubMedID 25238885

• A "Repair-All" Strategy for Degenerative Mitral Valve Disease Safely Minimizes Unnecessary Replacement. Annals of thoracic surgery Goldstone, A. B., Cohen, J. E., Howard, J. L., Edwards, B. B., Acker, A. L., Hiesinger, W., Macarthur, J. W., Atluri, P., Woo, Y. J. 2015; 99 (6): 1983-1990

  Abstract

  We examined the feasibility and efficacy of a "repair-all" strategy applied in all patients with degenerative mitral regurgitation, regardless of valve complexity, risk profile, and surgical approach.Between 2002 and 2011, 4,241 patients underwent mitral operations at our institution. Analysis was limited to 525 consecutive patients with mitral regurgitation due to leaflet prolapse (posterior, 75%; anterior, 5%; bileaflet, 20%) who underwent isolated mitral operations. A right minithoracotomy was used in 46% of procedures. Propensity scores identified 153 well-matched patient pairs for evaluation of the effect of surgical approach on valve reparability.Mitral repair was successful in 99% (520 of 525) of patients. The location of the leaflet prolapse did not significantly influence the repair rate or the need for intraoperative revision of the initial repair. The repair rate and the need for intraoperative repair revision also did not significantly differ by surgical approach. Intraoperative revision did not confer a greater risk of perioperative morbidity or longer length of stay. At 8 years, freedom from severe mitral regurgitation was 97% ± 2%. Development of residual mitral regurgitation did not differ by location of the leaflet prolapse, need for repair revision, or surgical approach. After discharge, the survival trend did not differ between patients who did and did not require intraoperative repair revision.In experienced centers, a "repair-all" strategy for degenerative mitral regurgitation can be used with nearly 100% repair rates and excellent outcomes, regardless of valve complexity. When necessary, intraoperative revision of the initial repair may be performed in most patients without a significant incremental risk, thereby further enhancing repair rates.

  View details for DOI 10.1016/j.athoracsur.2014.12.076

  View details for PubMedID 25865766

• A "Repair-All" Strategy for Degenerative Mitral Valve Disease Safely Minimizes Unnecessary Replacement ANNALS OF THORACIC SURGERY Goldstone, A. B., Cohen, J. E., Howard, J. L., Edwards, B. B., Acker, A. L., Hiesinger, W., MacArthur, J. W., Atluri, P., Woo, Y. J. 2015; 99 (6): 1983-1991

  Abstract

  We examined the feasibility and efficacy of a "repair-all" strategy applied in all patients with degenerative mitral regurgitation, regardless of valve complexity, risk profile, and surgical approach.Between 2002 and 2011, 4,241 patients underwent mitral operations at our institution. Analysis was limited to 525 consecutive patients with mitral regurgitation due to leaflet prolapse (posterior, 75%; anterior, 5%; bileaflet, 20%) who underwent isolated mitral operations. A right minithoracotomy was used in 46% of procedures. Propensity scores identified 153 well-matched patient pairs for evaluation of the effect of surgical approach on valve reparability.Mitral repair was successful in 99% (520 of 525) of patients. The location of the leaflet prolapse did not significantly influence the repair rate or the need for intraoperative revision of the initial repair. The repair rate and the need for intraoperative repair revision also did not significantly differ by surgical approach. Intraoperative revision did not confer a greater risk of perioperative morbidity or longer length of stay. At 8 years, freedom from severe mitral regurgitation was 97% ± 2%. Development of residual mitral regurgitation did not differ by location of the leaflet prolapse, need for repair revision, or surgical approach. After discharge, the survival trend did not differ between patients who did and did not require intraoperative repair revision.In experienced centers, a "repair-all" strategy for degenerative mitral regurgitation can be used with nearly 100% repair rates and excellent outcomes, regardless of valve complexity. When necessary, intraoperative revision of the initial repair may be performed in most patients without a significant incremental risk, thereby further enhancing repair rates.

  View details for DOI 10.1016/j.athoracsur.2014.12.076

  View details for Web of Science ID 000357521600028

  View details for PubMedID 25865766

• Early surgical intervention or watchful waiting for the management of asymptomatic mitral regurgitation: a systematic review and meta-analysis. Annals of cardiothoracic surgery Goldstone, A. B., Patrick, W. L., Cohen, J. E., Aribeana, C. N., Popat, R., Woo, Y. J. 2015; 4 (3): 220-229

  Abstract

  Discordance between studies drives continued debate regarding the best management of asymptomatic severe mitral regurgitation (MR). The aim of the present study was to conduct a systematic review and meta-analysis of management plans for asymptomatic severe MR, and compare the effectiveness of a strategy of early surgery to watchful waiting.A systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Studies were excluded if they: (I) lacked a watchful waiting cohort; (II) included symptomatic patients; or (III) included etiologies other than degenerative mitral valve disease. The primary outcome of the study was all-cause mortality at 10 years. Secondary outcomes included operative mortality, repair rate, repeat mitral valve surgery, and development of new atrial fibrillation.Five observational studies were eligible for review and three were included in the pooled analysis. In asymptomatic patients without class I triggers (symptoms or ventricular dysfunction), pooled analysis revealed a significant reduction in long-term mortality with an early surgery approach [hazard ratio (HR) =0.38; 95% confidence interval (CI): 0.21-0.71]. This survival benefit persisted in a sub-group analysis limited to patients without class II triggers (atrial fibrillation or pulmonary hypertension) [relative risk (RR) =0.85; 95% CI: 0.75-0.98]. Aggregate rates of operative mortality did not differ between treatment arms (0.7% vs. 0.7% for early surgery vs. watchful waiting). However, significantly higher repair rates were achieved in the early surgery cohorts (RR =1.10; 95% CI: 1.02-1.18).Despite disagreement between individual studies, the present meta-analysis demonstrates that a strategy of early surgery may improve survival and increase the likelihood of mitral valve repair compared with watchful waiting. Early surgery may also benefit patients when instituted prior to the development of class II triggers.

  View details for DOI 10.3978/j.issn.2225-319X.2015.04.01

  View details for PubMedID 26309823

• Mitral valve repair. Annals of cardiothoracic surgery Woo, Y. J. 2015; 4 (3): 219-?

  View details for DOI 10.3978/j.issn.2225-319X.2015.05.04

  View details for PubMedID 26309822

• The butterfly takes flight JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Woo, Y. 2015; 149 (5): 1244

  View details for PubMedID 25746032

• "Glow in the dark'' intraoperative imaging: Expanding the capabilities of robotic technology JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Goldstone, A. B., Woo, Y. 2015; 149 (5): 1458–59

  View details for PubMedID 25752375

• Non-resectional leaflet remodeling mitral valve repair preserves leaflet mobility: A quantitative echocardiographic analysis of mitral valve configuration INTERNATIONAL JOURNAL OF CARDIOLOGY Shudo, Y., Cohen, J. E., MacArthur, J. W., Goldstone, A. B., Hiraoka, A., Howard, J., Fairman, A. S., Patel, J., Edwards, B. B., Atluri, P., Woo, Y. J. 2015; 186: 16-18

  View details for DOI 10.1016/j.ijcard.2015.03.239

  View details for PubMedID 25804458

• Radical Resection of Cardiac Angiosarcoma with Atrioventricular Reconstruction JOURNAL OF HEART VALVE DISEASE Chiu, P., Black, A., Woo, Y. J. 2015; 24 (3): 379-382

  Abstract

  Cardiac sarcomas are rare and have a poor prognosis. The details are presented of a patient with a right atrial angiosarcoma who underwent radical resection with reconstruction of the right atrium with a bovine pericardial patch, tricuspid valve replacement, and bypass of the right coronary artery. Survival is improved in patients who successfully undergo total (R0) resection. For this reason, an aggressive approach to resection is recommended, with extensive reconstruction for all patients with cardiac sarcoma.

  View details for Web of Science ID 000369045600023

• Reply: To PMID 25069688. Annals of thoracic surgery Atluri, P., Woo, Y. J. 2015; 99 (4): 1489-?

  View details for DOI 10.1016/j.athoracsur.2015.01.039

  View details for PubMedID 25841847

• Invited commentary. Annals of thoracic surgery Woo, Y. J. 2015; 99 (4): 1412-1413

  View details for DOI 10.1016/j.athoracsur.2015.01.006

  View details for PubMedID 25841821

• Transaortic Aortomitral Junction Reconstruction and Mitral Valve Leaflet Repair for Recurrent Endocarditis JOURNAL OF HEART VALVE DISEASE Chiu, P., Allen, J. G., Woo, Y. J. 2015; 24 (2): 173-176

  Abstract

  Transaortic interventions on the mitral valve are rarely performed, but offer advantages over traditional approaches in certain circumstances, including either extensive involvement of the aortomitral junction with endocarditis or the patient requiring reoperation for aortic and mitral disease. Herein is presented a case of recurrent endocarditis involving aortomitral continuity, reconstructed using a transaortic mitral valve repair and reconstruction of the aortic and mitral annuli with a pericardial patch, followed by aortic root replacement.

  View details for Web of Science ID 000369045500006

  View details for PubMedID 26204680

• 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

• Shear-Thinning Supramolecular Hydrogels with Secondary Autonomous Covalent Crosslinking to Modulate Viscoelastic Properties In Vivo ADVANCED FUNCTIONAL MATERIALS Rodell, C. B., MacArthur, J. W., Dorsey, S. M., Wade, R. J., Wang, L. L., Woo, Y. J., Burdick, J. A. 2015; 25 (4): 636-644

  Abstract

  Clinical percutaneous delivery of synthetically engineered hydrogels remains limited due to challenges posed by crosslinking kinetics - too fast leads to delivery failure, too slow limits material retention. To overcome this challenge, we exploit supramolecular assembly to localize hydrogels at the injection site and introduce subsequent covalent crosslinking to control final material properties. Supramolecular gels were designed through the separate pendant modifications of hyaluronic acid (HA) by the guest-host pair cyclodextrin and adamantane, enabling shear-thinning injection and high target site retention (>98%). Secondary covalent crosslinking occurred via addition of thiols and Michael-acceptors (i.e., methacrylates, acrylates, vinyl sulfones) on HA and increased hydrogel moduli (E=25.0±4.5kPa) and stability (>3.5 fold in vivo at 28 days). Application of the dual-crosslinking hydrogel to a myocardial infarct model showed improved outcomes relative to untreated and supramolecular hydrogel alone controls, demonstrating its potential in a range of applications where the precise delivery of hydrogels with tunable properties is desired.

  View details for DOI 10.1002/adfm.201403550

  View details for Web of Science ID 000348856500015

  View details for PubMedCentralID PMC4624407

• Shear-Thinning Supramolecular Hydrogels with Secondary Autonomous Covalent Crosslinking to Modulate Viscoelastic Properties In Vivo. Advanced functional materials Rodell, C. B., MacArthur, J. W., Dorsey, S. M., Wade, R. J., Wang, L. L., Woo, Y. J., Burdick, J. A. 2015; 25 (4): 636-644

  Abstract

  Clinical percutaneous delivery of synthetically engineered hydrogels remains limited due to challenges posed by crosslinking kinetics - too fast leads to delivery failure, too slow limits material retention. To overcome this challenge, we exploit supramolecular assembly to localize hydrogels at the injection site and introduce subsequent covalent crosslinking to control final material properties. Supramolecular gels were designed through the separate pendant modifications of hyaluronic acid (HA) by the guest-host pair cyclodextrin and adamantane, enabling shear-thinning injection and high target site retention (>98%). Secondary covalent crosslinking occurred via addition of thiols and Michael-acceptors (i.e., methacrylates, acrylates, vinyl sulfones) on HA and increased hydrogel moduli (E=25.0±4.5kPa) and stability (>3.5 fold in vivo at 28 days). Application of the dual-crosslinking hydrogel to a myocardial infarct model showed improved outcomes relative to untreated and supramolecular hydrogel alone controls, demonstrating its potential in a range of applications where the precise delivery of hydrogels with tunable properties is desired.

  View details for DOI 10.1002/adfm.201403550

  View details for PubMedID 26526097

  View details for PubMedCentralID PMC4624407

• One Hundred Years of History at Stanford University: Thoracic and Cardiovascular Surgery. Seminars in thoracic and cardiovascular surgery Woo, Y. J., Reitz, B. A. 2015; 27 (4): 388-397

  Abstract

  The history of thoracic and cardiovascular surgery at Stanford spans a century long period, beginning not long after the founding of Stanford University. Pioneering Stanford surgeons have made landmark discoveries and innovations in pulmonary, transplantation, thoracic aortic, mechanical circulatory support, minimally invasive, valvular, and congenital heart surgery. Fundamental research formed the foundation underlying these and many other advances. Educating and training the subsequent leaders of cardiothoracic surgery has throughout this century-long history constituted a mission of the highest merit.

  View details for DOI 10.1053/j.semtcvs.2015.10.014

  View details for PubMedID 26811046

• A Crack in the Wall: Evolution of a Left Ventricular Apical Pseudoaneurysm. The Canadian journal of cardiology Parikh, R. V., Ahmadi-Kashani, M. n., Fleischmann, D. n., Woo, Y. J., McConnell, M. V. 2015

  View details for PubMedID 26514751

• Natural history of coexistent tricuspid regurgitation in patients with degenerative mitral valve disease: Implications for future guidelines JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Goldstone, A. B., Howard, J. L., Cohen, J. E., MacArthur, J. W., Atluri, P., Kirkpatrick, J. N., Woo, Y. J. 2014; 148 (6): 2802-2809

  Abstract

  The management of coexistent tricuspid regurgitation in patients with mitral regurgitation remains controversial. We sought to define the incidence and natural history of coexistent tricuspid regurgitation in patients undergoing isolated mitral surgery for degenerative mitral regurgitation, as well as the effect of late secondary tricuspid regurgitation on cardiovascular symptom burden and survival.To minimize confounding, analysis was limited to 495 consecutive patients who underwent isolated mitral surgery for degenerative mitral valve disease between 2002 and 2011. Patients with coexistent severe tricuspid regurgitation were excluded because such patients typically undergo concomitant tricuspid intervention.Grade 1 to 3 coexistent tricuspid regurgitation was present in 215 patients (43%) preoperatively. Actuarial freedom from grade 3 to 4 tricuspid regurgitation 1, 5, and 9 years after surgery was 100% ± 0%, 90% ± 2%, and 64% ± 7%, respectively. Older age (P < .001) and grade of preoperative tricuspid regurgitation (P = .006) independently predicted postoperative progression of tricuspid regurgitation on multivariable analysis. However, when limited to patients with mild or absent tricuspid regurgitation, indexed tricuspid annular diameter was the only significant risk factor for late tricuspid regurgitation (P = .04). New York Heart Association functional class and long-term survival did not worsen with development of late secondary tricuspid regurgitation (P = .4 and P = .6, respectively). However, right ventricular dysfunction was significantly more common in patients with more severe late tricuspid regurgitation (P = .007).Despite durable correction of degenerative mitral regurgitation, less than severe tricuspid regurgitation is likely to progress after surgery if uncorrected. Given the low incremental risk of tricuspid annuloplasty, a more aggressive strategy of concomitant tricuspid repair may be warranted.

  View details for DOI 10.1016/j.jtcvs.2014.08.001

  View details for PubMedID 25218532

• Ventricular assist device implantation in the elderly. Annals of cardiothoracic surgery Hiesinger, W., Boyd, J. H., Woo, Y. J. 2014; 3 (6): 570-572

  Abstract

  Dramatic advances in ventricular assist device (VAD) design and patient management have made mechanical circulatory support an attractive therapeutic option for the growing pool of elderly heart failure patients.A literature review of all relevant studies was performed. No time or language restrictions were imposed, and references of the selected studies were checked for additional relevant citations.In concordance with the universal trend in mechanical circulatory support, continuous flow devices appear to have particular benefits in the elderly. In addition, the literature suggests that early intervention before the development of cardiogenic shock, important in all patients, is particularly paramount in older patients.The ongoing refinement of patient selection, surgical technique, and post-operative care will continue to improve surgical outcomes, and absolute age may become a less pivotal criterion for mechanical circulatory support. However, clear guidelines for the use of mechanical circulatory support in the elderly remain undefined.

  View details for DOI 10.3978/j.issn.2225-319X.2014.09.07

  View details for PubMedID 25512896

• Combined heart and liver transplantation can be safely performed with excellent short- and long-term results. Annals of thoracic surgery Atluri, P., Gaffey, A., Howard, J., Phillips, E., Goldstone, A. B., Hornsby, N., MacArthur, J. W., Cohen, J. E., Gutsche, J., Woo, Y. J. 2014; 98 (3): 858-862

  Abstract

  Heart transplant has become the gold standard therapy for end-stage heart failure. Short- and long-term outcomes after orthotopic heart transplant have been excellent. Many patients with heart failure manifest hepatic failure as a result of a chronically elevated central venous pressure. Concomitant hepatic failure has been a contraindication to heart transplant in most centers. A few select institutions are currently performing combined heart-liver transplantation to treat dual organ failure. The outcomes after dual organ transplant are largely unknown, with limited data from a few select centers. We undertook this study to analyze our large experience with combined heart-liver transplant and determine the short-term and long-term outcomes associated with this procedure.We have performed 1,050 heart transplants at our center to date. Of these patients, 26 underwent combined heart and liver transplant (largest single-center experience). We reviewed demographic, perioperative, and short- and long-term outcomes after this combined procedure.All 26 patients underwent successful dual organ transplant, without any episodes of primary graft dysfunction. Average length of intensive care unit stay was 10 ± 5 days, and average hospital stay was 25 ± 11 days. Kaplan-Meier analysis demonstrated excellent short-term survival (1 year, 87% ± 7%) and long-term survival (5 years, 83% ± 8%). Interestingly, only 3 patients (11%) demonstrated any evidence of rejection long-term by myocardial biopsy, suggesting that concomitant hepatic transplantation may provide immunologic protection for the cardiac allograft.We present the largest single-center series of combined heart and liver transplant. This dual organ strategy is highly feasible, with excellent long-term survival. Concomitant liver transplant may confer immunologic protection for the cardiac allograft.

  View details for DOI 10.1016/j.athoracsur.2014.04.100

  View details for PubMedID 25069688

• Tissue-engineered, hydrogel-based endothelial progenitor cell therapy robustly revascularizes ischemic myocardium and preserves ventricular function. journal of thoracic and cardiovascular surgery Atluri, P., Miller, J. S., Emery, R. J., Hung, G., Trubelja, A., Cohen, J. E., Lloyd, K., Han, J., Gaffey, A. C., MacArthur, J. W., Chen, C. S., Woo, Y. J. 2014; 148 (3): 1090-1098

  Abstract

  Cell-based angiogenic therapy for ischemic heart failure has had limited clinical impact, likely related to low cell retention (<1%) and dispersion. We developed a novel, tissue-engineered, hydrogel-based cell-delivery strategy to overcome these limitations and provide prolonged regional retention of myocardial endothelial progenitor cells at high cell dosage.Endothelial progenitor cells were isolated from Wistar rats and encapsulated in fibrin gels. In vitro viability was quantified using a fluorescent live-dead stain of transgenic enhanced green fluorescent protein(+) endothelial progenitor cells. Endothelial progenitor cell-laden constructs were implanted onto ischemic rat myocardium in a model of acute myocardial infarction (left anterior descending ligation) for 4 weeks. Intramyocardial cell injection (2 × 10(6) endothelial progenitor cells), empty fibrin, and isolated left anterior descending ligation groups served as controls. Hemodynamics were quantified using echocardiography, Doppler flow analysis, and intraventricular pressure-volume analysis. Vasculogenesis and ventricular geometry were quantified. Endothelial progenitor cell migration was analyzed by using endothelial progenitor cells from transgenic enhanced green fluorescent protein(+) rodents.Endothelial progenitor cells demonstrated an overall 88.7% viability for all matrix and cell conditions investigated after 48 hours. Histologic assessment of 1-week implants demonstrated significant migration of transgenic enhanced green fluorescent protein(+) endothelial progenitor cells from the fibrin matrix to the infarcted myocardium compared with intramyocardial cell injection (28 ± 12.3 cells/high power field vs 2.4 ± 2.1 cells/high power field, P = .0001). We also observed a marked increase in vasculogenesis at the implant site. Significant improvements in ventricular hemodynamics and geometry were present after endothelial progenitor cell-hydrogel therapy compared with control.We present a tissue-engineered, hydrogel-based endothelial progenitor cell-mediated therapy to enhance cell delivery, cell retention, vasculogenesis, and preservation of myocardial structure and function.

  View details for DOI 10.1016/j.jtcvs.2014.06.038

  View details for PubMedID 25129603

• Bioengineered Stromal Cell- Derived Factor-1 alpha Analogue Delivered as an Angiogenic Therapy Significantly Restores Viscoelastic Material Properties of Infarcted Cardiac Muscle JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME Trubelja, A., MacArthur, J. W., Sarver, J. J., Cohen, J. E., Hung, G., Shudo, Y., Fairman, A. S., Patel, J., Edwards, B. B., Damrauer, S. M., Hiesinger, W., Atluri, P., Woo, Y. J. 2014; 136 (8)

  Abstract

  Ischemic heart disease is a major health problem worldwide, and current therapies fail to address microrevascularization. Previously, our group demonstrated that the sustained release of novel engineered stromal cell-derived factor 1-a analogue (ESA) limits infarct spreading, collagen deposition, improves cardiac function by promoting angiogenesis in the region surrounding the infarct, and restores the tensile properties of infarcted myocardium. In this study, using a well-established rat model of ischemic cardiomyopathy, we describe a novel and innovative method for analyzing the viscoelastic properties of infarcted myocardium. Our results demonstrate that, compared with a saline control group, animals treated with ESA have significantly improved myocardial relaxation rates, while reducing the transition strain, leading to restoration of left ventricular mechanics.

  View details for DOI 10.1115/1.4027731

  View details for Web of Science ID 000338507000012

• Increased Cholesterol Efflux Capacity is Associated with Improved Survival in Heart Transplant Recipients Javaheri, A., Zamani, P., Molina, M., Rodriguez, A., Chambers, S., Stutman, P., Maslanek, W., Williams, M., Lukmanova, D., Picataggi, A., Lilly, S., Christie, J., Woo, Y., Goldberg, L. R., Billheimer, J., Rader, D. J. CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS. 2014: S81

  View details for DOI 10.1016/j.cardfail.2014.06.231

  View details for Web of Science ID 000340214100204

• A bioengineered hydrogel system enables targeted and sustained intramyocardial delivery of neuregulin, activating the cardiomyocyte cell cycle and enhancing ventricular function in a murine model of ischemic cardiomyopathy. Circulation. Heart failure Cohen, J. E., Purcell, B. P., Macarthur, J. W., Mu, A., Shudo, Y., Patel, J. B., Brusalis, C. M., Trubelja, A., Fairman, A. S., Edwards, B. B., Davis, M. S., Hung, G., Hiesinger, W., Atluri, P., Margulies, K. B., Burdick, J. A., Woo, Y. J. 2014; 7 (4): 619-626

  Abstract

  Neuregulin-1β (NRG) is a member of the epidermal growth factor family possessing a critical role in cardiomyocyte development and proliferation. Systemic administration of NRG demonstrated efficacy in cardiomyopathy animal models, leading to clinical trials using daily NRG infusions. This approach is hindered by requiring daily infusions and off-target exposure. Therefore, this study aimed to encapsulate NRG in a hydrogel to be directly delivered to the myocardium, accomplishing sustained localized NRG delivery.NRG was encapsulated in hydrogel, and release over 14 days was confirmed by ELISA in vitro. Sprague-Dawley rats were used for cardiomyocyte isolation. Cells were stimulated by PBS, NRG, hydrogel, or NRG-hydrogel (NRG-HG) and evaluated for proliferation. Cardiomyocytes demonstrated EdU (5-ethynyl-2'-deoxyuridine) and phosphorylated histone H3 positivity in the NRG-HG group only. For in vivo studies, 2-month-old mice (n=60) underwent left anterior descending coronary artery ligation and were randomized to the 4 treatment groups mentioned. Only NRG-HG-treated mice demonstrated phosphorylated histone H3 and Ki67 positivity along with decreased caspase-3 activity compared with all controls. NRG was detected in myocardium 6 days after injection without evidence of off-target exposure in NRG-HG animals. At 2 weeks, the NRG-HG group exhibited enhanced left ventricular ejection fraction, decreased left ventricular area, and augmented borderzone thickness.Targeted and sustained delivery of NRG directly to the myocardial borderzone augments cardiomyocyte mitotic activity, decreases apoptosis, and greatly enhances left ventricular function in a model of ischemic cardiomyopathy. This novel approach to NRG administration avoids off-target exposure and represents a clinically translatable strategy in myocardial regenerative therapeutics.

  View details for DOI 10.1161/CIRCHEARTFAILURE.113.001273

  View details for PubMedID 24902740

• Mesenchymal precursor cells as adjunctive therapy in recipients of contemporary left ventricular assist devices. Circulation Ascheim, D. D., Gelijns, A. C., Goldstein, D., Moye, L. A., Smedira, N., Lee, S., Klodell, C. T., Szady, A., Parides, M. K., Jeffries, N. O., Skerrett, D., Taylor, D. A., Rame, J. E., Milano, C., Rogers, J. G., Lynch, J., Dewey, T., Eichhorn, E., Sun, B., Feldman, D., Simari, R., O'Gara, P. T., Taddei-Peters, W. C., Miller, M. A., Naka, Y., Bagiella, E., Rose, E. A., Woo, Y. J. 2014; 129 (22): 2287-2296

  Abstract

  Allogeneic mesenchymal precursor cells (MPCs) injected during left ventricular assist device (LVAD) implantation may contribute to myocardial recovery. This trial explores the safety and efficacy of this strategy.In this multicenter, double-blind, sham-procedure controlled trial, 30 patients were randomized (2:1) to intramyocardial injection of 25 million MPCs or medium during LVAD implantation. The primary safety end point was incidence of infectious myocarditis, myocardial rupture, neoplasm, hypersensitivity reaction, and immune sensitization (90 days after randomization). Key efficacy end points were functional status and ventricular function while temporarily weaned from LVAD support (90 days after randomization). Patients were followed up until transplant or 12 months after randomization, whichever came first. Mean age was 57.4 (±13.6) years, mean left ventricular ejection fraction was 18.1%, and 66.7% were destination therapy LVADs. No safety events were observed. Successful temporary LVAD weaning was achieved in 50% of MPC and 20% of control patients at 90 days (P=0.24); the posterior probability that MPCs increased the likelihood of successful weaning was 93%. At 90 days, 3 deaths (30%) occurred in control patients, and none occurred in MPC patients. Mean left ventricular ejection fraction after successful wean was 24.0% (MPC=10) and 22.5% (control=2; P=0.56). At 12 months, 30% of MPC patients and 40% of control patients were successfully temporarily weaned from LVAD support (P=0.69), and 6 deaths (30%) occurred in MPC patients. Donor-specific HLA sensitization developed in 2 MPC and 3 control patients and resolved by 12 months.In this preliminary trial, administration of MPCs appeared to be safe, and there was a potential signal of efficacy. Future studies will evaluate the potential for higher or additional doses to enhance the ability to wean LVAD recipients off support.http://www.clinicaltrials.gov. Unique identifier: NCT01442129.

  View details for DOI 10.1161/CIRCULATIONAHA.113.007412

  View details for PubMedID 24682346

• Mesenchymal precursor cells as adjunctive therapy in recipients of contemporary left ventricular assist devices. Circulation Ascheim, D. D., Gelijns, A. C., Goldstein, D., Moye, L. A., Smedira, N., Lee, S., Klodell, C. T., Szady, A., Parides, M. K., Jeffries, N. O., Skerrett, D., Taylor, D. A., Rame, J. E., Milano, C., Rogers, J. G., Lynch, J., Dewey, T., Eichhorn, E., Sun, B., Feldman, D., Simari, R., O'Gara, P. T., Taddei-Peters, W. C., Miller, M. A., Naka, Y., Bagiella, E., Rose, E. A., Woo, Y. J. 2014; 129 (22): 2287-2296

  View details for DOI 10.1161/CIRCULATIONAHA.113.007412

  View details for PubMedID 24682346

• Ex Vivo Allograft Mitral Valve Leaflet Repair Prior to Orthotopic Heart Transplantation JOURNAL OF CARDIAC SURGERY Okamura, H., Woo, Y. J. 2014; 29 (3): 424-426

  Abstract

  The shortage of donors has limited the number of heart transplantations. We report a successful ex vivo mitral valve repair of the allograft prior to heart transplantation.

  View details for DOI 10.1111/jocs.12297

  View details for Web of Science ID 000335168900031

  View details for PubMedID 24460568

• Minimally invasive surgical treatment of valvular heart disease. Seminars in thoracic and cardiovascular surgery Goldstone, A. B., Joseph Woo, Y. 2014; 26 (1): 36-43

  Abstract

  Cardiac surgery is in the midst of a practice revolution. Traditionally, surgery for valvular heart disease consisted of valve replacement via conventional sternotomy using cardiopulmonary bypass. However, over the past 20 years, the increasing popularity of less-invasive procedures, accompanied by advancements in imaging, surgical instrumentation, and robotic technology, has motivated and enabled surgeons to develop and perform complex cardiac surgical procedures through small incisions, often eliminating the need for sternotomy or cardiopulmonary bypass. In addition to the benefits of improved cosmesis, minimally invasive mitral valve surgery was pioneered with the intent of reducing morbidity, postoperative pain, blood loss, hospital length of stay, and time to return to normal activity. This article reviews the current state-of-the-art of minimally invasive approaches to the surgical treatment of valvular heart disease.

  View details for DOI 10.1053/j.semtcvs.2014.02.001

  View details for PubMedID 24952756

• Invited commentary. Annals of thoracic surgery Woo, Y. J. 2014; 97 (3): 756-757

  View details for DOI 10.1016/j.athoracsur.2013.11.004

  View details for PubMedID 24580898

• Preclinical evaluation of the engineered stem cell chemokine stromal cell-derived factor 1a analog in a translational ovine myocardial infarction model. Circulation research Macarthur, J. W., Cohen, J. E., McGarvey, J. R., Shudo, Y., Patel, J. B., Trubelja, A., Fairman, A. S., Edwards, B. B., Hung, G., Hiesinger, W., Goldstone, A. B., Atluri, P., Wilensky, R. L., Pilla, J. J., Gorman, J. H., Gorman, R. C., Woo, Y. J. 2014; 114 (4): 650-659

  Abstract

  After myocardial infarction, there is an inadequate blood supply to the myocardium, and the surrounding borderzone becomes hypocontractile.To develop a clinically translatable therapy, we hypothesized that in a preclinical ovine model of myocardial infarction, the modified endothelial progenitor stem cell chemokine, engineered stromal cell-derived factor 1α analog (ESA), would induce endothelial progenitor stem cell chemotaxis, limit adverse ventricular remodeling, and preserve borderzone contractility.Thirty-six adult male Dorset sheep underwent permanent ligation of the left anterior descending coronary artery, inducing an anteroapical infarction, and were randomized to borderzone injection of saline (n=18) or ESA (n=18). Ventricular function, geometry, and regional strain were assessed using cardiac MRI and pressure-volume catheter transduction. Bone marrow was harvested for in vitro analysis, and myocardial biopsies were taken for mRNA, protein, and immunohistochemical analysis. ESA induced greater chemotaxis of endothelial progenitor stem cells compared with saline (P<0.01) and was equivalent to recombinant stromal cell-derived factor 1α (P=0.27). Analysis of mRNA expression and protein levels in ESA-treated animals revealed reduced matrix metalloproteinase 2 in the borderzone (P<0.05), with elevated levels of tissue inhibitor of matrix metalloproteinase 1 and elastin in the infarct (P<0.05), whereas immunohistochemical analysis of borderzone myocardium showed increased capillary and arteriolar density in the ESA group (P<0.01). Animals in the ESA treatment group also had significant reductions in infarct size (P<0.01), increased maximal principle strain in the borderzone (P<0.01), and a steeper slope of the end-systolic pressure-volume relationship (P=0.01).The novel, biomolecularly designed peptide ESA induces chemotaxis of endothelial progenitor stem cells, stimulates neovasculogenesis, limits infarct expansion, and preserves contractility in an ovine model of myocardial infarction.

  View details for DOI 10.1161/CIRCRESAHA.114.302884

  View details for PubMedID 24366171

• Mitral-Valve Repair versus Replacement for Severe Ischemic Mitral Regurgitation NEW ENGLAND JOURNAL OF MEDICINE Acker, M. A., Parides, M. K., Perrault, L. P., Moskowitz, A. J., Gelijns, A. C., Voisine, P., Smith, P. K., Hung, J. W., Blackstone, E. H., Puskas, J. D., Argenziano, M., Gammie, J. S., Mack, M., Ascheim, D. D., Bagiella, E., Moquete, E. G., Ferguson, T. B., Horvath, K. A., Geller, N. L., Miller, M. A., Woo, Y. J., D'Alessandro, D. A., Ailawadi, G., Dagenais, F., Gardner, T. J., O'Gara, P. T., Michler, R. E., Kron, I. L. 2014; 370 (1): 23-32

  Abstract

  Ischemic mitral regurgitation is associated with a substantial risk of death. Practice guidelines recommend surgery for patients with a severe form of this condition but acknowledge that the supporting evidence for repair or replacement is limited.We randomly assigned 251 patients with severe ischemic mitral regurgitation to undergo either mitral-valve repair or chordal-sparing replacement in order to evaluate efficacy and safety. The primary end point was the left ventricular end-systolic volume index (LVESVI) at 12 months, as assessed with the use of a Wilcoxon rank-sum test in which deaths were categorized below the lowest LVESVI rank.At 12 months, the mean LVESVI among surviving patients was 54.6±25.0 ml per square meter of body-surface area in the repair group and 60.7±31.5 ml per square meter in the replacement group (mean change from baseline, -6.6 and -6.8 ml per square meter, respectively). The rate of death was 14.3% in the repair group and 17.6% in the replacement group (hazard ratio with repair, 0.79; 95% confidence interval, 0.42 to 1.47; P=0.45 by the log-rank test). There was no significant between-group difference in LVESVI after adjustment for death (z score, 1.33; P=0.18). The rate of moderate or severe recurrence of mitral regurgitation at 12 months was higher in the repair group than in the replacement group (32.6% vs. 2.3%, P<0.001). There were no significant between-group differences in the rate of a composite of major adverse cardiac or cerebrovascular events, in functional status, or in quality of life at 12 months.We observed no significant difference in left ventricular reverse remodeling or survival at 12 months between patients who underwent mitral-valve repair and those who underwent mitral-valve replacement. Replacement provided a more durable correction of mitral regurgitation, but there was no significant between-group difference in clinical outcomes. (Funded by the National Institutes of Health and the Canadian Institutes of Health; ClinicalTrials.gov number, NCT00807040.).

  View details for DOI 10.1056/NEJMoa1312808

  View details for Web of Science ID 000329354100007

  View details for PubMedID 24245543

• Regional Annular Geometry in Patients With Mitral Regurgitation: Implications for Annuloplasty Ring Selection ANNALS OF THORACIC SURGERY Jassar, A. S., Vergnat, M., Jackson, B. M., McGarvey, J. R., Cheung, A. T., Ferrari, G., Woo, Y. J., Acker, M. A., Gorman, R. C., Gorman, J. H. 2014; 97 (1): 64-70

  Abstract

  The saddle shape of the normal mitral annulus has been quantitatively described by several groups. There is strong evidence that this shape is important to valve function. A more complete understanding of regional annular geometry in diseased valves may provide a more educated approach to annuloplasty ring selection and design. We hypothesized that mitral annular shape is markedly distorted in patients with diseased valves.Real-time 3-dimensional echocardiography was performed in 20 patients with normal mitral valves, 10 with ischemic mitral regurgitation, and 20 with myxomatous mitral regurgitation (MMR). Thirty-six annular points were defined to generate a 3-dimensional model of the annulus. Regional annular parameters were measured from these renderings. Left ventricular inner diameter was obtained from 2-dimensional echocardiographic images.Annular geometry was significantly different among the three groups. The annuli were larger in the MMR and in the ischemic mitral regurgitation groups. The annular enlargement was greater and more pervasive in the MMR group. Both diseases were associated with annular flattening, although though the regional distribution of that flattening was different between groups. Left ventricular inner diameter was increased in both groups. However, relative to the Left ventricular inner diameter, the annulus was disproportionately dilated in the MMR group.Patients with MMR and ischemic mitral regurgitation have enlarged and flattened annuli. In the case of MMR, annular distortions may be the driving factor leading to valve incompetence. These data suggest that the goal of annuloplasty should be the restoration of normal annular saddle shape and that the use of flexible, partial, and flat rings may be ill advised.

  View details for DOI 10.1016/j.athoracsur.2013.07.048

  View details for Web of Science ID 000329155900020

  View details for PubMedID 24070698

• Mesenchymal Precursor Cells as Adjunctive Therapy in Recipients of Contemporary LVADs: A Multi-Center Prospective Randomized Placebo-Controlled Double-Blinded Clinical Trial. Circulation Ascheim , D. D., Geljins, A. C., Goldstein, D., Moye, L. A., Smedira, N., Lee, S., Klodell, C. T., Szady, A., Parides, M. K., Jefferies, N., Skerret, D., Taylor, D. A., Rame, J. E., Milano, C., Rodgers, J. G., Lynch, J., Dewey, T., Eichhorn, E., Sun, B., Feldman, D., Simiari, R., O'Gara, P. T., Taddei-Peters, W., Miller, M. A., Woo, Y. J., et al 2014; (in press)
• Nonresectional Single-Suture Leaflet Remodeling for Degenerative Mitral Regurgitation Facilitates Minimally Invasive Mitral Valve Repair ANNALS OF THORACIC SURGERY MacArthur, J. W., Cohen, J. E., Goldstone, A. B., Fairman, A. S., Edwards, B. B., Hornick, M. A., Atluri, P., Woo, Y. J. 2013; 96 (5): 1603-1606

  Abstract

  Both leaflet resection and neochordal construction are effective mitral repair techniques, but they may become incrementally time-consuming when using minimally invasive approaches. We have used a single-suture leaflet-remodeling technique of inverting the prolapsed or flail segment tissue into the left ventricle. This repair is straightforward, expeditious, and facilitates a minimally invasive approach.Ninety-nine patients with degenerative mitral regurgitation (MR) underwent a minimally invasive single-suture repair of the mitral valve from May 2007 through December 2012. Preoperative and perioperative echocardiograms as well as patient outcomes were analyzed and compared with those obtained from patients undergoing minimally invasive mitral valve repair using quadrangular resection at the same institution during the same period.All 99 patients had a successful mitral repair through a sternal-sparing minimally invasive approach. Ninety-one of the 99 patients had zero MR on postoperative echocardiogram, and 8 of 99 had trace to mild MR. Patients in the nonresectional group had significantly shorter cardiopulmonary bypass and cross-clamp times compared with the quadrangular resection group (115.8 ± 41.7 minutes versus 144.9 ± 38.2 minutes; p < 0.001; 76.2 ± 28.1 minutes versus 112.6 ± 33.5 minutes; p < 0.001, respectively). The mean length of stay was 7.5 ± 3 days. All patients were discharged alive and free from clinical symptoms of MR. There have been no reoperations for recurrent MR on subsequent average follow-up of 1 year.An effective, highly efficient, and thus far durable single-suture mitral leaflet-remodeling technique facilitates minimally invasive repair of degenerative MR.

  View details for DOI 10.1016/j.athoracsur.2013.05.053

  View details for Web of Science ID 000326375700020

  View details for PubMedID 23932318

• Continuous Flow Left Ventricular Assist Device Implant Significantly Improves Pulmonary Hypertension, Right Ventricular Contractility, and Tricuspid Valve Competence JOURNAL OF CARDIAC SURGERY Atluri, P., Fairman, A. S., MacArthur, J. W., Goldstone, A. B., Cohen, J. E., Howard, J. L., Zalewski, C. M., Shudo, Y., Woo, Y. J. 2013; 28 (6): 770-775

  Abstract

  Continuous flow left ventricular assist devices (CF LVAD) are being implanted with increasing frequency for end-stage heart failure. At the time of LVAD implant, a large proportion of patients have pulmonary hypertension, right ventricular (RV) dysfunction, and tricuspid regurgitation (TR). RV dysfunction and TR can exacerbate renal dysfunction, hepatic dysfunction, coagulopathy, edema, and even prohibit isolated LVAD implant. Repairing TR mandates increased cardiopulmonary bypass time and bicaval cannulation, which should be reserved for the time of orthotopic heart transplantation. We hypothesized that CF LVAD implant would improve pulmonary artery pressures, enhance RV function, and minimize TR, obviating need for surgical tricuspid repair.One hundred fourteen continuous flow LVADs implanted from 2005 through 2011 at a single center, with medical management of functional TR, were retrospectively analyzed. Pulmonary artery pressures were measured immediately prior to and following LVAD implant. RV function and TR were graded according to standard echocardiographic criteria, prior to, immediately following, and long-term following LVAD.There was a significant improvement in post-VAD mean pulmonary arterial pressures (26.6 ± 4.9 vs. 30.2 ± 7.4 mmHg, p = 0.008) with equivalent loading pressures (CVP = 12.0 ± 4.0 vs. 12.1 ± 5.1 p = NS). RV function significantly improved, as noted by right ventricular stroke work index (7.04 ± 2.60 vs. 6.05 ± 2.54, p = 0.02). There was an immediate improvement in TR grade and RV function following LVAD implant, which was sustained long term.Continuous flow LVAD implant improves pulmonary hypertension, RV function, and tricuspid regurgitation. TR may be managed nonoperatively during CF LVAD implant.

  View details for DOI 10.1111/jocs.12214

  View details for Web of Science ID 000326894300051

  View details for PubMedID 24118109

• Minimally Invasive Mitral Valve Surgery Can Be Performed With Optimal Outcomes in the Presence of Left Ventricular Dysfunction 49th Annual Meeting of the Society-of-Thoracic-Surgeons Atluri, P., Woo, Y. J., Goldstone, A. B., Fox, J., Acker, M. A., Szeto, W. Y., Hargrove, W. C. ELSEVIER SCIENCE INC. 2013: 1596–1602

  Abstract

  Minimally invasive approaches to mitral valve repair have demonstrated equivalent technical outcomes and more rapid recovery when compared with traditional sternotomy. These techniques have been widely accepted for mitral insufficiency and stenosis. The utilization of minimally invasive techniques in the presence of left ventricular (LV) dysfunction has been controversial. We hypothesized that minimally invasive mitral valve surgery could be safely performed in the presence of compromised myocardial function, thereby minimizing recovery time.All patients undergoing minimally invasive mitral valve surgery at our center from November 1998 through June 2012 were analyzed. During this time 1,103 patients underwent minimally invasive, port access, mitral valve surgery utilizing a video-assisted limited right thoracotomy approach. Patients with LV dysfunction (ejection fraction ≤ 0.40, n = 140) were compared with patients with normal ventricular function (n = 963). Preoperative, intraoperative, and postoperative variables were compared between cohorts.Patients with LV dysfunction were able to undergo mitral valve surgery with minimal mortality (2.1% vs 1.7%, p = 0.7) and morbidity, that was comparable with patients with normal ventricular function. Postoperative recovery was only slightly longer compared with patients with normal LV function as noted by time to extubation (6.0 vs 7.0 hours, p = 0.005) and hospital length of stay (7.0 vs 6.0 days, p < 0.001). A significant percentage of patients with LV dysfunction underwent redo cardiac surgery (40.0%) through minimally invasive approaches.Minimally invasive, port-access, mitral valve surgery can be safely performed with minimal morbidity and mortality in the presence of cardiomyopathy. This approach may be considered in patients with isolated mitral valve pathology and LV dysfunction in an experienced center.

  View details for DOI 10.1016/j.athoracsur.2013.05.098

  View details for Web of Science ID 000326375700019

  View details for PubMedID 23987894

• Valve-sparing aortic root replacement and neochordal repair of complex aortic leaflet pathology for ruptured sinus of valsalva aneurysm fistulizing to the right ventricle. Annals of thoracic surgery Woo, Y. J., Frederick, J. R. 2013; 96 (5): 1891-1893

  Abstract

  Sinus of Valsalva aneurysms (SVAs) are rare congenital entities arising from eccentric aortic root dilatation that can protrude and rupture into adjacent cardiac chambers. Treatment entails aneurysmal sac excision and aortic defect closure. We present a young patient with a ruptured SVA fistulizing into the right ventricle and acute decompensated heart failure. He also had moderate aortic root enlargement and a dysmorphic aortic valve with 3 highly asymmetrical leaflets. This pathologic condition was successfully repaired with a novel combination of valve-sparing root replacement, aortic valve leaflet neochordal repair, right ventricular reconstruction, and tricuspid valve annuloplasty.

  View details for DOI 10.1016/j.athoracsur.2013.05.008

  View details for PubMedID 24182491

• Valve-sparing aortic root replacement with translocation of anomalous left coronary artery. Annals of thoracic surgery Kaczorowski, D. J., Woo, Y. J. 2013; 96 (4): 1466-1469

  Abstract

  An anomalous left main coronary artery arising from the right coronary with a single coronary ostium is an exceptionally rare anatomic variant. Here, we report a patient with a left main coronary artery arising from the right coronary and also an aortic root aneurysm associated with mild aortic insufficiency. Valve-sparing aortic root replacement and coronary translocation were performed with an excellent outcome in this case.

  View details for DOI 10.1016/j.athoracsur.2013.01.090

  View details for PubMedID 24088463

• Continuous-flow left ventricular assist device implantation in the presence of a hostile ventricular apex. journal of thoracic and cardiovascular surgery Atluri, P., Dymond, D. J., Woo, Y. J. 2013; 146 (4): 981-982

  View details for DOI 10.1016/j.jtcvs.2012.01.090

  View details for PubMedID 23953985

• Sustained release of engineered stromal cell-derived factor 1-a from injectable hydrogels effectively recruits endothelial progenitor cells and preserves ventricular function after myocardial infarction. Circulation Macarthur, J. W., Purcell, B. P., Shudo, Y., Cohen, J. E., Fairman, A., Trubelja, A., Patel, J., Hsiao, P., Yang, E., Lloyd, K., Hiesinger, W., Atluri, P., Burdick, J. A., Woo, Y. J. 2013; 128 (11): S79-86

  Abstract

  Exogenously delivered chemokines have enabled neovasculogenic myocardial repair in models of ischemic cardiomyopathy; however, these molecules have short half-lives in vivo. In this study, we hypothesized that the sustained delivery of a synthetic analog of stromal cell-derived factor 1-α (engineered stromal cell-derived factor analog [ESA]) induces continuous homing of endothelial progenitor cells and improves left ventricular function in a rat model of myocardial infarction.Our previously designed ESA peptide was synthesized by the addition of a fluorophore tag for tracking. Hyaluronic acid was chemically modified with hydroxyethyl methacrylate to form hydrolytically degradable hydrogels through free-radical-initiated crosslinking. ESA was encapsulated in hyaluronic acid hydrogels during gel formation, and then ESA release, along with gel degradation, was monitored for more than 4 weeks in vitro. Chemotactic properties of the eluted ESA were assessed at multiple time points using rat endothelial progenitor cells in a transwell migration assay. Finally, adult male Wistar rats (n=33) underwent permanent ligation of the left anterior descending (LAD) coronary artery, and 100 µL of saline, hydrogel alone, or hydrogel+25 µg ESA was injected into the borderzone. ESA fluorescence was monitored in animals for more than 4 weeks, after which vasculogenic, geometric, and functional parameters were assessed to determine the therapeutic benefit of each treatment group. ESA release was sustained for 4 weeks in vitro, remained active, and enhanced endothelial progenitor cell chemotaxis. In addition, ESA was detected in the rat heart >3 weeks when delivered within the hydrogels and significantly improved vascularity, ventricular geometry, ejection fraction, cardiac output, and contractility compared with controls.We have developed a hydrogel delivery system that sustains the release of a bioactive endothelial progenitor cell chemokine during a 4-week period that preserves ventricular function in a rat model of myocardial infarction.

  View details for DOI 10.1161/CIRCULATIONAHA.112.000343

  View details for PubMedID 24030424

• Spatially oriented, temporally sequential smooth muscle cell-endothelial progenitor cell bi-level cell sheet neovascularizes ischemic myocardium. Circulation Shudo, Y., Cohen, J. E., MacArthur, J. W., Atluri, P., Hsiao, P. F., Yang, E. C., Fairman, A. S., Trubelja, A., Patel, J., Miyagawa, S., Sawa, Y., Woo, Y. J. 2013; 128 (11): S59-68

  Abstract

  Endothelial progenitor cells (EPCs) possess robust therapeutic angiogenic potential, yet may be limited in the capacity to develop into fully mature vasculature. This problem might be exacerbated by the absence of a neovascular foundation, namely pericytes, with simple EPC injection. We hypothesized that coculturing EPCs with smooth muscle cells (SMCs), components of the surrounding vascular wall, in a cell sheet will mimic the native spatial orientation and interaction between EPCs and SMCs to create a supratherapeutic angiogenic construct in a model of ischemic cardiomyopathy.Primary EPCs and SMCs were isolated from Wistar rats. Confluent SMCs topped with confluent EPCs were spontaneously detached from the Upcell dish to create an SMC-EPC bi-level cell sheet. A rodent ischemic cardiomyopathy model was created by ligating the left anterior descending coronary artery. Rats were then immediately divided into 3 groups: cell-sheet transplantation (n=14), cell injection (n=12), and no treatment (n=13). Cocultured EPCs and SMCs stimulated an abundant release of multiple cytokines in vitro. Increased capillary density and improved blood perfusion in the borderzone elucidated the significant in vivo angiogenic potential of this technology. Most interestingly, however, cell fate-tracking experiments demonstrated that the cell-sheet EPCs and SMCs directly migrated into the myocardium and differentiated into elements of newly formed functional vasculature. The robust angiogenic effect of this cell sheet translated to enhanced ventricular function as demonstrated by echocardiography.Spatially arranged EPC-SMC bi-level cell-sheet technology facilitated the natural interaction between EPCs and SMCs, thereby creating structurally mature, functional microvasculature in a rodent ischemic cardiomyopathy model, leading to improved myocardial function.

  View details for DOI 10.1161/CIRCULATIONAHA.112.000293

  View details for PubMedID 24030422

• Normalization of postinfarct biomechanics using a novel tissue-engineered angiogenic construct. Circulation Atluri, P., Trubelja, A., Fairman, A. S., Hsiao, P., MacArthur, J. W., Cohen, J. E., Shudo, Y., Frederick, J. R., Woo, Y. J. 2013; 128 (11): S95-104

  Abstract

  Cell-mediated angiogenic therapy for ischemic heart disease has had disappointing results. The lack of clinical translatability may be secondary to cell death and systemic dispersion with cell injection. We propose a novel tissue-engineered therapy, whereby extracellular matrix scaffold seeded with endothelial progenitor cells (EPCs) can overcome these limitations using an environment in which the cells can thrive, enabling an insult-free myocardial cell delivery to normalize myocardial biomechanics.EPCs were isolated from the long bones of Wistar rat bone marrow. The cells were cultured for 7 days in media or seeded at a density of 5 × 10(6) cells/cm(2) on a collagen/vitronectin matrix. Seeded EPCs underwent ex vivo modification with stromal cell-derived factor-1α (100 ng/mL) to potentiate angiogenic properties and enhance paracrine qualities before construct formation. Scanning electron microscopy and confocal imaging confirmed EPC-matrix adhesion. In vitro vasculogenic potential was assessed by quantifying EPC cell migration and vascular differentiation. There was a marked increase in vasculogenesis in vitro as measured by angiogenesis assay (8 versus 0 vessels/hpf; P=0.004). The construct was then implanted onto ischemic myocardium in a rat model of acute myocardial infarction. Confocal microscopy demonstrated a significant migration of EPCs from the construct to the myocardium, suggesting a direct angiogenic effect. Myocardial biomechanical properties were uniaxially quantified by elastic modulus at 5% to 20% strain. Myocardial elasticity normalized after implant of our tissue-engineered construct (239 kPa versus normal=193, P=0.1; versus infarct=304 kPa, P=0.01).We demonstrate restoration and normalization of post-myocardial infarction ventricular biomechanics after therapy with an angiogenic tissue-engineered EPC construct.

  View details for DOI 10.1161/CIRCULATIONAHA.112.000368

  View details for PubMedID 24030426

• Posterior ventricular anchoring neochordal repair of degenerative mitral regurgitation efficiently remodels and repositions posterior leaflet prolapse(dagger) 26th Annual Meeting of the European-Association-for-Cardio-Thoracic-Surgery (EACTS) Woo, Y. J., MacArthur, J. W. OXFORD UNIV PRESS INC. 2013: 485–89

  Abstract

  Mitral valve repair techniques for degenerative disease typically entail leaflet resection or neochordal construction, which may require extensive resection, leaflet detachment/reattachment, reliance on diseased native chords or precise neochordal measuring. Occasionally, impaired leaflet mobility, reduced coaptation surface and systolic anterior motion (SAM) may result. We describe a novel technique for addressing posterior leaflet prolapse/flail, which both simplifies repair and addresses these issues.Fifty-four patients (age 62 ± 11 years) with degenerative MR underwent this new repair, 36 of whom minimally-invasively. A CV5 Gore-Tex suture was placed into the posterior left ventricular myocardium underneath the prolapsing segment as an anchor. This suture was then used to imbricate a portion of the prolapsed segment into the ventricle, creating a smooth, broad, non-prolapsed coapting surface on a leaflet with preserved mobility, additional neochordal support and posteriorly positioned enough to preclude SAM.Repair was successful in all patients. The mean MR grade was reduced from +3.8 to +0.1 with 50 of 54 patients having zero MR and 4 of the 54 having trace or mild MR. All patients had proper antero-posterior location of the coaptation line of a mean length of 10.2 mm, and preserved posterior leaflet mobility. No patients had SAM or mitral stenosis. All patients were discharged and are currently doing well.This new technique facilitated efficient single-suture repair of the prolapsed posterior leaflet mitral regurgitation without the need for resection or sliding annuloplasty. It precluded the need for precise neochordal measurement and preserved the leaflet coaptation surface.

  View details for DOI 10.1093/ejcts/ezt092

  View details for Web of Science ID 000323350400043

  View details for PubMedID 23449863

• Predicting Right Ventricular Failure in the Modern, Continuous Flow Left Ventricular Assist Device Era 59th Annual Meeting of the Southern-Thoracic-Surgical-Association (STSA) Atluri, P., Goldstone, A. B., Fairman, A. S., MacArthur, J. W., Shudo, Y., Cohen, J. E., Acker, A. L., Hiesinger, W., Howard, J. L., Acker, M. A., Woo, Y. J. ELSEVIER SCIENCE INC. 2013: 857–64

  Abstract

  In the era of destination continuous flow left ventricular assist devices (LVAD), the decision of whether a patient will tolerate isolated LVAD support or will need biventricular support (BIVAD) can be challenging. Incorrect decision making with delayed right ventricular (RV) assist device implantation results in increased morbidity and mortality. Continuous flow LVADs have been shown to decrease pulmonary hypertension and improve RV function. We undertook this study to determine predictors in the continuous flow LVAD era that identify patients who are candidates for isolated LVAD therapy as opposed to biventricular support.We reviewed demographic, hemodynamic, laboratory, and echocardiographic variables for 218 patients who underwent VAD implant from 2003 through 2011 (LVAD=167, BIVAD=51), during the era of continuous flow LVADs.Fifty preoperative risk factors were compared between patients who were successfully managed with an LVAD and those who required a BIVAD. Seventeen variables demonstrated statistical significance by univariate analysis. Multivariable logistic regression analysis identified central venous pressure>15 mmHg (OR 2.0, "C"), severe RV dysfunction (OR 3.7, "R"), preoperative intubation (OR 4.3, "I"), severe tricuspid regurgitation (OR 4.1, "T"), heart rate>100 (OR 2.0, Tachycardia-"T")-CRITT as the major criteria predictive of the need for biventricular support. Utilizing these data, a highly sensitive and easy to use risk score for determining RV failure was generated that outperformed other established risk stratification tools.We present a preoperative risk calculator to determine suitability of a patient for isolated LVAD support in the current continuous flow ventricular assist device era.

  View details for DOI 10.1016/j.athoracsur.2013.03.099

  View details for Web of Science ID 000323940200026

  View details for PubMedID 23791165

• Pulmonary Autograft Leaflet Repair and Valve Sparing Root Replacement to Correct Late Failure of the Ross Procedure JOURNAL OF CARDIAC SURGERY Goldstone, A. B., Woo, Y. J. 2013; 28 (5): 496-499

  Abstract

  Delayed pulmonary autograft failure is the principal limitation of the Ross procedure. Although reoperation typically includes replacement of the neoaortic valve, strategies for autograft valve preservation are becoming increasingly employed. However, leaflet prolapse and asymmetry are deterrents to valve preservation in this technically complex surgical population. The present report illustrates the technical considerations in performing an autograft valve preserving aortic root replacement with direct leaflet repair for the surgical correction of aortic insufficiency and root aneurysm late after a successful Ross procedure.

  View details for DOI 10.1111/jocs.12150

  View details for Web of Science ID 000324070400005

  View details for PubMedID 23782261

• Ventricular Assist Device Implant in the Elderly Is Associated With Increased, but Respectable Risk: A Multi-Institutional Study 49th Annual Meeting of the Society-of-Thoracic-Surgeons Atluri, P., Goldstone, A. B., Kobrin, D. M., Cohen, J. E., MacArthur, J. W., Howard, J. L., Jessup, M. L., Rame, J. E., Acker, M. A., Woo, Y. J. ELSEVIER SCIENCE INC. 2013: 141–47

  Abstract

  There are an increasing number of elderly patients with end-stage heart failure. Destination mechanical circulatory support is often the only therapy available for these patients who are not transplant candidates. The outcomes after continuous flow left ventricular assist device (CF LVAD) implant in older patients remains unclear. We undertook this multi-institutional study to quantify short-term and midterm outcomes after CF LVAD implant in the elderly.We retrospectively analyzed all patients in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) national registry that underwent implant of a CF LVAD (June 2006 to April 2012). Patients were divided into 2 cohorts based upon age (<70 years [n = 4,439] and ≥ 70 years (n = 590]). Preoperative, intraoperative, and postoperative variables were analyzed. The primary endpoint, survival, was compared between cohorts.Patients age 70 and older were more hemodynamically stable pre-VAD implant as evidenced by INTERMACS profile and inotrope dependence. Perioperative outcomes, including median bypass time (89 vs 89 minutes) and length of stay (0.657 vs 0.657 months) were similar between cohorts (p = not significant). Kaplan-Meier analysis revealed a significant difference in 2-year survival between patients aged 70 years or greater (63%) and less than 70 (71%, p < 0.001). Multivariable Cox proportional hazard analysis revealed age as an independent predictor of mortality during follow-up (p < 0.001). Nonetheless, midterm cumulative survival in the older cohort was still reasonable (63% at 2 years).Multi-institutional analysis revealed advanced age as a predictor of increased mortality after CF LVAD implantation. Careful patient selection is critical in the elderly to optimize long-term outcomes after CF LVAD implantation.

  View details for DOI 10.1016/j.athoracsur.2013.04.010

  View details for Web of Science ID 000321741300032

  View details for PubMedID 23731606

• Dissected axillary artery cannulation in redo-total arch replacement surgery JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Vallabhajosyula, P., McClure, R. S., Hanson, C. W., Woo, Y. J. 2013; 145 (6): E57-E59

  View details for DOI 10.1016/j.jtcvs.2013.02.020

  View details for Web of Science ID 000319066300003

  View details for PubMedID 23490244

• Ascending Aortic Cannulation in Acute Type A Dissection Repair ANNALS OF THORACIC SURGERY Frederick, J. R., Yang, E., Trubelja, A., Desai, N. D., Szeto, W. Y., Pochettino, A., Bavaria, J. E., Woo, Y. J. 2013; 95 (5): 1808-1811

  Abstract

  Femoral and axillary cannulation for arterial inflow in acute type A aortic dissection are the most commonly used cannulation strategies in current practice. More recently, our group and others have successfully used a central cannulation technique with excellent results. Although this approach has been described, specific technical details have not been clearly defined. In addition, the ideal anatomic characteristics of different types of aortic dissections amenable to central cannulation have not been delineated. The purpose of this brief communication is to describe the technical and procedural details specific to cannulation of the dissected ascending aorta and to propose a classification scheme of ascending aortic dissection anatomy based on difficulty of central cannulation.

  View details for DOI 10.1016/j.athoracsur.2012.10.086

  View details for Web of Science ID 000318969500081

  View details for PubMedID 23608274

• Profound hyperacute cardiac allograft rejection rescue with biventricular mechanical circulatory support and plasmapheresis, intravenous immunoglobulin, and rituximab therapy JOURNAL OF CARDIOTHORACIC SURGERY Kaczorowski, D. J., Datta, J., Kamoun, M., Dries, D. L., Woo, Y. J. 2013; 8

  Abstract

  Hyperacute rejection is a rare but potentially catastrophic complication after cardiac transplantation. We describe an unusual case of hyperacute rejection due to preformed anti-donor antibodies despite a negative preoperative panel-reactive antibody (PRA) screen. An excellent outcome was achieved in this case and our strategy involving the use of CentriMag ventricular assist devices (VADs) for biventricular support during treatment with rituximab, intravenous immunoglobulin (IVIG), and plasmapheresis is illustrated.

  View details for DOI 10.1186/1749-8090-8-48

  View details for Web of Science ID 000317741900001

  View details for PubMedID 23497431

• Minimally invasive approach provides at least equivalent results for surgical correction of mitral regurgitation: A propensity-matched comparison 38th Annual Meeting of the Western-Thoracic-Surgical-Association Goldstone, A. B., Atluri, P., Szeto, W. Y., Trubelja, A., Howard, J. L., MacArthur, J. W., Newcomb, C., Donnelly, J. P., Kobrin, D. M., Sheridan, M. A., Powers, C., Gorman, R. C., Gorman, J. H., Pochettino, A., Bavaria, J. E., Acker, M. A., Hargrove, W. C., Woo, Y. J. MOSBY-ELSEVIER. 2013: 748–56

  Abstract

  Minimally invasive approaches to mitral valve surgery are increasingly used, but the surgical approach must not compromise the clinical outcome for improved cosmesis. We examined the outcomes of mitral repair performed through right minithoracotomy or median sternotomy.Between January 2002 and October 2011, 1011 isolated mitral valve repairs were performed in the University of Pennsylvania health system (455 sternotomies, 556 right minithoracotomies). To account for key differences in preoperative risk profiles, propensity scores identified 201 well-matched patient pairs with mitral regurgitation of any cause and 153 pairs with myxomatous disease.In-hospital mortality was similar between propensity-matched groups (0% vs 0% for the degenerative cohort; 0% vs 0.5%, P = .5 for the overall cohort; in minimally invasive and sternotomy groups, respectively). Incidence of stroke, infection, myocardial infarction, exploration for postoperative hemorrhage, renal failure, and atrial fibrillation also were comparable. Transfusion was less frequent in the minimally invasive groups (11.8% vs 20.3%, P = .04 for the degenerative cohort; 14.0% vs 22.9%, P = .03 for the overall cohort), but time to extubation and discharge was similar. A 99% repair rate was achieved in patients with myxomatous disease, and a minimally invasive approach did not significantly increase the likelihood of a failed repair resulting in mitral valve replacement. Patients undergoing minimally invasive mitral repair were more likely to have no residual post-repair mitral regurgitation (97.4% vs 92.1%, P = .04 for the degenerative cohort; 95.5% vs 89.6%, P = .02 for the overall cohort). In the overall matched cohort, early readmission rates were higher in patients undergoing sternotomies (12.6% vs 4.4%, P = .01). Over 9 years of follow-up, there was no significant difference in long-term survival between groups (P = .8).In appropriate patients with isolated mitral valve disease of any cause, a right minithoracotomy approach may be used without compromising clinical outcome.

  View details for DOI 10.1016/j.jtcvs.2012.09.093

  View details for Web of Science ID 000314882500024

  View details for PubMedID 23414991

• Clinical Risk Factors for Primary Graft Dysfunction after Lung Transplantation AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Diamond, J. M., Lee, J. C., Kawut, S. M., Shah, R. J., Localio, A. R., Bellamy, S. L., Lederer, D. J., Cantu, E., Kohl, B. A., Lama, V. N., Bhorade, S. M., Crespo, M., Demissie, E., Sonett, J., Wille, K., Orens, J., Shah, A. S., Weinacker, A., Arcasoy, S., Shah, P. D., Wilkes, D. S., Ware, L. B., Palmer, S. M., Christie, J. D. 2013; 187 (5): 527-534

  Abstract

  Rationale: Primary graft dysfunction (PGD) is the main cause of early morbidity and mortality after lung transplantation. Previous studies have yielded conflicting results for PGD risk factors. Objectives: We sought to identify donor, recipient, and perioperative risk factors for PGD. Methods: We performed a 10-center prospective cohort study enrolled between March 2002 and December 2010 (the Lung Transplant Outcomes Group). The primary outcome was International Society for Heart and Lung Transplantation grade 3 PGD at 48 or 72 hours post-transplant. The association of potential risk factors with PGD was analyzed using multivariable conditional logistic regression. Measurements and Main Results: A total of 1,255 patients from 10 centers were enrolled; 211 subjects (16.8%) developed grade 3 PGD. In multivariable models, independent risk factors for PGD were any history of donor smoking (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2-2.6; P = 0.002); FiO2 during allograft reperfusion (OR, 1.1 per 10% increase in FiO2; 95% CI, 1.0-1.2; P = 0.01); single lung transplant (OR, 2; 95% CI, 1.2-3.3; P = 0.008); use of cardiopulmonary bypass (OR, 3.4; 95% CI, 2.2-5.3; P < 0.001); overweight (OR, 1.8; 95% CI, 1.2-2.7; P = 0.01) and obese (OR, 2.3; 95% CI, 1.3-3.9; P = 0.004) recipient body mass index; preoperative sarcoidosis (OR, 2.5; 95% CI, 1.1-5.6; P = 0.03) or pulmonary arterial hypertension (OR, 3.5; 95% CI, 1.6-7.7; P = 0.002); and mean pulmonary artery pressure (OR, 1.3 per 10 mm Hg increase; 95% CI, 1.1-1.5; P < 0.001). PGD was significantly associated with 90-day (relative risk, 4.8; absolute risk increase, 18%; P < 0.001) and 1-year (relative risk, 3; absolute risk increase, 23%; P < 0.001) mortality. Conclusions: We identified grade 3 PGD risk factors, several of which are potentially modifiable and should be prioritized for future research aimed at preventative strategies. Clinical trial registered with www.clinicaltrials.gov (NCT 00552357).

  View details for DOI 10.1164/rccm.201210-1865OC

  View details for Web of Science ID 000315977200012

  View details for PubMedID 23306540

• Rapid onset of fulminant myocarditis portends a favourable prognosis and the ability to bridge mechanical circulatory support to recovery EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Atluri, P., Ullery, B. W., MacArthur, J. W., Goldstone, A. B., Fairman, A. S., Hiesinger, W., Acker, M. A., Woo, Y. J. 2013; 43 (2): 379-382

  Abstract

  Fulminant myocarditis with cardiogenic shock is fatal without mechanical circulatory support. Once haemodynamic stability has been established with a ventricular assist device (VAD), the decision to wait for myocardial recovery as opposed to listing for an orthotopic heart transplant (OHT) can be difficult. We have undertaken this study to establish the criteria for determining the need for heart transplantation following VAD implant for fulminant myocarditis.A total of 442 VADs were implanted between 1993 and 2011. Twenty-four VADs were implanted for fulminant myocarditis with refractory cardiogenic shock. We retrospectively analysed the variables and the pathology for this cohort. Patients who had a full recovery of myocardial function and subsequent VAD explant (Explant) were compared with those bridged to OHT. There was one acute death.There was no difference in the past medical history between the groups. Explant patients had a more acute onset of heart failure with a median of 7 days between the onset of symptoms and VAD implant, when compared with 22 days for OHT (P = 0.01). A rapid recovery in myocardial function was seen in the Explant group, with recovery of myocardial function (ejection fraction = 53 ± 24%) in 14 ± 7 days. Myocardial function was sustained for 5 years following the VAD explant. The female gender favoured myocardial recovery and VAD explantability. Two patients had giant cell myocarditis, neither of whom had a recovery of function, and they were bridged to heart transplant with a VAD.Fulminant myocarditis is a fatal condition without mechanical support. The rapid onset of symptoms is associated with a complete recovery of myocardial function and VAD explant. The absence of rapid recovery of myocardial function should prompt listing for a heart transplant.

  View details for DOI 10.1093/ejcts/ezs242

  View details for Web of Science ID 000313829300031

  View details for PubMedID 22564805

• Quantitative evaluation of change in coexistent mitral regurgitation after aortic valve replacement 38th Annual Meeting of the Western-Thoracic-Surgical-Association Kaczorowski, D. J., MacArthur, J. W., Howard, J., Kobrin, D., Fairman, A., Woo, Y. J. MOSBY-ELSEVIER. 2013: 341–48

  Abstract

  Management of intermediate degrees of mitral regurgitation during aortic valve replacement for aortic stenosis remains controversial. We sought to evaluate the degree of reduction of mitral regurgitation in patients undergoing aortic valve replacement, as well as a mathematical relationship between aortic valve gradient reduction and the degree of mitral regurgitation decrement.We retrospectively analyzed demographic, intraoperative, and echocardiographic data on 802 patients who underwent aortic valve replacement or aortic root replacement between January 2010 and March 2011. A total of 578 patients underwent aortic valve replacement or aortic root replacement without intervention on the mitral valve. We excluded 88 patients with severe aortic insufficiency, 3 patients who underwent ventricular assist device placement, 4 patients who underwent prior mitral valve replacement, and 21 patients with incomplete data, yielding 462 patients for analysis. For each patient, the degree of pre- and postoperative mitral regurgitation was graded on a standard 0 to 4+ scale.Of the 462 patients, 289 patients had at least mild mitral regurgitation. On average, mitral regurgitation decreased 0.24 degrees per patient for this cohort of 289 patients. Of the 56 patients with at least moderate mitral regurgitation, mitral regurgitation decreased 0.54 degrees per patient. Of 62 patients who underwent isolated aortic valve replacements, who had at least mild mitral regurgitation, and who had no evidence of structural mitral valve disease, mitral regurgitation decreased 0.24 degrees per patient. Linear regression analysis revealed no relationship between reduction in mitral regurgitation and gradient reduction across the aortic valve.Reduction in mitral regurgitation after relief of aortic outflow tract obstruction is modest at best. Further, the magnitude of gradient change across the aortic valve has little influence on the degree of reduction in mitral regurgitation. These observations argue at minimum for performing a prospective evaluation of the clinical benefits of addressing moderate mitral regurgitation at the time of aortic valve intervention and may support a more aggressive approach to concomitant mitral surgery.

  View details for DOI 10.1016/j.jtcvs.2012.10.043

  View details for Web of Science ID 000313634700010

  View details for PubMedID 23245347

  View details for PubMedCentralID PMC3660734

• 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction: Executive Summary A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines CIRCULATION O'Gara, P. T., Kushner, F. G., Ascheim, D. D., Casey, D. E., Chung, M. K., de Lemos, J. A., Ettinger, S. M., Fang, J. C., Fesmire, F. M., Franklin, B. A., Granger, C. B., Krumholz, H. M., Linderbaum, J. A., Morrow, D. A., Newby, L. K., Ornato, J. P., Ou, N., Radford, M. J., Tamis-Holland, J. E., Tommaso, C. L., Tracy, C. M., Woo, Y. J., Zhao, D. X. 2013; 127 (4): 529-?

  View details for DOI 10.1161/CIR.0b013e3182742c84

  View details for Web of Science ID 000314163600028

  View details for PubMedID 23247303

• 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction: Executive Summary A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY O'Gara, P. T., Kushner, F. G., Ascheim, D. D., Casey, D. E., Chung, M. K., de Lemos, J. A., Ettinger, S. M., Fang, J. C., Fesmire, F. M., Franklin, B. A., Granger, C. B., Krumholz, H. M., Linderbaum, J. A., Morrow, D. A., Newby, L. K., Ornato, J. P., Ou, N., Radford, M. J., Tamis-Holland, J. E., Tommaso, C. L., Tracy, C. M., Woo, Y. J., Zhao, D. X., Anderson, J. L., Jacobs, A. K., Halperin, J. L., Albert, N. M., Brindis, R. G., Creager, M. A., DeMets, D., Guyton, R. A., Hochman, J. S., Kovacs, R. J., Kushner, F. G., Ohman, E. M., Stevenson, W. G., Yancy, C. W. 2013; 61 (4): 485-510

  View details for DOI 10.1016/j.jacc.2012.11.018

  View details for Web of Science ID 000313835300023

  View details for PubMedID 23256913

• Mathematically engineered stromal cell-derived factor-1 alpha stem cell cytokine analog enhances mechanical properties of infarcted myocardium JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY MacArthur, J. W., Trubelja, A., Shudo, Y., Hsiao, P., Fairman, A. S., Yang, E., Hiesinger, W., Sarver, J. J., Atluri, P., Woo, Y. J. 2013; 145 (1): 278-284

  Abstract

  The biomechanical response to a myocardial infarction consists of ventricular remodeling that leads to dilatation, loss of contractile function, abnormal stress patterns, and ultimately heart failure. We hypothesized that intramyocardial injection of our previously designed pro-angiogenic chemokine, an engineered stromal cell-derived factor-1α analog (ESA), improves mechanical properties of the heart after infarction.Male rats (n = 54) underwent either sham surgery (n = 17) with no coronary artery ligation or ligation of the left anterior descending artery (n = 37). The rats in the myocardial infarction group were then randomized to receive either saline (0.1 mL, n = 18) or ESA (6 μg/kg, n = 19) injected into the myocardium at 4 predetermined spots around the border zone. Echocardiograms were performed preoperatively and before the terminal surgery. After 4 weeks, the hearts were explanted and longitudinally sectioned. Uniaxial tensile testing was completed using an Instron 5543 Microtester. Optical strain was evaluated using custom image acquisition software, Digi-Velpo, and analyzed in MATLAB.Compared with the saline control group at 4 weeks, the ESA-injected hearts had a greater ejection fraction (71.8% ± 9.0% vs 55.3% ± 12.6%, P = .0004), smaller end-diastolic left ventricular internal dimension (0.686 ± 0.110 cm vs 0.763 ± 0.160 cm, P = .04), greater cardiac output (36 ± 11.6 mL/min vs 26.9 ± 7.3 mL/min, P = .05), and a lower tensile modulus (251 ± 56 kPa vs 301 ± 81 kPa, P = .04). The tensile modulus for the sham group was 195 ± 56 kPa, indicating ESA injection results in a less stiff ventricle.Direct injection of ESA alters the biomechanical response to myocardial infarction, improving the mechanical properties in the postinfarct heart.

  View details for DOI 10.1016/j.jtcvs.2012.09.080

  View details for Web of Science ID 000312386300047

  View details for PubMedID 23244259

• Postoperative Right Ventricular Failure After Left Ventricular Assist Device Placement is Predicted by Preoperative Echocardiographic Structural, Hemodynamic, and Functional Parameters JOURNAL OF CARDIAC FAILURE Raina, A., Rammohan, H. R., Gertz, Z. M., Rame, J. E., Woo, Y. J., Kirkpatrick, J. N. 2013; 19 (1): 16-24

  Abstract

  Right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation results in significant morbidity and mortality. Preoperative parameters from transthoracic echocardiography (TTE) that predict RVF after LVAD implantation might identify patients in need of temporary or permanent right ventricular (RV) mechanical or inotropic support.Records of all patients who had preoperative TTE before implantation of a permanent LVAD at our institution from 2008 to 2011 were screened, and 55 patients (age 54 ± 16 years, 71% male) were included: 26 had LVAD implantation alone with no postoperative RVF, 16 had LVAD implantation alone but experienced postoperative RVF, and 13 had initial biventricular assist devices (BIVADs). The LVAD with RVF and BIVAD groups (RVF group) were pooled for comparison with the LVAD patients without RVF (No RVF group). RV fractional area change (RV FAC) was significantly lower in the RVF group versus the No RVF group (24% vs 30%; P = .04). Tricuspid annular plane systolic excursion was not different among the groups (1.6 cm vs 1.5 cm; P = .53). Estimated right atrial pressure (RAP) was significantly higher in the RVF group versus the No RVF group (11 mm Hg vs 8 mm Hg; P = .04). Left atrial volume (LAV) index was lower in patients with RVF versus No RVF (27 mL/m(2) vs 40 mL/m(2); P = .008). Combining RV FAC, estimated RAP, and LAV index into an echocardiographic scoring system revealed that the TTE score was highly predictive of RVF (5.0 vs 2.8; P = .0001). In multivariate models combining the TTE score with clinical variables, the score was the most predictive of RVF (odds ratio 1.66, 95% confidence interval 1.06-2.62).Preoperative RV FAC, estimated RAP, and LAV index predict postoperative RVF in patients undergoing LVAD implantation. These parameters may be combined into a simple echocardiographic scoring system to provide an additional tool to risk-stratify patients being evaluated for LVAD implantation.

  View details for DOI 10.1016/j.cardfail.2012.11.001

  View details for Web of Science ID 000313858100003

  View details for PubMedID 23273590

• Elevated Plasma Angiopoietin-2 Levels and Primary Graft Dysfunction after Lung Transplantation PLOS ONE Diamond, J. M., Porteous, M. K., Cantu, E., Meyer, N. J., Shah, R. J., Lederer, D. J., Kawut, S. M., Lee, J., Bellamy, S. L., Palmer, S. M., Lama, V. N., Bhorade, S. M., Crespo, M., Demissie, E., Wille, K., Orens, J., Shah, P. D., Weinacker, A., Weill, D., Arcasoy, S., Wilkes, D. S., Ware, L. B., Christie, J. D. 2012; 7 (12)

  Abstract

  Primary graft dysfunction (PGD) is a significant contributor to early morbidity and mortality after lung transplantation. Increased vascular permeability in the allograft has been identified as a possible mechanism leading to PGD. Angiopoietin-2 serves as a partial antagonist to the Tie-2 receptor and induces increased endothelial permeability. We hypothesized that elevated Ang2 levels would be associated with development of PGD.We performed a case-control study, nested within the multi-center Lung Transplant Outcomes Group cohort. Plasma angiopoietin-2 levels were measured pre-transplant and 6 and 24 hours post-reperfusion. The primary outcome was development of grade 3 PGD in the first 72 hours. The association of angiopoietin-2 plasma levels and PGD was evaluated using generalized estimating equations (GEE).There were 40 PGD subjects and 79 non-PGD subjects included for analysis. Twenty-four PGD subjects (40%) and 47 non-PGD subjects (59%) received a transplant for the diagnosis of idiopathic pulmonary fibrosis (IPF). Among all subjects, GEE modeling identified a significant change in angiopoietin-2 level over time in cases compared to controls (p = 0.03). The association between change in angiopoietin-2 level over the perioperative time period was most significant in patients with a pre-operative diagnosis of IPF (p = 0.02); there was no statistically significant correlation between angiopoietin-2 plasma levels and the development of PGD in the subset of patients transplanted for chronic obstructive pulmonary disease (COPD) (p = 0.9).Angiopoietin-2 levels were significantly associated with the development of PGD after lung transplantation. Further studies examining the regulation of endothelial cell permeability in the pathogenesis of PGD are indicated.

  View details for DOI 10.1371/journal.pone.0051932

  View details for Web of Science ID 000312694300063

  View details for PubMedID 23284823

  View details for PubMedCentralID PMC3526525

• Intracardiac exposure for transventricular mitral valve ring annuloplasty repair during Dor ventriculoplasty JOURNAL OF HEART AND LUNG TRANSPLANTATION Kaczorowski, D. J., Blank, M., Woo, Y. J. 2012; 31 (11): 1236-1238

  View details for DOI 10.1016/j.healun.2012.08.018

  View details for Web of Science ID 000310415600015

  View details for PubMedID 22980953

• Three-Dimensional Echocardiographic Analysis of Mitral Annular Dynamics Implication for Annuloplasty Selection Meeting of the American-Heart-Association Levack, M. M., Jassar, A. S., Shang, E. K., Vergnat, M., Woo, Y. J., Acker, M. A., Jackson, B. M., Gorman, J. H., Gorman, R. C. LIPPINCOTT WILLIAMS & WILKINS. 2012: S183–S188

  Abstract

  Proponents of flexible annuloplasty rings have hypothesized that such devices maintain annular dynamics. This hypothesis is based on the supposition that annular motion is relatively normal in patients undergoing mitral valve repair. We hypothesized that mitral annular dynamics are impaired in ischemic mitral regurgitation and myxomatous mitral regurgitation.A Philips iE33 echocardiographic module and X7-2t probe were used to acquire full-volume real-time 3-dimensional transesophageal echocardiography loops in 11 normal subjects, 11 patients with ischemic mitral regurgitation and 11 patients with myxomatous mitral regurgitation. Image analysis was performed using Tomtec Image Arena, 4D-MV Assessment, 2.1 (Munich, Germany). A midsystolic frame was selected for the initiation of annular tracking using the semiautomated program. Continuous parameters were normalized in time to provide for uniform systolic and diastolic periods. Both ischemic mitral regurgitation (9.98 ± 155 cm(2)) and myxomatous mitral regurgitation annuli (13.29 ± 3.05 cm(2)) were larger in area than normal annuli (7.95 ± 1.40 cm(2)) at midsystole. In general, ischemic mitral regurgitation annuli were less dynamic than controls. In myxomatous mitral regurgitation, annular dynamics were also markedly abnormal with the mitral annulus dilating rapidly in early systole in response to rising ventricular pressure.In both ischemic mitral regurgitation and myxomatous mitral regurgitation, annular dynamics and anatomy are abnormal. Flexible annuloplasty devices used in mitral valve repair are, therefore, unlikely to result in either normal annular dynamics or normal anatomy.

  View details for DOI 10.1161/CIRCULATIONAHA.111.084483

  View details for Web of Science ID 000314150200026

  View details for PubMedID 22965981

• The influence of saddle-shaped annuloplasty on leaflet curvature in patients with ischaemic mitral regurgitation EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Vergnat, M., Levack, M. M., Jassar, A. S., Jackson, B. M., Acker, M. A., Woo, Y. J., Gorman, R. C., Gorman, J. H. 2012; 42 (3): 493-499

  Abstract

  Reports indicate that repair procedures for ischaemic mitral regurgitation (IMR) are less durable than previously thought. Repair failure has been shown to be stress related. Leaflet curvature is the major determinant of valve stress. Theoretical and animal experiments have shown that saddle-shaped annuloplasty optimizes leaflet curvature when compared with standard flat ring annuloplasty. Despite this, the influence of the ring shape on leaflet curvature has not been described in patients with IMR. This study uses real-time three-dimensional echocardiography (rt-3DE) to assess the influence of the ring shape on leaflet curvature.Rt-3DE was performed in 21 patients with IMR after placement of either a flat (n = 10, CE-Physio, Edwards) or saddle-shaped (n = 11, Profile 3D, Medtronic) annuloplasty ring. A combination of commercially available and customized software was used to measure multiple leaflet curvature parameters across all regions of the mitral valve.Independently of the shape of the annuloplasty ring, all patients were subject to the same degree of annular undersizing. Patients who received saddle-shaped annuloplasty rings had greater leaflet curvature in all six mitral valve leaflet regions (A1 = 0.36 ± 0.10, A2 = 0.53 ± 0.13, A3 = 0.47 ± 0.13, P1 = 0.35 ± 0.23, P2 = 0.53 ± 0.34, P3 = 0.42 ± 0.20 cm(-2)) compared with patients who received flat annuloplasty rings (A1 = 0.16 ± 0.11, A2 = 0.18 ± 0.09, A3 = 0.16 ± 0.11, P1 = 0.20 ± 0.17, P2 = 0.21 ± 0.11, P3 = 0.18 ± 0.13 cm(-2)). These differences were statistically significant in all regions except the P1 region.Saddle-shaped annuloplasty rings increase leaflet curvature compared with flat rings in patients with IMR. As a result, saddle-shaped annuloplasty may decrease leaflet stress and potentially increases the durability of the repair in patients with IMR.

  View details for DOI 10.1093/ejcts/ezs040

  View details for Web of Science ID 000307784500018

  View details for PubMedID 22351705

• Aortic valve repair by sinotubular junctional remodeling to eliminate aortic regurgitation in donor cardiac allograft JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Kaczorowski, D. J., Woo, Y. J. 2012; 144 (3): 722-724

  View details for DOI 10.1016/j.jtcvs.2012.03.011

  View details for Web of Science ID 000308064200059

  View details for PubMedID 22487435

• Thoracoabdominal aortic aneurysm. Annals of cardiothoracic surgery Frederick, J. R., Woo, Y. J. 2012; 1 (3): 277-285

  View details for DOI 10.3978/j.issn.2225-319X.2012.09.01

  View details for PubMedID 23977509

• Re-Engineered Stromal Cell-Derived Factor-1 alpha and the Future of Translatable Angiogenic Polypeptide Design TRENDS IN CARDIOVASCULAR MEDICINE Hiesinger, W., Goldstone, A. B., Woo, Y. J. 2012; 22 (6): 139-144

  Abstract

  Smaller engineered analogs of angiogenic cytokines may provide translational advantages, including enhanced stability and function, ease of synthesis, lower cost, and, most important, the potential for modulated delivery via engineered biomaterials. In order to create such a peptide, computational molecular modeling and design was employed to engineer a minimized, highly efficient polypeptide analog of the stromal cell-derived factor-1α (SDF) molecule. After removal of the large, central β-sheet region, a designed diproline linker connected the native N-terminus (responsible for receptor activation and binding) and C-terminus (responsible for extracellular stabilization). This yielded energetic and conformational advantages resulting in a small, low-molecular-weight engineered SDF polypeptide analog (ESA) that was shown to have angiogenic activity comparable to or better than that of recombinant human SDF both in vitro and in a murine model of ischemic heart failure.

  View details for Web of Science ID 000311065900001

  View details for PubMedID 22902182

• Transaortic Mitral Valve Replacement ANNALS OF THORACIC SURGERY Frederick, J. R., Woo, Y. J. 2012; 94 (1): 302-304

  Abstract

  Transaortic replacement of the mitral valve at the time of aortic valve or root replacement is a rarely used technique that offers many possible advantages in the setting of multivalve replacement. Reports in the literature are few and dated. The purpose of this brief communication is to describe technical and procedural details specific to mitral procedures done through the aortic annulus.

  View details for DOI 10.1016/j.athoracsur.2012.01.081

  View details for Web of Science ID 000305801600068

  View details for PubMedID 22735004

• Effects of Atrial Fibrillation on Treatment of Mitral Regurgitation in the EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) Randomized Trial JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Herrmann, H. C., Gertz, Z. M., Silvestry, F. E., Wiegers, S. E., Woo, Y. J., Hermiller, J., Segar, D., Heimansohn, D., Gray, W., Homma, S., Argenziano, M., Wang, A., Jollis, J., Lampert, M. B., Alexander, J., Mauri, L., Foster, E., Glower, D., Feldman, T. 2012; 59 (14): 1312-1319

  Abstract

  The purpose of this study was to characterize patients with mitral regurgitation (MR) and atrial fibrillation (AF) treated percutaneously using the MitraClip device (Abbott Vascular, Abbott Park, Illinois) and compare the results with surgery in this population.The EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) randomized controlled trial compared a less invasive catheter-based treatment for MR with surgery, providing an opportunity to assess the impact of AF on the outcomes of both the MitraClip procedure and surgical repair.The study population included 264 patients with moderately severe or severe MR assessed by an independent echocardiographic core laboratory. Comparison of safety and effectiveness study endpoints at 30 days and 1 year were made using both intention-to-treat and per-protocol (cohort of patients with MR ≤2+ at discharge) analyses.Pre-existing AF was present in 27% of patients. These patients were older, had more advanced disease, and were more likely to have a functional etiology. Similar reduction of MR to ≤2+ before discharge was achieved in patients with AF (83%) and in patients without AF (75%, p = 0.3). Freedom from death, mitral valve surgery for valve dysfunction, and MR >2+ was similar at 12 months for AF patients (64%) and for no-AF patients (61%, p = 0.3). At 12 months, MR reduction to <2+ was greater with surgery than with MitraClip, but there was no interaction between rhythm and MR reduction, and no difference in all-cause mortality between patients with and patients without AF.Atrial fibrillation is associated with more advanced valvular disease and noncardiac comorbidities. However, acute procedural success, safety, and 1-year efficacy with MitraClip therapy is similar for patients with AF and without AF.

  View details for DOI 10.1016/j.jacc.2011.12.023

  View details for Web of Science ID 000302140800009

  View details for PubMedID 22464260

• Myocardial tissue elastic properties determined by atomic force microscopy after stromal cell-derived factor 1 alpha angiogenic therapy for acute myocardial infarction in a murine model 37th Annual Meeting of the Western-Thoracic-Surgical-Association Hiesinger, W., Brukman, M. J., McCormick, R. C., Fitzpatrick, J. R., Frederick, J. R., Yang, E. C., Muenzer, J. R., Marotta, N. A., Berry, M. F., Atluri, P., Woo, Y. J. MOSBY-ELSEVIER. 2012: 962–66

  Abstract

  Ventricular remodeling after myocardial infarction begins with massive extracellular matrix deposition and resultant fibrosis. This loss of functional tissue and stiffening of myocardial elastic and contractile elements starts the vicious cycle of mechanical inefficiency, adverse remodeling, and eventual heart failure. We hypothesized that stromal cell-derived factor 1α (SDF-1α) therapy to microrevascularize ischemic myocardium would rescue salvageable peri-infarct tissue and subsequently improve myocardial elasticity.Immediately after left anterior descending coronary artery ligation, mice were randomly assigned to receive peri-infarct injection of either saline solution or SDF-1α. After 6 weeks, animals were killed and samples were taken from the peri-infarct border zone and the infarct scar, as well as from the left ventricle of noninfarcted control mice. Determination of tissues' elastic moduli was carried out by mechanical testing in an atomic force microscope.SDF-1α-treated peri-infarct tissue most closely approximated the elasticity of normal ventricle and was significantly more elastic than saline-treated peri-infarct myocardium (109 ± 22.9 kPa vs 295 ± 42.3 kPa; P < .0001). Myocardial scar, the strength of which depends on matrix deposition from vasculature at the peri-infarct edge, was stiffer in SDF-1α-treated animals than in controls (804 ± 102.2 kPa vs 144 ± 27.5 kPa; P < .0001).Direct quantification of myocardial elastic properties demonstrates the ability of SDF-1α to re-engineer evolving myocardial infarct and peri-infarct tissues. By increasing elasticity of the ischemic and dysfunctional peri-infarct border zone and bolstering the weak, aneurysm-prone scar, SDF-1α therapy may confer a mechanical advantage to resist adverse remodeling after infarction.

  View details for DOI 10.1016/j.jtcvs.2011.12.028

  View details for Web of Science ID 000301609200036

  View details for PubMedID 22264415

• Simplified nonresectional leaflet remodeling mitral valve repair for degenerative mitral regurgitation JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Woo, Y. J., MacArthur, J. W. 2012; 143 (3): 749-753

  View details for DOI 10.1016/j.jtcvs.2011.08.024

  View details for Web of Science ID 000300617300039

  View details for PubMedID 21943963

• Design, rationale, and initiation of the Surgical Interventions for Moderate Ischemic Mitral Regurgitation Trial: A report from the Cardiothoracic Surgical Trials Network JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Smith, P. K., Michler, R. E., Woo, Y. J., Alexander, J. H., Puskas, J. D., Parides, M. K., Hahn, R. T., Williams, J. B., Dent, J. M., Ferguson, T. B., Moquete, E., Rose, E. A., Page, P., Jeffries, N. O., O'Gara, P. T., Ascheim, D. D. 2012; 143 (1): 111-U175

  Abstract

  Patients with coronary artery disease complicated by moderate ischemic mitral regurgitation have demonstrably poorer outcome than do patients with coronary artery disease but without mitral regurgitation. The optimal treatment of this condition has become increasingly controversial, and a randomized trial evaluating current practices is warranted.We describe the design and initial execution of the Cardiothoracic Surgical Trials Network Surgical Interventions for Moderate Ischemic Mitral Regurgitation Trial.This is an ongoing prospective, multicenter, randomized, controlled clinical trial designed to test the safety and efficacy of mitral repair in addition to coronary artery bypass grafting in the treatment of moderate ischemic mitral regurgitation.The results of the Cardiothoracic Surgical Trials Network Surgical Interventions for Moderate Ischemic Mitral Regurgitation Trial will provide long-awaited information on controversial therapies for this morbid disease process.

  View details for DOI 10.1016/j.jtcvs.2011.05.006

  View details for Web of Science ID 000298151800018

  View details for PubMedID 21788032

• Durability of Porcine Bioroots in Younger Patients With Aortic Root Pathology: A Propensity-Matched Comparison With Composite Mechanical Roots Surgical Motion Picture Session of the 46th Annual Meeting of the Society-of-Thoracic-Surgeons Desai, N. D., McCarthy, F., Moser, W., Szeto, W. Y., Zeeshan, A., Brown, D., Woo, Y. J., Pochettino, A., Moeller, P., Bavaria, J. E. ELSEVIER SCIENCE INC. 2011: 2054–61

  Abstract

  We present a comparison of porcine bioroot and composite mechanical root replacement in a large series of patients younger than 60 years who required full root replacement for true root pathology.Between 1997 and 2007, we performed 986 aortic root replacement procedures, including 391 porcine bioroots and 515 composite mechanical roots for true root indications. Of these, 504 patients were younger than 60 years old at time of the operation. Porcine bioroots were placed in 138 patients, including 38 St. Jude Toronto Root (St. Jude Inc, St. Paul, MN), 98 Medtronic Freestyle (Medtronic Inc, Minneapolis, MN), and 2 Edwards Prima (Edwards Lifesciences Inc, Irvine, CA). Standard univariate, logistic regression, Cox regression, and propensity matching techniques were used.To adjust for baseline differences in risk factor profiles, propensity matching yielded a final matched data set of 128 matched pairs, with no differences in preoperative risk factor profile or indication for operation. Overall 30-day operative mortality was 2.3% for porcine bioroot patients vs 1.6% for mechanical root patients (p = 0.6). Root type did not influence early (odds ratio, 0.8; 96% confidence interval, 0.2 to 3.2) or late mortality (hazard risk, 1.4; 95% confidence interval, 0 0.5 to 3.8). Multivariate predictors of late mortality included (hazard ratio, 95% confidence interval) age in years (1.01; 1.01 to 1.03), chronic renal failure (3.6; 1.1 to 12.6), and preoperative bacterial endocarditis (3.6; 1.1 to 11.8). Freedom from reoperation was similar between groups; however, bleeding events were more common among mechanical root patients.Porcine bioroots provide durable midterm to late-term outcomes after aortic root replacement for true root indications and are an appealing alternative in younger patients because they limit morbidity associated with anticoagulant-related bleeding.

  View details for DOI 10.1016/j.athoracsur.2011.02.020

  View details for Web of Science ID 000297333300026

  View details for PubMedID 21839980

• Who Needs an RVAD in Addition to an LVAD? CARDIOLOGY CLINICS Kaczorowski, D. J., Woo, Y. J. 2011; 29 (4): 599-?

  Abstract

  Mechanical circulatory support using left ventricular assist devices (LVAD) has become an accepted mode of therapy for both bridging patients with end-stage heart failure to transplant and as a destination therapy. Right ventricular (RV) dysfunction is common after LVAD insertion and is a significant source of morbidity and mortality in patients undergoing LVAD placement. Several studies have identified clinical, laboratory, hemodynamic, and echocardiographic parameters that may serve as risk factors for RV dysfunction after LVAD placement. Furthermore, scoring systems have been established to help quantitatively predict the potential need for RV support after LVAD placement.

  View details for DOI 10.1016/j.ccl.2011.08.011

  View details for Web of Science ID 000297822800018

  View details for PubMedID 22062210

• Obesity and Primary Graft Dysfunction after Lung Transplantation The Lung Transplant Outcomes Group Obesity Study AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Lederer, D. J., Kawut, S. M., Wickersham, N., Winterbottom, C., Bhorade, S., Palmer, S. M., Lee, J., Diamond, J. M., Wille, K. M., Weinacker, A., Lama, V. N., Crespo, M., Orens, J. B., Sonett, J. R., Arcasoy, S. M., Ware, L. B., Christie, J. D. 2011; 184 (9): 1055-1061

  Abstract

  Obesity has been linked to acute lung injury and is a risk factor for early mortality after lung transplantation.To examine the associations of obesity and plasma adipokines with the risk of primary graft dysfunction after lung transplantation.We performed a prospective cohort study of 512 adult lung transplant recipients with chronic obstructive pulmonary disease or interstitial lung disease enrolled in the Lung Transplant Outcomes Group Study. In a nested case-control study, we measured plasma leptin, adiponectin, and resistin before lung transplantation and 6 and 24 hours after lung transplantation in 40 cases of primary graft dysfunction and 80 control subjects. Generalized linear mixed models and logistic regression were used to estimate risk ratios and odds ratios.Grade 3 primary graft dysfunction developed within 72 hours of transplantation in 29% participants. Obesity was associated with a twofold increased risk of primary graft dysfunction (adjusted risk ratio 2.1; 95% confidence interval, 1.7-2.6). The risk of primary graft dysfunction increased by 40% (confidence interval, 30–50%) for each 5 kg/m(2) increase in body mass index after accounting for center, diagnosis, cardiopulmonary bypass, and transplant procedure. Higher plasma leptin levels were associated with a greater risk of primary graft dysfunction (sex-adjusted P = 0.02). The associations of both obesity and leptin with primary graft dysfunction tended to be stronger among those who did not undergo cardiopulmonary bypass.Obesity is an independent risk factor for primary graft dysfunction after lung transplantation.

  View details for DOI 10.1164/rccm.201104-0728OC

  View details for Web of Science ID 000296613900015

  View details for PubMedID 21799077

  View details for PubMedCentralID PMC3208644

• Transventricular mitral valve operations. Annals of thoracic surgery Joseph Woo, Y., McCormick, R. C. 2011; 92 (4): 1501-1503

  Abstract

  We report transventricular mitral valve operations in 2 patients with severe mitral regurgitation and postinfarction left ventricular rupture and pseudoaneurysm. The first patient had direct papillary muscle involvement necessitating replacement of the mitral valve. The second patient had indirect mitral involvement allowing for placement of an atrial mitral annuloplasty ring via the left ventricle. Both patients showed no mitral valve regurgitation after replacement or repair and had uneventful postoperative recoveries. These cases demonstrate a feasible, alternative, transventricular approach to mitral valve replacement and repair.

  View details for DOI 10.1016/j.athoracsur.2010.10.065

  View details for PubMedID 21958802

• Computational Protein Design to Reengineer Stromal Cell-Derived Factor-1 alpha Generates an Effective and Translatable Angiogenic Polypeptide Analog Annual Meeting of the American-Heart-Association Hiesinger, W., Perez-Aguilar, J. M., Atluri, P., Marotta, N. A., Frederick, J. R., Fitzpatrick, J. R., McCormick, R. C., Muenzer, J. R., Yang, E. C., Levit, R. D., Yuan, L., MacArthur, J. W., Saven, J. G., Woo, Y. J. LIPPINCOTT WILLIAMS & WILKINS. 2011: S18–S26

  Abstract

  Experimentally, exogenous administration of recombinant stromal cell-derived factor-1α (SDF) enhances neovasculogenesis and cardiac function after myocardial infarction. Smaller analogs of SDF may provide translational advantages including enhanced stability and function, ease of synthesis, lower cost, and potential modulated delivery via engineered biomaterials. In this study, computational protein design was used to create a more efficient evolution of the native SDF protein.Protein structure modeling was used to engineer an SDF polypeptide analog (engineered SDF analog [ESA]) that splices the N-terminus (activation and binding) and C-terminus (extracellular stabilization) with a diproline segment designed to limit the conformational flexibility of the peptide backbone and retain the relative orientation of these segments observed in the native structure of SDF. Endothelial progenitor cells (EPCs) in ESA gradient, assayed by Boyden chamber, showed significantly increased migration compared with both SDF and control gradients. EPC receptor activation was evaluated by quantification of phosphorylated AKT, and cells treated with ESA yielded significantly greater phosphorylated AKT levels than SDF and control cells. Angiogenic growth factor assays revealed a distinct increase in angiopoietin-1 expression in the ESA- and SDF-treated hearts. In addition, CD-1 mice (n=30) underwent ligation of the left anterior descending coronary artery and peri-infarct intramyocardial injection of ESA, SDF-1α, or saline. At 2 weeks, echocardiography demonstrated a significant gain in ejection fraction, cardiac output, stroke volume, and fractional area change in mice treated with ESA compared with controls.Compared with native SDF, a novel engineered SDF polypeptide analog (ESA) more efficiently induces EPC migration and improves post-myocardial infarction cardiac function and thus offers a more clinically translatable neovasculogenic therapy.

  View details for DOI 10.1161/CIRCULATIONAHA.110.009431

  View details for Web of Science ID 000294782800003

  View details for PubMedID 21911811

• Saddle-shape annuloplasty increases mitral leaflet coaptation after repair for flail posterior leaflet. Annals of thoracic surgery Vergnat, M., Jackson, B. M., Cheung, A. T., Weiss, S. J., Ratcliffe, S. J., Gillespie, M. J., Woo, Y. J., Bavaria, J. E., Acker, M. A., Gorman, R. C., Gorman, J. H. 2011; 92 (3): 797-803

  Abstract

  The primary goal of surgical mitral repair is the reestablishment of normal leaflet coaptation. Surgical techniques that maintain or restore leaflet geometry promote leaflet coaptation. Recent 3-dimensional (3D) echocardiographic studies have shown that saddle-shaped annuloplasty has a salutary influence on leaflet geometry. Therefore we hypothesized that saddle-shaped annuloplasty would improve leaflet coaptation in cases of repair for flail posterior leaflet segments.Sixteen patients with flail posterior segment and severe mitral regurgitation had valve repair using standard techniques. Eight patients received saddle-shaped annuloplasty and 8 patients received flat annuloplasty. Real-time 3D transesophageal echocardiography was performed before and after repair. Images were analyzed using custom software to calculate mitral annular area (MAA), septolateral dimension (SLD), intercommissural width (CW), total leaflet area (TLA), and leaflet coaptation area (LCA).Postrepair MAA (flat, 588.6±26.5 mm2; saddle, 628.0±35.3 mm2; p=0.12) and TLA (flat, 2198.5±151.6 mm2; saddle, 2303.9±183.8 mm2; p=0.67) were similar in both groups. Postrepair LCA was significantly greater in the saddle group than in the flat group (226.8±24.0 mm2 and 154.0±13.0 mm2, respectively; p=0.02).Real-time 3D echocardiography and novel imaging software provide a powerful tool for analyzing mitral leaflet coaptation. When compared with flat annuloplasty, saddle-shaped annuloplasty improves LCA after mitral valve repair for severe mitral regurgitation secondary to flail posterior leaflet segment. Use of saddle-shaped annuloplasty devices may increase repair durability.

  View details for DOI 10.1016/j.athoracsur.2011.04.047

  View details for PubMedID 21803330

• Oxygen-dependent quenching of phosphorescence used to characterize improved myocardial oxygenation resulting from vasculogenic cytokine therapy JOURNAL OF APPLIED PHYSIOLOGY Hiesinger, W., Vinogradov, S. A., Atluri, P., Fitzpatrick, J. R., Frederick, J. R., Levit, R. D., McCormick, R. C., Muenzer, J. R., Yang, E. C., Marotta, N. A., MacArthur, J. W., Wilson, D. F., Woo, Y. J. 2011; 110 (5): 1460-1465

  Abstract

  This study evaluates a therapy for infarct modulation and acute myocardial rescue and utilizes a novel technique to measure local myocardial oxygenation in vivo. Bone marrow-derived endothelial progenitor cells (EPCs) were targeted to the heart with peri-infarct intramyocardial injection of the potent EPC chemokine stromal cell-derived factor 1α (SDF). Myocardial oxygen pressure was assessed using a noninvasive, real-time optical technique for measuring oxygen pressures within microvasculature based on the oxygen-dependent quenching of the phosphorescence of Oxyphor G3. Myocardial infarction was induced in male Wistar rats (n = 15) through left anterior descending coronary artery ligation. At the time of infarction, animals were randomized into two groups: saline control (n = 8) and treatment with SDF (n = 7). After 48 h, the animals underwent repeat thoracotomy and 20 μl of the phosphor Oxyphor G3 was injected into three areas (peri-infarct myocardium, myocardial scar, and remote left hindlimb muscle). Measurements of the oxygen distribution within the tissue were then made in vivo by applying the end of a light guide to the beating heart. Compared with controls, animals in the SDF group exhibited a significantly decreased percentage of hypoxic (defined as oxygen pressure ≤ 15.0 Torr) peri-infarct myocardium (9.7 ± 6.7% vs. 21.8 ± 11.9%, P = 0.017). The peak oxygen pressures in the peri-infarct region of the animals in the SDF group were significantly higher than the saline controls (39.5 ± 36.7 vs. 9.2 ± 8.6 Torr, P = 0.02). This strategy for targeting EPCs to vulnerable peri-infarct myocardium via the potent chemokine SDF-1α significantly decreased the degree of hypoxia in peri-infarct myocardium as measured in vivo by phosphorescence quenching. This effect could potentially mitigate the vicious cycle of myocyte death, myocardial fibrosis, progressive ventricular dilatation, and eventual heart failure seen after acute myocardial infarction.

  View details for DOI 10.1152/japplphysiol.01138.2010

  View details for Web of Science ID 000290472400043

  View details for PubMedID 21292844

  View details for PubMedCentralID PMC3098666

• Tissue-Specific Variability in Human Epicardial Impedance JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY Jacobson, J. T., Hutchinson, M. D., Cooper, J. M., Woo, Y. J., Shandler, R. S., Callans, D. J. 2011; 22 (4): 436-439

  Abstract

  Epicardial ablation can be employed to treat ventricular tachycardia. Voltage attenuation in regions of fat can mimic epicardial scar, limiting its specificity. Ablation over fat may not be as effective. Prior animal data have shown that infarcted myocardium has lower impedance than normal, and human bioimpedance studies suggest peripheral fat displays higher impedance. Therefore, we tested the hypothesis that human epicardial fat has higher impedance than myocardium when measured with standard ablation tools.Patients undergoing elective surgery for coronary artery or valve disease were enrolled. A reference patch was placed on the patients' back between the scapulae and connected to a standard RF generator (Stockert, GmBH, Germany). Impedance was measured by passing a 1 μA, 50 kHz current from the catheter tip to the patch. After sternotomy but before initiation of cardiopulmonary bypass, an ablation catheter (Celsius, Biosense Webster, Diamond Bar, CA, USA) was placed onto the epicardial surface in ventricular regions visually identified as fat or myocardium. At each site, impedance was recorded from the generator.A total of 37 (7 patients) points were sampled. Impedance was significantly higher in regions of fat versus normal muscle (697 Ω vs. 301 Ω; P = 0.01). Moreover, normal sites from the LV had higher impedance than from the RV (381 Ω vs. 271 Ω; P = 0.01).Human epicardial fat has higher tissue impedance than normal muscle. Using epicardial impedance and voltage mapping in conjunction may improve differentiation of arrhythmia substrate from epicardial fat and improve the efficacy of epicardial ablation.

  View details for DOI 10.1111/j.1540-8167.2010.01929.x

  View details for Web of Science ID 000289470700013

  View details for PubMedID 20946231

• Forecasting the Future of Cardiovascular Disease in the United States A Policy Statement From the American Heart Association CIRCULATION Heidenreich, P. A., Trogdon, J. G., Khavjou, O. A., Butler, J., Dracup, K., Ezekowitz, M. D., Finkelstein, E. A., Hong, Y., Johnston, S. C., Khera, A., Lloyd-Jones, D. M., Nelson, S. A., Nichol, G., Orenstein, D., Wilson, P. W., Woo, Y. J. 2011; 123 (8): 933-944

  Abstract

  Cardiovascular disease (CVD) is the leading cause of death in the United States and is responsible for 17% of national health expenditures. As the population ages, these costs are expected to increase substantially.To prepare for future cardiovascular care needs, the American Heart Association developed methodology to project future costs of care for hypertension, coronary heart disease, heart failure, stroke, and all other CVD from 2010 to 2030. This methodology avoided double counting of costs for patients with multiple cardiovascular conditions. By 2030, 40.5% of the US population is projected to have some form of CVD. Between 2010 and 2030, real (2008$) total direct medical costs of CVD are projected to triple, from $273 billion to $818 billion. Real indirect costs (due to lost productivity) for all CVD are estimated to increase from $172 billion in 2010 to $276 billion in 2030, an increase of 61%.These findings indicate CVD prevalence and costs are projected to increase substantially. Effective prevention strategies are needed if we are to limit the growing burden of CVD.

  View details for DOI 10.1161/CIR.0b013e31820a55f5

  View details for Web of Science ID 000287801300021

  View details for PubMedID 21262990

• Implantable Ventricular Assist Device Exchange With Focused Intravascular Deairing Techniques ANNALS OF THORACIC SURGERY Woo, Y. J., Acker, M. A. 2011; 91 (1): 306-307

  Abstract

  As ventricular assist devices are increasingly adopted and widely implemented as a highly effective therapy for end-stage heart disease, extended utilization periods for destination therapy or bridge-to-transplantation have created the possibility of device failure, infection, or thrombosis, requiring challenging implant exchanges. A major problem in these operations is the risk of air embolization, particularly in a nonsternotomy approach that precludes access to the outflow aortic graft and to the ascending aorta. We report a minimally invasive, nonsternotomy HeartMate II implantable left ventricular assist device (LVAD) exchange, using peripheral cardiopulmonary support and a novel approach to continuous intravascular ascending aortic air removal.

  View details for DOI 10.1016/j.athoracsur.2010.04.012

  View details for Web of Science ID 000285411700063

  View details for PubMedID 21172546

• Mechanical Circulatory Assistance - An Evolving Therapy CIRCULATION JOURNAL Fitzpatrick, J. R., Woo, Y. J. 2011; 75 (1): 38-46

  Abstract

  Although heart transplantation is the gold standard for the treatment of advanced stage heart failure, the implantation of mechanical circulatory support devices (MCSDs) has become a well-established therapy for this disease. As the population of patients with severe heart failure has grown, the utilization of MCSDs has increased considerably. That trend is expected to continue, especially in light of dramatic advances in MCSD technology. This review outlines the current status and future directions of mechanical circulatory support therapy in the setting of a constantly evolving field of supportive devices and adjuvant therapies.

  View details for DOI 10.1253/circj.CJ-10-1091

  View details for Web of Science ID 000285814300005

• Outcomes of coronary artery bypass grafting and reduction annuloplasty for functional ischemic mitral regurgitation: A prospective multicenter study (Randomized Evaluation of a Surgical Treatment for Off-Pump Repair of the Mitral Valve) 36th Annual Meeting of the Western-Thoracic-Surgical-Association Grossi, E. A., Woo, J., Patel, N., Goldberg, J. D., Schwartz, C. F., Subramanian, V. A., Genco, C., Goldman, S. M., Zenati, M. A., Wolfe, J. A., Mishra, Y. K., Trehan, N. MOSBY-ELSEVIER. 2011: 91–97

  Abstract

  Functional ischemic mitral regurgitation is a complication of ventricular remodeling; standard therapy is reduction annuloplasty and coronary artery bypass grafting. Unfortunately, outcomes are retrospective and contradictory. We report a multicenter study that documents the outcomes of reduction annuloplasty for functional ischemic mitral regurgitation.Twenty-one centers randomized 75 patients to the coronary artery bypass grafting + reduction annuloplasty subgroup that was the control arm of the Randomized Evaluation of a Surgical Treatment for Off-pump Repair of the Mitral Valve trial. Entry criteria included patients requiring revascularization, patients with severe or symptomatic moderate functional ischemic mitral regurgitation, an ejection fraction 25% or greater, a left ventricular end-diastolic dimension 7.0 cm or less, and more than 30 days since acute myocardial infarction. All echocardiograms were independently scored by a core laboratory. Reduction annuloplasty was achieved by device annuloplasty. Two patients underwent immediate intraoperative conversion to a valve replacement because reduction annuloplasty was unable to correct mitral regurgitation; as-treated results are presented.Thirty-day mortality was 4.1% (3/73). Patients received an average of 2.8 bypass grafts. Mean follow-up was 24.6 months. Mitral regurgitation was reduced from 2.6 ± 0.8 preoperatively to 0.3 ± 0.6 at 2 years. Freedom from death or valve reoperation was 78% ± 5% at 2 years. There was significant improvement in ejection fraction and New York Heart Association class with reduction of left ventricular end-diastolic dimension. Cox regression analyses suggested that increasing age (P = .001; hazard ratio, 1.16 per year; 95% confidence interval, 1.06-1.26) and renal disease (P = .018; hazard ratio, 3.48; 95% confidence interval, 1.25-9.72) were associated with decreased survival.Coronary artery bypass grafting + reduction annuloplasty for functional ischemic mitral regurgitation predictably reduces mitral regurgitation and relieves symptoms. This treatment of moderate to severe mitral regurgitation is associated with improved indices of ventricular function, improved New York Heart Association class, and excellent freedom from recurrent mitral insufficiency. Although long-term prognosis remains guarded, this multicenter study delineates the intermediate-term benefits of such an approach.

  View details for DOI 10.1016/j.jtcvs.2010.08.057

  View details for Web of Science ID 000285407500019

  View details for PubMedID 21168015

• Minimally invasive robotic mitral valve surgery EXPERT REVIEW OF MEDICAL DEVICES Atluri, P., Woo, Y. J. 2011; 8 (1): 115-120

  Abstract

  Over the past two decades, significant advances have been made in mitral valve surgery. Cardiac surgeons have successfully repaired degenerative and ischemic regurgitant mitral valves via a traditional midline sternotomy. In recent years, alternate incisions have yielded minimally invasive approaches to the mitral valve. Technological advances have made robotically assisted minimally invasive mitral valve surgery feasible. Decreased pain, more rapid return to work, diminished blood loss and reduced length of hospitalization have been witnessed following robotic mitral valve surgery when compared with a traditional sternotomy. Equivalent long-term mortality and freedom from recurrent mitral regurgitation are evident between mitral valve repair performed via a traditional sternotomy and minimally invasive and robotic techniques. As a result, an increasing number of patients and referring cardiologists are seeking minimally invasive approaches to mitral valve surgery.

  View details for DOI 10.1586/ERD.10.66

  View details for Web of Science ID 000289451500017

  View details for PubMedID 21158546

• Outcomes of the RESTOR-MV Trial (Randomized Evaluation of a Surgical Treatment for Off-Pump Repair of the Mitral Valve) JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Grossi, E. A., Patel, N., Woo, Y. J., Goldberg, J. D., Schwartz, C. F., Subramanian, V., Feldman, T., Bourge, R., Baumgartner, N., Genco, C., Goldman, S., Zenati, M., Wolfe, J. A., Mishra, Y. K., Trehan, N., Mittal, S., Shang, S., Mortier, T. J., Schweich, C. J. 2010; 56 (24): 1984-1993

  Abstract

  we sought to determine whether patients with functional mitral regurgitation (FMR) would benefit from ventricular reshaping by the Coapsys device (Myocor, Inc., Maple Grove, Minnesota).FMR occurs when ventricular remodeling impairs valve function. Coapsys is a ventricular shape change device placed without cardiopulmonary bypass to reduce FMR. It compresses the mitral annulus and reshapes the ventricle. We hypothesized that Coapsys for FMR would improve clinical outcomes compared with standard therapies.RESTOR-MV (Randomized Evaluation of a Surgical Treatment for Off-Pump Repair of the Mitral Valve) was a randomized, prospective, multicenter study of patients with FMR and coronary disease with core laboratory analysis. After enrollment, patients were stratified to the standard indicated surgery: either coronary artery bypass graft alone or coronary artery bypass graft with mitral valve repair. In each stratum, randomization was to either control (indicated surgery) or treatment (coronary artery bypass graft with Coapsys ventricular reshaping).the study was terminated when the sponsor failed to secure ongoing funding; 165 patients were randomized. Control and Coapsys both produced decreases in left ventricular (LV) end-diastolic dimension and MR at 2 years (p < 0.001); Coapsys provided a greater decrease in LV end-diastolic dimension (p = 0.021). Control had lower MR grades during follow-up (p = 0.01). Coapsys showed a survival advantage compared with control at 2 years (87% vs. 77%) (hazard ratio: 0.421; 95% confidence interval: 0.200 to 0.886; stratified log-rank test; p = 0.038). Complication-free survival (including death, stroke, myocardial infarction, and valve reoperation) was significantly greater with Coapsys at 2 years (85% vs. 71%) (hazard ratio: 0.372; 95% confidence interval: 0.185 to 0.749; adjusted log-rank test; p = 0.019).analysis of RESTOR-MV indicates that patients with FMR requiring revascularization treated with ventricular reshaping rather than standard surgery had improved survival and a significant decrease in major adverse outcomes. This trial validates the concept of the ventricular reshaping strategy in this subset of patients with heart failure. (Randomized Evaluation of a Surgical Treatment for Off-Pump Repair of the Mitral Valve [RESTOR-MV]; NCT00120276).

  View details for DOI 10.1016/j.jacc.2010.06.051

  View details for Web of Science ID 000284822500003

  View details for PubMedID 21126639

• Acute Myocardial Rescue with Endogenous Endothelial Progenitor Cell Therapy HEART LUNG AND CIRCULATION Atluri, P., Panlilio, C. M., Liao, G. P., Hiesinger, W., Harris, D. A., McCormick, R. C., Cohen, J. E., Jin, T., Feng, W., Levit, R. D., Dong, N., Woo, Y. J. 2010; 19 (11): 644-654

  Abstract

  Post-myocardial infarction heart failure is a major health concern with limited therapy. Molecular revascularisation utilising granulocyte-macrophage colony stimulating factor (GMCSF) mediated endothelial progenitor cell (EPC) upregulation and stromal cell derived factor-1α (SDF) mediated myocardial EPC chemokinesis, may prevent myocardial loss and adverse remodelling. Vasculogenesis, viability, and haemodynamic improvements following therapy were investigated.Lewis rats (n=91) underwent LAD ligation and received either intramyocardial SDF and subcutaneous GMCSF or saline injections at the time of infarction. Molecular and haemodynamic assessments were performed at pre-determined time points following ligation.SDF/GMCSF therapy upregulated EPC density as shown by flow cytometry (0.12±0.02% vs. 0.06±0.01% circulating lymphocytes, p=0.005), 48hours following infarction. A marked increase in perfusion was evident eight weeks after therapy, utilising confocal angiography (5.02±1.7×10(-2)μm(3)blood/μm(3)myocardial tissue vs. 2.03±0.710(-2)μm(3)blood/μm(3)myocardial tissue, p=0.00004). Planimetric analysis demonstrated preservation of wall thickness (0.98±0.09mm vs. 0.67±0.06mm, p=0.003) and ventricular diameter (7.81±0.99mm vs. 9.41±1.1mm, p=0.03). Improved haemodynamic function was evidenced by echocardiography and PV analysis (ejection fraction: 56.4±18.1% vs. 25.3±15.6%, p=0.001; pre-load adjusted maximal power: 6.6±2.6mW/μl(2) vs. 2.7±1.4mW/μl(2), p=0.01).Neovasculogenic therapy with GMCSF-mediated EPC upregulation and SDF-mediated EPC chemokinesis maybe an effective therapy for infarct modulation and preservation of myocardial function following acute myocardial infarction.

  View details for DOI 10.1016/j.hlc.2010.06.1056

  View details for Web of Science ID 000283908600002

  View details for PubMedID 20719564

  View details for PubMedCentralID PMC3235678

• Spliced stromal cell-derived factor-1 alpha analog stimulates endothelial progenitor cell migration and improves cardiac function in a dose-dependent manner after myocardial infarction JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Hiesinger, W., Frederick, J. R., Atluri, P., McCormick, R. C., Marotta, N., Muenzer, J. R., Woo, Y. J. 2010; 140 (5): 1174-1180

  Abstract

  Stromal cell-derived factor (SDF)-1α is a potent endogenous endothelial progenitor cell (EPC) chemokine and key angiogenic precursor. Recombinant SDF-1α has been demonstrated to improve neovasculogenesis and cardiac function after myocardial infarction (MI) but SDF-1α is a bulky protein with a short half-life. Small peptide analogs might provide translational advantages, including ease of synthesis, low manufacturing costs, and the potential to control delivery within tissues using engineered biomaterials. We hypothesized that a minimized peptide analog of SDF-1α, designed by splicing the N-terminus (activation and binding) and C-terminus (extracellular stabilization) with a truncated amino acid linker, would induce EPC migration and preserve ventricular function after MI.EPC migration was first determined in vitro using a Boyden chamber assay. For in vivo analysis, male rats (n = 48) underwent left anterior descending coronary artery ligation. At infarction, the rats were randomized into 4 groups and received peri-infarct intramyocardial injections of saline, 3 μg/kg of SDF-1α, 3 μg/kg of spliced SDF analog, or 6 μg/kg spliced SDF analog. After 4 weeks, the rats underwent closed chest pressure volume conductance catheter analysis.EPCs showed significantly increased migration when placed in both a recombinant SDF-1α and spliced SDF analog gradient. The rats treated with spliced SDF analog at MI demonstrated a significant dose-dependent improvement in end-diastolic pressure, stroke volume, ejection fraction, cardiac output, and stroke work compared with the control rats.A spliced peptide analog of SDF-1α containing both the N- and C- termini of the native protein induced EPC migration, improved ventricular function after acute MI, and provided translational advantages compared with recombinant human SDF-1α.

  View details for DOI 10.1016/j.jtcvs.2010.08.012

  View details for Web of Science ID 000283057600043

  View details for PubMedID 20951261

• Stromal Cell-Derived Factor-1 alpha Activation of Tissue-Engineered Endothelial Progenitor Cell Matrix Enhances Ventricular Function After Myocardial Infarction by Inducing Neovasculogenesis 82nd National Conference and Exhibitions and Annual Scientific Session of the American-Heart-Association Frederick, J. R., Fitzpatrick, J. R., McCormick, R. C., Harris, D. A., Kim, A., Muenzer, J. R., Marotta, N., Smith, M. J., Cohen, J. E., Hiesinger, W., Atluri, P., Woo, Y. J. LIPPINCOTT WILLIAMS & WILKINS. 2010: S107–S117

  Abstract

  Myocardial ischemia causes cardiomyocyte death, adverse ventricular remodeling, and ventricular dysfunction. Endothelial progenitor cells (EPCs) have been shown to ameliorate this process, particularly when activated with stromal cell-derived factor-1α (SDF), known to be the most potent EPC chemokine. We hypothesized that implantation of a tissue-engineered extracellular matrix (ECM) scaffold seeded with EPCs primed with SDF could induce borderzone neovasculogenesis, prevent adverse geometric remodeling, and preserve ventricular function after myocardial infarction.Lewis rats (n=82) underwent left anterior descending artery ligation to induce myocardial infarction. EPCs were isolated, characterized, and cultured on a vitronectin/collagen scaffold and primed with SDF to generate the activated EPC matrix (EPCM). EPCM was sutured to the anterolateral left ventricular wall, which included the region of ischemia. Control animals received sutures but no EPCM. Additional groups underwent application of the ECM alone, ECM primed with SDF (ECM+SDF), and ECM seeded with EPCs but not primed with SDF (ECM+SDF). At 4 weeks, borderzone myocardial tissue demonstrated increased levels of vascular endothelial growth factor in the EPCM group. When compared to controls, Vessel density as assessed by immunohistochemical microscopy was significantly increased in the EPCM group (4.1 versus 6.2 vessels/high-powered field; P<0.001), and microvascular perfusion measured by lectin microangiography was enhanced 4-fold (0.7% versus 2.7% vessel volume/section volume; P=0.04). Comparisons to additional groups also showed a significantly improved vasculogenic response in the EPCM group. Ventricular geometry and scar fraction assessed by digital planimetric analysis of sectioned hearts exhibited significantly preserved left ventricular internal diameter (9.7 mm versus 8.6 mm; P=0.005) and decreased infarct scar formation expressed as percent of total section area (16% versus 7%; P=0.002) when compared with all other groups. In addition, EPCM animals showed a significant preservation of function as measured by echocardiography, pressure-volume conductance, and Doppler flow.Extracellular matrix seeded with EPCs primed with SDF induces borderzone neovasculogenesis, attenuates adverse ventricular remodeling, and preserves ventricular function after myocardial infarction.

  View details for DOI 10.1161/C1RCULATIONAHA.109.930404

  View details for Web of Science ID 000282294800017

  View details for PubMedID 20837901

• Tissue-engineered pro-angiogenic fibroblast scaffold improves myocardial perfusion and function and limits ventricular remodeling after infarction JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Fitzpatrick, J. R., Frederick, J. R., McCormick, R. C., Harris, D. A., Kim, A., Muenzer, J. R., Gambogi, A. J., Liu, J. P., Paulson, E. C., Woo, Y. J. 2010; 140 (3): 667-676

  Abstract

  Microvascular malperfusion after myocardial infarction leads to infarct expansion, adverse remodeling, and functional impairment. Native reparative mechanisms exist but are inadequate to vascularize ischemic myocardium. We hypothesized that a 3-dimensional human fibroblast culture (3DFC) functions as a sustained source of angiogenic cytokines, thereby augmenting native angiogenesis and limiting adverse effects of myocardial ischemia.Lewis rats underwent ligation of the left anterior descending coronary artery to induce heart failure; experimental animals received a 3DFC scaffold to the ischemic region. Border-zone tissue was analyzed for the presence of human fibroblast surface protein, vascular endothelial growth factor, and hepatocyte growth factor. Cardiac function was assessed with echocardiography and pressure-volume conductance. Hearts underwent immunohistochemical analysis of angiogenesis by co-localization of platelet endothelial cell adhesion molecule and alpha smooth muscle actin and by digital analysis of ventricular geometry. Microvascular angiography was performed with fluorescein-labeled lectin to assess perfusion.Immunoblotting confirmed the presence of human fibroblast surface protein in rats receiving 3DFC, indicating survival of transplanted cells. Increased expression of vascular endothelial growth factor and hepatocyte growth factor in experimental rats confirmed elution by the 3DFC. Microvasculature expressing platelet endothelial cell adhesion molecule/alpha smooth muscle actin was increased in infarct and border-zone regions of rats receiving 3DFC. Microvascular perfusion was also improved in infarct and border-zone regions in these rats. Rats receiving 3DFC had increased wall thickness, smaller infarct area, and smaller infarct fraction. Echocardiography and pressure-volume measurements showed that cardiac function was preserved in these rats.Application of a bioengineered 3DFC augments native angiogenesis through delivery of angiogenic cytokines to ischemic myocardium. This yields improved microvascular perfusion, limits infarct progression and adverse remodeling, and improves ventricular function.

  View details for DOI 10.1016/j.jtcvs.2009.12.037

  View details for Web of Science ID 000281116000026

  View details for PubMedID 20363480

• Cavopulmonary Bypass to Facilitate Infrahepatic Vena Cava Gunshot Wound Repair ANNALS OF THORACIC SURGERY Liao, G. P., Braslow, B., Schwab, C. W., Woo, Y. J. 2010; 89 (6): 2026-2028

  Abstract

  Traumatic injuries to the inferior vena cava continue to be associated with high mortality. The management of these injuries has been technically challenging and highly variable, often depending on factors that include the anatomic complexity and the severity of the insult. We report the first case in which a patient with massive exsanguination from an infrahepatic vena cava gunshot wound underwent successful repair with the aid of a novel variant active venovenous bypass circuit between the inferior vena cava and the pulmonary artery.

  View details for DOI 10.1016/j.athoracsur.2009.10.014

  View details for Web of Science ID 000277934200059

  View details for PubMedID 20494078

• Retrograde and Antegrade Cerebral Perfusion: Results in Short Elective Arch Reconstructive Times Surgical Motion Picture Session of the 45th Annual Meeting of the Society-of-Thoracic-Surgeons Milewski, R. K., Pacini, D., Moser, G. W., Moeller, P., Cowie, D., Szeto, W. Y., Woo, Y. J., Desai, N., Di Marco, L., Pochettino, A., Di Bartolomeo, R., Bavaria, J. E. ELSEVIER SCIENCE INC. 2010: 1448–57

  Abstract

  Debate remains regarding optimal cerebral circulatory management during relatively noncomplex, short arch reconstructive times. Both retrograde cerebral perfusion with deep hypothermic circulatory arrest (RCP/DHCA) and antegrade cerebral perfusion with moderate hypothermic circulatory arrest (ACP/MHCA) have emerged as established techniques. The aim of the study was to evaluate perioperative outcomes between antegrade and retrograde cerebral perfusion techniques for elective arch reconstruction times less than 45 minutes.Between 1997 and September 2008, 776 cases from two institutions were reviewed to compare RCP/DHCA and ACP/MHCA perfusion techniques. At the University of Pennsylvania, 682 were treated utilizing RCP/DHCA cerebral protection. At the University of Bologna, 94 were treated with ACP/MHCA and bilateral cerebral perfusion.Mean cerebral ischemic time and visceral ischemic time differed between RCP/DHCA and ACP/MHCA (p < 0.001). Multivariate analysis showed age more than 65 years, atherosclerotic aneurysm, and cross-clamp time as predictors of the composite endpoint of mortality, neurologic event, and acute myocardial infarction. There was no significant difference in permanent neurologic deficit, temporary neurologic dysfunction, or renal failure, between RCP/DHCA and ACP/MHCA. Mortality was comparable across both techniques.Both RCP/DHCA and ACP/MHCA have emerged as effective techniques for selected aortic arch operations with low morbidity and mortality. Univariate analysis revealed no statistically significant differences in primary or secondary outcomes between techniques for aortic reconstruction times less than 45 minutes. Data from this study demonstrate that selective use of either RCP/DHCA or ACP/MHCA provides excellent cerebral and visceral outcomes for elective open aortic surgery with short arch reconstructive times.

  View details for DOI 10.1016/j.athoracsur.2010.01.056

  View details for Web of Science ID 000276991200016

  View details for PubMedID 20417760

• Repair of type A aortic dissection in nonagenarian. Asian cardiovascular & thoracic annals Woo, Y. J., Kozin, E. D. 2010; 18 (2): 183-184

  Abstract

  Without emergency surgical management, acute type A aortic dissection carries a high risk of death. Controversy exists as to whether extreme age remains a contraindication to surgery. We describe successful repair of type A aortic dissection with ascending aortic graft replacement, aortic valve repair, hemiarch reconstruction, and ablation of atrial fibrillation in a 93-year-old man.

  View details for DOI 10.1177/0218492310361628

  View details for PubMedID 20304857

• Surgical Revision After Percutaneous Mitral Repair With the MitraClip Device 44th Annual Meeting of the Society-of-Thoracic-Surgeons Argenziano, M., Skipper, E., Heimansohn, D., Letsou, G. V., Woo, Y. J., Kron, I., Alexander, J., Cleveland, J., Kong, B., Davidson, M., Vassiliades, T., Krieger, K., Sako, E., Tibi, P., Galloway, A., Foster, E., Feldman, T., Glower, D. ELSEVIER SCIENCE INC. 2010: 72–80

  Abstract

  Percutaneous mitral repair with the MitraClip device (Evalve, Menlo Park, CA) has been reported. Preserving conventional surgical options in the event of percutaneous treatment failure is important. We describe surgical treatment at varying intervals after the MitraClip procedure in 32 patients.One hundred seven patients with moderate-to-severe or severe mitral regurgitation who were either symptomatic (91%) or, if asymptomatic (9%), had evidence of left ventricular dysfunction were enrolled as part of the Endovascular Valve Edge-to-Edge REpair STudy (EVEREST) phase I registry study or as "roll-in" subjects in the EVEREST II study. Thirty-two of the 107 patients (30%) underwent surgery after an attempted MitraClip procedure.Of the 32 patients undergoing post-clip mitral valve surgery, 23 patients (72%) had one or more clips implanted and 9 patients (28%) received no clip implant. The indications for mitral valve surgery in the 23 patients with a clip included partial clip detachment (n = 10), residual or recurrent mitral regurgitation greater than 2+ (n = 9), and other (atrial septal defect [n = 2], device malfunction [n = 1], and incorrectly diagnosed mitral stenosis [n = 1]). Twenty-seven of 31 patients (87%) underwent the surgical procedure planned before surgery (planned procedure unknown in 1 patient). Four of 25 patients (16%) with planned repair underwent mitral valve replacement.Standard surgical options were preserved in patients who had surgery after percutaneous repair with the MitraClip device. Successful repair was feasible in the majority of patients after the MitraClip procedure, with repair performed as late as 18 months after clip implantation.

  View details for DOI 10.1016/j.athoracsur.2009.08.063

  View details for Web of Science ID 000272939700011

  View details for PubMedID 20103209

• Plasma Levels of Receptor for Advanced Glycation End Products, Blood Transfusion, and Risk of Primary Graft Dysfunction AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Christie, J. D., Shah, C. V., Kawut, S. M., Mangalmurti, N., Lederer, D. J., Sonett, J. R., Ahya, V. N., Palmer, S. M., Wille, K., Lama, V., Shah, P. D., Shah, A., Weinacker, A., Deutschman, C. S., Kohl, B. A., Demissie, E., Bellamy, S., Ware, L. B. 2009; 180 (10): 1010-1015

  Abstract

  The receptor for advanced glycation end products (RAGE) is an important marker of lung epithelial injury and may be associated with impaired alveolar fluid clearance. We hypothesized that patients with primary graft dysfunction (PGD) after lung transplantation would have higher RAGE levels in plasma than patients without PGD.To test the association of soluble RAGE (sRAGE) levels with PGD in a prospective, multicenter cohort study.We measured plasma levels of sRAGE at 6 and 24 hours after allograft reperfusion in 317 lung transplant recipients at seven centers. The primary outcome was grade 3 PGD (Pa(O(2))/Fi(O(2)) < 200 with alveolar infiltrates) within the first 72 hours after transplantation.Patients who developed PGD had higher levels of sRAGE than patients without PGD at both 6 hours (median 9.3 ng/ml vs. 7.5 ng/ml, respectively; P = 0.028) and at 24 hours post-transplantation (median 4.3 ng/ml vs. 1.9 ng/ml, respectively; P < 0.001). Multivariable logistic regression analyses indicated that the relationship between levels of sRAGE and PGD was attenuated by elevated right heart pressures and by the use of cardiopulmonary bypass. Median sRAGE levels were higher in subjects with cardiopulmonary bypass at both 6 hours (P = 0.003) and 24 hours (P < 0.001). sRAGE levels at 6 hours were significantly associated with intraoperative red cell transfusion (Spearman's rho = 0.39, P = 0.002 in those with PGD), and in multivariable linear regression analyses this association was independent of confounding variables (P = 0.02).Elevated plasma levels of sRAGE are associated with PGD after lung transplantation. Furthermore, plasma sRAGE levels are associated with blood product transfusion and use of cardiopulmonary bypass.

  View details for DOI 10.1164/rccm.200901-0118OC

  View details for Web of Science ID 000271797600017

  View details for PubMedID 19661249

  View details for PubMedCentralID PMC2778153

• Late Surgical Mitral Valve Repair after Percutaneous Repair with the MitraClip (R) System JOURNAL OF CARDIAC SURGERY Rogers, J. H., Yeo, K. K., Carroll, J. D., Cleveland, J., Reece, T. B., Gillinov, A. M., Rodriguez, L., Whitlow, P., Woo, Y. J., Herrmann, H. C., Young, J. N. 2009; 24 (6): 677-681

  Abstract

  Percutaneous approaches for treating mitral regurgitation are under investigation, including repair with the MitraClip percutaneous mitral repair system (Evalve, Inc., Menlo Park, CA, USA), which has undergone extensive preclinical and clinical evaluation in the EVEREST I and II trials. The procedure involves the transcatheter placement of one or two MitraClip devices under echocardiographic and fluoroscopic guidance to restore leaflet coaptation. A desirable feature of any percutaneous mitral valve (MV) repair system is that the device should not impede subsequent surgical repair if needed. To date, the majority of reported MV surgeries after MitraClip device implantation have occurred earlier, within one year of treatment. We herein describe four previously unreported cases of successful surgical MV repair up to five years after MitraClip device implantation, demonstrating that late MV repair remains possible, including after implantation of two clips.

  View details for DOI 10.1111/j.1540-8191.2009.00901.x

  View details for Web of Science ID 000271523400015

  View details for PubMedID 19682161

• Minimally Invasive Valve Surgery SURGICAL CLINICS OF NORTH AMERICA Woo, Y. J. 2009; 89 (4): 923-?

  Abstract

  Traditional cardiac valve replacement surgery is being rapidly supplanted by innovative, minimally invasive approaches toward the repair of these valves. Patients are experiencing benefits ranging from less bleeding and pain to faster recovery and greater satisfaction. These operations are proving to be safe, highly effective, and durable, and their use will likely continue to increase and become even more widely applicable.

  View details for DOI 10.1016/j.suc.2009.05.005

  View details for Web of Science ID 000270918500013

  View details for PubMedID 19782845

• Antegrade Thoracic Stent Grafting During Repair of Acute DeBakey I Dissection Prevents Development of Thoracoabdominal Aortic Aneurysms 55th Annual Meeting of the Southern-Thoracic-Surgical-Association Pochettino, A., Brinkman, W. T., Moeller, P., Szeto, W. Y., Moser, W., Cornelius, K., Bowen, F. W., Woo, Y. J., Bavaria, J. E. ELSEVIER SCIENCE INC. 2009: 482–90

  Abstract

  Acute DeBakey I dissection repair consists of ascending aortic resection, aortic root repair or replacement, and variable aortic arch replacement. This "proximal" strategy leaves most patients with a patent residual "type B" dissection which leads to greater than 30% distal "open" reoperations for dissecting aneurysm. This report tests whether antegrade stent-grafting of the proximal descending thoracic aorta during acute DeBakey I dissection decreases future distal aortic aneurysms without an increase in surgical risk.Between June 2005 and June 2008, 150 patients were treated surgically for acute type A aortic dissection at the Hospital of the University of Pennsylvania. Of these, 78 were DeBakey I dissections: 42 patients underwent standard open repair, while 36 underwent additional thoracic stent-grafting by the open arch. Arch repairs were performed with a combination of retrograde cerebral and selective antegrade perfusion.Mean follow-up was 15.9 months. Hospital mortality was 5 of 36 (14%) for stented and 6 of 42 (14%) for nonstented repairs. Postoperative strokes were 1 of 36 (3%) in stented versus 4 of 42 (10%) in nonstented repairs (p = not significant [NS]) despite longer circulatory arrest times in the stented group; 60 +/- 13 minutes versus 41 +/- 18 minutes (p < 0.0001). Transient paraparesis was 3 of 36 (9%) in the stented versus 1 of 42 (2%) in the nonstented group (p = NS) with no permanent deficits. Stented thoracic false lumen obliteration was achieved in 24 of 30 (80%) with 5 of these (17%) achieving complete thoracoabdominal false lumen thrombosis. Eight of 31 (26%) stented patients underwent endovascular reintervention to achieve the desired false lumen obliteration. Open thoracoabdominal aortic aneurysm repairs were performed in 0 of 31 in the stented group and 4 of 36 (11%) in the standard group (p = 0.083).Antegrade stent graft deployment during acute DeBakey I dissection repair is a safe method to obliterate the thoracic false lumen. Endovascular reinterventions were well-tolerated. "Elephant trunk" thoracic stent-grafting as part of the repair for acute DeBakey I dissection gives equal short-term results compared with standard repair, and lowers morbidity and mortality during follow-up.

  View details for DOI 10.1016/j.athoracsur.2009.04.046

  View details for Web of Science ID 000268316400019

  View details for PubMedID 19632398

• Early planned institution of biventricular mechanical circulatory support results in improved outcomes compared with delayed conversion of a left ventricular assist device to a biventricular assist device JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Fitzpatrick, J. R., Frederick, J. R., Hiesinger, W., Hsu, V. M., McCormick, R. C., Kozin, E. D., Laporte, C. M., O'Hara, M. L., Howell, E., Dougherty, D., Cohen, J. E., Southerland, K. W., Howard, J. L., Paulson, C., Acker, M. A., Morris, R. J., Woo, Y. J. 2009; 137 (4): 971-977

  Abstract

  It is generally accepted that patients who require biventricular assist device support have poorer outcomes than those requiring isolated left ventricular assist device support. However, it is unknown how the timing of biventricular assist device insertion affects outcomes. We hypothesized that planned biventricular assist device insertion improves survival compared with delayed conversion of left ventricular assist device support to biventricular assist device support.We reviewed and compared outcomes of 266 patients undergoing left ventricular assist device or biventricular assist device placement at the University of Pennsylvania from April 1995 to June 2007. We subdivided patients receiving biventricular assist devices into planned biventricular assist device (P-BiVAD) and delayed biventricular assist device (D-BiVAD) groups based on the timing of right ventricular assist device insertion. We defined the D-BiVAD group as any failure of isolated left ventricular assist device support.Of 266 patients who received left ventricular assist devices, 99 (37%) required biventricular assist device support. We compared preoperative characteristics, successful bridging to transplantation, survival to hospital discharge, and Kaplan-Meier 1-year survival between the P-BiVAD (n = 71) and D-BiVAD (n = 28) groups. Preoperative comparison showed that patients who ultimately require biventricular support have similar preoperative status. Left ventricular assist device (n = 167) outcomes in all categories exceeded both P-BiVAD and D-BiVAD group outcomes. Furthermore, patients in the P-BiVAD group had superior survival to discharge than patients in the D-BiVAD group (51% vs 29%, P < .05). One-year and long-term Kaplan-Meier survival distribution confirmed this finding. There was also a trend toward improved bridging to transplantation in the P-BiVAD (n = 55) versus D-BiVAD (n = 22) groups (65% vs 45%, P = .10).When patients at high risk for failure of isolated left ventricular assist device support are identified, proceeding directly to biventricular assist device implantation is advised because early institution of biventricular support results in dramatic improvement in survival.

  View details for DOI 10.1016/j.jtcvs.2008.09.021

  View details for Web of Science ID 000264562000028

  View details for PubMedID 19327526

  View details for PubMedCentralID PMC3232461

• Off-pump, minimally invasive and robotic coronary revascularization yield improved outcomes over traditional on-pump CABG INTERNATIONAL JOURNAL OF MEDICAL ROBOTICS AND COMPUTER ASSISTED SURGERY Atluri, P., Kozin, E. D., Hiesinger, W., Woo, Y. J. 2009; 5 (1): 1-12

  Abstract

  Coronary artery disease is a global health concern, with increasing morbidity and mortality. Surgical coronary artery bypass grafting has been performed on cardiopulmonary bypass for nearly four decades, with excellent long-term durability. Beating-heart coronary surgery has been increasing in frequency in an attempt to decrease cardiopulmonary bypass-related morbidity. Furthermore, with increasing expertise and technology, minimally invasive and robotic techniques have been developed to enhance post-operative recovery, patient satisfaction and cosmesis. Several clinical trials have demonstrated decreased morbidity and more rapid recovery following off-pump, minimally invasive and robotic procedures when compared to on-pump coronary artery bypass grafts (CABGs). An equivalent extent of revascularization and medium-term anastomotic patency has been demonstrated among all approaches. Furthermore, for a large number of patients who do not have anatomy amenable to traditional coronary revascularization, adjunctive molecular therapies may provide alternative myocardial micro-revascularization.

  View details for DOI 10.1002/rcs.230

  View details for Web of Science ID 000263998300001

  View details for PubMedID 19117020

• Endocarditis with massive aortic root abscess and atrioventricular septal destruction. Interactive cardiovascular and thoracic surgery Parish, L. M., Liu, L., Woo, Y. J. 2009; 8 (2): 280-282

  Abstract

  Endocarditis involving the aortic root and intervalvular fibrous skeleton presents a reconstructive dilemma. We report a case of endocarditis involving the aortic root and tricuspid valve with extensive destruction of the atrioventricular septum. Debridement necessitated resection of the aortic root, aortic valve, tricuspid valve, and a large portion of atrioventricular septum, leaving the right atrium, right ventricle, left ventricle and aorta in open communication. Reconstruction was accomplished by separating the left and right hearts with a Dacron patch, tricuspid valve replacement, and aortic root replacement. Proper planar localization of the aortic root was necessary to avoid left ventricular outflow obstruction and coronary torsion.

  View details for DOI 10.1510/icvts.2008.181966

  View details for PubMedID 19042930

• Outcomes Using Extracorporeal Life Support for Adult Respiratory Failure due to Status Asthmaticus ASAIO JOURNAL Mikkelsen, M. E., Woo, Y. J., Sager, J. S., Fuchs, B. D., Christif, J. D. 2009; 55 (1): 47-52

  Abstract

  Our objective was to describe the outcomes for extracorporeal life support (ECLS) use in adult respiratory failure because of status asthmaticus and to determine whether ECLS use in status asthmaticus is associated with greater survival than other indications for ECLS. This retrospective cohort study used the multicenter, International ECLS Organization Registry. The study population included 1,257 adults with respiratory failure requiring ECLS. Status asthmaticus was the primary indication for ECLS in 24 patients. A total of 83.3% of asthmatics survived to hospital discharge compared with 50.8% of nonasthmatics (n=1,233) [odds ratio (OR) favoring survival for asthmatics=4.86, 95% confidence interval (CI) 1.65-14.31, p=0.004]. The survival advantage for asthmatics remained significant after adjustment for potential confounders. Complications were noted in 19 of 24 asthmatics (79.2%). In conclusion, we found that status asthmaticus, as an indication for ECLS in adult respiratory failure, seemed to be associated with greater survival than other indications for ECLS. However, complications are common and whether ECLS confers a survival advantage compared with other salvage treatment options remains unknown. More detailed information and complete reporting of ECLS use for status asthmaticus are needed to determine whether and when the potentially life-saving intervention of ECLS should be initiated in the asthmatic failing conventional therapy.

  View details for DOI 10.1097/MAT.0b013e3181901ea5

  View details for Web of Science ID 000262425400011

  View details for PubMedID 19092662

• Neurologic Outcomes from High Risk Descending Thoracic and Thoracoabdominal Aortic Operations in the Era of Endovascular Repair NEUROCRITICAL CARE Messe, S. R., Bavaria, J. E., Mullen, M., Cheung, A. T., Davis, R., Augoustides, J. G., Gutsche, J., Woo, E. Y., Szeto, W. Y., Pochettino, A., Woo, Y. J., Kasner, S. E., McGarvey, M. 2008; 9 (3): 344-351

  Abstract

  Spinal cord ischemia and stroke are recognized complications of descending thoracic (DTA) and thoracoabdominal aortic (TAA) operations. However, there are limited data available on outcomes since the advent of thoracic endovascular aortic repair (TEVAR).We reviewed charts from consecutive patients who underwent open DTA and TAA operations, excluding type IV repair, from January, 2000 through April, 2005.A total of 224 open DTA and TAA operations were included in the analysis. During this period 108 additional patients received TEVAR, accounting for 66% of all DTA repairs. Among the 224 patients who underwent open surgery, 63 patients (28%) developed spinal ischemia postprocedure, 13 (6%) had a stroke, and 9 (4%) had both. The 30 day in-hospital mortality was 18%. Neurologic complications were strongly associated with mortality: 64% of patients with stroke died compared to 17% without (P < 0.001) and 39% of patients with spinal ischemia died compared to 14% without (P < 0.001). At discharge, 29% had a poor outcome from surgery, defined as death or moderate-to-severe neurologic disability. A multivariable logistic regression incorporating characteristics known prior to surgery resulted in a score to stratify risk of poor outcome by giving one point each for age > or =60, history of cerebrovascular disease, Crawford extent II or III repair, and acute rupture. Patients with score > or =3 had an estimated 60% risk for poor outcome, while those with score < or =1 had an estimated risk of 7-11%.Ischemic neurologic complications were frequent and strongly associated with poor outcomes after open DTA and TAA repair among patients not eligible for TEVAR. Risk of death or neurologic disability can be estimated based on factors known prior to surgery.

  View details for DOI 10.1007/s12028-008-9104-9

  View details for Web of Science ID 000260542100011

  View details for PubMedID 18483880

• Risk Score Derived from Pre-operative Data Analysis Predicts the Need for Biventricular Mechanical Circulatory Support 28th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation Fitzpatrick, J. R., Frederick, J. R., Hsu, V. M., Kozin, E. D., O'Hara, M. L., Howell, E., Dougherty, D., McCormick, R. C., Laporte, C. A., Cohen, J. E., Southerland, K. W., Howard, J. L., Jessup, M. L., Morris, R. J., Acker, M. A., Woo, Y. J. ELSEVIER SCIENCE INC. 2008: 1286–92

  Abstract

  Right ventricular (RV) failure after left ventricular assist device (LVAD) placement is a serious complication and is difficult to predict. In the era of destination therapy and the total artificial heart, predicting post-LVAD RV failure requiring mechanical support is extremely important.We reviewed patient characteristics, laboratory values and hemodynamic data from 266 patients who underwent LVAD placement at the University of Pennsylvania from April 1995 to June 2007.Of 266 LVAD recipients, 99 required RV assist device (BiVAD) placement (37%). We compared 36 parameters between LVAD (n = 167) and BiVAD patients (n = 99) to determine pre-operative risk factors for RV assist device (RVAD) need. By univariate analysis, 23 variables showed statistically significant differences between the two groups (p < or = 0.05). By multivariate logistic regression, cardiac index < or =2.2 liters/min/m(2) (odds ratio [OR] 5.7), RV stroke work index < or =0.25 mm Hg . liter/m(2) (OR 5.1), severe pre-operative RV dysfunction (OR 5.0), pre-operative creatinine > or =1.9 mg/dl (OR 4.8), previous cardiac surgery (OR 4.5) and systolic blood pressure < or =96 mm Hg (OR 2.9) were the best predictors of RVAD need.The most significant predictors for RVAD need were cardiac index, RV stroke work index, severe pre-operative RV dysfunction, creatinine, previous cardiac surgery and systolic blood pressure. Using these data, we constructed an algorithm that can predict which LVAD patients will require RVAD with >80% sensitivity and specificity.

  View details for DOI 10.1016/j.healun.2008.09.006

  View details for Web of Science ID 000261772600004

  View details for PubMedID 19059108

• Acute myocardial infarction requiring mechanical bridge to transplantation in a patient with undiagnosed anti-phospholipid antibody syndrome JOURNAL OF HEART AND LUNG TRANSPLANTATION Reade, C. C., Morris, R. J., Acker, M. A., Jessup, M., Banbury, M. K., Woo, Y. J. 2008; 27 (6): 682-684

  Abstract

  We present a young man who sustained an acute myocardial infarction with hemodynamic instability requiring placement of a left ventricular assist device and subsequent cardiac transplantation. Hematologic work-up revealed anti-phospholipid antibody syndrome. To our knowledge this is the first reported case of severe acute heart failure due to anti-phospholipid antibody syndrome in which the patient survived through assist device placement and successful transplantation.

  View details for DOI 10.1016/j.healun.2008-03.002

  View details for Web of Science ID 000256597500016

  View details for PubMedID 18503970

• Cardiac retransplantation is an efficacious therapy for primary cardiac allograft failure JOURNAL OF CARDIOTHORACIC SURGERY Atluri, P., Hiesinger, W., Gorman, R. C., Pochettino, A., Jessup, M., Acker, M. A., Morris, R. J., Woo, Y. J. 2008; 3

  Abstract

  Although orthotopic heart transplantation has been an effective treatment for end-stage heart failure, the incidence of allograft failure has increased, necessitating treatment options. Cardiac retransplantation remains the only viable long-term solution for end-stage cardiac allograft failure. Given the limited number of available donor hearts, the long term results of this treatment option need to be evaluated.709 heart transplants were performed over a 20 year period at our institution. Repeat cardiac transplantation was performed in 15 patients (2.1%). A retrospective analysis was performed to determine the efficacy of cardiac retransplantation. Variables investigated included: 1 yr and 5 yr survival, length of hospitalization, post-operative complications, allograft failure, recipient and donor demographics, renal function, allograft ischemic time, UNOS listing status, blood group, allograft rejection, and hemodynamic function.Etiology of primary graft failure included transplant arteriopathy (n = 10), acute rejection (n = 3), hyperacute rejection (n = 1), and a post-transplant diagnosis of metastatic melanoma in the donor (n = 1). Mean age at retransplantation was 45.5 +/- 9.7 years. 1 and 5 year survival for retransplantation were 86.6% and 71.4% respectively, as compared to 90.9% and 79.1% for primary transplantation. Mean ejection fraction was 67.3 +/- 12.2% at a mean follow-up of 32.6 +/- 18.5 mos post-retransplant; follow-up biopsy demonstrated either ISHLT grade 1A or 0 rejection (77.5 +/- 95.7 mos post-transplant).Cardiac retransplantation is an efficacious treatment strategy for cardiac allograft failure.

  View details for DOI 10.1186/1749-8090-3-26

  View details for Web of Science ID 000262855000001

  View details for PubMedID 18462494

  View details for PubMedCentralID PMC2432055

• Transmyocardial revascularization to enhance myocardial vasculogenesis and hemodynamic function JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Atluri, P., Panlilio, C. M., Liao, G. P., Suarez, E. E., McCormick, R. C., Hiesinger, W., Cohen, J. E., Smith, M. J., Patel, A. B., Feng, W., Woo, Y. J. 2008; 135 (2): 283-U50

  Abstract

  A significant number of patients have coronary artery disease that is not amenable to traditional revascularization. Prospective, randomized clinical trials have demonstrated therapeutic benefits with transmyocardial laser revascularization in this cohort. The molecular mechanisms underlying this therapy, however, are poorly understood. The focus of this study was evaluation of the proposed vasculogenic mechanisms involved in transmyocardial laser revascularization.Male Yorkshire pigs (30-35 kg, n = 25) underwent left thoracotomy and placement of ameroid constrictors around the proximal left circumflex coronary artery. During the next 4 weeks, a well-defined region of myocardial ischemia developed, and the animals underwent a redo left thoracotomy. The animals were randomly assigned to sham treatment (thoracotomy only, control, n = 11) or transmyocardial laser revascularization of hibernating myocardium with a holmium:yttrium-aluminum-garnet laser (n = 14). After an additional 4 weeks, the animals underwent median sternotomy, echocardiographic analysis of wall motion, and hemodynamic analysis with an ascending aortic flow probe and pulmonary artery catheter. The hearts were explanted for molecular analysis.Molecular analysis demonstrated statistically significant increases in the proangiogenic proteins nuclear factor kappaB (42 +/- 27 intensity units vs 591 +/- 383 intensity units, P = .03) and angiopoietin 1 (0 +/- 0 intensity units vs 241 +/- 87 intensity units, P = .003) relative to sham control values with transmyocardial laser revascularization within the ischemic myocardium. There were also increases in vasculogenesis (18.8 +/- 8.7 vessels/high-power field vs 31.4 +/- 10.2 vessels/high-power field, P = .02), and perfusion (0.028 +/- 0.009 microm3 blood/microm3 tissue vs 0.044 +/- 0.004 microm3 blood/microm3 tissue, P = .01). Enhanced myocardial viability was demonstrated by increased myofilament density (40.7 +/- 8.5 cardiomyocytes/high-power field vs 50.8 +/- 7.5 cardiomyocytes/high-power field, P = .03). Regional myocardial function within the treated territory demonstrated augmented contractility. Global hemodynamic function was significantly improved relative to the control group with transmyocardial laser revascularization (cardiac output 2.1 +/- 0.2 L/min vs 2.7 +/- 0.2 L/min, P = .007, mixed venous oxygen saturation 64.7% +/- 3.6% vs 76.1% +/- 3.4%, P = .008).Transmyocardial laser revascularization with the holmium-YAG laser enhances perfusion, with resultant improvement in myocardial contractility.

  View details for DOI 10.1016/j.jtcvs.2007.09.043

  View details for Web of Science ID 000252830400009

  View details for PubMedID 18242252

• Pro-angiogenic cytokines as cardiovascular therapeutics - Assessing the potential BIODRUGS Atluri, P., Woo, Y. J. 2008; 22 (4): 209-222

  Abstract

  Coronary artery and peripheral vascular disease are global health concerns with limited therapies. Currently available medical and surgical therapies for these disease processes are highly effective for only a fraction of patients. Extensive effort has been devoted to finding molecular therapies to enhance perfusion and function of ischemic myocardial and peripheral skeletal muscle. Angiogenic cytokines (fibroblast growth factor [FGF], vascular endothelial growth factor [VEGF], hepatocyte growth factor [HGF], placental growth factor, stromal cell-derived factor-1alpha) have shown theoretical and experimental promise in upregulating endogenous endothelial progenitor cell-mediated angiogenesis. Preliminary clinical trials have suggested improvements in myocardial and peripheral perfusion following therapy with FGF, VEGF, and HGF. Further studies on the efficacy of cytokine-mediated angiogenesis are required before widespread clinical application is possible. Investigation into adjunctive cytokine therapies for myocardial and peripheral muscle ischemia is warranted. Based on experimental evidence, appropriate angiogenic cytokine therapy should provide benefits in both perfusion and hemodynamic function.

  View details for Web of Science ID 000258127300001

  View details for PubMedID 18611064

• Fate of the residual distal and proximal aorta after acute type a dissection repair using a contemporary surgical reconstruction algorithm 43rd Annual Meeting of the Society-of-Thoracic-Surgeons Geirsson, A., Bavaria, J. E., Swarr, D., Keane, M. G., Woo, Y. J., Szeto, W. Y., Pochettino, A. ELSEVIER SCIENCE INC. 2007: 1955–64

  Abstract

  In this study, we evaluated the long-term results of our contemporary, standardized surgical management algorithm for repair of acute type A aortic dissections. Prior reports have analyzed heterogeneous techniques and populations.From 1993 to 2004, 221 consecutive patients underwent repair of acute type A aortic dissection at our aortic center. Hemiarch repair was performed in 97.7% (216 of 221), and total arch in 2.3% (5 of 221). Of these, 72.9% (161 of 221) underwent aortic valve resuspension, and 27.1% (60 of 221) had aortic root replacement.In-hospital mortality for a primary operation was 12.7% (28 of 221). Actuarial survival was 79.2% at 1 year, 62.8% at 5 years, and 46.3% at 10 years. Significant risk factors for decreased survival included prior stroke, cerebral malperfusion, and length of cardiopulmonary bypass. Freedom from proximal reoperation after aortic valve resuspension was 94.6% at 5 years and 76.8% at 10 years, with cardiac malperfusion as the main risk factor. Freedom from distal reoperation was 87.6% at 5 years and 76.4% at 10 years, with Marfan syndrome, age, and extent of dissection as significant risk factors for reoperation. In-hospital mortality was 18.2% (2 of 11) after proximal reoperation and 31.2% (5 of 16) after distal reoperation.We report improved long-term durability of our proximal root repair, with cardiac malperfusion as a significant risk factor. Marfan disease, younger age, and DeBakey type I dissection are risk factors for distal reoperation. To further improve long-term outcome, means to prevent progression of distal aortic disease need to be developed.

  View details for DOI 10.1016/j.athoracsur.2007.07.017

  View details for Web of Science ID 000251176300022

  View details for PubMedID 18036916

• Emergency extracorporeal life support for asphyxic status asthmaticus 35th Critical Care Congress of the Society-of-Critical-Care-Medicine Mikkelsen, M. E., Pugh, M. E., Hansen-Flaschen, J. H., Woo, Y. J., Sager, J. S. DAEDALUS ENTERPRISES INC. 2007: 1525–29

  Abstract

  We report a case of successful use of extracorporeal life support (ECLS) as salvage treatment in an adult with acute, severe, reversible respiratory failure due to asphyxic status asthmaticus. Conventional measures were ineffective to combat the dynamic hyperinflation; the patient had intrinsic positive end-expiratory pressure > 30 cm H(2)O. We initiated emergency ECLS at the bedside, and after 55 hours of ECLS his respiratory mechanics had markedly improved and he was subsequently weaned off of ECLS and decannulated, without vascular, pulmonary, or neurologic complications. This article reviews the history of ECLS for adult respiratory failure and its application for life-threatening status asthmaticus. This case illustrates the effective use of ECLS for acute respiratory failure due to asphyxic status asthmaticus, and to our knowledge is the first reported case in which the patient's impending cardiopulmonary arrest was due to an unsustainable level of intrinsic positive end-expiratory pressure.

  View details for Web of Science ID 000250788200012

  View details for PubMedID 17971256

• Significance of malperfusion syndromes prior to contemporary surgical repair for acute type A dissection: outcomes and need for additional revascularizations 55th Annual Meeting of the Scandinavian-Association-for-Thoracic-Surgery/26th Annual Meeting of the Scandinavian-Society-for-Extracorporeal-Technology Geirsson, A., Szeto, W. Y., Pochettino, A., McGarvey, M. L., Keane, M. G., Woo, Y. J., Augoustides, J. G., Bavaria, J. E. OXFORD UNIV PRESS INC. 2007: 255–62

  Abstract

  The aim of this study was to assess the significance of malperfusion syndromes in patients with acute type A aortic dissection following a contemporary surgical management algorithm and the effects on morbidity, hospital mortality, and long-term survival. We believe that obliteration of the primary tear site with restoration of flow in the true aortic lumen results in decreased need for revascularization of malperfused organ systems.Our operative approach aims at replacing the entire ascending aorta, resuspension of the aortic valve with repair or replacement of the sinus segment, and routine open replacement of the arch under hypothermic circulatory arrest with retrograde cerebral perfusion with obliteration of false lumen at the distal arch/proximal descending thoracic aorta, thus reestablishing normal flow in the descending thoracic true lumen. From January 1993 to December 2004, 221 consecutive patients underwent repair of acute type A aortic dissection at our institution. Data were collected retrospectively and prospectively. Various types of malperfusion syndromes were present in 26.7% of patients. The organ systems with malperfusion were as follows: cardiac, 7.2%; cerebral, 7.2%; ileofemoral, 12.7%; renal, 4.1%; mesenteric, 1.4%; innominate, 5.4%; and spine, 2.2%.Coronary malperfusion required coronary revascularization in 62.5% of cases. Distal revascularization was needed in 42.9% of patients with ileofemoral malperfusion. Patients with malperfusion were more likely to suffer perioperative myocardial infarction (p<0.001), postoperative coma (p=0.012), delirium (p=0.011), sepsis (p=0.006), acute renal failure (p=0.017), dialysis (p=0.018), and acute limb ischemia (p<0.001). The in-hospital mortality was 30.5% in patients presenting with any malperfusion syndrome while only 6.2% in patients without malperfusion syndrome (p<0.001). Both cardiac (p=0.020) and cerebral malperfusions (p<0.001) were risk factors for in-hospital mortality. The actuarial long-term survival in patients with malperfusion syndrome was estimated by Kaplan-Meier methods to be 67.8%+/-6.1% at 1 year, 54.0%+/-7.0% at 5 years, and 43.1%+/-8.0% at 10 years and for patient without malperfusion 82.7%+/-3.0% at 1 year, 66.3%+/-3.9% at 5 years, and 46.1%+/-6.7% at 10 years (log rank 2.55, p=0.110). Cerebral malperfusion was a significant risk factor for decreased long-term survival (p=0.0002).The occurrence of malperfusion in patients with acute type A dissection is associated with significant increased risk of in-hospital mortality and complications. Additional revascularization is generally needed in patients with coronary malperfusion and ileofemoral malperfusion. Patients presenting with cardiac and cerebral malperfusions have a high hospital mortality and preoperative cerebral malperfusion is associated with dismal long-term survival.

  View details for DOI 10.1016/j.ejcts.2007.04.012

  View details for Web of Science ID 000249150300012

  View details for PubMedID 17500002

• Association between elevated whole blood Epstein-Barr virus (EBV)-encoded RNA EBV polymerase chain reaction and reduced incidence of acute lung allograft rejection JOURNAL OF HEART AND LUNG TRANSPLANTATION Ahya, V. N., Douglas, L. P., Andreadis, C., Arnoldi, S., Svoboda, J., Kotloff, R. M., Hadjiliadis, D., Sager, J. S., Woo, Y. J., Pochettino, A., Schuster, S. J., Stadtmauer, E. A., Tsai, D. E. 2007; 26 (8): 839-844

  Abstract

  Accurate functional assessment of patient immunosuppression after solid-organ transplantation remains elusive. Despite therapeutic serum immunosuppressive drug levels many lung transplant recipients still develop allograft rejection. We investigated the hypothesis that detection of latent Epstein-Barr virus (EBV) in peripheral blood may be a functional marker for the net effects of administered immunosuppression.A retrospective analysis was performed on data obtained from a prospective trial investigating the ability of a novel EBV polymerase chain reaction (PCR) panel for LMP (latent membrane protein 1), EBNA (EBV nuclear antigen) and EBER (EBV-encoded RNA) to predict future development of post-transplant lymphoproliferative disorder (PTLD). Thirty-one lung transplant patients were followed for up to 2 years after transplantation with EBV PCR panels performed on plasma and whole blood. Patients were assessed for occurrences of Grade 2 or higher acute rejection and episodes of infection.Patients with whole blood EBER-positive PCR had a statistically significant lower incidence (45% vs 83%) of Grade 2 or higher acute allograft rejection than patients with no positive assays (odds ratio [OR] = 0.17, 95% confidence interval [CI] 0.021 to 1.2, p = 0.048). Positive whole blood EBER PCR did not correlate with increased risk for infectious complications (OR = 1.6, 95% CI 0.22 to 11, p = 0.69).These results suggest that whole blood EBER EBV PCR load may represent an important functional measure of immunosuppression in solid-organ transplant patients.

  View details for DOI 10.1016/j.healun.2007.05.009

  View details for Web of Science ID 000248992200010

  View details for PubMedID 17692789

• Minimally invasive resection of papillary fibroelastoma in a high-risk patient JOURNAL OF CARDIOVASCULAR MEDICINE Kim, R. W., Jeffery, M. E., Smith, M. J., Wilensky, R. L., Woo, E. Y., Woo, Y. J. 2007; 8 (8): 639-641

  Abstract

  Papillary fibroelastomas are rare, benign cardiac tumors that typically mandate surgical resection. These are usually approached through a median sternotomy with cardioplegic arrest and aortic cross-clamping. We describe the minimally invasive resection of a right atrial fibroelastoma performed on a beating heart via right mini-thoracotomy in a patient complicated by a previous laryngectomy, radiation therapy, and a left-sided pulmonary malignancy.

  View details for Web of Science ID 000248548700016

  View details for PubMedID 17667039

• High-risk repair of ascending aortic aneurysm due to giant cell aortitis. Asian cardiovascular & thoracic annals Atluri, P., Woo, Y. J. 2007; 15 (3): 252-254

  Abstract

  Giant cell arteritis increases the risk of developing a thoracic aortic aneurysm. Thoracic aortic aneurysm repair in octogenarians carries a profound increase in postoperative morbidity and mortality. We report the successful repair of an ascending aortic aneurysm in an 83-year-old woman with a history of treatment for temporal arteritis and pathologic evidence of giant cell aortitis.

  View details for PubMedID 17541000

• Myocardial regeneration therapy for ischemic cardiomyopathy with cyclin A2 86th Annual Meeting of the American-Association-for-Thoracic-Surgery Woo, Y. J., Panlilio, C. M., Cheng, R. K., Liao, G. P., Suarez, E. E., Atluri, P., Chaudhry, H. W. MOSBY-ELSEVIER. 2007: 927–33

  Abstract

  Heart failure therapies ranging from revascularization to remodeling to replacement are variably effective. Theoretically, endogenous repair via myocardial regeneration would be an ideal therapy. This study examined the ability to initiate regeneration by adenoviral-mediated expression of the cell cycle regulator cyclin A2. Our prior studies have demonstrated robust cyclin A2 transgene expression and marked antiphosphorylated histone H3 activity with this strategy, indicating the induction of cardiomyocyte mitosis.Adult male, Lewis rats underwent left anterior descending coronary artery ligation followed by intramyocardial delivery of either cyclin A2 adenoviral vector (n = 8) or empty adeno-null vector as a control (n = 8) into the peri-infarct border zone. In vivo myocardial function was analyzed by echocardiography and invasive left ventricular pressure catheter at 6 weeks, when the animals are traditionally in heart failure. Hearts were explanted for immunoblotting and left ventricular geometric analysis. Cellular proliferation was assessed by proliferating cellular nuclear antigen expression.Cyclin A2 hearts exhibited improved left ventricular function as compared with controls including enhanced cardiac output (32 +/- 3.3 vs 26 +/- 5.0 mL/min, P < .05), stroke volume (0.16 +/- 0.04 vs 0.11 +/- 0.04 mL, P < .05), ejection fraction (72% +/- 7.4% vs 46.% +/- 8.5%, P < .05), fractional shortening (35% +/- 5.4% vs 19% +/- 4.3%, P < .002), maximum pressure (72 +/- 9.3 vs 61 +/- 2.9 mm Hg, P < .05), and end-systolic pressure (67 +/- 7.0 vs 55 +/- 7.0 mm Hg, P < .05). Enhanced myocardial preservation was demonstrated by enhanced left ventricular border zone wall thickness. Increased myocardial proliferation was evidenced by increased expression of proliferating cell nuclear antigen expression in cyclin A2-treated hearts.In failing hearts, targeted delivery of cyclin A2 improves hemodynamic function, as measured by echocardiography and pressure catheter analysis, preserves ventricular wall thickness, and may serve as an ideal myocardial regenerative therapy.

  View details for DOI 10.1016/j.jtcvs.2006.07.057

  View details for Web of Science ID 000245118100013

  View details for PubMedID 17382628

• Integrity of the cerebral blood-flow response to hyperoxia after cardiopulmonary bypass JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA Floyd, T. F., Ratcliffe, S. J., Detre, J. A., Woo, Y. J., Acker, M. A., Bavaria, J. E., Resh, B. F., Pochettino, A. A., Eckenhoff, R. A. 2007; 21 (2): 212-217

  Abstract

  In this study, the hypothesis that cardiopulmonary bypass (CPB) alters the cerebral blood flow (CBF) vasoconstrictive response to hyperoxia was tested.A prospective, observational study was conducted.The study was conducted at a single university hospital.Subjects were patients who presented for cardiac surgery with CPB.CBF was measured before and after CPB in 12 subjects while breathing 21% O(2) and 100% O(2). CBF was measured by using continuous arterial spin labeling (CASL) perfusion magnetic resonance imaging. Arterial pO(2) (mmHg), pCO(2) (mmHg), hemoglobin (Hgb), and oxygen content (CaO(2)) were also measured.Mean age of the 12 subjects was 63 +/- 16 years. Hgb decreased from 12.0 (+/-2.4) g/dL to 9.2 (+/-2.9) g/dL postoperatively (p = 0.008). CBF increased by 39%, from 37.2 (+/-10.8) mL/100 g/min to 49.2 (+/-14.3)mL/100 g/min postoperatively (p = 0.01). In response to the hyperoxic challenge CBF decreased by 8.0 (+/-7.1) mL/100 g/min (21%) preoperatively and by 9.4 (+/-6.4) mL/100 g/min (19%) postoperatively (p = 0.58). By using multiple regression, the contribution of CPB to the hyperoxic CBF response (DeltaCBF) was evaluated, while controlling for other potentially important covariates known to influence CBF, including age, baseline CBF on 21% O(2), and changes in arterial pO(2), pCO(2), and CaO(2). CPB state was not found to be a significant covariate in controlling the CBF response to hyperoxia.CPB does not impair the CBF response to hyperoxia.

  View details for DOI 10.1053/j.jvca.2006.02.017

  View details for Web of Science ID 000245872800009

  View details for PubMedID 17418734

• Ischemic heart failure enhances endogenous myocardial apelin and APJ receptor expression CELLULAR & MOLECULAR BIOLOGY LETTERS Atluri, P., Morine, K. J., Liao, G. P., Panlilio, C. M., Berry, M. F., Hsu, V. M., Hiesinger, W., Cohen, J. E., Woo, Y. J. 2007; 12 (1): 127-138

  Abstract

  Apelin interacts with the APJ receptor to enhance inotropy. In heart failure, apelin-APJ coupling may provide a means of enhancing myocardial function. The alterations in apelin and APJ receptor concentrations with ischemic cardiomyopathy are poorly understood. We investigated the compensatory changes in endogenous apelin and APJ levels in the setting of ischemic cardiomyopathy.Male, Lewis rats underwent LAD ligation and progressed into heart failure over 6 weeks. Corresponding animals underwent sham thoracotomy as control. Six weeks after initial surgery, the animals underwent hemodynamic functional analysis in the presence of exogenous apelin-13 infusion and the hearts were explanted for western blot and enzyme immunoassay analysis. Western blot analysis of myocardial APJ concentration demonstrated increased APJ receptor protein levels with heart failure (1890750+/-133500 vs. 901600+/-143120 intensity units, n=8, p=0.00001). Total apelin protein levels increased with ischemic heart failure as demonstrated by enzyme immunoassay (12.0+/-4.6 vs. 1.0+/-1.2 ng/ml, n=5, p=0.006) and western blot (1579400+/-477733 vs. 943000+/-157600 intensity units, n=10, p=0.008). Infusion of apelin-13 significantly enhanced myocardial function in sham and failing hearts. We conclude that total myocardial apelin and APJ receptor levels increase in compensation for ischemic cardiomyopathy.

  View details for DOI 10.2478/s11658-006-0058-7

  View details for Web of Science ID 000244632300011

  View details for PubMedID 17119870

• Minimally invasive valve surgery. Seminars in thoracic and cardiovascular surgery Woo, Y. J., Seeburger, J., Mohr, F. W. 2007; 19 (4): 289-298

  Abstract

  As alternatives to standard sternotomy, surgeons have developed innovative, minimally invasive approaches to conducting valve surgery. Through very small skin incisions and partial upper sternal division for aortic valve surgery and right minithoracotomy for mitral surgery, surgeons have become adept at performing complex valve procedures. Beyond cosmetic appeal, apparent benefits range from decreased pain and bleeding to improved respiratory function and recovery time. The large retrospective studies and few small prospective randomized studies are herein briefly summarized. The focus is then directed toward describing specific intraoperative technical details in current clinical use, covering anesthetic preparation, incision, mediastinal access, cardiovascular cannulation, valve exposure, and valve reconstruction. Finally, unique situations such as pulmonic valve surgery, reoperations, beating heart surgery, and robotics are discussed.

  View details for DOI 10.1053/j.semtcvs.2007.10.005

  View details for PubMedID 18395627

• Minimally invasive aortic valve papillary fibroelastoma resection. Interactive cardiovascular and thoracic surgery Hsu, V. M., Atluri, P., Keane, M. G., Woo, Y. J. 2006; 5 (6): 779-781

  Abstract

  The standard approach to the resection of aortic valve papillary fibroelastoma has involved traditional full median sternotomy. In this case series, we demonstrate a minimally invasive approach to the resection of these cardiac tumors to decrease operative trauma, reduce postoperative bleeding, decrease pulmonary complications, and expedite recovery from surgery. All patients recovered without incident.

  View details for PubMedID 17670711

• Placental growth factor provides a novel local angiogenic therapy for ischemic cardiomyopathy JOURNAL OF CARDIAC SURGERY Kolakowski, S., Berry, M. F., Atluri, P., Grand, T., Fisher, O., Moise, A., Cohen, J., Hsu, V., Woo, Y. J. 2006; 21 (6): 559-564

  Abstract

  Heart failure occurs predominantly due to coronary artery disease and may be amenable to novel revascularization therapies. This study evaluated the effects of placental growth factor (PlGF), a potent angiogenic agent, in a rat model of ischemic cardiomyopathy.Wistar rats underwent high proximal ligation of the left anterior descending coronary artery and direct injection of PlGF (n = 10) or saline as a control (n = 10) into the myocardium bordering the ischemic area. After 2 weeks, the following parameters were evaluated: ventricular function with an aortic flow probe and a pressure/volume conductance catheter, left ventricular (LV) geometry by histology, and angiogenesis by immunofluorescence.PlGF animals had increased angiogenesis compared to controls (22.8 +/- 3.5 vs. 12.4 +/- 3.2 endothelial cells/high-powered field, p < 0.03). PlGF animals had less ventricular cavity dilation (LV diameter 8.4 +/- 0.2 vs. 9.2 +/- 0.2 mm, p < 0.03) and increased border zone wall thickness (1.85 +/- 0.1 vs. 1.38 +/- 0.2 mm, p < 0.03). PlGF animals had improved cardiac function as measured by maximum LV pressure (95.7 +/- 4 vs. 73.7 +/- 2 mmHg, p = 0.001), maximum dP/dt (4206 +/- 362 vs. 2978 +/- 236 mmHg/sec, p = 0.007), and ejection fraction (25.7 +/- 2 vs. 18.6 +/- 1%, p = 0.02).Intramyocardial delivery of PlGF following a large myocardial infarction enhanced border zone angiogenesis, attenuated adverse ventricular remodeling, and preserved cardiac function. This therapy may be useful as an adjunct or alternative to standard revascularization techniques in patients with ischemic heart failure.

  View details for DOI 10.1111/j.1540-8191.2006.00296.x

  View details for Web of Science ID 000241625300007

  View details for PubMedID 17073953

• Techniques for preserving vertebral artery perfusion during thoracic aortic stent grafting requiring aortic arch landing. Vascular and endovascular surgery Woo, E. Y., Bavaria, J. E., Pochettino, A., Gleason, T. G., Woo, Y. J., Velazquez, O. C., Carpenter, J. P., Cheung, A. T., Fairman, R. M. 2006; 40 (5): 367-373

  Abstract

  Thoracic endografting offers many advantages over open repair. However, delivery of the device can be difficult and may necessitate adjunctive procedures. We describe our techniques for preserving perfusion to the left subclavian artery despite endograft coverage to obtain a proximal seal zone. We reviewed our experience with the Talent thoracic stent graft (Medtronic, Santa Rosa, CA). From 1999 to 2003, 49 patients received this device (29 men, 20 women). Seventeen patients required adjunctive procedures to facilitate proximal graft placement. We performed left subclavian-to-left common carotid artery transposition (6), left common carotid-to-left subclavian artery bypass with ligation proximal to the vertebral artery (7), and left common carotid-to-left subclavian artery bypass with proximal coil embolization (4). Patients who had anatomy unfavorable to transposition or bypass with proximal ligation (large aneurysms or proximal vertebral artery origin) were treated with coil embolization of the proximal left subclavian artery in order to prevent subsequent type II endoleaks. Technical success rate of the carotid subclavian bypass was 100%. Patient follow-up ranged from 3 to 48 months with a mean of 12 months. Six patients had follow-up <6 months owing to recent graft placement. Primary patency was 100%. No neurologic events occurred during the procedure or upon follow-up. One patient had a transient chyle leak that spontaneously resolved in 24 hours. Another patient had a phrenic nerve paresis that resolved after 3 weeks. We believe that it is important to maintain patency of the vertebral artery specifically when a patent right vertebral system and an intact basilar artery is not demonstrated. Furthermore, we describe a novel technique of coil embolization of the proximal left subclavian artery in conjunction with left common carotid-to-left subclavian artery bypass. This circumvents the need for potentially hazardous mediastinal dissection and ligation of the proximal left subclavian artery in cases of large proximal aneurysms or unfavorable vertebral artery anatomy.

  View details for PubMedID 17038570

• Combined DOR ventriculoplasty and aortic valve replacement in the treatment of post infarction ventricular aneurysm and aortic regurgitation JOURNAL OF CARDIAC SURGERY Suarez, E. E., Keane, M. G., Woo, Y. J. 2006; 21 (5): 486-488

  Abstract

  There has been only one other case of endoventricular circular patch plasty performed in conjunction with aortic valve replacement reported in the literature. We present the unique case of a patient suffering from congestive heart failure due to both post-infarct aortic regurgitation and ventricular aneurysm along with his successful surgical treatment.

  View details for DOI 10.1111/j.15408191.2006.00305.x

  View details for Web of Science ID 000240029300014

  View details for PubMedID 16948765

• Robotic cardiac surgery INTERNATIONAL JOURNAL OF MEDICAL ROBOTICS AND COMPUTER ASSISTED SURGERY Woo, Y. J. 2006; 2 (3): 225-232

  Abstract

  Cardiac surgery, traditionally conducted via median sternotomy, has been recently forwarded by progressively advanced technology facilitating sternal-sparing minimally invasive, access to the heart. Robotic systems, comprised of miniaturized surgical instruments mounted on long thin shafts with multiple degrees of range of motion coupled with a dual camera endoscope providing true three-dimentional high-magnification visualization have greatly propelled this field.The robotic system and the literature base pertaining to robotic cardiac surgery is reviewed in depth.Robotic cardiac surgical procedures have been performed to repair and replace the mitral valve, bypass coronary arteries, close atrial septal defects, implant left ventricular pacing leads, and resect intracardiac tumors.As minimally invasive and robotic surgical technology advances, so proceeds the spectrum of potential applications for robotic cardiac surgery.

  View details for DOI 10.1002/rcs.98

  View details for Web of Science ID 000241078300004

  View details for PubMedID 17520636

• Off-pump revascularization for significant left ventricular dysfunction. Asian cardiovascular & thoracic annals Woo, Y. J., Grand, T. J., Liao, G. P., Panlilio, C. M. 2006; 14 (4): 306-309

  Abstract

  Left ventricular dysfunction is a predictor of perioperative morbidity and mortality in on-pump coronary artery bypass grafting. Obligatory global myocardial ischemia and injury induced during crossclamping as well as adverse systemic effects of cardiopulmonary bypass may induce a disproportionately greater overall physiologic insult in patients with poor ventricular function. All patients undergoing nonemergency off-pump coronary artery bypass by a single surgeon during an 18-month period were retrospectively analyzed. Two groups with preoperative ejection fraction classified as poor (10%-35%; n = 31) or normal (55%-80%; n = 60) were compared. The mean ejection fractions were 26% +/- 1% and 63% +/- 1% respectively, p < 0.000001. In those with significant left ventricular dysfunction, there were 2.8 +/- 0.1 grafts per patient, time to extubation was 8.4 +/- 1.2 hours, and discharge was after 4.9 +/- 0.6 days. These results were statistically equivalent to those in the group with normal left ventricular function. There was no intraaortic balloon pump insertion or mortality in either group. This technique provides an effective means of safely revascularizing patients with significant left ventricular dysfunction, and it may provide a valuable alternative approach in patients with ischemic cardiomyopathy.

  View details for PubMedID 16868104

• Robotic minimally invasive mitral valve reconstruction yields less blood product transfusion and shorter length of stay 67th Annual Meeting of the Society-of-University-Surgeons/1st Annual Academic Surgical Congress Woo, Y. J., Nacke, E. A. MOSBY-ELSEVIER. 2006: 263–67

  Abstract

  Robotic-assisted minimally invasive mitral valve reconstruction has gained popularity recently. Initial reports suggest that this approach can be used with relative safety and efficacy. Direct comparisons with a traditional sternotomy approach have not yet been explored extensively.All mitral valve procedures that were performed by a single surgeon during a 3-year period of time were analyzed (n = 142 procedures). Patients whose condition required concomitant coronary artery bypass grafting or aortic valve surgery were excluded subsequently from analysis, because all of these patients were approached obligatorily by sternotomy (n = 71 patients). Six patients underwent right thoracotomy mitral valve procedures without robotic assistance, and 1 patient in cardiogenic shock underwent emergent mitral valve reconstruction by sternotomy. Of the remaining 64 patients who were eligible theoretically for sternotomy or robotic-assisted minimally invasive surgery, 39 patients underwent sternotomy, and 25 patients underwent right chest minimally invasive robotic-assisted surgery. Randomization between these 2 approaches would be almost impossible in the United States. The primary determinant for the choice of approach was request of the referring physician or patient. Multiple perioperative outcomes were then compared.Patients who underwent sternotomy and robotic-assisted surgery exhibited equivalent preoperative characteristics and experienced an equivalent degree of correction of mitral regurgitation in repairs and in need for replacement. Complex mitral valve repairs that entailed leaflet resection and reapproximation, annular plication, sliding annuloplasty, chordal transfer, and GoreTex neochordal construction were accomplished successfully with the robotic system. Cross-clamp and bypass times were longer for patients in the minimally invasive group (110 vs 151 minutes; P = .0015; 162 vs 239 minutes; P < .001, respectively). Mean packed red blood cell transfusion was lower among patients who underwent robotic-assisted surgery (5.0 vs 2.8 units; P = .04). Patients who underwent robotic-assisted surgeries experienced shorter mean duration of postoperative hospitalization (10.6 vs 7.1 days; P = .04). There was 1 death among the patients who underwent sternotomy, and no deaths among the patients who underwent robotic-assisted surgery.Patients can undergo mitral valve reconstruction with minimally invasive robotic assistance, avoid a sternotomy, require less blood product transfusion, and experience shorter hospitalization.

  View details for DOI 10.1016/j.surg.2006.05.003

  View details for Web of Science ID 000240043200018

  View details for PubMedID 16904978

• Therapeutic delivery of cyclin A2 induces myocardial regeneration and enhances cardiac function in ischemic heart failure 78th Annual Scientific Session of the American-Heart-Association Woo, Y. J., Panlilio, C. M., Cheng, R. K., Liao, G. P., Atluri, P., Hsu, V. M., Cohen, J. E., Chaudhry, H. W. LIPPINCOTT WILLIAMS & WILKINS. 2006: I206–I213

  Abstract

  Heart failure is a global health concern. As a novel therapeutic strategy, the induction of endogenous myocardial regeneration was investigated by initiating cardiomyocyte mitosis by expressing the cell cycle regulator cyclin A2.Lewis rats underwent left anterior descending coronary artery ligation followed by peri-infarct intramyocardial delivery of adenoviral vector expressing cyclin A2 (n =32) or empty adeno-null (n =32). Cyclin A2 expression was characterized by Western Blot and immunohistochemistry. Six weeks after surgery, in vivo myocardial function was analyzed using an ascending aortic flow probe and pressure-volume catheter. DNA synthesis was analyzed by proliferating cell nuclear antigen (PCNA), Ki-67, and BrdU. Mitosis was analyzed by phosphohistone-H3 expression. Myofilament density and ventricular geometry were assessed. Cyclin A2 levels peaked at 2 weeks and tapered off by 4 weeks. Borderzone cardiomyocyte cell cycle activation was demonstrated by increased PCNA (40.1+/-2.6 versus 9.3+/-1.1; P<0.0001), Ki-67 (46.3+/-7.2 versus 20.4+/-6.0; P<0.0001), BrdU (44.2+/-13.7 versus 5.2+/-5.2; P<0.05), and phosphohistone-H3 (12.7+/-1.4 versus 0+/-0; P<0.0001) positive cells/hpf. Cyclin A2 hearts demonstrated increased borderzone myofilament density (39.8+/-1.1 versus 31.8+/-1.0 cells/hpf; P=0.0011). Borderzone wall thickness was greater in cyclin A2 hearts (1.7+/-0.4 versus 1.4+/-0.04 mm; P<0.0001). Cyclin A2 animals manifested improved hemodynamics: Pmax (70.6+/-8.9 versus 60.4+/-11.8 mm Hg; P=0.017), max dP/dt (3000+/-588 versus 2500+/-643 mm Hg/sec; P<0.05), preload adjusted maximal power (5.75+/-4.40 versus 2.75+/-0.98 mWatts/microL2; P<0.05), and cardiac output (26.8+/-3.7 versus 22.7+/-2.6 mL/min; P=0.004).A therapeutic strategy of cyclin A2 expression via gene transfer induced cardiomyocyte cell cycle activation yielded increased borderzone myofilament density and improved myocardial function. This approach of inducing endogenous myocardial regeneration provides proof-of-concept evidence that cyclin A2 may ultimately serve as an efficient, alternative therapy for heart failure.

  View details for DOI 10.1161/CIRCULATIONAHA.105.000455

  View details for Web of Science ID 000238688200034

  View details for PubMedID 16820573

• Minimally invasive, robotic, and off-pump mitral valve surgery. Seminars in thoracic and cardiovascular surgery Woo, Y. J., Rodriguez, E., Atluri, P., Chitwood, W. R. 2006; 18 (2): 139-147

  Abstract

  A significant transformation is occurring in the management of mitral valve disease. Earlier surgery is now recommended. Mitral valve repair is the standard of care, and newer methods of reconstructing the mitral valve are developing. Surgery with videoscopic assistance can be effectively performed without sternotomy. Robotics systems are gaining wider adoption. Implantable devices to repair or replace the mitral valve off-pump and percutaneously are emerging.

  View details for PubMedID 17157235

• Left main coronary embolism. journal of invasive cardiology Mejia, V. M., Woo, Y. J., Herrmann, H. C. 2006; 18 (6): 296-?

  Abstract

  This is a case of a 58-year-old female with a history of mitral regurgitation who had undergone mitral valve repair and was readmitted in cardiogenic shock with pericardial effusion, and then developed an anterior ST-elevation myocardial infarction. Coronary angiography revealed an embolus in the left main artery which was treated with rheolytic thrombectomy. This represents an uncommon cause of acute myocardial infarction.

  View details for PubMedID 16775900

• Clinically silent cerebral ischemic events after cardiac surgery: Their incidence, regional vascular occurrence, and procedural dependence ANNALS OF THORACIC SURGERY Floyd, T. F., Shah, P. N., Price, C. C., Harris, F., Ratcliffe, S. J., Acker, M. A., Bavaria, J. E., Rahmouni, H., Kuersten, B., Wiegers, S., McGarvey, M. L., Woo, J. Y., Pochettino, A. A., Melhem, E. R. 2006; 81 (6): 2160-2166

  Abstract

  The reported frequency of stroke after coronary artery bypass grafting varies between 1.5% and 6%, approaches 10% after aortic valve replacement, and may occur in between 40 to 70% in high-risk groups. Clinically silent infarction may be far more frequent and could contribute to long-term cognitive dysfunction in patients after cardiac procedures. Using diffusion-weighted magnetic resonance imaging we document the occurrence, vascular distribution, and procedural dependence of silent infarction after cardiac surgery with cardiopulmonary bypass. We also document the association of preexisting white matter lesions with new postoperative ischemic lesions.Thirty-four patients underwent T2-weighted fluid attenuated inversion recovery and diffusion-weighted magnetic resonance imaging before and after cardiac surgery with cardiopulmonary bypass for coronary artery bypass grafting, aortic valve replacement, and mitral valve repair or replacement surgery. Images were evaluated by experienced neuroradiologists for number, size, and vascular distribution of lesions.Mean age of participants was 67 +/- 15 years. Imaging occurred before and 6 +/- 2 days after surgery. New cerebral infarctions were evident in 6 of 34 patients (18%), were often multiple, and in 67% of patients were clinically silent. The occurrence of new infarctions by surgical procedure was as follows: aortic valve replacement (2 of 6), coronary artery bypass grafting and aortic valve replacement (3 of 8), aortic valve replacement with root replacement (1 of 1), coronary artery bypass grafting and mitral valve repair or replacement (0 of 4), mitral valve repair or replacement (0 of 2), and isolated coronary artery bypass grafting (0 of 13). New infarction occurred in 6 of 15 (40%) of all procedures involving aortic valve replacement. The severity of preexisting white matter lesions trended toward predicting the occurrence of new lesions (p = 0.055).Diffusion-weighted imaging reveals new cerebral infarctions in nearly 40% of patients after aortic valve replacement.

  View details for DOI 10.1016/j.athoracsur.2006.01.080

  View details for Web of Science ID 000238027600032

  View details for PubMedID 16731147

• Mesenchymal stem cell injection after myocardial infarction improves myocardial compliance AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Berry, M. F., Engler, A. J., Woo, Y. J., Pirolli, T. J., Bish, L. T., Jayasankar, V., Morine, K. J., Gardner, T. J., Discher, D. E., Sweeney, H. L. 2006; 290 (6): H2196-H2203

  Abstract

  Cellular therapy for myocardial injury has improved ventricular function in both animal and clinical studies, though the mechanism of benefit is unclear. This study was undertaken to examine the effects of cellular injection after infarction on myocardial elasticity. Coronary artery ligation of Lewis rats was followed by direct injection of human mesenchymal stem cells (MSCs) into the acutely ischemic myocardium. Two weeks postinfarct, myocardial elasticity was mapped by atomic force microscopy. MSC-injected hearts near the infarct region were twofold stiffer than myocardium from noninfarcted animals but softer than myocardium from vehicle-treated infarcted animals. After 8 wk, the following variables were evaluated: MSC engraftment and left ventricular geometry by histological methods, cardiac function with a pressure-volume conductance catheter, myocardial fibrosis by Masson Trichrome staining, vascularity by immunohistochemistry, and apoptosis by TdT-mediated dUTP nick-end labeling assay. The human cells engrafted and expressed a cardiomyocyte protein but stopped short of full differentiation and did not stimulate significant angiogenesis. MSC-injected hearts showed significantly less fibrosis than controls, as well as less left ventricular dilation, reduced apoptosis, increased myocardial thickness, and preservation of systolic and diastolic cardiac function. In summary, MSC injection after myocardial infarction did not regenerate contracting cardiomyocytes but reduced the stiffness of the subsequent scar and attenuated postinfarction remodeling, preserving some cardiac function. Improving scarred heart muscle compliance could be a functional benefit of cellular cardiomyoplasty.

  View details for DOI 10.1152/ajpheart.01017.2005

  View details for Web of Science ID 000237419600009

  View details for PubMedID 16473959

• Comparison of Coapsys annuloplasty and internal reduction mitral annuloplasty in the randomized treatment of functional ischemic mitral regurgitation: Impact on the left ventricle 31st Annual Meeting of the Western-Thoracic-Surgical-Association Grossi, E. A., Woo, Y. J., Schwartz, C. F., Gangahar, D. M., Subramanian, V. A., Patel, N., Wudel, J., DiGiorgi, P. L., Singh, A., Davis, R. D. MOSBY-ELSEVIER. 2006: 1095–98

  Abstract

  Functional mitral regurgitation is associated with both annular and ventricular distortion. Aggressive reduction annuloplasty for functional mitral regurgitation acts primarily at the annulus, with variable impact on the left ventricle. The Coapsys device externally reshapes the left ventricle to correct functional mitral regurgitation. Left ventricular reshaping was analyzed in a randomized study.The RESTOR-MV study randomizes patients with coronary artery disease and functional mitral regurgitation to either reduction annuloplasty and coronary artery bypass grafting (the RA group) or Coapsys annuloplasty and bypass grafting (the CO group). The Coapsys device consists of epicardial pads connected by a cord. It was placed without cardiopulmonary bypass under echocardiographic guidance and sized to reduce annular dimension and improve leaflet coaptation. Internal reduction annuloplasty was performed by device placement. Intraoperative transesophageal echocardiograms were analyzed in 7 patients having reduction annuloplasty and 7 having Coapsys annuloplasty.Baseline mitral regurgitation (0-4 scale) was similar for the RA (3.0 +/- 0.6) and the CO groups (3.0 +/- 0.6). Intraoperative mitral regurgitation was reduced from 2.86 +/- 0.7 to 0.5 +/- 0.7 (P < .01 pre vs post) for the RA group and from 2.64 +/- 0.9 to 05 +/- 0.7 (P < .01 pre vs post) for the CO group. Annular anteroposterior diameter was reduced with both techniques: RA, 3.45 +/- 0.39 to 2.34 +/- 0.37 cm (P < .01 pre vs post); CO, 3.40 +/- 0.27 to 2.85 +/- 0.34 cm (P < .05 pre vs post). Long-axis dimensions were unchanged with both techniques. Short-axis dimensions measured at three levels were significantly reduced only in the CO patients: basal diameter 4.77 +/- 0.58 to 3.58 +/- 0.38 cm (P < .01 pre vs post); mid diameter 4.88 +/- 0.55 to 3.57 +/- 0.43 cm (P < .01 pre vs post); and apical diameter 4.39 +/- 0.46 to 3.38 +/- 0.34 cm (P < .01 pre vs post).Coapsys and reduction annuloplasty techniques both acutely reduce functional mitral regurgitation and annular dimension. The Coapsys device provided significantly greater left ventricular reshaping than did reduction annuloplasty. Further evaluation will assess the long-term valvular function and ventricular geometric stability associated with both techniques.

  View details for DOI 10.1016/j.jtcvs.2005.11.046

  View details for Web of Science ID 000237322500026

  View details for PubMedID 16678595

• Neovasculogenic therapy to augment perfusion and preserve viability in ischemic cardiomyopathy. Annals of thoracic surgery Atluri, P., Liao, G. P., Panlilio, C. M., Hsu, V. M., Leskowitz, M. J., Morine, K. J., Cohen, J. E., Berry, M. F., Suarez, E. E., Murphy, D. A., Lee, W. M., Gardner, T. J., Sweeney, H. L., Woo, Y. J. 2006; 81 (5): 1728-1736

  Abstract

  Ischemic cardiomyopathy is a global health concern with limited therapy. We recently described endogenous revascularization utilizing granulocyte-macrophage colony stimulating factor (GMCSF) to induce endothelial progenitor cell (EPC) production and intramyocardial stromal cell-derived factor-1alpha (SDF) as a specific EPC chemokine. The EPC-mediated neovascularization and enhancement of myocardial function was observed. In this study we examined the regional biologic mechanisms underlying this therapy.Lewis rats underwent left anterior descending coronary artery (LAD) ligation and developed ischemic cardiomyopathy over 6 weeks. Three weeks after ligation, the animals received either subcutaneous GMCSF and intramyocardial SDF injections or saline injections as control. Six weeks after LAD ligation circulating EPC density was studied by flow cytometry. Quadruple immunofluorescent vessel staining for mature, proliferating vasculature was performed. Confocal angiography was utilized to identify fluorescein lectin-lined vessels to assess perfusion. Ischemia reversal was studied by measuring myocardial adenosine triphosphate (ATP) levels. Myocardial viability was assayed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling detection of apoptosis and quantitation of myofilament density.The GMCSF/SDF therapy enhanced circulating leukocyte (13.1 +/- 4.5 x 10(6) vs 3.1 +/- 0.5 x 10(6)/cc, p = 0.001, n = 6) and EPC (14.2 +/- 6.6 vs 2.2 +/- 2.1/cc, p = 0.001, n = 6) concentrations. Tetraimmunofluorescent labeling demonstrated enhanced stable vasculature with this therapy (39.2 +/- 8.1 vs 25.4 +/- 5.1%, p = 0.006, n = 7). Enhanced perfusion was shown by confocal microangiography of borderzone lectin-labeled vessels (28.2 +/- 5.4 vs 11.5 +/- 3.0 vessels/high power field [hpf], p = 0.00001, n = 10). Ischemia reversal was demonstrated by enhanced cellular ATP levels in the GMCSF/SDF borderzone myocardium (102.5 +/- 31.0 vs 26.9 +/- 4.1 nmol/g, p = 0.008, n = 5). Borderzone cardiomyocyte viability was noted by decreased apoptosis (3.2 +/- 1.4% vs 5.4 +/- 1.0%, p = 0.004, n = 10) and enhanced cardiomyocyte density (40.0 +/- 5.6 vs 27.0 +/- 6 myofilaments/hpf, p = 0.01, n=10).Endogenous revascularization for ischemic cardiomyopathy utilizing GMCSF EPC upregulation and SDF EPC chemokinesis upregulates circulating EPCs, enhances vascular stability, and augments myocardial function by enhancing perfusion, reversing cellular ischemia, and increasing cardiomyocyte viability.

  View details for PubMedID 16631663

• Fructose 1,6-diphosphate administration attenuates post-ischemic ventricular dysfunction. Heart, lung & circulation Cohen, J. E., Atluri, P., Taylor, M. D., Grand, T. J., Liao, G. P., Panlilio, C. M., Suarez, E. E., Zentko, S. E., Hsu, V. M., Berry, M. F., Smith, M. J., Gardner, T. J., Sweeney, H. L., Woo, Y. J. 2006; 15 (2): 119-123

  Abstract

  Cardiomyocyte energy production during ischemia depends upon anaerobic glycolysis inefficiently yielding two ATP per glucose. Substrate augmentation with fructose 1,6-diphosphate (FDP) bypasses the ATP consuming steps of glucokinase and phosphofructokinase thus yielding four ATP per FDP. This study evaluated the impact of FDP administration on myocardial function after acute ischemia.Male Wistar rats, 250-300 g, underwent 30 min occlusion of the left anterior descending coronary artery followed by 30 min reperfusion. Immediately prior to both ischemia and reperfusion, animals received an intravenous bolus of FDP or saline control. After 30 min reperfusion, myocardial function was evaluated with a left ventricular intracavitary pressure/volume conductance microcatheter. For bioenergetics studies, myocardium was isolated at 5 min of ischemia and assayed for ATP levels.Compared to controls (n=8), FDP animals (n=8) demonstrated significantly improved maximal left ventricular pressure (100.5+/-5.4 mmHg versus 69.1+/-1.9 mmHg; p<0.0005), dP/dt (5296+/-531 mmHg/s versus 2940+/-175 mmHg/s; p<0.0028), ejection fraction (29.1+/-1.7% versus 20.4+/-1.4%; p<0.0017), and preload adjusted maximal power (59.3+/-5.0 mW/microL(2) versus 44.4+/-4.6 mW/microL(2); p<0.0477). Additionally, significantly enhanced ATP levels were observed in FDP animals (n=5) compared to controls (n=5) (535+/-156 nmol/g ischemic tissue versus 160+/-9.0 nmol/g ischemic tissue; p<0.0369).The administration of the glycolytic intermediate, FDP, by intravenous injection, resulted in significantly improved myocardial function after ischemia and improved bioenergetics during ischemia.

  View details for PubMedID 16469539

• Safety and efficacy of left ventricular assist device support in postmyocardial infarction cardiogenic shock 52nd Annual Meeting of the Southern-Thoracic-Surgical-Association Leshnower, B. G., Gleason, T. G., O'Hara, M. L., Pochettino, A., Woo, Y. J., Morris, R. J., Gardner, T. J., Acker, M. A. ELSEVIER SCIENCE INC. 2006: 1365–71

  Abstract

  Cardiogenic shock secondary to acute myocardial infarction (CS-AMI) is the leading cause of death in all acute coronary syndromes. Experience with the use of left ventricular assist devices (LVADs) in patients with CS-AMI is limited. One of the surgical dilemmas when implanting an LVAD into a patient with an acute anterior wall myocardial infarction is the safety of apical cannulation. We present a decade of experience with the use of LVAD with apical cannulation in patients with CS-AMI.A retrospective review of the ventricular assist device (VAD) database at the Hospital of the University of Pennsylvania was instituted.From April 1995 to February 2005, 49 patients received LVAD support for CS-AMI (group I). The majority of these patients suffered anterior wall myocardial infarctions. This group of patients was compared with a separate cohort of 61 patients with chronic ischemic cardiomyopathy who received LVAD support (group II). The VAD support successfully bridged 38 (74%) group I patients and 37 (61%) group II patients to heart transplantation. Of the 38 patients transplanted in group I, 33 (87%) were discharged from the hospital. In group II, 36 of the 37 patients transplanted (97%) survived to hospital discharge. The overall in-hospital mortality rates for the series were 33% for group I patients, and 41% for group II patients.Left ventricular assist device support in patients with CS-AMI is a safe and effective therapy which should be incorporated into the standard treatment paradigm for appropriate patients presenting with this lethal disease.

  View details for DOI 10.1016/j.athoracsur.2005.11.040

  View details for Web of Science ID 000236239200030

  View details for PubMedID 16564274

• Neurological monitoring and off-pump surgery in a very high-risk stroke patient ANNALS OF THORACIC SURGERY Berry, M. F., McGarvey, M. L., Zeng, L., Woo, Y. J. 2005; 80 (6): 2372-2374

  Abstract

  Stroke remains a high risk of coronary artery bypass grafting. We present a patient with progressively symptomatic coronary disease and severe four-vessel cerebrovascular disease not amenable to revascularization. This patient underwent coronary revascularization without neurologic complication using off-pump coronary surgery to avoid aortic manipulation and intraoperative electroencephalographic monitoring of cerebral perfusion. This management strategy may reduce the stroke risk in similar patients.

  View details for DOI 10.1016/j.athoracsur.2004.06.064

  View details for Web of Science ID 000233926800070

  View details for PubMedID 16305918

• Intraoperative effects of the coapsys annuloplasty system in a randomized evaluation (RESTOR-MV) of functional ischemic mitral regurgitation ANNALS OF THORACIC SURGERY Grossi, E. A., Saunders, P. C., Woo, Y. J., Gangahar, D. M., Laschinger, J. C., Kress, D. C., Caskey, M. P., Schwartz, C. F., Wudel, J. 2005; 80 (5): 1706-1711

  Abstract

  Functional ischemic mitral regurgitation (MR) frequently arises after myocardial infarction; it is characterized by annular enlargement or lateral displacement of the subvalvular apparatus. Coapsys is a ventricular-annular remodeling device designed to treat functional ischemic MR; it does not require cardiopulmonary bypass. Initial intraoperative results of the RESTOR-MV randomized clinical trial are presented.Patients referred for coronary artery bypass grafting with preoperative MR grade of 2 or greater were studied, excluding those with structural valve abnormalities. The Coapsys device, which consists of two epicardial pads connected by a flexible cord, was surgically implanted in 19 patients. Under epicardial echocardiographic guidance, the cord was passed through the left ventricle and tightened externally to improve leaflet coaptation and stabilize the ventricular wall; tightening was conducted with color flow Doppler imaging.Patients were 64.5 +/- 9.2 years old with an ejection fraction of 0.383 +/- 0.089 and received 2.7 +/- 1.1 grafts. Intraoperative MR grade was 2.7 +/- 0.8 after induction and was reduced to 0.4 +/- 0.7 after implantation (p < 0.0001). Mean epicardial dimension was reduced from 8.5 +/- 1.2 to 6.4 +/- 0.9 cm (p < 0.0001). Intraoperative MR was reduced in 95% (18 of 19) of patients, and 84% (16 of 19) had MR grade 1 or less after implantation. All implants were performed without cardiopulmonary bypass or conversion to standard annuloplasty. No hemodynamic compromise or structural damage to the mitral apparatus was noted. Significant acute remodeling was noted in the left ventricular dimensions.In patients without structural valve disease, the Coapsys device acutely reduces functional MR. Further randomized evaluation will assess long-term stability and compare it with standard annuloplasty techniques.

  View details for DOI 10.1016/j.athoracsur.2005.04.034

  View details for Web of Science ID 000232970500022

  View details for PubMedID 16242443

• Robotic resection of an aortic valve papillary fibroelastoma ANNALS OF THORACIC SURGERY Woo, Y. J., Grand, T. J., Weiss, S. J. 2005; 80 (3): 1100-1102

  Abstract

  Robotic technology has been applied to multiple cardiac surgical procedures. Purported benefits include decreased tissue trauma, reduced postoperative bleeding, fewer blood product transfusions, and shorter lengths of stay. We describe the case of a 50-year-old man with an incidentally discovered 1-cm mobile mass on the edge of the aortic valve noncoronary leaflet. The patient underwent robotic minimally invasive resection. The pathologic examination revealed papillary fibroelastoma.

  View details for DOI 10.1016/j.athoracsur.2004.02.108

  View details for Web of Science ID 000231683700056

  View details for PubMedID 16122498

• Stromal cell-derived factor and granulocyte-monocyte colony-stimulating factor form a combined neovasculogenic therapy for ischemic cardiomyopathy JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Woo, Y. J., Grand, T. J., Berry, M. F., Atluri, P., Moise, M. A., Hsu, V. M., Cohen, J., Fisher, O., Burdick, J., Taylor, M., Zentko, S., Liao, G., Smith, M., Kolakowski, S., Jayasankar, V., Gardner, T. J., Sweeney, H. L. 2005; 130 (2): 321-329

  Abstract

  Ischemic heart failure is an increasingly prevalent global health concern with major morbidity and mortality. Currently, therapies are limited, and novel revascularization methods might have a role. This study examined enhancing endogenous myocardial revascularization by expanding bone marrow-derived endothelial progenitor cells with the marrow stimulant granulocyte-monocyte colony-stimulating factor and recruiting the endothelial progenitor cells with intramyocardial administration of the potent endothelial progenitor cell chemokine stromal cell-derived factor.Ischemic cardiomyopathy was induced in Lewis rats (n = 40) through left anterior descending coronary artery ligation. After 3 weeks, animals were randomized into 4 groups: saline control, granulocyte-monocyte colony-stimulating factor only (GM-CSF only), stromal cell-derived factor only (SDF only), and combined stromal cell-derived factor/granulocyte-monocyte colony-stimulating factor (SDF/GM-CSF) (n = 10 each). After another 3 weeks, hearts were analyzed for endothelial progenitor cell density by endothelial progenitor cell marker colocalization immunohistochemistry, vasculogenesis by von Willebrand immunohistochemistry, ventricular geometry by hematoxylin-and-eosin microscopy, and in vivo myocardial function with an intracavitary pressure-volume conductance microcatheter.The saline control, GM-CSF only, and SDF only groups were equivalent. Compared with the saline control group, animals in the SDF/GM-CSF group exhibited increased endothelial progenitor cell density (21.7 +/- 3.2 vs 9.6 +/- 3.1 CD34 + /vascular endothelial growth factor receptor 2-positive cells per high-power field, P = .01). There was enhanced vascularity (44.1 +/- 5.5 versus 23.8 +/- 2.2 von Willebrand factor-positive vessels per high-power field, P = .007). SDF/GM-CSF group animals experienced less adverse ventricular remodeling, as manifested by less cavitary dilatation (9.8 +/- 0.1 mm vs 10.1 +/- 0.1 mm [control], P = .04) and increased border-zone wall thickness (1.78 +/- 0.19 vs 1.41 +/- 0.16 mm [control], P = .03). (SDF/GM-CSF group animals had improved cardiac function compared with animals in the saline control group (maximum pressure: 93.9 +/- 3.2 vs 71.7 +/- 3.1 mm Hg, P < .001; maximum dP/dt: 3513 +/- 303 vs 2602 +/- 201 mm Hg/s, P < .05; cardiac output: 21.3 +/- 2.7 vs 13.3 +/- 1.3 mL/min, P < .01; end-systolic pressure-volume relationship slope: 1.7 +/- 0.4 vs 0.5 +/- 0.2 mm Hg/microL, P < .01.)This novel revascularization strategy of bone marrow stimulation and intramyocardial delivery of the endothelial progenitor cell chemokine stromal cell-derived factor yielded significantly enhanced myocardial endothelial progenitor cell density, vasculogenesis, geometric preservation, and contractility in a model of ischemic cardiomyopathy.

  View details for DOI 10.1016/j.jtcvs.2004.11.041

  View details for Web of Science ID 000231069700015

  View details for PubMedID 16077394

• Robot-assisted pharyngeal and laryngeal microsuirgery: Results of robotic cadaverb dissections Annual Meeting of the Triologic-Society Hockstein, N. G., Nolan, J. P., O'Malley, B. W., Woo, Y. J. JOHN WILEY & SONS INC. 2005: 1003–8

  Abstract

  Robotic surgery has significant potential in pharyngeal and microlaryngeal surgery. We demonstrate the use of a surgical robot in pharyngeal and microlaryngeal surgery in a cadaver.Six experimental surgical dissections, modeled after commonly performed pharyngeal and microlaryngeal procedures, were performed in a cadaver with a commercially available surgical robot in an operating room suite to demonstrate proof of concept.Using the daVinci Surgical Robot (Intuitive Surgical, Sunnyvale, CA), surgical procedures were performed on an edentulous, female cadaver. The procedures included 1) bilateral true vocal cord stripping, 2) rotation of a mucosal flap from the epiglottis to the anterior commissure, 3) partial vocal cordectomy, 4) arytenoidectomy, 5) partial epiglottectomy and thyrohyoid dissection and 6) partial resection of the base of tongue with primary closure. All procedures were timed and documented with still and video photography.The daVinci Surgical Robot, with currently available instruments, enabled performance of several laryngeal and pharyngeal surgical procedures on a cadaver. Laryngeal and pharyngeal exposure was excellent, instruments movement was unimpeded, tissue handling was delicate and precise, and endolaryngeal suturing was relatively easily performed. The duration of the different robotic cadaver dissections was comparable to procedure duration using conventional techniques.Using the daVinci Surgical Robot, six different pharyngeal and microlaryngeal dissections were successfully performed in a cadaver. The recent development of surgical robotics has a potential role in pharyngeal and microlaryngeal surgery. Surgical robots offer the ability to manipulate instruments at their distal ends with increased freedom of movement, scaled movement, tremor buffering, and under stereoscopic three-dimensional visualization. Surgical robots may increase the precision with which we perform currently described procedures; additionally, surgical robots may advance the field of endoscopic laryngeal and pharyngeal surgery.

  View details for DOI 10.1212/01.WNL.0000164714.90354.7D

  View details for Web of Science ID 000229682900014

  View details for PubMedID 15933510

• Creatine phosphate administration preserves myocardial function in a model of off-pump coronary revascularization JOURNAL OF CARDIOVASCULAR SURGERY Woo, Y. J., Grand, T. J., Zentko, S., Cohen, J. E., Hsu, V., Atluri, P., Berry, M. F., Taylor, M. D., Moise, M. A., Fisher, O., Kolakowski, S. 2005; 46 (3): 297-303

  Abstract

  Off pump coronary artery bypass grafting (OPCAB) involves, and is occasionally impaired by obligatory regional myocardial ischemia, particularly with the use of proximal coronary in-flow occlusion techniques. Intracoronary shunts do not guarantee absence of distal ischemia given their small inner diameter and the presence of proximal coronary stenosis. Additional adjunctive measures to provide short-term myocardial protection may facilitate OPCAB. High-energy phosphate supplementation with creatine phosphate prior to ischemia may attenuate ischemic dysfunction.In a rodent model of a transient coronary occlusion and myocardial ischemia, 36 animals underwent preischemic intravenous infusion of either creatine phosphate or saline, 10 minutes of proximal left anterior descending (LAD) occlusion, and 10 minutes of reperfusion. Rats underwent continuous intracavitary pressure monitoring and cellular ATP levels were quantified using a luciferin/luciferase bioluminescence assay.Within 2 minutes of ischemia onset, creatine phosphate animals exhibited statistically significant greater preservation of myocardial function compared to controls, an augmentation which persisted throughout the duration of ischemia and subsequent reperfusion. Furthermore, significantly greater cellular ATP levels were observed among creatine phosphate treated animals (344+/-55 nMol/g tissue, n=5) compared to control animals (160+/-9 nMol/g tissue, n=5)(p=0.014).A strategy of intravenous high-energy phosphate administration successfully prevented ischemic ventricular dysfunction in a rodent model of OPCAB.

  View details for Web of Science ID 000231101300014

  View details for PubMedID 15956929

• Active thermoregulation improves outcome of off-pump coronary artery bypass. Asian cardiovascular & thoracic annals Woo, Y. J., Atluri, P., Grand, T. J., Hsu, V. M., Cheung, A. 2005; 13 (2): 157-160

  Abstract

  During off-pump coronary artery bypass grafting, hypothermia increases vasoconstriction, myocardial afterload, coagulopathy and postoperative bleeding. Traditional thermoregulatory techniques do not maintain core body temperature intraoperatively. The efficacy of a commercially available, computer-controlled, water-circulating, dorsal surface, active warming system for thermoregulatory control was evaluated. All patients who underwent non-emergency off-pump coronary bypass grafting by a single surgeon in a 1-year period were studied: the thermoregulation device was used in 50 cases and unavailable for use in 19. The patients who underwent active thermoregulation demonstrated significantly improved core body temperatures compared to the controls: lowest intraoperative, 35.8 degrees C +/- 0.1 degrees C vs. 35.0 degrees C +/- 0.2 degrees C; immediately postoperative, 36.5 degrees C +/- 0.1 degrees C vs. 35.6 degrees C +/- 0.2 degrees C; and 1-hour postoperative, 36.6 degrees C +/- 0.1 degrees C vs. 35.9 degrees C +/- 0.2 degrees C. Thermoregulated patients had significantly reduced 24-hour chest tube drainage (764 +/- 38 vs. 1227 +/- 183 mL), packed red blood cell transfusions (1.4 +/- 0.2 vs. 3.3 +/- 0.7 units), time to extubation (6.8 +/- 0.5 vs. 11.4 +/- 2.3 hours), intensive care unit stay (1.3 +/- 0.1 vs. 2.0 +/- 0.3 days), and hospital stay (4.3 +/- 0.1 vs. 5.1 +/- 0.3 days).

  View details for PubMedID 15905346

• Robotic microlaryngeal surgery: A technical feasibility study using the daVinci surgical robot and an airway mannequin LARYNGOSCOPE Hockstein, N. G., Nolan, J. P., O'Malley, B. W., Woo, Y. J. 2005; 115 (5): 780-785

  Abstract

  The trend toward minimally invasive surgery has led to the development and mastery of endoscopic and laparoscopic surgical techniques. These minimally invasive approaches, which only two decades ago were either novel or experimental, are now mainstream. More recently, robot-assisted surgery has evolved as an adjunct to open and endoscopic techniques. Surgical robots are now approved by the United States Food and Drug Administration for a variety of thoracic and abdominal/pelvic surgical procedures. The purpose of this study is to demonstrate the technical feasibility of robot-assisted microlaryngeal surgery.Experimental surgical manipulation of the larynx in an airway mannequin with a surgical robot.A variety of laryngoscopes and mouthgags, coupled with the daVinci Surgical Robot's (Intuitive Surgical, Sunnyvale, CA) 0-degree and 30-degree, two-dimensional and three-dimensional endoscopes, were utilized to optimize visualization of the larynx in an airway mannequin. Five millimeter and 8 mm microinstruments compatible with the daVinci robot were utilized to manipulate different elements of the larynx. Experiments were recorded with both still and video photography.The endoscope and robotic arms of the daVinci robot are well suited to airway surgery.Robot-assisted laryngeal surgery can be performed with currently available technology. The potential for fine manipulation of tissues, increased freedom of instrument movement, and endolaryngeal suturing may increase the precision of endoscopic laryngeal microsurgery and offers the potential to increase the variety of laryngeal procedures that can be performed endoscopically.

  View details for Web of Science ID 000229047800006

  View details for PubMedID 15867639

• One year transgene expression with adeno-associated virus cardiac gene transfer INTERNATIONAL JOURNAL OF CARDIOLOGY Woo, Y. J., Zhang, J. C., Taylor, M. D., Cohen, J. E., Hsu, V. M., Sweeney, H. L. 2005; 100 (3): 421-426

  Abstract

  Adeno-associated virus (AAV) has shown promise as a vector for cardiac gene transfer given its ability to stably integrate into the host genome and its lack of immune reactivity. This study examined the feasibility of AAV-mediated myocardial gene transfer in mice, the animal which, because of transgenic technology, has become the disease model of choice for cardiovascular research.AAV encoding the cytomegalovirus promoter driven LacZ reporter gene (10(7) LacZ-forming units per animal) or vehicle control was injected into the hearts of young adult C57Bl/6 mice by a transdiaphragmatic approach. At one, two, three, six, and twelve months post-injection, cardiac function was assessed by transthoracic echocardiography and hearts were assayed by X-gal histochemical staining.Echocardiography revealed normal left ventricular function in both AAV and control groups at all time points. X-gal staining of cryostat sections of hearts revealed uniform LacZ expression at all time points. There were minimal signs of immunologic infiltration by hematoxylin and eosin staining.AAV-mediated myocardial gene transfer by transdiaphragmatic injection can be conducted safely and results in long-term expression of the LacZ gene for at least one year without causing significant inflammatory response or adversely affecting LV systolic function.

  View details for DOI 10.1016/j.ijcard.2004.09.003

  View details for Web of Science ID 000228814600012

  View details for PubMedID 15837086

• Cardiac surgery in patients on antiplatelet and antithrombotic agents. Seminars in thoracic and cardiovascular surgery Woo, Y. J. 2005; 17 (1): 66-72

  Abstract

  The widespread application of antithrombotic agents carries significant potential for inducing excessive peri-operative hemorrhage during cardiac surgery. Specific surgical and medical strategies can be employed to attenuate this bleeding. These antithrombotic agents and anti-hemorrhagic measures will be reviewed in depth.

  View details for PubMedID 16104363

• Ethyl pyruvate enhances ATP levels, reduces oxidative stress and preserves cardiac function in a rat model of off-pump coronary bypass. Heart, lung & circulation Taylor, M. D., Grand, T. J., Cohen, J. E., Hsu, V., Liao, G. P., Zentko, S., Berry, M. F., Gardner, T. J., Woo, Y. J. 2005; 14 (1): 25-31

  Abstract

  Off-pump coronary artery bypass grafting is associated with transient periods of myocardial ischemia during revascularization resulting in myocardial contractile dysfunction and oxidative injury. The purpose of this study was to investigate the efficacy of ethyl pyruvate as a myocardial protective agent in a rat model of off-pump coronary artery bypass grafting associated with transient myocardial dysfunction without infarction.Wistar rats were subjected to transient ischemia via 10 min occlusion of the LAD coronary artery followed by 10 min of reperfusion. Animals received an IV bolus of Ringer's solution as a control (n=10) or Ringer's ethyl pyruvate (n=10) immediately before the initiation of ischemia and reperfusion. Myocardial ATP and lipid peroxidation levels were quantified for an estimation of energetics and oxidative stress, respectively. In vivo cardiac function was assessed throughout the ischemia and reperfusion periods.Ethyl pyruvate significantly increased myocardial ATP levels compared to controls (2650+/-759 nmol/g versus 892+/-276 nmol/g, p=0.04). Myocardial oxidative stress was significantly reduced in animals treated with ethyl pyruvate compared to controls (70.4+/-2.6 nmol/g versus 81.8+/-2.4 nmol/g, p=0.04). dP/dt max and cardiac output were significantly greater in the ethyl pyruvate group compared to controls during ischemia and reperfusion.Ethyl pyruvate enhances myocardial ATP levels, reduces oxidative stress, and preserves myocardial function in a model of transient ischemia/reperfusion injury not subject to myocardial infarction.

  View details for PubMedID 16352248

• Minimally invasive aortic valve replacement combined with radiofrequency-modified maze procedure JOURNAL OF CARDIAC SURGERY Kolakowski, S., Woo, Y. J. 2005; 20 (2): 164-166

  Abstract

  The treatment of chronic atrial fibrillation undergoing concomitant cardiac surgery is gaining greater acceptance. This is the first reported case of a minimally invasive aortic valve replacement combined with a radiofrequency-modified maze procedure.

  View details for Web of Science ID 000235710700011

  View details for PubMedID 15725142

• Induction of angiogenesis and inhibition of apoptosis by hepatocyt growth factor effectively treats postischemic heart failure JOURNAL OF CARDIAC SURGERY Jayasankar, V., Woo, Y. J., Pirolli, T. J., Bish, L. T., Berry, M. F., Burdick, J., Gardner, T. J., Sweeney, H. L. 2005; 20 (1): 93-101

  Abstract

  Heart failure following myocardial infarction (MI) is a significant cause of morbidity and mortality and remains a difficult therapeutic challenge. Hepatocyte growth factor (HGF) is a potent angiogenic and anti-apoptotic protein whose receptor is upregulated following MI. This study was designed to investigate the ability of HGF to prevent heart failure in a rat model of experimental MI.The rats underwent direct intramyocardial injection with replication-deficient adenovirus encoding HGF (n = 7) or null virus as control (n = 7) 3 weeks following ligation of the left anterior descending coronary artery. Analysis of the following was performed 3 weeks after injection: cardiac function by pressure-volume conductance catheter measurements; LV wall thickness; angiogenesis by Von Willebrand's factor staining; and apoptosis by the TUNEL assay. The expression levels of HGF and the anti-apoptotic factor Bcl-2 were analyzed by Western blot.Adeno-HGF-treated animals had greater preservation of maximum LV pressure (HGF 77 +/- 3 vs. control 64 +/- 5 mmHg, p < 0.05), maximum dP/dt (3024 +/- 266 vs. 1907 +/- 360 mmHg/sec, p < 0.05), maximum dV/dt (133 +/- 20 vs. 84 +/- 6 muL/sec, p < 0.05), and LV border zone wall thickness (1.98 +/- 0.06 vs. 1.53 +/- 0.07 mm, p < 0.005). Angiogenesis was enhanced (151 +/- 10.0 vs. 90 +/- 4.5 endothelial cells/hpf, p < 0.005) and apoptosis was reduced (3.9 +/- 0.3 vs. 8.2 +/- 0.5%, p < 0.005). Increased expression of HGF and Bcl-2 protein was observed in the Adeno-HGF-treated group.Overexpression of HGF 3 weeks post-MI resulted in enhanced angiogenesis, reduced apoptosis, greater preservation of ventricular geometry, and preservation of cardiac contractile function. This technique may be useful to treat or prevent postinfarction heart failure.

  View details for Web of Science ID 000226958900019

  View details for PubMedID 15673421

• Targeted overexpression of leukemia inhibitory factor to preserve myocardium in a rat model of postinfarction heart failure 84th Annual Meeting of the American-Association-for-Thoracic-Surgery Berry, M. F., Pirolli, T. J., Jayasankar, V., Morine, K. J., Moise, M. A., Fisher, O., Gardner, T. J., Patterson, P. H., Woo, Y. J. MOSBY-ELSEVIER. 2004: 866–75

  Abstract

  Myocardial infarction leads to cardiomyocyte loss. The cytokine leukemia inhibitory factor regulates the differentiation and growth of embryonic and adult heart tissue. This study examined the effects of gene transfer of leukemia inhibitory factor in infarcted rat hearts.Lewis rats underwent ligation of the left anterior descending coronary artery and direct injection of adenovirus encoding leukemia inhibitory factor (n = 10) or null transgene as control (n = 10) into the myocardium bordering the ischemic area. A sham operation group (n = 10) underwent thoracotomy without ligation. After 6 weeks, the following parameters were evaluated: cardiac function with a pressure-volume conductance catheter, left ventricular geometry and architecture by histologic methods; myocardial fibrosis by Masson trichrome staining, apoptosis by terminal deoxynucleotidal transferase-mediated deoxyuridine triphosphate nick-end labeling assay, and cardiomyocyte size by immunofluorescence.Rats with overexpression of leukemia inhibitory factor had more preserved myocardium and less fibrosis in both the infarct and its border zone. The border zone in leukemia inhibitory factor-treated animals contained fewer apoptotic nuclei (1.6% +/- 0.1% vs 3.3% +/- 0.2%, P < .05) than that in control animals and demonstrated cardiomyocytes with larger cross-sectional areas (910 +/- 60 microm 2 vs 480 +/- 30 microm 2 , P < .05). Leukemia inhibitory factor-treated animals had increased left ventricular wall thickness (2.1 +/- 0.1 mm vs 1.8 +/- 0.1 mm, P < .05) and less dilation of the left ventricular cavity (237 +/- 22 microL vs 301 +/- 16 microL, P < .05). They also had improved cardiac function, as measured by maximum change in pressure over time (3950 +/- 360 mm Hg/s vs 2750 +/- 230 mm Hg/s, P < .05) and the slopes of the maximum change in pressure over time-end-diastolic volume relationship (68 +/- 5 mm Hg/[s . microL] vs 46 +/- 6 mm Hg/[s . microL], P < .05) and the preload recruitable stroke work relationship (89 +/- 10 mm Hg vs 44 +/- 4 mm Hg, P < .05).Myocardial gene transfer of leukemia inhibitory factor preserved cardiac tissue, geometry, and function after myocardial infarction in rats.

  View details for DOI 10.1016/j.jtcvs.2004.06.046

  View details for Web of Science ID 000225475700012

  View details for PubMedID 15573071

• Innominate artery transection in the setting of a bovine arch JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Moise, M. A., Hsu, V., Braslow, B., Woo, Y. J. 2004; 128 (4): 632-634

  View details for DOI 10.1016/j.jtcvs.2004.03.006

  View details for Web of Science ID 000224255600026

  View details for PubMedID 15457173

• Inhibition of matrix metalloproteinase activity by TIMP-1 gene transfer effectively treats ischemic cardiomyopathy CIRCULATION Jayasankar, V., Woo, Y. J., Bish, L. T., Pirolli, T. J., Berry, M. F., Burdick, J., Bhalla, R. C., Sharma, R. V., Gardner, T. J., Sweeney, H. L. 2004; 110 (11): II180-II186

  Abstract

  Enhanced activity of matrix metalloproteinases (MMPs) has been associated with extracellular matrix degradation and ischemic heart failure in animal models and human patients. This study evaluated the effects of MMP inhibition by gene transfer of TIMP-1 in a rat model of ischemic cardiomyopathy.Rats underwent ligation of the left anterior descending coronary artery with direct intramyocardial injection of replication-deficient adenovirus encoding TIMP-1 (n=8) or null virus as control vector (n=8), and animals were analyzed after 6 weeks. Both systolic and diastolic cardiac function was significantly preserved in the TIMP-1 group compared with control animals (maximum left ventricular [LV] pressure: TIMP-1 70+/-10 versus control 56+/-12 mmHg, P<0.05; maximum dP/dt 2697+/-842 versus 1622+/-527 mmHg/sec, P<0.01; minimum dP/dt -2900+/-917 versus -1195+/-593, P<0.001). Ventricular geometry was significantly preserved in the TIMP-1 group (LV diameter 13.0+/-0.7 versus control 14.4+/-0.4 mm, P<0.001; border-zone wall thickness 1.59+/-0.11 versus control 1.28+/-0.19 mm, P<0.05), and this was associated with a reduction in myocardial fibrosis (2.36+/-0.87 versus control 3.89+/-1.79 microg hydroxyproline/mg tissue, P<0.05). MMP activity was reduced in the TIMP-1 animals (1.5+/-0.9 versus control 43.1+/-14.9 ng of MMP-1 activity, P<0.05).TIMP-1 gene transfer inhibits MMP activity and preserves cardiac function and geometry in ischemic cardiomyopathy. The reduction in myocardial fibrosis may be primarily responsible for the improved diastolic function in treated animals. TIMP-1 overexpression is a promising therapeutic target for continued investigation.

  View details for DOI 10.1161/01.CIR.0000138946.29375.49

  View details for Web of Science ID 000224023600032

  View details for PubMedID 15364860

• Apelin has in vivo inotropic effects on normal and failing hearts CIRCULATION Berry, M. F., Pirolli, T. J., Jayasankar, V., Burdick, J., Morine, K. J., Gardner, T. J., Woo, Y. J. 2004; 110 (11): II187-II193

  Abstract

  Apelin has been shown ex vivo to be a potent cardiac inotrope. This study was undertaken to evaluate the in vivo effects of apelin on cardiac function in native and ischemic cardiomyopathic rat hearts using a novel combination of a perivascular flow probe and a conductance catheter.Native rats (n =32) and rats in heart failure 6 weeks after left anterior descending coronary artery ligation (n =22) underwent median sternotomy with placement of a perivascular flow probe around the ascending aorta and a pressure volume conductance catheter into the left ventricle. Compared with sham-operated rats, the ligated rats had significantly decreased baseline Pmax and max dP/dt. Continuous infusion of apelin at a rate of 0.01 microg/min for 20 minutes significantly increased Pmax and max dP/dt compared with infusion of vehicle alone in both native and failing hearts. Apelin infusion increased cardiac contractility, indicated by a significant increase in stroke volume (SV) without a change in left ventricular end diastolic volume (102+/-16% change from initial SV versus 26+/-20% for native animals, and 110+/-30% versus 26+/-11% for ligated animals), as well as an increase in preload recruitable stroke work (180+/-24 mm Hg versus 107+/-9 mm Hg for native animals).The present study is the first to show that apelin has positive inotropic effects in vivo in both normal rat hearts and rat hearts in failure after myocardial infarction. Apelin may have use as an acute inotropic agent in patients with ischemic heart failure.

  View details for DOI 10.1161/01.CIR.0000138382.57325.5c

  View details for Web of Science ID 000224023600033

  View details for PubMedID 15364861

• Administration of a tumor necrosis factor inhibitor at the time of myocardial infarction attenuates subsequent ventricular remodeling JOURNAL OF HEART AND LUNG TRANSPLANTATION Berry, M. F., Woo, Y. J., Pirolli, T. J., Bish, L. T., Moise, M. A., Burdick, J. W., Morine, K. J., Jayasankar, V., Gardner, T. J., Sweeney, H. L. 2004; 23 (9): 1061-1068

  Abstract

  Tumor necrosis factor (TNF) causes myocardial extracellular matrix remodeling and fibrosis in myocardial infarction and chronic heart failure models. Pre-clinical and clinical trials of TNF inhibition in chronic heart failure have shown conflicting results. This study examined the effects of the administration of a TNF inhibitor immediately after myocardial infarction on the development of heart failure.Lewis rats underwent coronary artery ligation and then received either intravenous etanercept (n = 14), a soluble dimerized TNF receptor that inhibits TNF, or saline as control (n = 13). Leukocyte infiltration into the infarct borderzone was evaluated 4 days post-ligation in 7 animals (etanercept = 4, control = 3). After 6 weeks, the following parameters were evaluated in the remaining animals: cardiac function with a pressure-volume conductance catheter, left ventricular (LV) geometry, and borderzone collagenase activity.Etanercept rats had significantly less borderzone leukocyte infiltration 4 days post-infarction than controls (10.7 +/- 0.5 vs 18.0, +/-2.0 cells/high power field; p < 0.05). At 6 weeks, TNF inhibition resulted in significantly reduced borderzone collagenase activity (110 +/- 30 vs 470 +/- 140 activity units; p < 0.05) and increased LV wall thickness (2.1 +/- 0.1 vs 1.8 +/- 0.1 mm, p < 0.05). Etanercept rats had better systolic function as measured by maximum LV pressure (84 +/- 3 mm Hg vs 68 +/- 5 mm Hg, p < 0.05) and the maximum change in left ventricular pressure over time (maximum dP/dt) (3,110 +/- 230 vs 2,260 +/- 190 mm Hg/sec, p < 0.05), and better diastolic function as measured by minimum dP/dt (-3,060 +/- 240 vs -1,860 +/- 230 mm Hg/sec; p < 0.05) and the relaxation time constant (14.6 +/- 0.6 vs 17.9 +/- 1.2 msec; p < 0.05).TNF inhibition after infarction reduced leukocyte infiltration and extracellular matrix turnover and preserved cardiac function.

  View details for DOI 10.1016/j.healun.2004.06.021

  View details for Web of Science ID 000224230300007

  View details for PubMedID 15454172

• Local myocardial overexpression of growth hormone attenuates postinfarction remodeling and preserves cardiac function ANNALS OF THORACIC SURGERY Jayasankar, V., Bish, L. T., Pirolli, T. J., Berry, M. F., Burdick, J., Woo, Y. J. 2004; 77 (6): 2122-2129

  Abstract

  Ventricular remodeling with chamber dilation and wall thinning is seen in postinfarction heart failure. Growth hormone induces myocardial hypertrophy when oversecreted. We hypothesized that localized myocardial hypertrophy induced by gene transfer of growth hormone could inhibit remodeling and preserve cardiac function after myocardial infarction.Rats underwent direct intramyocardial injection of adenovirus encoding either human growth hormone (n = 9) or empty null vector as control (n = 9) 3 weeks after ligation of the left anterior descending coronary artery. Analysis of the following was performed 3 weeks after delivery: hemodynamics, ventricular geometry, cardiomyocyte fiber size, and serum growth hormone levels.The growth hormone group had significantly better systolic cardiac function as measured by maximum left ventricular pressure (73.6 +/- 6.9 mm Hg versus control 63.7 +/- 7.8 mm Hg, p < 0.05) and maximum dP/dt (2845 +/- 453 mm Hg/s versus 1949 +/- 605 mm Hg/s, p < 0.005), and diastolic function as measured by minimum dP/dt (-2520 +/- 402 mm Hg/s versus -1500 +/- 774 mm Hg/s, p < 0.01). Ventricular geometry was preserved in the growth hormone group (ventricular diameter 12.2 +/- 0.7 mm versus control 13.1 +/- 0.4 mm, p < 0.05; borderzone wall thickness 2.0 +/- 0.2 mm versus 1.5 +/- 0.1 mm, p < 0.001), and was associated with cardiomyocyte hypertrophy (6.09 +/- 0.63 microm versus 4.66 +/- 0.55 microm, p < 0.005). Local myocardial expression of growth hormone was confirmed, whereas serum levels were undetectable after 3 weeks.Local myocardial overexpression of growth hormone after myocardial infarction resulted in cardiomyocyte hypertrophy, attenuated ventricular remodeling, and improved systolic and diastolic cardiac function. The induction of localized myocardial hypertrophy presents a novel therapeutic approach for the treatment of ischemic heart failure.

  View details for DOI 10.1016/j.athoracsur.2003.12.043

  View details for Web of Science ID 000221717200039

  View details for PubMedID 15172279

• Ethyl pyruvate preserves cardiac function and attenuates oxidative injury after prolonged myocardial ischemia 83rd Annual Meeting of the American-Association-for-Thoracic-Surgery Woo, Y. J., Taylor, M. D., Cohen, J. E., Jayasankar, V., Bish, L. T., Burdick, J., Pirolli, T. J., Berry, M. F., Hsu, V., Grand, T. MOSBY-ELSEVIER. 2004: 1262–69

  Abstract

  Myocardial injury and dysfunction following ischemia are mediated in part by reactive oxygen species. Pyruvate, a key glycolytic intermediary, is an effective free radical scavenger but unfortunately is limited by aqueous instability. The ester derivative, ethyl pyruvate, is stable in solution and should function as an antioxidant and energy precursor. This study sought to evaluate ethyl pyruvate as a myocardial protective agent in a rat model of ischemia-reperfusion injury.Rats underwent 30-minute ischemia and 30-minute reperfusion of the left anterior descending coronary artery territory. Immediately prior to both ischemia and reperfusion, animals received an intravenous bolus of either ethyl pyruvate (n = 26) or vehicle control (n = 26). Myocardial high-energy phosphate levels were determined by adenosine triphosphate assay, oxidative injury was measured by lipid peroxidation assay, infarct size was quantified by triphenyltetrazolium chloride staining, and cardiac function was assessed in vivo.Ethyl pyruvate administration significantly increased myocardial adenosine triphosphate levels compared with control (87.6 +/- 29.2 nmol/g vs 10.0 +/- 2.4 nmol/g, P =.03). In ischemic myocardium, ethyl pyruvate reduced oxidative injury compared with control (63.8 +/- 3.3 nmol/g vs 89.5 +/- 3.0 nmol/g, P <.001). Ethyl pyruvate diminished infarct size as a percentage of area at risk (25.3% +/- 1.5% vs 33.6% +/- 2.1%, P =.005). Ethyl pyruvate improved myocardial function compared with control (maximum pressure: 86.6 +/- 2.9 mm Hg vs 73.5 +/- 2.5 mm Hg, P <.001; maximum rate of pressure rise: 3518 +/- 243 mm Hg/s vs 2703 +/- 175 mm Hg/s, P =.005; maximal rate of ventricular systolic volume ejection: 3097 +/- 479 microL/s vs 2120 +/- 287 microL/s, P =.04; ejection fraction: 41.9% +/- 3.8% vs 31.4% +/- 4.1%, P =.03; cardiac output: 26.7 +/- 0.9 mL/min vs 22.7 +/- 1.3 mL/min, P =.01; and end-systolic pressure-volume relationship slope: 1.09 +/- 0.22 vs 0.59 +/- 0.2, P =.02).In this study of myocardial ischemia-reperfusion injury, ethyl pyruvate enhanced myocardial adenosine triphosphate levels, attenuated myocardial oxidative injury, decreased infarct size, and preserved cardiac function.

  View details for DOI 10.1016/j.jtcvs.2003.11.032

  View details for Web of Science ID 000221134600006

  View details for PubMedID 15115981

• Targeted overexpression of growth hormone by adenoviral gene transfer preserves myocardial function and ventricular geometry in ischemic cardiomyopathy JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY Jayasankar, V., Pirolli, T. J., Bish, L. T., Berry, M. F., Burdick, J., Grand, T., Woo, Y. J. 2004; 36 (4): 531-538

  Abstract

  Post-infarction heart failure is characterized by progressive left ventricular dilatation and wall thinning, with both systolic and diastolic cardiac dysfunction. Human growth hormone (GH) stimulates cardiac hypertrophy when secreted in excess and directly enhances cardiomyocyte contractile function. We hypothesized that local myocardial overexpression of GH could prevent ventricular remodeling and heart failure following myocardial infarction (MI) in rats.Rats underwent ligation of the left anterior descending coronary artery with direct intramyocardial injection of adenovirus encoding human GH (n = 8) or null virus as control (n = 8). Six weeks following MI, Adeno-GH treated animals had significant preservation of both systolic and diastolic cardiac function compared to Null animals (maximum dP/dt GH 2927 +/- 83 vs Null 1622 +/- 159 mmHg/sec, p < 0.001; minimum dP/dt -2409 +/- 82 vs -1195 +/- 179 mmHg/sec, p < 0.01). GH animals had improved ventricular geometry with decreased chamber dilatation (13.2 +/- 0.13 vs 14.4+/-0.15 mm, p < 0.001) and increased wall thickness (2.02 +/- 0.10 vs 1.28 +/- 0.07 mm, p < 0.001), and this was associated with advantageous myocardial hypertrophy with increased cardiomyocyte fiber size. Local myocardial overexpression of GH protein was seen in Adeno-GH animals, while serum levels of human GH were undetectable after 6 weeks.Treatment with Adeno-GH following MI resulted in reduced ventricular dilatation, increased local myocardial hypertrophy, and preservation of both systolic and diastolic cardiac function. No significant systemic exposure to growth hormone transgene was observed. The induction of regional hypertrophy is a novel approach to treating heart failure, and may be useful to treat or prevent post-infarction ischemic cardiomyopathy.

  View details for DOI 10.1016/j.yjmcc.2004.01.010

  View details for Web of Science ID 000221181400008

  View details for PubMedID 15081312

• Should Standard On-Pump Protamine Dosing Formulas Be Recalculated for Off-Pump Coronary Artery Bypass Grafting? heart surgery forum Woo, Y. J., Atluri, P., Grand, T. J., Hsu, V., Gardner, T. J. 2004; 7 (1): 42-44

  Abstract

  Abstract Background: Since 1994 at the authors' institution, approximately 9000 cardiac surgical procedures were performed using activated clotting time (ACT)-monitored heparin anticoagulation for cardiopulmonary bypass and protamine administration calculated from a standard unchanged formula. This formula incorporates physiologic consequences of bypass pump-induced dilutional coagulopathy, platelet dysfunction, and coagulation/fibrinolytic cascade component activation, and thus may overcorrect in a subset of off-pump coronary artery bypass graft (OPCAB) patients who may in fact manifest a relative perioperative hypercoagulability state. This study evaluated a strategy of decreased protamine dosing in OPCAB. Methods: Eighty consecutive OPCAB patients who underwent surgery performed by a single surgeon at a single institution over a 12-month period were retrospectively analyzed. Patients underwent a mean of 2.91 +/- 0.1 OPCAB grafts with full heparinization and 50% of the calculated protamine dose was administered. ACT, partial thromboplastin times, thoracostomy tube outputs, transfusions, and clinical outcomes were assessed. Results: Of 80 patients, 76 (95%) returned to baseline ACT values with 50% protamine dosing. All patients demonstrated intraoperative clinical evidence of hemostasis. Mean 8- and 24-hour thoracostomy tube outputs were 424 +/- 24 mL and 806 +/- 38 mL, respectively. A mean of 1.7 +/- 0.2 packed red blood cell transfusions/patient was administered. There were no transfusions of platelets, fresh frozen plasma, or cryoprecipitate; no reexplorations; and no mortalities. Patients were discharged a mean of 4.4 +/- 0.1 days postoperatively. Conclusion: A standard protamine dosing formula adequate for on-pump cardiac surgical procedures significantly overestimates protamine requirements for OPCAB. Patients treated with decreased protamine do not appear to have adverse outcomes.

  View details for PubMedID 14980850

• Repair of acute type A aortic dissection associated with temporal arteritis ANNALS OF THORACIC SURGERY Berry, M. F., Woo, Y. J. 2003; 76 (5): 1717-1718

  Abstract

  The most common predisposing factor for aortic dissection is hypertension. Dissection is also seen in primary aortic diseases, including those that involve aortic inflammation. We report a case of successful repair of an acute type A aortic dissection in a patient with a history of temporal arteritis and pathologic evidence of giant cell aortitis. The literature concerning the association of aortic dissection and temporal arteritis is reviewed.

  View details for DOI 10.1016/S0003-4975(03)00695-7

  View details for Web of Science ID 000186358600081

  View details for PubMedID 14602321

• Gene transfer of hepatocyte growth factor attenuates postinfarction heart failure. Circulation Jayasankar, V., Woo, Y. J., Bish, L. T., Pirolli, T. J., Chatterjee, S., Berry, M. F., Burdick, J., Gardner, T. J., Sweeney, H. L. 2003; 108: II230-6

  Abstract

  Despite advances in surgical and percutaneous coronary revascularization, ongoing ischemia that is not amenable to standard revascularization techniques is a major cause of morbidity and mortality. Hepatocyte Growth Factor (HGF) has potent angiogenic and anti-apoptotic activities, and this study evaluated the functional and biochemical effects of HGF gene transfer in a rat model of postinfarction heart failure.Lewis rats underwent ligation of the left anterior descending coronary artery with direct intramyocardial injection of replication-deficient recombinant adenovirus encoding HGF (n=10) or empty null virus as control (n=9), and animals were analyzed after six weeks. Pressure-volume conductance catheter measurements demonstrated significantly preserved contractile function in the HGF group compared with Null control animals as measured by maximum developed LV pressure (79+/-5 versus 56+/-4 mm Hg, P<0.001) and maximum dP/dt (2890+/-326 versus 1622+/-159 mm Hg/sec, P<0.01). Significant preservation of LV geometry was associated with HGF treatment (LV Diameter HGF 13.1+/-0.54 versus Null 14.4+/-0.15 mm P<0.01; LV wall thickness 1.73+/-0.10 versus 1.28+/-0.07 mm P<0.01). Angiogenesis was significantly enhanced in HGF treated animals as measured by both Von Willebrand's Factor immunohistochemical staining and a microsphere assay. TUNEL analysis revealed a significant reduction in apoptosis in the HGF group (3.42+/-0.83% versus 8.36+/-1.16%, P<0.01), which correlated with increased Bcl-2 and Bcl-xL expression in the HGF animals.Hepatocyte Growth Factor gene transfer following a large myocardial infarction results in significantly preserved myocardial function and geometry, and is associated with significant angiogenesis and a reduction in apoptosis. This therapy may be useful as an adjunct or alternative to standard revascularization techniques in patients with ischemic heart failure.

  View details for PubMedID 12970238

• Blocking the development of postischemic cardiomyopathy with viral gene transfer of the apoptosis repressor with caspase recruitment domain 82nd Annual Meeting of the American-Association-for-Thoracic-Surgery Chatterjee, S., Bish, L. T., Jayasankar, V., Stewart, A. S., Woo, Y. J., Crow, M. T., Gardner, T. J., Sweeney, H. L. MOSBY-ELSEVIER. 2003: 1461–69

  Abstract

  Apoptosis caused by acute ischemia and subsequent ventricular remodeling is implicated as a mediator of heart failure. This study was designed to assess the efficacy of in vivo viral gene transfer of the antiapoptotic factor apoptosis repressor with caspase recruitment domain to block apoptosis and preserve ventricular geometry and function.In a rabbit model of regional ischemia followed by reperfusion, an experimental group treated with adenovirus-apoptosis repressor with caspase recruitment domain was compared with empty vector adenovirus-null controls. Cardiac function was assessed by echocardiography and sonomicrometry of the border zone compared with the normal left ventricle. Animals were killed at 6 weeks with measurements of ventricular geometry and apoptosis.Animals with the apoptosis repressor with caspase recruitment domain (ARC group) maintained higher ejection fractions at 4 and 6 weeks, and sonomicrometry demonstrated greater protection of border zone fractional shortening at 6 weeks compared with the control group. The ARC group maintained superior preservation of left ventricular geometry with less ventricular dilation and wall thinning. Finally, there was reduced apoptosis in the rabbits treated with apoptosis repressor with caspase recruitment domain compared with the controls.Gene transfer of apoptosis repressor with caspase recruitment domain preserves left ventricular function after ischemia. The benefit at 6 weeks is postulated to result from an apoptosis repressor with caspase recruitment domain-mediated reduction in apoptosis and ventricular remodeling. Adenovirus-apoptosis repressor with caspase recruitment domain administration offers a potential strategy after myocardial ischemia to protect the heart from late postischemic cardiomyopathy.

  View details for DOI 10.1016/S0022-5223(02)73229-7

  View details for Web of Science ID 000183864700036

  View details for PubMedID 12830068

• Off-pump coronary artery bypass grafting attenuates postoperative bleeding associated with preoperative clopidogrel administration 9th Annual CTT Meeting Woo, Y. J., Grand, T., Valettas, N. FORUM MULTIMEDIA PUBLISHING, LLC. 2003: 282–85

  Abstract

  Clopidogrel is being increasingly administered as primary therapy for acute coronary syndromes and prior to planned percutaneous coronary intervention (PCI). In these settings, surgical revascularization results in signifi- cantly increased postoperative bleeding, transfusion, and reexploration. Off-pump coronary artery bypass grafting (OPCAB) may decrease the extent of postoperative bleeding in patients exposed to clopidogrel.The cases of 78 consecutive patients undergoing OPCAB by a single surgeon were retrospectively analyzed, and the patients were divided into 2 groups, those with immediately preoperative clopidogrel exposure (clopidogrel OPCAB, n = 15) and those without (control OPCAB, n = 63). Multiple perioperative parameters were statistically compared. The clopidogrel OPCAB group also was compared with a group of previously described on-pump coronary bypass patients who made up a historical control group (n = 59).Postoperative bleeding, transfusion requirements, reexploration rates, duration of mechanical ventilation, and length of stay were markedly less for clopidogrel OPCAB patients than for historical controls and were statistically equivalent to those of control OPCAB patients.Among these 15 OPCAB patients with immediately preoperative administration of clopidogrel and aspirin, outcome was improved compared with published results for on-pump coronary bypass patients and was equivalent to results among OPCAB patients not exposed to clopidogrel. Published, recommended approaches to clopidogrel administration, such as avoidance of pre-PCI clopidogrel, delay of surgery, and platelet transfusion do not appear to be necessary with OPCAB.

  View details for Web of Science ID 000185916500002

  View details for PubMedID 14721793

• Minimally invasive video-assisted graft replacement of a descending thoracic aortic aneurysm 5th Annual Meeting of the International-Society-for-Minimally-Invasive-Cardiac-Surgery Woo, Y. J., Childers, H. FORUM MULTIMEDIA PUBLISHING, LLC. 2003: E59–E61

  Abstract

  Standard surgical therapy of descending thoracic aortic aneurysms entails obligate extensive operative exposure that is associated with significant postoperative pain and morbidity. A 70-year-old patient with multiple significant comorbidities including severe chronic obstructive pulmonary disease (force expiratory volume at 1 second, 0.66 L) presented with a highly symptomatic, eccentric, descending thoracic aortic aneurysm. The patient underwent successful minimally invasive video-assisted graft repair of this aneurysm. This report represents the first known clinical application of this operative approach.

  View details for Web of Science ID 000183699400033

  View details for PubMedID 12821441

• Advances in the treatment of acute type A dissection: An integrated approach Aortic Surgery Symposium VIII Bavaria, J. E., Brinster, D. R., Gorman, R. C., Woo, Y. J., Gleason, T., Pochettino, A. ELSEVIER SCIENCE INC. 2002: S1848–S1852

  Abstract

  Acute type A dissections require surgery to prevent death from proximal aortic rupture or malperfusion. Most series over the past decade have reported a death rate in the range of 15% to 30%. The objective of this study is to examine the effect of an integrated surgical approach on the treatment of acute type A dissections.From January 1994 to April 2002, 163 consecutive patients underwent repair of acute type A dissection. All had an integrated operative management as follows: intraoperative transesophageal echocardiography; hypothermic circulatory arrest (HCA) with retrograde cerebral perfusion to replace the aortic arch; HCA established after 3 minutes of electroencephalographic silence in neuromonitored patients (60%) or after 45 minutes of cooling in patients who were not neuromonitored (40%); reinforcement of the residual arch tissue with a Teflon felt "neo-media;" cannulation of the arch graft to reestablish cardiopulmonary bypass at the completion of HCA (antegrade graft perfusion); and remodeling of the sinus of Valsalva segments with Teflon felt "neo-media" and aortic valve resuspension or replacement with a biological or mechanical valved conduit. When HCA times were greater than 50 minutes, antegrade cerebral perfusion is used. Since Februay 1999, BioGlue has been used as an anastomotic adjunct in the repair of type A dissections.Mean age was 62 +/- 14 years, with 68% men and 15% with previous cardiac surgery. Seven percent of patients presented with a preoperative neurologic deficit, and 3% developed a new cerebrovascular accident after dissection repair. The in-hospital death rate was 9.8%. Excluding the patients with preoperative strokes (7%) and those with postoperative stroke (3%), the in-hospital death rate was 6.6%. In 6 patients, prompt changes in circulatory management consisting of switching cannulation sites or cross-clamp release with direct temporary aortic arch fenestration occurred when there were sudden changes in electroencephalogram during cooling.A standardized approach to the treatment of acute type A dissections has improved outcomes. Our 55% mortality in patients with preoperative cerebral vascular accident (CVA) suggests that this group may be candidates for medical or delayed surgical treatment. Conversely, our 6.6% mortality rate for neurologically intact patients warrants aggressive and expeditious surgical intervention.

  View details for Web of Science ID 000179262300109

  View details for PubMedID 12440679

• Viral gene transfer of the antiapoptotic factor Bcl-2 protects against chronic postischemic heart failure. Circulation Chatterjee, S., Stewart, A. S., Bish, L. T., Jayasankar, V., Kim, E. M., Pirolli, T., Burdick, J., Woo, Y. J., Gardner, T. J., Sweeney, H. L. 2002; 106 (12): I212-7

  Abstract

  Apoptosis secondary to acute ischemia and chronic remodeling is implicated as a mediator of heart failure. This study was designed to assess the effect of in vivo viral gene transfer of the anti-apoptotic factor Bcl-2 to block apoptosis and preserve ventricular geometry and function.In a rabbit model of regional ischemia followed by reperfusion, an experimental group treated with adeno-Bcl-2 was compared with a control group receiving empty vector adeno-null. Function was assessed by echocardiography, and sonomicrometry of the border zone was compared with the normal left ventricle (LV). Animals were killed at 6 weeks, and an additional group was killed after 3 days to see whether virus administration conferred an immediate effect. Animals that were administered Bcl-2 maintained higher ejection fractions at 2, 4, and 6 weeks compared with controls. Sonomicrocrystals demonstrated greater protection of border zone fractional shortening at 6 weeks. The Bcl-2 group had superior preservation of LV geometry with less ventricular dilatation and wall thinning. There was also reduced apoptosis compared with the controls. Finally, in the animals killed at 3 days, no functional difference was observed between the Bcl-2 and control groups.Gene transfer of Bcl-2 preserves LV function after ischemia despite the absence of an observed acute protective effect. The benefit at 6 weeks is postulated to result from a Bcl-2-mediated reduction in apoptosis and ventricular remodeling. Adeno-Bcl-2 administration offers a potential strategy to protect the heart from late postischemic heart failure.

  View details for PubMedID 12354736

• Efficient transmural cardiac gene transfer by intrapericardial injection in neonatal mice JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY Zhang, J. C., Woo, Y. J., Chen, J. A., Swain, J. L., Sweeney, H. L. 1999; 31 (4): 721-732

  Abstract

  An efficient cardiac gene transfer technique in murine models would greatly facilitate the elucidation of the pathophysiology of cardiomyopathies and the development of genetic therapies. Direct myocardial injection or catheter-based intracoronary infusion is not easily achievable in mice and resultant transgene expression is often limited in distribution. A replication-defective, recombinant adenovirus encoding luciferase (5x10(9)pfu) or lacZ (4-5x10(10)particles/animal) was injected percutaneously into the pericardial cavity of 4-5 day old mice. Chemiluminescence assay for luciferase activity at 3 days post-injection revealed the highest activity in the heart (heart=288+/-110, lungs=19+/-5, liver=11+/-5 ng/gm tissue, n=11). X-gal staining of cryostat sections demonstrated widespread transmural lacZ expression in the left ventricle, interventricular septum, right ventricle, and atrial appendages, and the average fractional area of X-gal staining in a left ventricle was 66+/-16% (range 40-92%, n=21 sections). However, the long-term survival of these mice was compromised. Reduction in the injectate volume by 50% significantly improved survival but concurrently reduced lacZ expression. Significant lacZ expression was observed in the right ventricle and interventricular septum but left ventricular expression was predominantly epicardial, with variable myocardial penetration. At 2 months post-injection, lacZ expression persisted only in atrial tissues, pulmonary veins, and great vessels. Despite lack of persistent transgene expression in ventricular tissues, the high degree of transgene expression achieved may be sufficient to allow evaluation of short-term effects of specific genetic manipulations in the heart.

  View details for Web of Science ID 000079914600003

  View details for PubMedID 10329200

• Recombinant adenovirus-mediated cardiac gene transfer of superoxide dismutase and catalase attenuates postischemic contractile dysfunction CIRCULATION Woo, Y. J., Zhang, J. C., Vijayasarathy, C., Zwacka, R. M., Englehardt, J. F., Gardner, T. J., Sweeney, H. L. 1998; 98 (19): II255-II260

  Abstract

  Coronary revascularization entails obligatory myocardial ischemia followed by reperfusion with occasional resultant postischemic contractile dysfunction, a state associated with significant morbidity and mortality. This injury is attributed in part to oxygen free radicals and has been partially ameliorated with exogenous antioxidants, a strategy limited by agent instability, low titer, and inadequate cardiomyocyte uptake. Cardiac gene transfer with antioxidant encoding vectors may significantly enhance intracellular free radical scavenger activity.C57/BL6 neonatal mice (age, 2 days; n = 131) underwent intrapericardial delivery of recombinant adenoviruses encoding superoxide dismutase (SOD) and catalase (Cat) (n = 76) or beta-galactosidase (LacZ) as a control (n = 55). After 3 days, hearts were explanted, and SOD and Cat transgene expression was detected by Western blot analysis. Spectrophotometric enzyme assays demonstrated enhanced SOD activity 1.6-fold (P < 0.0001) and Cat 3.6-fold (P < 0.00001) in experimental versus LacZ hearts. Isolated perfused hearts were subjected to 5 minutes of warm ischemia, and at 5, 10, and 15 minutes after initiation of reperfusion, LacZ controls lost 24%, 33%, and 41% of peak systolic apicobasal force, respectively, whereas experimental hearts lost 5%, 12%, and 20% (P < 0.001, each time point). In controls, rate of force generation diminished 8%, 17%, and 35%; in experimental hearts, it increased 1% at 5 minutes and decreased 5% and 15% and 10 and 15 minutes (P < 0.01, P < 0.05, P < 0.05). LacZ hearts exhibited dysfunction similar to hearts from uninjected animals (P = NS, each time point).Adenovirus-mediated cardiac gene transfer and expression of SOD and Cat augment antioxidant enzyme activity and minimize contractile dysfunction after ischemic reperfusion in the isolated perfused neonatal mouse heart.

  View details for Web of Science ID 000076886100067

  View details for PubMedID 9852911

• In utero cardiac gene transfer via intraplacental delivery of recombinant adenovirus CIRCULATION Woo, Y. J., Raju, G. P., Swain, J. L., Richmond, M. E., Gardner, T. J., BALICEGORDON, R. J. 1997; 96 (10): 3561-3569

  Abstract

  The relationship among the maternal, placental, and uniquely shunted embryonic circulation was explored to provide access to the embryonic cardiovascular system in utero. Manipulation of gene expression in the developing heart would be particularly useful for studying the effects of altered gene expression on cardiac development and in the etiology of congenital cardiac anomalies.Dye studies demonstrated that intraplacental injection allows direct access to the embryonic cardiac and systemic circulation. To evaluate the efficacy of cardiac gene transfer using this approach, replication-deficient recombinant adenoviral vectors encoding luciferase or beta-galactosidase as reporter genes were injected intraplacentally into embryonic day (E)12.5 murine embryos, an age at which the mass of the heart was observed to be large compared with other organs. Embryos were assayed for transgene expression at E15.5 and at birth. Survival rates at these times were similar among vector-injected and control groups. At E15.5 and at birth, luciferase activity within the heart was 9- and 23-fold higher, respectively, than in the remainder of the embryo, although levels of expression were generally lower at birth than during embryonic life. Beta-galactosidase expression was observed within all regions of the embryonic heart and was localized to approximately 15% of atrial and ventricular cells.Intraplacental delivery of adenovirus at embryonic day 12.5 results in somatic gene transfer to the murine embryonic heart, which persists at least until birth. The combination of intraplacental injection to directly access the fetal coronary circulation and injection at E12.5 when the mass of the heart is large compared with other organs results in transgene expression in cardiac cells. Intraplacental injections early in embryonic life may thus be useful to study the effects of temporal manipulation of gene expression on cardiac development and disease.

  View details for Web of Science ID A1997YH18800049

  View details for PubMedID 9396456

• Circulatory management with retrograde cerebral perfusion for acute type A aortic dissection. Circulation Bavaria, J. E., Woo, Y. J., Hall, R. A., Wahl, P. M., Acker, M. A., Gardner, T. J. 1996; 94 (9): II173-6

  Abstract

  Cerebral circulation during urgent repair of acute type A aortic dissection has traditionally been managed with cardiopulmonary bypass and aortic cross clamping proximal to the innominate artery or by the use of hypothermic circulatory arrest (HCA). The more recently introduced retrograde cerebral perfusion (RCP) may confer additional cerebral protection during elective aortic arch reconstruction. The purpose of this study was to demonstrate the efficacy of RCP in the urgent repair of acute type A aortic dissection.We evaluated 60 consecutive patients who underwent repair of acute type A aortic dissection over a 6-year period. Patients were grouped according to intraoperative circulatory management strategies. Group 1 consisted of 41 patients operated on early in the series who were managed by cardiopulmonary bypass and standard aortic cross clamping (n = 21) with conversion to HCA (n = 20) if the intimal tear extended into the aortic arch. Since 1993, 19 patients, who make up group 2, were managed with routine open distal anastomosis and HCA with RCP. Data were analyzed for clinically evident, radiographically confirmed cerebrovascular accidents and 60-day mortality and evaluated by chi 2 analysis. Stroke and mortality rates of patients managed with either cardiopulmonary bypass or HCA were 26.3% and 29.3%, respectively. Patients undergoing RCP experienced statistically significant reductions in rates of confirmed cerebrovascular accidents (0%, P = .015) and mortality (5.3%, P = .04).We conclude that the introduction of circulatory management using RCP with HCA during urgent operative repair of acute type A aortic dissection has significantly improved both stroke and mortality rates.

  View details for PubMedID 8901741

• Retrograde cerebral and distal aortic perfusion during ascending and thoracoabdominal aortic surgery Annals Thoracic Surg Bavaria, J. E., Woo, Y. J., Hall, R. A., Carpenter, J. P., Gardner, T. J. 1995; 60: 345-353