William Fearon, MD

All Publications

• 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

• Fractional Flow Reserve-Guided PCI as Compared with Coronary Bypass Surgery. Reply. The New England journal of medicine Fearon, W. F., Zimmermann, F. M., Pijls, N. H. 2022; 386 (19): 1865-1866

  View details for DOI 10.1056/NEJMc2202491

  View details for PubMedID 35544403

• 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

• Microcirculatory Resistance Predicts Allograft Rejection and Cardiac Events After Heart Transplantation. Journal of the American College of Cardiology Ahn, J., Zimmermann, F. M., Gullestad, L., Angeras, O., Karason, K., Russell, K., Lunde, K., Okada, K., Luikart, H., Khush, K. K., Honda, Y., Pijls, N. H., Lee, S. E., Kim, J., Park, S., Solberg, O., Fearon, W. F. 2021; 78 (24): 2425-2435

  Abstract

  BACKGROUND: Single-center data suggest that the index of microcirculatory resistance (IMR) measured early after heart transplantation predicts subsequent acute rejection.OBJECTIVES: The goal of this study was to validate whether IMR measured early after transplantation can predict subsequent acute rejection and long-term outcome in a large multicenter cohort.METHODS: From 5 international cohorts, 237 patients who underwent IMR measurement early after transplantation were enrolled. The primary outcome was acute allograft rejection (AAR) within 1 year after transplantation. A key secondary outcome was major adverse cardiac events (MACE) (the composite of death, re-transplantation, myocardial infarction, stroke, graft dysfunction, and readmission) at 10 years.RESULTS: IMR was measured at a median of 7weeks (interquartile range: 3-10weeks) post-transplantation. At 1 year, the incidence of AAR was 14.4%. IMR was associated proportionally with the risk of AAR (per increase of 1-U IMR; adjusted hazard ratio [aHR]: 1.04; 95% confidence interval [CI]: 1.02-1.06; p < 0.001). The incidence of AAR in patients with an IMR≥18 was 23.8%, whereas the incidence of AAR in those with an IMR<18 was 6.3% (aHR: 3.93; 95%CI: 1.77-8.73; P=0.001). At 10 years, MACE occurred in 86 (36.3%) patients. IMR was significantly associated with the risk of MACE (per increase of 1-U IMR; aHR: 1.02; 95%CI: 1.01-1.04; P=0.005).CONCLUSIONS: IMR measured early after heart transplantation is associated with subsequent AAR at 1 year and clinical events at 10 years. Early IMR measurement after transplantation identifies patients at higher risk and may guide personalized posttransplantation management.

  View details for DOI 10.1016/j.jacc.2021.10.009

  View details for PubMedID 34886963

• 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

• Utilization and Outcomes of Measuring Fractional Flow Reserve in Patients With Stable Ischemic Heart Disease. Journal of the American College of Cardiology Parikh, R. V., Liu, G. n., Plomondon, M. E., Sehested, T. S., Hlatky, M. A., Waldo, S. W., Fearon, W. F. 2020; 75 (4): 409–19

  Abstract

  The use and clinical outcomes of fractional flow reserve (FFR) measurement in patients with stable ischemic heart disease (SIHD) are uncertain, as prior studies have been based on selected populations.This study sought to evaluate contemporary, real-world patterns of FFR use and its effect on outcomes among unselected patients with SIHD and angiographically intermediate stenoses.The authors used data from the Veterans Affairs Clinical Assessment, Reporting, and Tracking (CART) Program to analyze patients who underwent coronary angiography between January 1, 2009, and September 30, 2017, and had SIHD with angiographically intermediate disease (40% to 69% diameter stenosis on visual inspection). The authors documented trends in FFR utilization and evaluated predictors using generalized mixed models. They applied Cox proportional hazards models to determine the association between an FFR-guided revascularization strategy and all-cause mortality at 1 year.A total of 17,989 patients at 66 sites were included. The rate of FFR use gradually increased from 14.8% to 18.5% among all patients with intermediate lesions, and from 44% to 75% among patients who underwent percutaneous coronary intervention. One-year mortality was 2.8% in the FFR group and 5.9% in the angiography-only group (p < 0.0001). After adjustment for patient, site-level, and procedural factors, FFR-guided revascularization was associated with a 43% lower risk of mortality at 1 year compared with angiography-only revascularization (hazard ratio: 0.57; 95% confidence interval: 0.45 to 0.71; p < 0.0001).In patients with SIHD and angiographically intermediate stenoses, use of FFR has slowly risen, and was associated with significantly lower 1-year mortality.

  View details for DOI 10.1016/j.jacc.2019.10.060

  View details for PubMedID 32000953

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

  Abstract

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

  View details for DOI 10.1056/NEJMoa1910555

  View details for PubMedID 31995682

• Accuracy of Fractional Flow Reserve Derived From Coronary Angiography CIRCULATION Fearon, W. F., Achenbach, S., Engstrom, T., Assali, A., Shlofmitz, R., Jeremias, A., Fournier, S., Kirtane, A. J., Kornowski, R., Greenberg, G., Jubeh, R., Kolansky, D. M., McAndrew, T., Dressler, O., Maehara, A., Matsumura, M., Leon, M. B., De Bruyne, B., FAST-FFR Study Investigators 2019; 139 (4): 477–84

  View details for DOI 10.1161/CIRCULATIONAHA.118.037350

  View details for Web of Science ID 000459430400009

• Fractional Flow Reserve and Quality-of-Life Improvement After Percutaneous Coronary Intervention in Patients With Stable Coronary Artery Disease. Circulation Nishi, T., Piroth, Z., De Bruyne, B., Jagic, N., Mobius-Winkler, S., Kobayashi, Y., Derimay, F., Fournier, S., Barbato, E., Tonino, P., Juni, P., Pijls, N. H., Fearon, W. F. 2018; 138 (17): 1797–1804

  Abstract

  BACKGROUND: Whether the benefit in quality of life (QOL) after percutaneous coronary intervention depends on the severity of the stenosis as determined by fractional flow reserve (FFR) remains unknown. This study sought to investigate the relationship between FFR values and improvement in QOL.METHODS: From the FAME 1 and 2 trials (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation), we identified 706 stable patients with coronary artery disease who had at least 1 lesion with an FFR≤0.80 that was treated with percutaneous coronary intervention and 185 patients with coronary artery disease who had no lesion with an FFR≤0.80 and were treated medically who served as a reference group. QOL was assessed by the European Quality of Life-5 Dimensions index at baseline, 1 month, and 1 year. We assessed the relationship between QOL improvement (defined as the change in European Quality of Life-5 Dimensions index from baseline) and FFR as a continuous value and according to abnormal FFR tertile.RESULTS: QOL improved significantly after percutaneous coronary intervention in each abnormal FFR tertile, whereas it did not change in the reference group. The lowest abnormal FFR subgroup had the greatest improvement in QOL at 1 month ( P<0.001). In mixed-effects models for repeated measures, lower FFR ( P=0.002 for 1 month and 0.049 for 1 year), greater delta FFR ( P=0.021 for 1 month and 0.025 for 1 year), and higher angina class ( P=0.001 for 1 month and <0.001 for 1 year) were associated with the greatest magnitude of QOL improvement at both 1 month and 1 year.CONCLUSIONS: Among patients with stable coronary artery disease, FFR and angina severity predict QOL improvement after percutaneous coronary intervention.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT00267774 and NCT01132495.

  View details for PubMedID 30354650

• Accuracy of Fractional Flow Reserve Derived From Coronary Angiography. Circulation Fearon, W. F., Achenbach, S., Engstrom, T., Assali, A., Shlofmitz, R., Jeremias, A., Fournier, S., J Kirtane, A., Kornowski, R., Greenberg, G., Jubeh, R., Kolansky, D. M., McAndrew, T., Dressler, O., Maehara, A., Matsumura, M., Leon, M. B., De Bruyne, B. 2018

  Abstract

  BACKGROUND: Measuring fractional flow reserve (FFR) with a pressure wire remains underutilized due to the invasiveness of guide wire placement and/or the need for a hyperemic stimulus. FFR derived from routine coronary angiography (FFRangio) eliminates both of these requirements and displays FFR values of the entire coronary tree. The FFRangio Accuracy versus Standard FFR (FAST-FFR) study is a prospective, multicenter, international trial with the primary goal of determining the accuracy of FFRangio.METHODS: Coronary angiography was performed in a routine fashion in patients with suspected coronary artery disease. FFR was measured in vessels with coronary lesions of varying severity using a coronary pressure wire and hyperemic stimulus. Based on angiograms of the respective arteries acquired in at least two different projections, on-site operators blinded to FFR then calculated FFRangio using proprietary software. Co-primary endpoints were the sensitivity and specificity of the dichotomously scored FFRangio for predicting pressure wire-derived FFR using a cutoff value of 0.80. The study was powered to meet pre-specified performance goals for sensitivity and specificity.RESULTS: Ten centers in the United States, Europe and Israel enrolled a total of 301 subjects and 319 vessels meeting inclusion/exclusion criteria which were included in the final analysis. The mean FFR was 0.81 and 43% of vessels had an FFR≤0.80. The per-vessel sensitivity and specificity were 94% (95% CI 88-97%) and 91% (86-95%), respectively, both of which exceeded the pre-specified performance goals. The diagnostic accuracy of FFRangio was 92% overall and remained high when only considering FFR values between 0.75-0.85 (87%). FFRangio values correlated well with FFR measurements (r=0.80, p<0.001) and the Bland Altman 95% confidence limits were between -0.14 and 0.12. The device success rate for FFRangio was 99%.CONCLUSIONS: FFRangio measured from the coronary angiogram alone has a high sensitivity, specificity and accuracy compared with pressure-wire derived FFR. FFRangio has the promise to substantially increase physiologic coronary lesion assessment in the catheterization laboratory, thereby potentially leading to improved patient outcomes.CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov Unique Identifier: NCT03226262.

  View details for PubMedID 30586699

• Prognostic Value of the Residual SYNTAX Score After Functionally Complete Revascularization in ACS. Journal of the American College of Cardiology Kobayashi, Y., Lonborg, J., Jong, A., Nishi, T., De Bruyne, B., Hofsten, D. E., Kelbak, H., Layland, J., Nam, C., Pijls, N. H., Tonino, P. A., Warnoe, J., Oldroyd, K. G., Berry, C., Engstrom, T., Fearon, W. F., DANAMI-3-PRIMULTI, F. 2018; 72 (12): 1321–29

  Abstract

  BACKGROUND: The residual SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (RSS) quantitatively assesses angiographic completeness of revascularization after percutaneous coronary intervention (PCI) and has been shown to be a predictor of events after angiography-guided PCI. In stable patients undergoing functionally complete revascularization with fractional flow reserve (FFR) guidance, RSS did not predict outcome. Whether this is also true in patients with acute coronary syndromes (ACS) is unknown.OBJECTIVES: The purpose of this study was to determine whether the RSS could predict outcomes in patients with ACS.METHODS: From the DANAMI-3-PRIMULTI (Primary PCI in Patients With ST-elevation Myocardial Infarction and Multivessel Disease: Treatment of Culprit Lesion Only or Complete Revascularization), FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation), and FAMOUS-NSTEMI (Fractional Flow Reserve Versus Angiographically Guided Management to Optimise Outcomes in Unstable Coronary Syndromes) trials, 547patients presented with ACS and underwent functionally complete revascularization. Major adverse cardiac events (MACE) were defined as the composite endpoint of all-cause death, nonfatal myocardial infarction, and any repeat revascularization. The RSS was based on the recalculation of the SYNTAX score after PCI. We compared differences in 2-year outcome by the RSS subgroups: 0, 1 to<5, 5 to<10,≥10 (RSS=0 represents angiographically complete revascularization).RESULTS: The study population consisted of 271 patients with unstable angina/non-ST-segment elevation myocardial infarction and 276 with ST-segment elevation myocardial infarction. The mean RSS was 6.7 ± 5.8. MACE at 2 years occurred in 69patients (12.6%). Patients with and without MACE had similar RSS after PCI (RSS: 7.2 ± 5.5 vs. 6.6 ± 5.9; p=0.23). Kaplan-Meier curve analysis showed a similar incidence of MACE regardless of the RSS subgroups (p=0.54). With and without adjustment of clinical variables, RSS was not a significant predictor of MACE or of each component of MACE.CONCLUSIONS: After complete revascularization of functionally significant stenosis by FFR, the extent of residual angiographic disease is not associated with subsequent ischemic events in patients presenting with ACS. These results suggest that the concept of functionally complete revascularization is applicable even in ACS patients. (Fractional FlowReserve Versus Angiography for Multivessel Evaluation [F.A.M.E.] NCT00267774; Fractional Flow Reserve Versus Angiographically Guided Management to Optimise Outcomes in Unstable Coronary Syndromes [FAMOUS NSTEMI] NCT01764334; Primary PCI in Patients With ST-elevation Myocardial Infarction and Multivessel Disease: TreatmentofCulprit Lesion Only or Complete Revascularization [DANAMI-3-PRIMULTI]; NCT01960933).

  View details for PubMedID 30213322

• Five-Year Outcomes with PCI Guided by Fractional Flow Reserve. The New England journal of medicine Xaplanteris, P., Fournier, S., Pijls, N. H., Fearon, W. F., Barbato, E., Tonino, P. A., Engstrom, T., Kaab, S., Dambrink, J., Rioufol, G., Toth, G. G., Piroth, Z., Witt, N., Frobert, O., Kala, P., Linke, A., Jagic, N., Mates, M., Mavromatis, K., Samady, H., Irimpen, A., Oldroyd, K., Campo, G., Rothenbuhler, M., Juni, P., De Bruyne, B., FAME 2 Investigators 2018

  Abstract

  Background We hypothesized that fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) would be superior to medical therapy as initial treatment in patients with stable coronary artery disease. Methods Among 1220 patients with angiographically significant stenoses, those in whom at least one stenosis was hemodynamically significant (FFR, ≤0.80) were randomly assigned to FFR-guided PCI plus medical therapy or to medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy and were entered into a registry. The primary end point was a composite of death, myocardial infarction, or urgent revascularization. Results A total of 888 patients underwent randomization (447 patients in the PCI group and 441 in the medical-therapy group). At 5 years, the rate of the primary end point was lower in the PCI group than in the medical-therapy group (13.9% vs. 27.0%; hazard ratio, 0.46; 95% confidence interval [CI], 0.34 to 0.63; P<0.001). The difference was driven by urgent revascularizations, which occurred in 6.3% of the patients in the PCI group as compared with 21.1% of those in the medical-therapy group (hazard ratio, 0.27; 95% CI, 0.18 to 0.41). There were no significant differences between the PCI group and the medical-therapy group in the rates of death (5.1% and 5.2%, respectively; hazard ratio, 0.98; 95% CI, 0.55 to 1.75) or myocardial infarction (8.1% and 12.0%; hazard ratio, 0.66; 95% CI, 0.43 to 1.00). There was no significant difference in the rate of the primary end point between the PCI group and the registry cohort (13.9% and 15.7%, respectively; hazard ratio, 0.88; 95% CI, 0.55 to 1.39). Relief from angina was more pronounced after PCI than after medical therapy. Conclusions In patients with stable coronary artery disease, an initial FFR-guided PCI strategy was associated with a significantly lower rate of the primary composite end point of death, myocardial infarction, or urgent revascularization at 5 years than medical therapy alone. Patients without hemodynamically significant stenoses had a favorable long-term outcome with medical therapy alone. (Funded by St. Jude Medical and others; FAME 2 ClinicalTrials.gov number, NCT01132495 .).

  View details for PubMedID 29785878

• Clinical Outcomes and Cost-Effectiveness of Fractional Flow Reserve-Guided Percutaneous Coronary Intervention in Patients With Stable Coronary Artery Disease: Three-Year Follow-Up of the FAME 2 Trial (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) CIRCULATION Fearon, W. F., Nishi, T., De Bruyne, B., Boothroyd, D. B., Barbato, E., Tonino, P., Juni, P., Pijls, N. J., Hlatky, M. A., FAME 2 Trial Investigators 2018; 137 (5): 480–87

  Abstract

  Previous studies found that percutaneous coronary intervention (PCI) does not improve outcome compared with medical therapy (MT) in patients with stable coronary artery disease, but PCI was guided by angiography alone. FAME 2 trial (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) compared PCI guided by fractional flow reserve with best MT in patients with stable coronary artery disease to assess clinical outcomes and cost-effectiveness.A total of 888 patients with stable single-vessel or multivessel coronary artery disease with reduced fractional flow reserve were randomly assigned to PCI plus MT (n=447) or MT alone (n=441). Major adverse cardiac events included death, myocardial infarction, and urgent revascularization. Costs were calculated on the basis of resource use and Medicare reimbursement rates. Changes in quality-adjusted life-years were assessed with utilities determined by the European Quality of Life-5 Dimensions health survey at baseline and over follow-up.Major adverse cardiac events at 3 years were significantly lower in the PCI group compared with the MT group (10.1% versus 22.0%; P<0.001), primarily as a result of a lower rate of urgent revascularization (4.3% versus 17.2%; P<0.001). Death and myocardial infarction were numerically lower in the PCI group (8.3% versus 10.4%; P=0.28). Angina was significantly less severe in the PCI group at all follow-up points to 3 years. Mean initial costs were higher in the PCI group ($9944 versus $4440; P<0.001) but by 3 years were similar between the 2 groups ($16 792 versus $16 737; P=0.94). The incremental cost-effectiveness ratio for PCI compared with MT was $17 300 per quality-adjusted life-year at 2 years and $1600 per quality-adjusted life-year at 3 years. The above findings were robust in sensitivity analyses.PCI of lesions with reduced fractional flow reserve improves long-term outcome and is economically attractive compared with MT alone in patients with stable coronary artery disease.URL: https://www.clinicaltrials.gov. Unique identifier: NCT01132495.

  View details for PubMedID 29097450

• Invasive Assessment of the Coronary Microvasculature: The Index of Microcirculatory Resistance. Circulation. Cardiovascular interventions Fearon, W. F., Kobayashi, Y. n. 2017; 10 (12)

  Abstract

  Traditionally, invasive coronary physiological assessment has focused on the epicardial coronary artery. More recently, appreciation of the importance of the coronary microvasculature in determining patient outcomes has grown. Several invasive modalities for interrogating microvascular function have been proposed. Angiographic techniques have been limited by their qualitative and subjective nature. Doppler wire-derived coronary flow reserve has been applied in research studies, but its clinical role has been limited by its lack of reproducibility, its lack of a clear normal value, and the fact that it is not specific for the microvasculature but interrogates the entire coronary circulation. The index of microcirculatory resistance-a thermodilution-derived measure of the minimum achievable microvascular resistance-is relatively easy to measure, more reproducible, has a clearer normal value, and is independent of epicardial coronary artery stenosis. The index of microcirculatory resistance has been shown to have prognostic value in patients with ST-segment-elevation myocardial infarction and cardiac allograft vasculopathy after heart transplantation. Emerging data demonstrate its role in evaluating patients with chest pain and nonobstructive coronary artery disease. Increasingly, the index of microcirculatory resistance is used as a reference standard for invasively assessing the microvasculature in clinical trials.

  View details for PubMedID 29222132

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

  Abstract

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

  View details for DOI 10.1056/NEJMoa1514616

  View details for PubMedID 27040324

• The Prognostic Value of Residual Coronary Stenoses After Functionally Complete Revascularization JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Kobayashi, Y., Nam, C., Tonino, P. A., Kimura, T., De Bruyne, B., Pijls, N. H., Fearon, W. F. 2016; 67 (14): 1701-1711

  Abstract

  The residual SYNTAX score (RSS) and SYNTAX revascularization index (SRI) quantitatively assess angiographic completeness of revascularization for patients with multivessel coronary artery disease. Whether residual angiographic disease remains of prognostic importance after "functionally" complete revascularization with fractional flow reserve (FFR) guidance is unknown.This study sought to investigate the prognostic value of the RSS and SRI after FFR-guided functionally complete revascularization.From the FFR-guided percutaneous coronary intervention (PCI) cohort of the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) trial, the RSS and SRI were calculated in 427 patients after functionally complete revascularization. The RSS was defined as the SYNTAX score (SS) recalculated after PCI. The SRI was calculated as: 100 × (1 - RSS/baseline SS) (%). We compared differences in 1- and 2-year outcomes among patients with RSS of 0, >0 to 4, >4 to 8, and >8, and with SRI of 100%, 50% to <100%, and 0 to <50%.The mean baseline SS, RSS, and SRI were 14.4 ± 7.2, 6.5 ± 5.8, and 55.1 ± 32.5%, respectively. Major adverse cardiac events (MACE) at 1 year occurred in 53 patients (12.4%). Patients with MACE had higher SS than those without (18.0 [interquartile range (IQR): 11.0 to 21.0] vs. 12.0 [IQR: 9.0 to 18.0], p = 0.001), but had similar RSS and SRI after PCI (RSS: 6.0 [IQR: 3.0 to 10.0] vs. 5.0 [IQR: 2.0 to 9.5], p = 0.51 and SRI: 60.0% [IQR: 40.9% to 78.9%] vs. 58.8% [IQR: 26.7% to 81.8%], p = 0.24, respectively). Kaplan-Meier analysis showed similar 1-year incidence of MACE with RSS/SRI stratifications (log-rank p = 0.55 and p = 0.54, respectively). Results were similar with 2-year outcome data analysis.After functionally complete revascularization with FFR guidance, residual angiographic lesions that are not functionally significant do not reflect residual ischemia or predict a worse outcome, supporting functionally complete, rather than angiographically complete, revascularization. (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation [FAME]; NCT00267774).

  View details for DOI 10.1016/j.jacc.2016.01.056

  View details for PubMedID 27056776

• Invasive Coronary Physiology for Assessing Intermediate Lesions CIRCULATION-CARDIOVASCULAR INTERVENTIONS Fearon, W. F. 2015; 8 (2)

  View details for DOI 10.1161/CIRCINTERVENTIONS.114.001942

  View details for PubMedID 25657316

• Fractional Flow Reserve-Guided PCI for Stable Coronary Artery Disease NEW ENGLAND JOURNAL OF MEDICINE De Bruyne, B., Fearon, W. F., Pijls, N. H., Barbato, E., Tonino, P., Piroth, Z., Jagic, N., Mobius-Winckler, S., Rioufol, G., Witt, N., Kala, P., MacCarthy, P., Engstroem, T., Oldroyd, K., Mavromatis, K., Manoharan, G., VerLee, P., Frobert, O., Curzen, N., Johnson, J. B., Limacher, A., Nueesch, E., Jueni, P. 2014; 371 (13): 1208-1217

  Abstract

  We hypothesized that in patients with stable coronary artery disease and stenosis, percutaneous coronary intervention (PCI) performed on the basis of the fractional flow reserve (FFR) would be superior to medical therapy.In 1220 patients with stable coronary artery disease, we assessed the FFR in all stenoses that were visible on angiography. Patients who had at least one stenosis with an FFR of 0.80 or less were randomly assigned to undergo FFR-guided PCI plus medical therapy or to receive medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy alone and were included in a registry. The primary end point was a composite of death from any cause, nonfatal myocardial infarction, or urgent revascularization within 2 years.The rate of the primary end point was significantly lower in the PCI group than in the medical-therapy group (8.1% vs. 19.5%; hazard ratio, 0.39; 95% confidence interval [CI], 0.26 to 0.57; P<0.001). This reduction was driven by a lower rate of urgent revascularization in the PCI group (4.0% vs. 16.3%; hazard ratio, 0.23; 95% CI, 0.14 to 0.38; P<0.001), with no significant between-group differences in the rates of death and myocardial infarction. Urgent revascularizations that were triggered by myocardial infarction or ischemic changes on electrocardiography were less frequent in the PCI group (3.4% vs. 7.0%, P=0.01). In a landmark analysis, the rate of death or myocardial infarction from 8 days to 2 years was lower in the PCI group than in the medical-therapy group (4.6% vs. 8.0%, P=0.04). Among registry patients, the rate of the primary end point was 9.0% at 2 years.In patients with stable coronary artery disease, FFR-guided PCI, as compared with medical therapy alone, improved the outcome. Patients without ischemia had a favorable outcome with medical therapy alone. (Funded by St. Jude Medical; FAME 2 ClinicalTrials.gov number, NCT01132495.).

  View details for DOI 10.1056/NEJMoa1408758

  View details for Web of Science ID 000342079700008

• Fractional flow reserve-guided PCI for stable coronary artery disease. New England journal of medicine De Bruyne, B., Fearon, W. F., Pijls, N. H., Barbato, E., Tonino, P., Piroth, Z., Jagic, N., Mobius-Winckler, S., Rioufol, G., Witt, N., Kala, P., MacCarthy, P., Engström, T., Oldroyd, K., Mavromatis, K., Manoharan, G., VerLee, P., Frobert, O., Curzen, N., Johnson, J. B., Limacher, A., Nüesch, E., Jüni, P. 2014; 371 (13): 1208-1217

  Abstract

  We hypothesized that in patients with stable coronary artery disease and stenosis, percutaneous coronary intervention (PCI) performed on the basis of the fractional flow reserve (FFR) would be superior to medical therapy.In 1220 patients with stable coronary artery disease, we assessed the FFR in all stenoses that were visible on angiography. Patients who had at least one stenosis with an FFR of 0.80 or less were randomly assigned to undergo FFR-guided PCI plus medical therapy or to receive medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy alone and were included in a registry. The primary end point was a composite of death from any cause, nonfatal myocardial infarction, or urgent revascularization within 2 years.The rate of the primary end point was significantly lower in the PCI group than in the medical-therapy group (8.1% vs. 19.5%; hazard ratio, 0.39; 95% confidence interval [CI], 0.26 to 0.57; P<0.001). This reduction was driven by a lower rate of urgent revascularization in the PCI group (4.0% vs. 16.3%; hazard ratio, 0.23; 95% CI, 0.14 to 0.38; P<0.001), with no significant between-group differences in the rates of death and myocardial infarction. Urgent revascularizations that were triggered by myocardial infarction or ischemic changes on electrocardiography were less frequent in the PCI group (3.4% vs. 7.0%, P=0.01). In a landmark analysis, the rate of death or myocardial infarction from 8 days to 2 years was lower in the PCI group than in the medical-therapy group (4.6% vs. 8.0%, P=0.04). Among registry patients, the rate of the primary end point was 9.0% at 2 years.In patients with stable coronary artery disease, FFR-guided PCI, as compared with medical therapy alone, improved the outcome. Patients without ischemia had a favorable outcome with medical therapy alone. (Funded by St. Jude Medical; FAME 2 ClinicalTrials.gov number, NCT01132495.).

  View details for DOI 10.1056/NEJMoa1408758

  View details for PubMedID 25176289

• Fractional Flow Reserve- Guided Percutaneous Coronary Intervention: Is it a Valid Concept? CIRCULATION Fearon, W. F. 2014; 129 (18): 1860-1870

  View details for DOI 10.1161/CIRCULATIONAHA.113.004300

  View details for Web of Science ID 000335367500013

  View details for PubMedCentralID PMC5544937

• Cost-Effectiveness of Percutaneous Coronary Intervention in Patients With Stable Coronary Artery Disease and Abnormal Fractional Flow Reserve CIRCULATION Fearon, W. F., Shilane, D., Pijls, N. H., Boothroyd, D. B., Tonino, P. A., Barbato, E., Jueni, P., De Bruyne, B., Hlatky, M. A. 2013; 128 (12): 1335-1340

  Abstract

  The Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) 2 trial demonstrated a significant reduction in subsequent coronary revascularization among patients with stable angina and at least 1 coronary lesion with a fractional flow reserve ≤0.80 who were randomized to percutaneous coronary intervention (PCI) compared with best medical therapy. The economic and quality-of-life implications of PCI in the setting of an abnormal fractional flow reserve are unknown.We calculated the cost of the index hospitalization based on initial resource use and follow-up costs based on Medicare reimbursements. We assessed patient utility using the EQ-5D health survey with US weights at baseline and 1 month and projected quality-adjusted life-years assuming a linear decline over 3 years in the 1-month utility improvements. We calculated the incremental cost-effectiveness ratio based on cumulative costs over 12 months. Initial costs were significantly higher for PCI in the setting of an abnormal fractional flow reserve than with medical therapy ($9927 versus $3900, P<0.001), but the $6027 difference narrowed over 1-year follow-up to $2883 (P<0.001), mostly because of the cost of subsequent revascularization procedures. Patient utility was improved more at 1 month with PCI than with medical therapy (0.054 versus 0.001 units, P<0.001). The incremental cost-effectiveness ratio of PCI was $36 000 per quality-adjusted life-year, which was robust in bootstrap replications and in sensitivity analyses.PCI of coronary lesions with reduced fractional flow reserve improves outcomes and appears economically attractive compared with best medical therapy among patients with stable angina.

  View details for DOI 10.1161/CIRCULATIONAHA.113.003059

  View details for PubMedID 23946263

• Prognostic Value of the Index of Microcirculatory Resistance Measured After Primary Percutaneous Coronary Intervention CIRCULATION Fearon, W. F., Low, A. F., Yong, A. S., McGeoch, R., Berry, C., Shah, M. G., Ho, M. Y., Kim, H., Loh, J. P., Oldroyd, K. G. 2013; 127 (24): 2436-2441

  Abstract

  BACKGROUND: Most methods for assessing microvascular function are not readily available in the cardiac catheterization laboratory. The aim of this study is to determine whether the Index of Microcirculatory Resistance (IMR), measured at the time of primary percutaneous coronary intervention (PCI) is predictive of death and rehospitalization for heart failure. METHODS AND RESULTS: IMR was measured immediately after primary PCI in 253 patients from 3 institutions using a pressure-temperature sensor wire. The primary endpoint was the rate of death or rehospitalization for heart failure. The prognostic value of IMR was compared to coronary flow reserve, TIMI myocardial perfusion grade and clinical variables. The mean IMR was 40.3 ±32.5. Patients with an IMR>40 had a higher rate of the primary end point at one year compared to patients with an IMR≤40 (17.1% vs. 6.6%, p=0.027). During a median follow-up period of 2.8 years, 13.8% suffered the primary end point and 4.3% died. An IMR>40 was associated with an increased risk of death or rehospitalization for heart failure (HR 2.1, p=0.034) and of death alone (HR 3.95, p=0.028). On multivariate analysis, independent predictors of death or rehospitalization for heart failure included IMR>40 (HR 2.2, p=0.026), fractional flow reserve ≤0.8 (HR 3.24, p=0.008) and diabetes (HR 4.4, p<0.001). An IMR>40 was the only independent predictor of death alone (HR 4.3, p=0.02). CONCLUSIONS: An elevated IMR at the time of primary PCI predicts poor long term outcomes.

  View details for DOI 10.1161/CIRCULATIONAHA.112.000298

  View details for PubMedID 23681066

• Fractional Flow Reserve-Guided PCI versus Medical Therapy in Stable Coronary Disease NEW ENGLAND JOURNAL OF MEDICINE De Bruyne, B., Pijls, N. H., Kalesan, B., Barbato, E., Tonino, P. A., Piroth, Z., Jagic, N., Mobius-Winckler, S., Rioufol, G., Witt, N., Kala, P., MacCarthy, P., Engstrom, T., Oldroyd, K. G., Mavromatis, K., Manoharan, G., VerLee, P., Frobert, O., Curzen, N., Johnson, J. B., Jueni, P., Fearon, W. F. 2012; 367 (11): 991-1001

  Abstract

  The preferred initial treatment for patients with stable coronary artery disease is the best available medical therapy. We hypothesized that in patients with functionally significant stenoses, as determined by measurement of fractional flow reserve (FFR), percutaneous coronary intervention (PCI) plus the best available medical therapy would be superior to the best available medical therapy alone.In patients with stable coronary artery disease for whom PCI was being considered, we assessed all stenoses by measuring FFR. Patients in whom at least one stenosis was functionally significant (FFR, ≤0.80) were randomly assigned to FFR-guided PCI plus the best available medical therapy (PCI group) or the best available medical therapy alone (medical-therapy group). Patients in whom all stenoses had an FFR of more than 0.80 were entered into a registry and received the best available medical therapy. The primary end point was a composite of death, myocardial infarction, or urgent revascularization.Recruitment was halted prematurely after enrollment of 1220 patients (888 who underwent randomization and 332 enrolled in the registry) because of a significant between-group difference in the percentage of patients who had a primary end-point event: 4.3% in the PCI group and 12.7% in the medical-therapy group (hazard ratio with PCI, 0.32; 95% confidence interval [CI], 0.19 to 0.53; P<0.001). The difference was driven by a lower rate of urgent revascularization in the PCI group than in the medical-therapy group (1.6% vs. 11.1%; hazard ratio, 0.13; 95% CI, 0.06 to 0.30; P<0.001); in particular, in the PCI group, fewer urgent revascularizations were triggered by a myocardial infarction or evidence of ischemia on electrocardiography (hazard ratio, 0.13; 95% CI, 0.04 to 0.43; P<0.001). Among patients in the registry, 3.0% had a primary end-point event.In patients with stable coronary artery disease and functionally significant stenoses, FFR-guided PCI plus the best available medical therapy, as compared with the best available medical therapy alone, decreased the need for urgent revascularization. In patients without ischemia, the outcome appeared to be favorable with the best available medical therapy alone. (Funded by St. Jude Medical; ClinicalTrials.gov number, NCT01132495.).

  View details for DOI 10.1056/NEJMoa1205361

  View details for Web of Science ID 000308649100005

  View details for PubMedID 22924638

• Functional SYNTAX Score for Risk Assessment in Multivessel Coronary Artery Disease JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Nam, C., Mangiacapra, F., Entjes, R., Chung, I., Sels, J., Tonino, P. A., De Bruyne, B., Pijls, N. H., Fearon, W. F. 2011; 58 (12): 1211-1218

  Abstract

  This study was aimed at investigating whether a fractional flow reserve (FFR)-guided SYNTAX score (SS), termed "functional SYNTAX score" (FSS), would predict clinical outcome better than the classic SS in patients with multivessel coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI).The SS is a purely anatomic score based on the coronary angiogram and predicts outcome after PCI in patients with multivessel CAD. FFR-guided PCI improves outcomes by adding functional information to the anatomic information obtained from the angiogram.The SS was prospectively collected in 497 patients enrolled in the FAME (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) study. FSS was determined by only counting ischemia-producing lesions (FFR ≤ 0.80). The ability of each score to predict major adverse cardiac events (MACE) at 1 year was compared.The 497 patients were divided into tertiles of risk based on the SS. After determining the FSS for each patient, 32% moved to a lower-risk group as follows. MACE occurred in 9.0%, 11.3%, and 26.7% of patients in the low-, medium-, and high-FSS groups, respectively (p < 0.001). Only FSS and procedure time were independent predictors of 1-year MACE. FSS demonstrated a better predictive accuracy for MACE compared with SS (Harrell's C of FSS, 0.677 vs. SS, 0.630, p = 0.02; integrated discrimination improvement of 1.94%, p < 0.001).Recalculating SS by only incorporating ischemia-producing lesions as determined by FFR decreases the number of higher-risk patients and better discriminates risk for adverse events in patients with multivessel CAD undergoing PCI.

  View details for DOI 10.1016/j.jacc.2011.06.020

  View details for PubMedID 21903052

• Economic Evaluation of Fractional Flow Reserve-Guided Percutaneous Coronary Intervention in Patients With Multivessel Disease CIRCULATION Fearon, W. F., Bornschein, B., Tonino, P. A., Gothe, R. M., De Bruyne, B., Pijls, N. H., Siebert, U. 2010; 122 (24): 2545-2550

  Abstract

  The Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) study demonstrated significantly improved health outcomes at 1 year in patients randomized to multivessel percutaneous coronary intervention guided by fractional flow reserve (FFR) compared with percutaneous coronary intervention guided by angiography alone. The economic impact of routine measurement of FFR in this setting is not known.In this study, 1005 patients were randomly assigned to FFR-guided or angiography-guided percutaneous coronary intervention and followed up for 1 year. A prospective cost-utility analysis comparing costs and quality-adjusted life-years was performed with a time horizon of 1 year. Quality-adjusted life-years were calculated with the use of utilities determined by the EuroQuol 5 dimension health survey with US weights. Direct medical costs included those of the index procedure and hospitalization and costs for major adverse cardiac events during follow-up. Confidence intervals for both quality-adjusted life-years and costs were estimated by the bootstrap percentile method. Major adverse cardiac events at 1 year occurred in 13.2% of those in the FFR-guided arm and 18.3% of those in the angiography-guided arm (P=0.02). Quality-adjusted life-years were slightly greater in the FFR-guided arm (0.853 versus 0.838; P=0.2). Mean overall costs at 1 year were significantly less in the FFR-guided arm ($14 315 versus $16 700; P<0.001). Bootstrap simulation indicated that the FFR-guided strategy was cost-saving in 90.74% and cost-effective at a threshold of US $50 000 per quality-adjusted life-years in 99.96%. Sensitivity analyses demonstrated robust results.Economic evaluation of the FAME study reveals that FFR-guided percutaneous coronary intervention in patients with multivessel coronary disease is one of those rare situations in which a new technology not only improves outcomes but also saves resources. Clinical Trial Registration- URL: http://ClinicalTrials.gov. Unique identifier: NCT00267774.

  View details for DOI 10.1161/CIRCULATIONAHA.109.925396

  View details for PubMedID 21126973

• Fractional Flow Reserve versus Angiography for Guiding Percutaneous Coronary Intervention NEW ENGLAND JOURNAL OF MEDICINE Tonino, P. A., De Bruyne, B., Pijls, N. H., Siebert, U., Ikeno, F., van 't Veer, M., Klauss, V., Manoharan, G., Engstrom, T., Oldroyd, K. G., Lee, P. N., MacCarthy, P. A., Fearon, W. F. 2009; 360 (3): 213-224

  Abstract

  In patients with multivessel coronary artery disease who are undergoing percutaneous coronary intervention (PCI), coronary angiography is the standard method for guiding the placement of the stent. It is unclear whether routine measurement of fractional flow reserve (FFR; the ratio of maximal blood flow in a stenotic artery to normal maximal flow), in addition to angiography, improves outcomes.In 20 medical centers in the United States and Europe, we randomly assigned 1005 patients with multivessel coronary artery disease to undergo PCI with implantation of drug-eluting stents guided by angiography alone or guided by FFR measurements in addition to angiography. Before randomization, lesions requiring PCI were identified on the basis of their angiographic appearance. Patients assigned to angiography-guided PCI underwent stenting of all indicated lesions, whereas those assigned to FFR-guided PCI underwent stenting of indicated lesions only if the FFR was 0.80 or less. The primary end point was the rate of death, nonfatal myocardial infarction, and repeat revascularization at 1 year.The mean (+/-SD) number of indicated lesions per patient was 2.7+/-0.9 in the angiography group and 2.8+/-1.0 in the FFR group (P=0.34). The number of stents used per patient was 2.7+/-1.2 and 1.9+/-1.3, respectively (P<0.001). The 1-year event rate was 18.3% (91 patients) in the angiography group and 13.2% (67 patients) in the FFR group (P=0.02). Seventy-eight percent of the patients in the angiography group were free from angina at 1 year, as compared with 81% of patients in the FFR group (P=0.20).Routine measurement of FFR in patients with multivessel coronary artery disease who are undergoing PCI with drug-eluting stents significantly reduces the rate of the composite end point of death, nonfatal myocardial infarction, and repeat revascularization at 1 year. (ClinicalTrials.gov number, NCT00267774.)

  View details for Web of Science ID 000262434500004

  View details for PubMedID 19144937

• Predictive value of the index of microcirculatory resistance in patients with ST-segment elevation myocardial infarction JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Fearon, W. F., Shah, M., Ng, M., Brinton, T., Wilson, A., Trernmel, J. A., Schnittger, I., Lee, D. P., Vagelos, R. H., Fitzgerald, P. J., Yock, P. G., Yeung, A. C. 2008; 51 (5): 560-565

  Abstract

  The objective of this study is to evaluate the predictive value of the index of microcirculatory resistance (IMR) in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI).Despite adequate epicardial artery reperfusion, a number of patients with STEMI have a poor prognosis because of microvascular damage. Assessing the status of the microvasculature in this setting remains challenging.In 29 patients after primary PCI for STEMI, IMR was measured with a pressure sensor/thermistor-tipped guidewire. The Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade, TIMI frame count, coronary flow reserve, and ST-segment resolution were also recorded.The IMR correlated significantly with the peak creatinine kinase (CK) (R = 0.61, p = 0.0005) while the other measures of microvascular dysfunction did not. In patients with an IMR greater than the median value of 32 U, the peak CK was significantly higher compared with those having values 32 U compared with

  View details for DOI 10.1016/j.jacc.2007.08.062

  View details for PubMedID 18237685

• Rationale and design of the fractional flow reserve versus angiography for multivessel evaluation (FAME) study AMERICAN HEART JOURNAL Fearon, W. F., Tonino, P. A., De Bruyne, B., Siebert, U., Pijls, N. H. 2007; 154 (4): 632-636

  Abstract

  Although its limitations for diagnosing critical coronary artery disease are well described, coronary angiography remains the predominant method for guiding decisions about stent implantation in patients with multivessel coronary artery disease. However, some have suggested that invasive physiologic guidance may improve decision making.The objective of this multicenter, randomized clinical trial is to compare the efficacy of 2 strategies, one based on angiographic guidance to one based on physiologic guidance with fractional flow reserve (FFR), for deciding which coronary lesions to stent in patients with multivessel coronary disease. Eligible patients must have coronary narrowings > 50% diameter stenosis in > or = 2 major epicardial vessels, > or = 2 of which the investigator feels require drug-eluting stent placement. Patients with previous coronary bypass surgery or left main coronary disease are excluded. Based on angiographic evaluation, the investigator notes the lesions that require stenting. The patient is then randomly assigned to either angiographic guidance or FFR guidance. Patients assigned to angiographic guidance undergo stenting as planned. Patients assigned to FFR guidance first have FFR measured in each diseased vessel and only undergo stenting if the FFR is < or = 0.80. The primary end point of the study is a composite of major adverse cardiac events, including death, myocardial infarction, and repeat coronary revascularization, at 1 year. Secondary end points will include the individual adverse events, cost-effectiveness, quality of life, and 30-day, 6-month, 2-year, and 5-year outcomes.The FAME study will examine for the first time in a large, multicenter, randomized fashion the role of measuring FFR in patients undergoing multivessel percutaneous coronary intervention.

  View details for DOI 10.1016/j.ahj.2007.06.012

  View details for PubMedID 17892983

• Invasive assessment of the coronary microcirculation - Superior reproducibility and less hemodynamic dependence of index of microcirculatory resistance compared with coronary flow reserve CIRCULATION Ng, M. K., Yeung, A. C., Fearon, W. F. 2006; 113 (17): 2054-2061

  Abstract

  A simple, reproducible invasive method for assessing the coronary microcirculation is lacking. A novel index of microcirculatory resistance (IMR) has been shown in animals to correlate with true microvascular resistance and, unlike coronary flow reserve (CFR), to be independent of the epicardial artery. We sought to compare the reproducibility and hemodynamic dependence of IMR with CFR in humans.Using a pressure-temperature sensor-tipped coronary wire, thermodilution-derived CFR and IMR were measured, along with fractional flow reserve (FFR), in 15 coronary arteries (15 patients) under the following hemodynamic conditions: (1) twice at baseline; (2) during right ventricular pacing at 110 bpm; (3) during intravenous infusion of nitroprusside; and (4) during intravenous dobutamine infusion. Mean CFR did not change during baseline measurements or during nitroprusside infusion but decreased during pacing (from 3.1+/-1.1 at baseline to 2.3+/-1.2 during pacing, P<0.05) and during dobutamine infusion (from 3.0+/-1.0 to 1.7+/-0.6 with dobutamine, P<0.0001). By comparison, mean values for IMR and FFR remained similar throughout all hemodynamic conditions. The mean coefficient of variation between 2 baseline measurements was significantly lower for IMR (6.9+/-6.5%) and FFR (1.6+/-1.6%) than for CFR (18.6+/-9.6%; P<0.01). Mean correlation between baseline measurements and each hemodynamic intervention was superior for IMR (r=0.90+/-0.05) and FFR (r=0.86+/-0.12) compared with CFR (r=0.70+/-0.05; P<0.05).Compared with CFR, IMR provides a more reproducible assessment of the microcirculation, which is independent of hemodynamic perturbations. Simultaneous measurement of FFR and IMR may provide a comprehensive and specific assessment of coronary physiology at both epicardial and microvascular levels, respectively.

  View details for DOI 10.1161/CIRCULATIONAHA.105.603522

  View details for PubMedID 16636168

• Microvascular resistance is not influenced by epicardial coronary artery stenosis severity - Experimental validation CIRCULATION Fearon, W. F., Aarnoudse, W., Pijls, N. H., De Bruyne, B., Balsam, L. B., Cooke, D. T., Robbins, R. C., Fitzgerald, P. J., Yeung, A. C., Yock, P. G. 2004; 109 (19): 2269-2272

  Abstract

  The effect of epicardial artery stenosis on myocardial microvascular resistance remains controversial. Recruitable collateral flow, which may affect resistance, was not incorporated into previous measurements.In an open-chest pig model, distal coronary pressure was measured with a pressure wire, and the apparent minimal microvascular resistance was calculated during peak hyperemia as pressure divided by flow, measured either with a flow probe around the coronary artery (R(micro app)) or with a novel thermodilution technique (apparent index of microcirculatory resistance [IMR(app)]). These apparent resistances were compared with the actual R(micro) and IMR after the coronary wedge pressure and collateral flow were incorporated into the calculation. Measurements were made at baseline (no stenosis) and after creation of moderate and severe epicardial artery stenoses. In 6 pigs, 189 measurements of R(micro) and IMR were made under the various epicardial artery conditions. Without consideration of collateral flow, R(micro app) (0.43+/-0.12 to 0.46+/-0.10 to 0.51+/-0.11 mm Hg/mL per minute) and IMR(app) (14+/-4 to 17+/-7 to 20+/-10 U) increased progressively and significantly with increasing epicardial artery stenosis (P<0.001 for both). With the incorporation of collateral flow, neither R(micro) nor IMR increased as a result of increasing epicardial artery stenosis.After collateral flow is taken into account, the minimum achievable microvascular resistance is not affected by increasing epicardial artery stenosis.

  View details for DOI 10.1161/01.CIR.0000128669.99355.CB

  View details for PubMedID 15136503

• Novel index for invasively assessing the coronary microcirculation CIRCULATION Fearon, W. F., Balsam, L. B., Farouque, H. M., Robbins, R. C., Fitzgerald, P. J., Yock, P. G., Yeung, A. C. 2003; 107 (25): 3129-3132

  Abstract

  A relatively simple, invasive method for quantitatively assessing the status of the coronary microcirculation independent of the epicardial artery is lacking.By using a coronary pressure wire and modified software, it is possible to calculate the mean transit time of room-temperature saline injected down a coronary artery. The inverse of the hyperemic mean transit time has been shown to correlate with absolute flow. We hypothesize that distal coronary pressure divided by the inverse of the hyperemic mean transit time provides an index of microcirculatory resistance (IMR) that will correlate with true microcirculatory resistance (TMR), defined as the distal left anterior descending (LAD) pressure divided by hyperemic flow, measured with an external ultrasonic flow probe. A total of 61 measurements were made in 9 Yorkshire swine at baseline and after disruption of the coronary microcirculation, both with and without an epicardial LAD stenosis. The mean IMR (16.9+/-6.5 U to 25.9+/-14.4 U, P=0.002) and TMR (0.51+/-0.14 to 0.79+/-0.32 mm Hg x mL(-1) x min(-1), P=0.0001), as well as the % change in IMR (147+/-66%) and TMR (159+/-105%, P=NS versus IMR % change), increased significantly and to a similar degree after disruption of the microcirculation. These changes were independent of the status of the epicardial artery. There was a significant correlation between mean IMR and TMR values, as well as between the % change in IMR and % change in TMR.Measuring IMR may provide a simple, quantitative, invasive assessment of the coronary microcirculation.

  View details for DOI 10.1161/01.CIR.0000080700.98607.D1

  View details for PubMedID 12821539

• Optical Coherence Tomography-Based Functional Stenosis Assessment: FUSION-A Prospective Multicenter Trial. Circulation. Cardiovascular interventions Jeremias, A., Maehara, A., Matsumura, M., Shlofmitz, R. A., Maksoud, A., Akasaka, T., Bezerra, H. G., Fearon, W. F., Samady, H., Samuels, B., Rapkin, J., Gopinath, A., Teraphongphom, N. T., Buccola, J., Ali, Z. A. 2024: e013702

  Abstract

  Intravascular imaging and intracoronary physiology may both be used to guide and optimize percutaneous coronary intervention; however, they are rarely used together. The virtual flow reserve (VFR) is an optical coherence tomography (OCT)-based model of fractional flow reserve (FFR) facilitating the assessment of the physiological significance of coronary lesions. We aimed to validate the VFR assessment of intermediate coronary artery stenoses.FUSION (Validation of OCT-Based Functional Diagnosis of Coronary Stenosis) was a multicenter, prospective, observational study comparing OCT-derived VFR to invasive FFR. VFR was mathematically derived from a lumped parameter flow model based on 3-dimensional lumen morphology. Patients undergoing coronary angiography with intermediate angiographic stenosis (40%-90%) requiring physiological assessment were enrolled. Investigational sites were blinded to the VFR analysis, and all OCT and FFR data were reviewed by an independent core laboratory. The coprimary end points were the sensitivity and specificity of VFR against FFR as the reference standard, each of which was tested against prespecified performance goals.After core laboratory review, 266 vessels in 224 patients from 25 US centers were included in the analysis. The mean angiographic diameter stenosis was 65.5%±14.9%, and the mean FFR was 0.83±0.11. Overall accuracy, sensitivity, and specificity of VFR versus FFR using a binary cutoff point of 0.80 were 82.0%, 80.4%, and 82.9%, respectively. The 97.5% lower confidence bound met the prespecified performance goal for sensitivity (71.6% versus 70%; P=0.01) and specificity (76.6% versus 75%; P=0.01). The area under the curve was 0.88 (95% CI, 0.84-0.92; P<0.0001).OCT-derived VFR demonstrates high sensitivity and specificity for predicting invasive FFR. Integrating high-resolution intravascular imaging with imaging-derived physiology may provide synergistic benefits as an adjunct to percutaneous coronary intervention.URL: https://clinicaltrials.gov; Unique identifier: NCT04356027.

  View details for DOI 10.1161/CIRCINTERVENTIONS.123.013702

  View details for PubMedID 38525609

• Response by Zimmermann et al to Letter Regarding Article, "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., Fearon, W. F. 2024; 149 (11): 896

  View details for DOI 10.1161/CIRCULATIONAHA.123.068238

  View details for PubMedID 38466782

• Long-term prognostic implications of CT angiography-derived fractional flow reserve: Results from the DISCOVER-FLOW study. Journal of cardiovascular computed tomography Yang, S., Chung, J., Lesina, K., Doh, J. H., Jegere, S., Erglis, A., Leipsic, J. A., Fearon, W. F., Narula, J., Koo, B. K. 2024

  Abstract

  The long-term prognostic implications of CT angiography-derived fractional flow reserve (FFRCT) remains unclear. We aimed to explore the long-term outcomes of FFRCT in the first-in-human study of it.A total of 156 vessels from 102 patients with stable coronary artery disease, who underwent coronary CT angiography (CCTA) and invasive FFR measurement, were followed. The primary endpoint was target vessel failure (TVF), including cardiovascular death, target vessel myocardial infarction, and target vessel revascularization. Outcome analysis with FFRCT was performed on a per-vessel basis using a marginal Cox proportional hazard model.During median 9.9 years of follow-up, TVF occurred in 20 (12.8%) vessels. FFRCT ​≤0.80 discriminated TVF (hazard ratio [HR] 2.61, 95% confidence interval [CI] 1.06, 6.45). Among 94 vessels with deferral of percutaneous coronary intervention (PCI), TVF risk was inversely correlated with FFRCT ​(HR 0.62 per 0.1 increase, 95% CI 0.44, 0.86), with the cumulative incidence of TVF being 2.6%, 15.2%, and 28.6% for vessels with FFRCT ​>0.90, 0.81-0.90, and ≤0.80, respectively (p-for-trend 0.005). Predictive value for clinical outcomes of FFRCT was similar to that of invasive FFR (c-index 0.79 vs 0.71, P ​= ​0.28). The estimated TVF risk was higher in the deferral of PCI group than the PCI group for vessels with FFRCT ≤0.81.FFRCT showed improved long-term risk stratification and displayed a risk continuum similar to invasive FFR.NCT01189331.

  View details for DOI 10.1016/j.jcct.2024.01.016

  View details for PubMedID 38378313

• Measuring Absolute Coronary Flow andMicrovascular Resistance byThermodilution: JACCReview Topic of the Week. Journal of the American College of Cardiology Belmonte, M., Gallinoro, E., Pijls, N. H., Bertolone, D. T., Keulards, D. C., Viscusi, M. M., Storozhenko, T., Mizukami, T., Mahendiran, T., Seki, R., Fournier, S., de Vos, A., Adjedj, J., Barbato, E., Sonck, J., Damman, P., Keeble, T., Fawaz, S., Gutierrez-Barrios, A., Paradies, V., Bouisset, F., Kern, M. J., Fearon, W. F., Collet, C., De Bruyne, B. 2024; 83 (6): 699-709

  Abstract

  Diagnosing coronary microvascular dysfunction remains challenging, primarily due to the lack of direct measurements of absolute coronary blood flow (Q) and microvascular resistance (Rmu). However, there has been recent progress with the development and validation of continuous intracoronary thermodilution, which offers a simplified and validated approach for clinical use. This technique enables direct quantification of Q and Rmu, leading to precise and accurate evaluation of the coronary microcirculation. To ensure consistent and reliable results, it is crucial to follow a standardized protocol when performing continuous intracoronary thermodilution measurements. This document aims to summarize the principles of thermodilution-derived absolute coronary flow measurements and propose a standardized method for conducting these assessments. The proposed standardization serves as a guide to ensure the best practice of the method, enhancing the clinical assessment of the coronary microcirculation.

  View details for DOI 10.1016/j.jacc.2023.12.014

  View details for PubMedID 38325996

• Associations of Sarcopenia and Body Composition Measures With Mortality After Transcatheter Aortic Valve Replacement. Circulation. Cardiovascular interventions Stein, E. J., Neill, C., Nair, S., Terry, J. G., Carr, J. J., Fearon, W. F., Elmariah, S., Kim, J. B., Kapadia, S., Kumbhani, D. J., Gillam, L., Whisenant, B., Quader, N., Zajarias, A., Welt, F. G., Bavry, A. A., Coylewright, M., Piana, R., Mallugari, R. R., Vatterott, A., Jackson, N., Huang, S., Lindman, B. R. 2024: e013298

  Abstract

  BACKGROUND: Frailty associates with worse outcomes after transcatheter aortic valve replacement (TAVR). Sarcopenia underlies frailty, but the association between a comprehensive assessment of sarcopenia-muscle mass, strength, and performance-and outcomes after TAVR has not been examined.METHODS: From a multicenter prospective registry of patients with symptomatic severe aortic stenosis undergoing TAVR, 445 who had a preprocedure computed tomography and clinical assessment of frailty were included. Cross-sectional muscle (psoas and paraspinal) areas were measured on computed tomography and indexed to height. Gait speed and handgrip strength were obtained, and patients were dichotomized into fast versus slow; strong versus weak; and normal versus low muscle mass. As measures of body composition, cross-sectional fat (subcutaneous and visceral) was measured and indexed to height.RESULTS: The frequency of patients who were slow, weak, and had low muscle mass was 56%, 59%, and 42%, respectively. Among the 3 components of sarcopenia, only slower gait speed (muscle performance) was independently associated with increased post-TAVR mortality (adjusted hazard ratio, 1.12 per 0.1 m/s decrease [95% CI, 1.04-1.21]; P=0.004; adjusted hazard ratio, 1.38 per 1 SD decrease [95% CI, 1.11-1.72]; P=0.004). Meeting multiple sarcopenia criteria was not associated with higher mortality risk than fewer. Lower indexed visceral fat area (adjusted hazard ratio, 1.48 per 1 SD decrease [95% CI, 1.15-1.89]; P=0.002) was associated with mortality but indexed subcutaneous fat was not. Death occurred in 169 (38%) patients.CONCLUSIONS: Among patients with symptomatic severe aortic stenosis and comprehensive sarcopenia and body composition phenotyping, gait speed was the only sarcopenia measure associated with post-TAVR mortality. Lower visceral fat was also associated with increased risk pointing to an obesity paradox also observed in other patient populations. These findings reinforce the clinical utility of gait speed as a measure of risk and a potential target for adjunctive interventions alongside TAVR to optimize clinical outcomes.

  View details for DOI 10.1161/CIRCINTERVENTIONS.123.013298

  View details for PubMedID 38235547

• REPLY: Decoding the Index of Microcirculatory Resistance What Does it Mean in Myocardial Infarction? JACC-CARDIOVASCULAR INTERVENTIONS El Farissi, M., Zimmermann, F. M., Fearon, W. F. 2024; 17 (1): 105

  View details for DOI 10.1016/j.jcin.2023.12.001

  View details for Web of Science ID 001156224200001

  View details for PubMedID 38199748

• Cost-Effectiveness of Fractional Flow Reserve-Guided Complete Revascularization in Acute Myocardial Infarction-Tipping the Scales? JAMA network open Chester, R. C., Fearon, W. F., Parikh, R. V. 2024; 7 (1): e2352425

  View details for DOI 10.1001/jamanetworkopen.2023.52425

  View details for PubMedID 38270956

• Diagnostic performances of Nonhyperemic Pressure Ratios and Coronary Angiography-Based Fractional Flow Reserve against conventional Wire-Based Fractional Flow Reserve. Coronary artery disease Li, W., Takahashi, T., Sehatbakhsh, S., Parikh, M. A., Garcia-Garcia, H. M., Fearon, W. F., Kobayashi, Y. 2023

  Abstract

  Nonhyperemic pressure ratios (NHPRs) have been proposed as alternatives to fractional flow reserve (FFR) without induction of hyperemia. More recently, imaging based-FFR estimation, especially coronary angiography-derived FFR (Angio-FFR) measurement, is proposed to estimate wire-based FFR. However, little is known about the diagnostic performance of these indices against conventional FFR.We aimed to assess and compare the diagnostic performance of both NHPRs and coronary Angio-FFR against wire-based conventional FFR.PubMed and Embase databases were systematically searched for peer-reviewed original articles up to 08/2022. The primary outcomes were the pooled sensitivity and specificity as well as the area under the curve (AUC) of the summary receiver-operating characteristic curve of those indices.A total of 6693 records were identified after a literature search, including 37 reports for NHPRs and 34 for Angio-FFR. Overall, NHPRs have a lower diagnostic performance in estimating wire-based FFR with an AUC of 0.85 (0.81, 0.88) when compared with Angio-FFR of 0.95 (0.93, 0.97). When all four modalities of NHPRs (iFR, Pd/Pa, DPR, RFR) were compared, those had overlapping AUCs without major differences among each other. Similarly, when the two most commonly used Angio-FFR (QFR, FFRangio) were compared, those had overlapping AUCs without major differences among each other.Angio-FFR may offer a better estimation of wire-based FFR than NHPRs. Our results support a wider use of Angio-FFR in the cardiac catheterization laboratory to streamline our workflow for coronary physiologic assessment.FFR,, stable ischemic disease and non-ST elevation acute coronary syndrome.

  View details for DOI 10.1097/MCA.0000000000001309

  View details for PubMedID 38088790

• Where Do We Go With Abnormal Flow? JACC. Asia Wong, C. C., Fearon, W. F. 2023; 3 (6): 878-880

  View details for DOI 10.1016/j.jacasi.2023.08.012

  View details for PubMedID 38155800

  View details for PubMedCentralID PMC10751635

• Practical Application of Coronary Physiologic Assessment: Asia-Pacific Expert Consensus Document: Part 2. JACC. Asia Koo, B. K., Hwang, D., Park, S., Kuramitsu, S., Yonetsu, T., Kim, C. H., Zhang, J., Yang, S., Doh, J. H., Jeong, Y. H., Choi, K. H., Lee, J. M., Ahn, J. M., Matsuo, H., Shin, E. S., Hu, X., Low, A. F., Kubo, T., Nam, C. W., Yong, A. S., Harding, S. A., Xu, B., Hur, S. H., Choo, G. H., Tan, H. C., Mullasari, A., Hsieh, I. C., Kakuta, T., Akasaka, T., Wang, J., Tahk, S. J., Fearon, W. F., Escaned, J., Park, S. J. 2023; 3 (6): 825-842

  Abstract

  Coronary physiologic assessment is performed to measure coronary pressure, flow, and resistance or their surrogates to enable the selection of appropriate management strategy and its optimization for patients with coronary artery disease. The value of physiologic assessment is supported by a large body of clinical data that has led to major recommendations in all practice guidelines. This expert consensus document aims to convey practical and balanced recommendations and future perspectives for coronary physiologic assessment for physicians and patients in the Asia-Pacific region, based on updated information in the field that includes both wire- and image-based physiologic assessment. This is Part 2 of the whole consensus document, which provides theoretical and practical information on physiologic indexes for specific clinical conditions and patient statuses.

  View details for DOI 10.1016/j.jacasi.2023.07.004

  View details for PubMedID 38155788

  View details for PubMedCentralID PMC10751650

• 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

• Impact of Chronic Total Occlusions on Outcomes in the FAME 3 Trial Otsuki, H., Takahashi, K., Zimmermann, F., Mavromatis, K., Aminian, A., Dambrink, J., Kala, P., MacCarthy, P., Witt, N., de Bruyne, B., Pijls, N., Fearon, W. ELSEVIER SCIENCE INC. 2023: B55

  View details for Web of Science ID 001108754600137

• Prognostic value of intravascular ultrasound early after heart transplantation. European heart journal Arora, S., Zimmermann, F. M., Solberg, O. G., Nytrøen, K., Aaberge, L., Okada, K., Ahn, J. M., Honda, Y., Khush, K. K., Angeras, O., Karason, K., Gullestad, L., Fearon, W. F. 2023

  View details for DOI 10.1093/eurheartj/ehad648

  View details for PubMedID 37850514

• Impact of Post-PCI FFR Stratified by Coronary Artery. JACC. Cardiovascular interventions Collet, C., Johnson, N. P., Mizukami, T., Fearon, W. F., Berry, C., Sonck, J., Collison, D., Koo, B. K., Meneveau, N., Agarwal, S. K., Uretsky, B., Hakeem, A., Doh, J. H., Da Costa, B. R., Oldroyd, K. G., Leipsic, J. A., Morbiducci, U., Taylor, C., Ko, B., Tonino, P. A., Perera, D., Shinke, T., Chiastra, C., Sposito, A. C., Leone, A. M., Muller, O., Fournier, S., Matsuo, H., Adjedj, J., Amabile, N., Piróth, Z., Alfonso, F., Rivero, F., Ahn, J. M., Toth, G. G., Ihdayhid, A., West, N. E., Amano, T., Wyffels, E., Munhoz, D., Belmonte, M., Ohashi, H., Sakai, K., Gallinoro, E., Barbato, E., Engstrøm, T., Escaned, J., Ali, Z. A., Kern, M. J., Pijls, N. H., Jüni, P., De Bruyne, B. 2023; 16 (19): 2396-2408

  Abstract

  Low fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) has been associated with adverse clinical outcomes. Hitherto, this assessment has been independent of the epicardial vessel interrogated.This study sought to assess the predictive capacity of post-PCI FFR for target vessel failure (TVF) stratified by coronary artery.We performed a systematic review and individual patient-level data meta-analysis of randomized clinical trials and observational studies with protocol-recommended post-PCI FFR assessment. The difference in post-PCI FFR between left anterior descending (LAD) and non-LAD arteries was assessed using a random-effect models meta-analysis of mean differences. TVF was defined as a composite of cardiac death, target vessel myocardial infarction, and clinically driven target vessel revascularization.Overall, 3,336 vessels (n = 2,760 patients) with post-PCI FFR measurements were included in 9 studies. The weighted mean post-PCI FFR was 0.89 (95% CI: 0.87-0.90) and differed significantly between coronary vessels (LAD = 0.86; 95% CI: 0.85 to 0.88 vs non-LAD = 0.93; 95% CI: 0.91-0.94; P < 0.001). Post-PCI FFR was an independent predictor of TVF, with its risk increasing by 52% for every reduction of 0.10 FFR units, and this was mainly driven by TVR. The predictive capacity for TVF was poor for LAD arteries (AUC: 0.52; 95% CI: 0.47-0.58) and moderate for non-LAD arteries (AUC: 0.66; 95% CI: 0.59-0.73; LAD vs non-LAD arteries, P = 0.005).The LAD is associated with a lower post-PCI FFR than non-LAD arteries, emphasizing the importance of interpreting post-PCI FFR on a vessel-specific basis. Although a higher post-PCI FFR was associated with improved prognosis, its predictive capacity for events differs between the LAD and non-LAD arteries, being poor in the LAD and moderate in the non-LAD vessels.

  View details for DOI 10.1016/j.jcin.2023.08.018

  View details for PubMedID 37821185

• The Index of Microcirculatory Resistance After Primary PCI: A Pooled Analysis of Individual Patient Data. JACC. Cardiovascular interventions El Farissi, M., Zimmermann, F. M., De Maria, G. L., van Royen, N., van Leeuwen, M. A., Carrick, D., Carberry, J., Wijnbergen, I. F., Konijnenberg, L. S., Hoole, S. P., Marin, F., Fineschi, M., Pijls, N. H., Oldroyd, K. G., Banning, A. P., Berry, C., Fearon, W. F. 2023; 16 (19): 2383-2392

  Abstract

  Despite treatment with primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI), the risk of heart failure and late death remains high. Microvascular dysfunction, as assessed by the index of microcirculatory resistance (IMR), after primary PCI for STEMI has been associated with worse outcomes. It is unclear whether IMR after primary PCI predicts cardiac death.The aims of this analysis were: 1) to determine if IMR is an independent predictor of cardiac death; 2) to assess the optimal cutoff value of IMR after STEMI; and 3) to compare IMR with several cardiac magnetic resonance parameters, including infarct size.In a collaborative, pooled analysis of individual patient data from 6 cohorts that measured IMR directly after primary PCI, cardiac mortality up to 5 years was estimated using Kaplan-Meier analyses. The primary endpoint was cardiac death using the predefined IMR cutoff value of 40.In total, 1,265 patients were included in this study with a median follow-up of 2.8 years (IQR: 1.2-5.0 years). Cardiac death at 5 years occurred in 2.2% and 4.9% of patients (HR: 2.81; 95% CI: 1.34-5.88; P = 0.006) in the IMR ≤40 and IMR >40 groups, respectively. The composite of cardiac death or hospitalization for heart failure occurred in 4.9% and 8.9% (HR: 1.98; 95% CI: 1.20-3.29; P = 0.008) in the IMR ≤40 and IMR >40 groups, respectively. IMR was an independent predictor of cardiac death, whereas coronary flow reserve was not. The optimal cutoff value of IMR for the prediction of cardiac death in this cohort was 70 (HR: 4.73; 95% CI: 2.27-9.83; P < 0.001). Infarct size was 17.6% ± 13.3% and 23.9% ± 14.6% of the left ventricular mass in the IMR ≤40 and IMR >40 groups, respectively (P < 0.001). Microvascular obstruction and intramyocardial hemorrhage occurred more frequently in the IMR >40 group than in the IMR ≤40 group.In this large, pooled analysis of individual patient data, IMR measured directly after primary PCI in STEMI was an independent predictor of cardiac death. IMR may be used as a tool to identify patients at the time of primary PCI who are at highest risk for late cardiac mortality and who might benefit most from additional cardioprotective therapies and monitoring.

  View details for DOI 10.1016/j.jcin.2023.08.030

  View details for PubMedID 37821183

• Practical Application of Coronary Physiologic Assessment: Asia-Pacific Expert Consensus Document: Part 1. JACC. Asia Koo, B., Lee, J. M., Hwang, D., Park, S., Shiono, Y., Yonetsu, T., Lee, S. H., Kawase, Y., Ahn, J., Matsuo, H., Shin, E., Hu, X., Ding, D., Fezzi, S., Tu, S., Low, A. F., Kubo, T., Nam, C., Yong, A. S., Harding, S. A., Xu, B., Hur, S., Choo, G. H., Tan, H. C., Mullasari, A., Hsieh, I., Kakuta, T., Akasaka, T., Wang, J., Tahk, S., Fearon, W. F., Escaned, J., Park, S. 2023; 3 (5): 689-706

  Abstract

  Coronary physiologic assessment is performed to measure coronary pressure, flow, and resistance or their surrogates to enable the selection of appropriate management strategy and its optimization for patients with coronary artery disease. The value of physiologic assessment is supported by a large body of evidence that has led to major recommendations in clinical practice guidelines. This expert consensus document aims to convey practical and balanced recommendations and future perspectives for coronary physiologic assessment for physicians and patients in the Asia-Pacific region based on updated information in the field that including both wire- and image-based physiologic assessment. This is Part 1 of the whole consensus document, which describes the general concept of coronary physiology, as well as practical information on the clinical application of physiologic indices and novel image-based physiologic assessment.

  View details for DOI 10.1016/j.jacasi.2023.07.003

  View details for PubMedID 38095005

• Proteomic architecture of frailty across the spectrum of cardiovascular disease. Aging cell Perry, A. S., Zhao, S., Gajjar, P., Murthy, V. L., Lehallier, B., Miller, P., Nair, S., Neill, C., Carr, J. J., Fearon, W., Kapadia, S., Kumbhani, D., Gillam, L., Lindenfeld, J., Farrell, L., Marron, M. M., Tian, Q., Newman, A. B., Murabito, J., Gerszten, R. E., Nayor, M., Elmariah, S., Lindman, B. R., Shah, R. 2023

  Abstract

  While frailty is a prominent risk factor in an aging population, the underlying biology of frailty is incompletely described. Here, we integrate 979 circulating proteins across a wide range of physiologies with 12 measures of frailty in a prospective discovery cohort of 809 individuals with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation. Our aim was to characterize the proteomic architecture of frailty in a highly susceptible population and study its relation to clinical outcome and systems-wide phenotypes to define potential novel, clinically relevant frailty biology. Proteomic signatures (specifically of physical function) were related to post-intervention outcome in AS, specifying pathways of innate immunity, cell growth/senescence, fibrosis/metabolism, and a host of proteins not widely described in human aging. In published cohorts, the "frailty proteome" displayed heterogeneous trajectories across age (20-100years, age only explaining a small fraction of variance) and were associated with cardiac and non-cardiac phenotypes and outcomes across two broad validation cohorts (N>35,000) over 2-3 decades. These findings suggest the importance of precision biomarkers of underlying multi-organ health status in age-related morbidity and frailty.

  View details for DOI 10.1111/acel.13978

  View details for PubMedID 37731195

• Comprehensive Management of ANOCA, Part 2-Program Development, Treatment, and Research Initiatives: JACC State-of-the-Art Review. Journal of the American College of Cardiology Smilowitz, N. R., Prasad, M., Widmer, R. J., Toleva, O., Quesada, O., Sutton, N. R., Lerman, A., Reynolds, H. R., Kesarwani, M., Savage, M. P., Sweeny, J. M., Janaszek, K. B., Barseghian El-Farra, A., Holoshitz, N., Park, K., Albadri, A., Blair, J. A., Jeremias, A., Kearney, K. E., Kobayashi, Y., Miner, S. E., Samuels, B. A., Shah, S. M., Taqueti, V. R., Wei, J., Fearon, W. F., Moses, J. W., Henry, T. D., Tremmel, J. A. 2023; 82 (12): 1264-1279

  Abstract

  Centers specializing in coronary function testing are critical to ensure a systematic approach to the diagnosis and treatment of angina with nonobstructive coronary arteries (ANOCA). Management leveraging lifestyle, pharmacology, and device-based therapeutic options for ANOCA can improve angina burden and quality of life in affected patients. Multidisciplinary care teams that can tailor and titrate therapies based on individual patient needs are critical to the success of comprehensive programs. As coronary function testing for ANOCA is more widely adopted, collaborative research initiatives will be fundamental to improve ANOCA care. These efforts will require standardized symptom assessments and data collection, which will propel future large-scale clinical trials.

  View details for DOI 10.1016/j.jacc.2023.06.044

  View details for PubMedID 37704316

• Comprehensive Management of ANOCA, Part 1-Definition, Patient Population, and Diagnosis: JACC State-of-the-Art Review. Journal of the American College of Cardiology Samuels, B. A., Shah, S. M., Widmer, R. J., Kobayashi, Y., Miner, S. E., Taqueti, V. R., Jeremias, A., Albadri, A., Blair, J. A., Kearney, K. E., Wei, J., Park, K., Barseghian El-Farra, A., Holoshitz, N., Janaszek, K. B., Kesarwani, M., Lerman, A., Prasad, M., Quesada, O., Reynolds, H. R., Savage, M. P., Smilowitz, N. R., Sutton, N. R., Sweeny, J. M., Toleva, O., Henry, T. D., Moses, J. W., Fearon, W. F., Tremmel, J. A. 2023; 82 (12): 1245-1263

  Abstract

  Angina with nonobstructive coronary arteries (ANOCA) is increasingly recognized and may affect nearly one-half of patients undergoing invasive coronary angiography for suspected ischemic heart disease. This working diagnosis encompasses coronary microvascular dysfunction, microvascular and epicardial spasm, myocardial bridging, and other occult coronary abnormalities. Patients with ANOCA often face a high burden of symptoms and may experience repeated presentations to multiple medical providers before receiving a diagnosis. Given the challenges of establishing a diagnosis, patients with ANOCA frequently experience invalidation and recidivism, possibly leading to anxiety and depression. Advances in scientific knowledge and diagnostic testing now allow for routine evaluation of ANOCA noninvasively and in the cardiac catheterization laboratory with coronary function testing (CFT). CFT includes diagnostic coronary angiography, assessment of coronary flow reserve and microcirculatory resistance, provocative testing for endothelial dysfunction and coronary vasospasm, and intravascular imaging for identification of myocardial bridging, with hemodynamic assessment as needed.

  View details for DOI 10.1016/j.jacc.2023.06.043

  View details for PubMedID 37704315

• 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

• Is COMPLETE Revascularization Beneficial in Diabetic Patients With Multivessel CAD Undergoing Primary PCI for STEMI? CIRCULATION-CARDIOVASCULAR INTERVENTIONS Ryan, N., Fearon, W. F. 2023; 16 (9): e013462

  View details for DOI 10.1161/CIRCINTERVENTIONS.123.013462

  View details for Web of Science ID 001067186600003

  View details for PubMedID 37725678

• 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines CIRCULATION Virani, S. S., Newby, L., Arnold, S. V., Bittner, V., Brewer, L. C., Demeter, S., Dixon, D. L., Fearon, W. F., Hess, B., Johnson, H. M., Kazi, D. S., Kolte, D., Kumbhani, D. J., Lofaso, J., Mahtta, D., Mark, D. B., Minissian, M., Navar, A., Patel, A. R., Piano, M. R., Rodriguez, F., Talbot, A. W., Taqueti, V. R., Thomas, R. J., van Diepen, S., Wiggins, B., Williams, M. S. 2023; 148 (9): E9-E119

  Abstract

  The "2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease" provides an update to and consolidates new evidence since the "2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease" and the corresponding "2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease."A comprehensive literature search was conducted from September 2021 to May 2022. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.This guideline provides an evidenced-based and patient-centered approach to management of patients with chronic coronary disease, considering social determinants of health and incorporating the principles of shared decision-making and team-based care. Relevant topics include general approaches to treatment decisions, guideline-directed management and therapy to reduce symptoms and future cardiovascular events, decision-making pertaining to revascularization in patients with chronic coronary disease, recommendations for management in special populations, patient follow-up and monitoring, evidence gaps, and areas in need of future research. Where applicable, and based on availability of cost-effectiveness data, cost-value recommendations are also provided for clinicians. Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

  View details for DOI 10.1161/CIR.0000000000001168

  View details for Web of Science ID 001057951100001

  View details for PubMedID 37471501

• 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Arnold, S. V., Bittner, V., Brewer, L. C., Demeter, S., Dixon, D. L., Fearon, W. F., Hess, B., Johnson, H. M., Kazi, D. S., Kolte, D., Kumbhani, D. J., Lofaso, J., Mahtta, D., Mark, D. B., Minissian, M., Navar, A., Patel, A. R., Piano, M. R., Rodriguez, F., Talbot, A. W., Taqueti, V. R., Thomas, R. J., van Diepen, S., Wiggins, B., Williams, M. S. 2023; 82 (9): 833-955

  View details for DOI 10.1016/j.jacc.2023.04.003

  View details for Web of Science ID 001068846800001

• Rationale and Design of the Pullback Pressure Gradient (PPG) Global Registry. American heart journal Munhoz, D., Collet, C., Mizukami, T., Yong, A., Leone, A. M., Eftekhari, A., Ko, B., da Costa, B. R., Berry, C., Collison, D., Perera, D., Christiansen, E. H., Rivero, F., Zimmermann, F. M., Ando, H., Matsuo, H., Nakayama, M., Escaned, J., Sonck, J., Sakai, K., Adjedj, J., Desta, L., van Nunen, L. X., West, N. E., Fournier, S., Storozhenko, T., Amano, T., Engstrøm, T., Johnson, T., Shinke, T., Biscaglia, S., Fearon, W. F., Ali, Z., De Bruyne, B., Johnson, N. P. 2023

  Abstract

  Diffuse disease has been identified as one of the main reasons leading to low post-PCI fractional flow reserve (FFR) and residual angina after PCI. Coronary pressure pullbacks allow for the evaluation of hemodynamic coronary artery disease (CAD) patterns. The pullback pressure gradient (PPG) is a novel metric that quantifies the distribution and magnitude of pressure losses along the coronary artery in a focal-to-diffuse continuum.The primary objective is to determine the predictive capacity of the PPG for post-PCI FFR.This prospective, large-scale, controlled, investigator-initiated, multicenter study is enrolling patients with at least one lesion in a major epicardial vessel with a distal FFR ≤ 0.80 intended to be treated by PCI. The study will include 982 subjects. A standardized physiological assessment will be performed pre-PCI, including the online calculation of PPG from FFR pullbacks performed manually. PPG quantifies the CAD pattern by combining several parameters from the FFR pullback curve. Post-PCI physiology will be recorded using a standardized protocol with FFR pullbacks. We hypothesize that PPG will predict optimal PCI results (post-PCI FFR ≥ 0.88) with an area under the ROC curve (AUC) ≥ 0.80. Secondary objectives include patient-reported and clinical outcomes in patients with focal vs. diffuse CAD defined by the PPG. Clinical follow-up will be collected for up to 36 months, and an independent clinical event committee will adjudicate events.Recruitment is ongoing and is expected to be completed in the second half of 2023.This international, large-scale, prospective study with pre-specified powered hypotheses will determine the ability of the pre-procedural PPG index to predict optimal revascularization assessed by post-PCI FFR. In addition, it will evaluate the impact of PPG on treatment decisions and the predictive performance of PPG for angina relief and clinical outcomes.gov Identifier: NCT04789317.

  View details for DOI 10.1016/j.ahj.2023.07.016

  View details for PubMedID 37611857

• Association of Depression and Cognitive Dysfunction With Patient-Centered Outcomes After Transcatheter Aortic Valve Replacement. Circulation. Cardiovascular interventions El-Sabawi, B., Cloud, H., Patel, J. N., Bell, S. P., Elmariah, S., Fearon, W. F., Kim, J. B., Piana, R. N., Kapadia, S. R., Kumbhani, D. J., Gillam, L. D., Whisenant, B. K., Quader, N., Zajarias, A., Welt, F. G., Bavry, A. A., Coylewright, M., Vatterott, A., Jackson, N., Huang, S., Lindman, B. R. 2023: e012875

  Abstract

  BACKGROUND: Depression and cognitive dysfunction (CD) are not routinely screened for in patients before transcatheter aortic valve replacement (TAVR) and their association with postprocedural outcomes is poorly understood. The objectives of this study are to determine the prevalence of depression and CD in patients with aortic stenosis undergoing TAVR and evaluate their association with mortality and quality of life.METHODS: We analyzed a prospective, multicenter TAVR registry that systematically screened patients for preexisting depression and CD with the Patient Health Questionnaire-2 and Mini-Cog, respectively. The associations with mortality were assessed with Cox proportional hazard models and quality of life (Kansas City Cardiomyopathy Questionnaire and EuroQol visual analogue scale) were evaluated using multivariable ordinal regression models.RESULTS: A total of 884 patients were included; median follow-up was 2.88 years (interquartile range=1.2-3.7). At baseline, depression was observed in 19.6% and CD in 31.8%. In separate models, after adjustment, depression (HR, 1.45 [95% CI, 1.13-1.86]; P<0.01) and CD (HR, 1.27 [95% CI, 1.02-1.59]; P=0.04) were each associated with increased mortality. Combining depression and CD into a single model, mortality was greatest among those with both depression and CD (n=62; HR, 2.06 [CI, 1.44-2.96]; P<0.01). After adjustment, depression was associated with 6.6 (0.3-13.6) points lower on the Kansas City Cardiomyopathy Questionnaire 1-year post-TAVR and 6.7 (0.5-12.7) points lower on the EuroQol visual analogue scale. CD was only associated with lower EuroQol visual analogue scale.CONCLUSIONS: Depression and CD are common in patients that undergo TAVR and are associated with increased mortality and worse quality of life. Depression may be a modifiable therapeutic target to improve outcomes after TAVR.

  View details for DOI 10.1161/CIRCINTERVENTIONS.123.012875

  View details for PubMedID 37503662

• Myocardial Infarction Across COVID-19 Pandemic Phases: Insights From the Veterans Health Affairs System. Journal of the American Heart Association Yong, C. M., Graham, L., Beyene, T. J., Sadri, S., Hong, J., Burdon, T., Fearon, W. F., Asch, S. M., Turakhia, M., Heidenreich, P. 2023: e029910

  Abstract

  Background Cardiovascular procedural treatments were deferred at scale during the COVID-19 pandemic, with unclear impact on patients presenting with non-ST-segment-elevation myocardial infarction (NSTEMI). Methods and Results In a retrospective cohort study of all patients diagnosed with NSTEMI in the US Veterans Affairs Healthcare System from January 1, 2019 to October 30, 2022 (n=67 125), procedural treatments and outcomes were compared between the prepandemic period and 6 unique pandemic phases: (1) acute phase, (2) community spread, (3) first peak, (4) post vaccine, (5) second peak, and (6) recovery. Multivariable regression analysis was performed to assess the association between pandemic phases and 30-day mortality. NSTEMI volumes dropped significantly with the pandemic onset (62.7% of prepandemic peak) and did not revert to prepandemic levels in subsequent phases, even after vaccine availability. Percutaneous coronary intervention and coronary artery bypass grafting volumes declined proportionally. Compared with the prepandemic period, patients with NSTEMI experienced higher 30-day mortality during Phases 2 and 3, even after adjustment for COVID-19-positive status, demographics, baseline comorbidities, and receipt of procedural treatment (adjusted odds ratio for Phases 2 and 3 combined, 1.26 [95% CI, 1.13-1.43], P<0.01). Patients receiving Veterans Affairs-paid community care had a higher adjusted risk of 30-day mortality compared with those at Veterans Affairs hospitals across all 6 pandemic phases. Conclusions Higher mortality after NSTEMI occurred during the initial spread and first peak of the pandemic but resolved before the second, higher peak-suggesting effective adaptation of care delivery but a costly delay to implementation. Investigation into the vulnerabilities of the early pandemic spread are vital to informing future resource-constrained practices.

  View details for DOI 10.1161/JAHA.123.029910

  View details for PubMedID 37421288

• Metabolic Signatures of Cardiac Dysfunction, Multimorbidity, and Post-Transcatheter Aortic Valve Implantation Death. Journal of the American Heart Association Perry, A. S., Zhao, S., Murthy, V., Gupta, D. K., Fearon, W. F., Kim, J. B., Kapadia, S., Kumbhani, D. J., Gillam, L., Whisenant, B., Quader, N., Zajarias, A., Mallugari, R. R., Clark, D. E., Patel, J. N., Gonzales, H., Welt, F. G., Bavry, A. A., Coylewright, M., Piana, R. N., Vatterott, A., Jackson, N., Gerszten, R. E., Lindman, B. R., Shah, R., Elmariah, S. 2023: e029542

  Abstract

  Background Studies in mice and small patient subsets implicate metabolic dysfunction in cardiac remodeling in aortic stenosis, but no large comprehensive studies of human metabolism in aortic stenosis with long-term follow-up and characterization currently exist. Methods and Results Within a multicenter prospective cohort study, we used principal components analysis to summarize 12 echocardiographic measures of left ventricular structure and function pre-transcatheter aortic valve implantation in 519 subjects (derivation). We used least absolute shrinkage and selection operator regression across 221 metabolites to define metabolic signatures for each structural pattern and measured their relation to death and multimorbidity in the original cohort and up to 2 validation cohorts (N=543 for overall validation). In the derivation cohort (519 individuals; median age, 84years, 45% women, 95% White individuals), we identified 3 axes of left ventricular remodeling, broadly specifying systolic function, diastolic function, and chamber volumes. Metabolite signatures of each axis specified both known and novel pathways in hypertrophy and cardiac dysfunction. Over a median of 3.1years (205 deaths), a metabolite score for diastolic function was independently associated with post-transcatheter aortic valve implantation death (adjusted hazard ratio per 1 SD increase in score, 1.54 [95% CI, 1.25-1.90]; P<0.001), with similar effects in each validation cohort. This metabolite score of diastolic function was simultaneously associated with measures of multimorbidity, suggesting a metabolic link between cardiac and noncardiac state in aortic stenosis. Conclusions Metabolite profiles of cardiac structure identify individuals at high risk for death following transcatheter aortic valve implantation and concurrent multimorbidity. These results call for efforts to address potentially reversible metabolic biology associated with risk to optimize post-transcatheter aortic valve implantation recovery, rehabilitation, and survival.

  View details for DOI 10.1161/JAHA.123.029542

  View details for PubMedID 37345820

• Coronary Angiography-Derived Index of Microcirculatory Resistance and Evolution of Infarct Pathology after STEMI. European heart journal. Cardiovascular Imaging Wang, X., Guo, Q., Guo, R., Guo, Y., Yan, Y., Gong, W., Zheng, W., Wang, H., Ai, H., Que, B., Xu, L., Huo, Y., Fearon, W. F., Nie, S. 2023

  Abstract

  This study sought to evaluate the association of coronary angiography-derived index of microcirculatory resistance (angio-IMR) measured after primary percutaneous coronary intervention (PPCI) with evolution of infarct pathology during 3-month follow-up after ST-segment-elevation myocardial infarction (STEMI).Patients with STEMI undergoing PPCI were prospectively enrolled between October 2019 and August 2021. Angio-IMR was calculated using computational flow and pressure simulation immediately after PPCI. Cardiac magnetic resonance (CMR) imaging was performed at a median of 3.6 days and 3 months. A total of 286 STEMI patients (mean age 57.8 years, 84.3% men) with both angio-IMR and CMR at baseline were included. High angio-IMR (>40 U) occurred in 84 patients (29.4%) patients. Patients with angio-IMR >40 U had higher prevalence and extent of MVO. An angio-IMR >40 U was a multivariable predictor of infarct size with 3-fold higher risk of final infarct size >25% (adjusted OR 3.00, 95% CI 1.23-7.32, p = 0.016). Post-procedure angio-IMR >40 U significantly predicted presence (adjusted OR 5.52, 95% CI 1.65-18.51, p = 0.006) and extent (beta coefficient 0.27, 95% CI 0.01-0.53, p = 0.041) of myocardial iron at follow-up. Compared with patients with angio-IMR ≤40 U, those with angio-IMR >40 U had less regression of infarct size and less resolution of myocardial iron at follow-up.Angio-IMR immediately post PPCI showed a significant association with extent and evolution of infarct pathology. An angio-IMR >40 U indicated extensive microvascular damage with less regression of infarct size and more persistent iron at follow-up.

  View details for DOI 10.1093/ehjci/jead141

  View details for PubMedID 37319341

• Race-Specific Impact of Conventional Surgical Risk Score on 1-Year Mortality After Transcatheter Aortic Valve Replacement. JACC. Asia Kim, H., Kang, D. Y., Ahn, J. M., Kim, J. B., Yeung, A. C., Nishi, T., Fearon, W. F., Cantey, E. P., Flaherty, J. D., Davidson, C. J., Malaisrie, S. C., Kim, N., Kim, M., Lee, J., Park, J., Choi, Y., Park, S. J., Park, D. W. 2023; 3 (3): 376-387

  Abstract

  Interracial differences in the distribution and prognostic value of conventional Society of Thoracic Surgeons (STS) score on long-term mortality after transcatheter aortic valve replacement (TAVR) are uncertain.This study aims to compare the impact of STS scores on clinical outcomes at 1-year after TAVR between Asian and non-Asian populations.We used the Trans-Pacific TAVR (TP-TAVR) registry, a multinational multicenter, observational registry involving patients undergoing TAVR at 2 major centers in the United States and 1 major center in Korea. Patients were classified into 3 groups (low, intermediate, and high-risk) according to the STS score and compared between STS risk groups and race. The primary outcome was all-cause mortality at 1-year.Among 1,412 patients, 581 were Asian and 831 were non-Asian. The distribution of the STS risk score group was different between Asian and non-Asian groups (62.5% low-, 29.8% intermediate-, and 7.7% high-risk in Asian vs 40.6% low-, 39.1% intermediate-, and 20.3% high-risk in non-Asian). In the Asian population, the all-cause mortality at 1-year was substantially higher in the high-risk STS group than in the low- and intermediate-risk groups (3.6% low-risk, 8.7% intermediate-risk, and 24.4% high-risk; log-rank P < 0.001), which was primarily driven by noncardiac mortality. In the non-Asian group, there was a proportional increase in all-cause mortality at 1-year according to the STS risk category (5.3% low-risk, 12.6% intermediate-risk, and 17.8% high-risk; log-rank P < 0.001).In this multiracial registry of patients with severe aortic stenosis who underwent TAVR, we identified a differential proportion and prognostic impact of STS score on 1-year mortality between Asian and non-Asian patients (TP-TAVR [Transpacific TAVR Registry]; NCT03826264).

  View details for DOI 10.1016/j.jacasi.2022.11.007

  View details for PubMedID 37323869

  View details for PubMedCentralID PMC10261892

• Long-Term Outcomes of Early Coronary Artery Disease Testing After New-Onset Heart Failure. Circulation. Heart failure Zheng, J., Heidenreich, P. A., Kohsaka, S., Fearon, W. F., Sandhu, A. T. 2023: e010426

  Abstract

  BACKGROUND: Coronary artery disease (CAD) testing remains underutilized in patients with newly diagnosed heart failure (HF). The longitudinal clinical impact of early CAD testing has not been well-characterized. We investigated changes in clinical management and long-term outcomes after early CAD evaluation in patients with incident HF.METHODS: We identified Medicare patients with incident HF from 2006 to 2018. The exposure variable was early CAD testing within 1 month of initial HF diagnosis. Covariate-adjusted rates of cardiovascular interventions after testing, including CAD-related management, were modeled using mixed-effects regression with clinician as a random intercept. We assessed mortality and hospitalization outcomes using landmark analyses with inverse probability-weighted Cox proportional hazards models. Falsification end points and mediation analysis were employed for bias assessment.RESULTS: Among 309 559 patients with new-onset HF without prior CAD, 15.7% underwent early CAD testing. Patients who underwent prompt CAD evaluation had higher adjusted rates of subsequent antiplatelet/statin prescriptions and revascularization, guideline-directed therapy for HF, and stroke prophylaxis for atrial fibrillation/flutter than controls. In weighted Cox models, 1-month CAD testing was associated with significantly reduced all-cause mortality (hazard ratio, 0.93 [95% CI, 0.91-0.96]). Mediation analyses indicated that 70% of this association was explained by CAD management, largely from new statin prescriptions. Falsification end points (outpatient diagnoses of urinary tract infection and hospitalizations for hip/vertebral fracture) were nonsignificant.CONCLUSIONS: Early CAD testing after incident HF was associated with a modest mortality benefit, driven mostly by subsequent statin therapy. Further investigation on clinician barriers to testing and treating high-risk patients may improve adherence to guideline-recommended cardiovascular interventions.

  View details for DOI 10.1161/CIRCHEARTFAILURE.122.010426

  View details for PubMedID 37212148

• Reduced Pulmonary Artery Distensibility Predicts Persistent Pulmonary Hypertension and 2-Year Mortality in Patients with Severe Aortic Stenosis Undergoing TAVR. Academic radiology Turner, V., Maret, E., Kim, J. B., Codari, M., Hinostroza, V., Mastrodicasa, D., Watkins, A. C., Fearon, W. F., Fischbein, M. P., Haddad, F., Willemink, M. J., Fleischmann, D. 2023

  Abstract

  RATIONALE AND OBJECTIVES: Post-TAVR persistent pulmonary hypertension (PH) is a better predictor of poor outcome than pre-TAVR PH. In this longitudinal study we sought to evaluate whether pulmonary artery (distensibility (DPA) measured on preprocedural ECG-gated CTA is associated with persistent-PH and 2-year mortality after TAVR.MATERIALS AND METHODS: Three hundred and thirty-six patients undergoing TAVR between July 2012 and March 2016 were retrospectively included and followed for all-cause mortality until November 2017. All patients underwent retrospectively ECG-gated CTA prior to TAVR. Main pulmonary artery (MPA) area was measured in systole and in diastole. DPA was calculated as: [(area-MPAmax-area-MPAmin)/area-MPAmax]%. ROC analysis was performed to assess the AUC for persistent-PH. Youden Index was used to determine the optimal threshold of DPA for persistent-PH. Two groups were compared based on a DPA threshold of 8% (specificity of 70% for persistent-PH). Kaplan-Meier, Cox proportional-hazard, and logistic regression analyses were performed. The primary clinical endpoint was defined as persistent-PH post-TAVR. The secondary endpoint was defined as all-cause mortality 2 years after TAVR.RESULTS: Median follow-up time was 413 (interquartiles 339-757) days. A total of 183 (54%) had persistent-PH and 68 (20%) patients died within 2-years after TAVR. Patients with DPA<8% had significantly more persistent-PH (67% vs 47%, p<0.001) and 2-year deaths (28% vs 15%, p=0.006), compared to patients with DPA>8%. Adjusted multivariable regression analyses showed that DPA<8% was independently associated with persistent-PH (OR 2.10 [95%-CI 1.3-4.5], p=0.007) and 2-year mortality (HR 2.91 [95%-CI 1.5-5.8], p=0.002). Kaplan-Meier analysis showed that 2-year mortality of patients with DPA<8% was significantly higher compared to patients with DPA≥8% (mortality 28% vs 15%; log-rank p=0.003).CONCLUSION: DPA on preprocedural CTA is independently associated with persistent-PH and two-year mortality in patients who undergo TAVR.

  View details for DOI 10.1016/j.acra.2023.03.014

  View details for PubMedID 37147161

• Long-Term Prognostic Value of Lesion- And Vessel-Specific Physiological and Plaque Features at Coronary CT Angiography Yang, S., Doh, J., Jegere, S., Erglis, A., Leipsic, J., Choi, G., Zarins, K., Taylor, C., Fearon, W. F., Koo, B. ELSEVIER SCIENCE INC. 2023: S42-S43

  View details for Web of Science ID 000979459800064

• Angiography-Derived FFR as Novel Parameter in Assessing Flow-Limiting CAD? JACC. Cardiovascular imaging Schindler, T. H., Fearon, W. F. 2023

  View details for DOI 10.1016/j.jcmg.2023.03.004

  View details for PubMedID 37115161

• IMPACT OF MYOCARDIAL BRIDGING ON LONG TERM OUTCOMES AFTER HEART TRANSPLANTATION: AN INTRAVASCULAR ULTRASOUND OBSERVATION FROM AN INTERNATIONAL MULTICENTER HEART TRANSPLANT REGISTRY Saito, K., Okada, K., Sakagami, A., Angeras, O., Arora, S., Gullestad, L., Ahn, J., Park, S., Zimmermann, F., Luikart, H., Khush, K., Fearon, W., Honda, Y. ELSEVIER SCIENCE INC. 2023: 1390

  View details for Web of Science ID 000990866101402

• Impact of myocardial bridging on coronary artery plaque formation and long-term mortality after heart transplantation. International journal of cardiology Tanaka, S., Okada, K., Kitahara, H., Luikart, H., Yock, P. G., Yeung, A. C., Schnittger, I., Tremmel, J. A., Fitzgerald, P. J., Khush, K. K., Fearon, W. F., Honda, Y. 2023

  Abstract

  OBJECTIVES: This study aimed to explore the impact of myocardial bridging (MB) on early development of cardiac allograft vasculopathy and long-term graft survival after heart transplantation.BACKGROUND: MB has been reported to be associated with acceleration of proximal plaque development and endothelial dysfunction in native coronary atherosclerosis. However, its clinical significance in heart transplantation remains unclear.METHODS: In 103 heart-transplant recipients, serial (baseline and 1-year post-transplant) volumetric intravascular ultrasound (IVUS) analyses were performed in the first 50 mm of the left anterior descending (LAD) artery. Standard IVUS indices were evaluated in 3 equally divided LAD segments (proximal, middle, and distal segments). MB was defined by IVUS as an echolucent muscular band lying on top of the artery. The primary endpoint was death or re-transplantation, assessed for up to 12.2 years (median follow-up: 4.7 years).RESULTS: IVUS identified MB in 62% of the study population. At baseline, MB patients had smaller intimal volume in the distal LAD than non-MB patients (p = 0.002). During the first year, vessel volume decreased diffusely irrespective of the presence of MB. Intimal growth diffusely distributed in non-MB patients, whereas MB patients demonstrated significantly augmented intimal formation in the proximal LAD. Kaplan-Meier analysis revealed significantly lower event-free survival in patients with versus without MB (log-rank p = 0.02). In multivariate analysis, the presence of MB was independently associated with late adverse events [hazard ratio 5.1 (1.6-22.2)].CONCLUSION: MB appears to relate to accelerated proximal intimal growth and reduced long-term survival in heart-transplant recipients.

  View details for DOI 10.1016/j.ijcard.2023.03.014

  View details for PubMedID 36893856

• Long-term prognostic implications of hemodynamic and plaque assessment using coronary CT angiography. Atherosclerosis Yang, S., Lesina, K., Doh, J., Jegere, S., Erglis, A., Leipsic, J. A., Chun, E. J., Choi, G., Schaap, M., Zarins, C., Taylor, C. A., Fearon, W. F., Narula, J., Koo, B. 2023

  Abstract

  BACKGROUND AND AIMS: Hemodynamic and plaque characteristics can be analyzed using coronary CT angiography (CTA). We aimed to explore long-term prognostic implications of hemodynamic and plaque characteristics using coronary CT angiography (CTA).METHODS: Invasive fractional flow reserve (FFR) and CTA-derived FFR (FFRCT) were undertaken for 136 lesions in 78 vessels and followed-up to 10 years until December 2020. FFRCT, wall shear stress (WSS), change in FFRCT across the lesion (DeltaFFRCT), total plaque volume (TPV), percent atheroma volume (PAV), and low-attenuation plaque volume (LAPV) for target lesions [L] and vessels [V] were obtained by independent core laboratories. Their collective influence was evaluated for the clinical endpoints of target vessel failure (TVF) and target lesion failure (TLF).RESULTS: During a median follow-up of 10.1 years, PAV[V] (per 10% increase, HR 2.32 [95% CI 1.11-4.86], p=0.025), and FFRCT[V] (per 0.1 increase, HR 0.56 [95% CI 0.37-0.84], p=0.006) were independent predictors of TVF for the per-vessel analysis, and WSS[L] (per 100dyne/cm2 increase, HR 1.43 [1.09-1.88], p=0.010), LAPV[L] (per 10mm3 increase, HR 3.81 [1.16-12.5], p=0.028), and DeltaFFRCT[L] (per 0.1 increase, HR 1.39 [1.02-1.90], p=0.040) were independent predictors of TLF for the per-lesion analysis after adjustment for clinical and lesion characteristics. The addition of both plaque and hemodynamic predictors improved the predictability for 10-year TVF and TLF of clinical and lesion characteristics (all p<0.05).CONCLUSIONS: Vessel- and lesion-level hemodynamic characteristics, and vessel-level plaque quantity, and lesion-level plaque compositional characteristics assessed by CTA offer independent and additive long-term prognostic value.

  View details for DOI 10.1016/j.atherosclerosis.2023.02.005

  View details for PubMedID 36872186

• Ongoing experience with patient-specific computer simulation of transcatheter aortic valve replacement in bicuspid aortic valve. Cardiovascular revascularization medicine : including molecular interventions Dowling, C., Gooley, R., McCormick, L., Sharma, R. P., Yeung, A. C., Fearon, W. F., Dargan, J., Khan, F., Firoozi, S., Brecker, S. J. 2023

  Abstract

  Transcatheter aortic valve replacement (TAVR) is increasingly being used to treat younger, lower-risk patients with bicuspid aortic valve (BAV). Patient-specific computer simulation may identify patients at risk for developing paravalvular regurgitation (PVR) and major conduction disturbance. Only limited prospective experience of this technology exist. We wished to describe our ongoing experience with patient-specific computer simulation.Patients who were referred for consideration of TAVR with a self-expanding transcatheter heart valve (THV) and had BAV identified on pre-procedural cardiac computed tomography imaging underwent patient-specific computer simulation. The computer simulations were reviewed by the Heart Team and used to guide surgical or transcatheter treatment approaches and to aid in THV sizing and positioning. Clinical outcomes were recorded.Between May 2019 and May 2021, 16 patients with BAV were referred for consideration of TAVR with a self-expanding THV. Sievers Type 1 morphology was present in 15 patients and Type 0 in the remaining patient. Two patients were predicted to develop moderate-to-severe PVR with a TAVR procedure and these patients underwent successful surgical aortic valve replacement. In the remaining 14 patients, computer simulation was used to optimize THV sizing and positioning to minimise PVR and conduction disturbance. One patient with a low valve implantation depth developed moderate PVR and this complication was correctly predicted by the computer simulations. No patient required insertion of a new permanent pacemaker.Patient-specific computer simulation may be used to guide the most appropriate treatment modality for patients with BAV. The usage of computer simulation to guide THV sizing and positioning was associated with favourable clinical outcomes.

  View details for DOI 10.1016/j.carrev.2023.01.015

  View details for PubMedID 36740551

• PET for Detection and Reporting Coronary Microvascular Dysfunction: A JACC: Cardiovascular Imaging Expert Panel Statement. JACC. Cardiovascular imaging Schindler, T. H., Fearon, W. F., Pelletier-Galarneau, M., Ambrosio, G., Sechtem, U., Ruddy, T. D., Patel, K. K., Bhatt, D. L., Bateman, T. M., Gewirtz, H., Shirani, J., Knuuti, J., Gropler, R. J., Chareonthaitawee, P., Slart, R. H., Windecker, S., Kaufmann, P. A., Abraham, M. R., Taqueti, V. R., Ford, T. J., Camici, P. G., Schelbert, H. R., Dilsizian, V. 2023

  Abstract

  Angina pectoris and dyspnea in patients with normal or nonobstructive coronary vessels remains a diagnostic challenge. Invasive coronary angiography may identify up to 60% of patients with nonobstructive coronary artery disease (CAD), of whom nearly two-thirds may, in fact, have coronary microvascular dysfunction (CMD) that may account for their symptoms. Positron emission tomography (PET) determined absolute quantitative myocardial blood flow (MBF) at rest and during hyperemic vasodilation with subsequent derivation of myocardial flow reserve (MFR) affords the noninvasive detection and delineation of CMD. Individualized or intensified medical therapies with nitrates, calcium-channel blockers, statins, angiotensin-converting enzyme inhibitors, angiotensin II type 1-receptor blockers, beta-blockers, ivabradine, or ranolazine may improve symptoms, quality of life, and outcome in these patients. Standardized diagnosis and reporting criteria for ischemic symptoms caused by CMD are critical for optimized and individualized treatment decisions in such patients. In this respect, it was proposed by the cardiovascular council leadership of the Society of Nuclear Medicine and Molecular Imaging to convene thoughtful leaders from around the world to serve as an independent expert panel to develop standardized diagnosis, nomenclature and nosology, and cardiac PET reporting criteria for CMD. This consensus document aims to provide an overview of the pathophysiology and clinical evidence of CMD, its invasive and noninvasive assessment, standardization of PET-determined MBFs and MFR into "classical" (predominantly related to hyperemic MBFs) and "endogen" (predominantly related to resting MBF) normal coronary microvascular function or CMD that may be critical for diagnosis of microvascular angina, subsequent patient care, and outcome of clinical CMD trials.

  View details for DOI 10.1016/j.jcmg.2022.12.015

  View details for PubMedID 36881418

• Association of Pretransplant Coronary Heart Disease Testing With Early Kidney Transplant Outcomes. JAMA internal medicine Cheng, X. S., Liu, S., Han, J., Stedman, M. R., Baiocchi, M., Tan, J. C., Chertow, G. M., Fearon, W. F. 2023

  Abstract

  Importance: Testing for coronary heart disease (CHD) in asymptomatic kidney transplant candidates before transplant is widespread and endorsed by various professional societies, but its association with perioperative outcomes is unclear.Objective: To estimate the association of pretransplant CHD testing with rates of death and myocardial infarction (MI).Design, Setting, and Participants: This retrospective cohort study included all adult, first-time kidney transplant recipients from January 2000 through December 2014 in the US Renal Data System with at least 1 year of Medicare enrollment before and after transplant. An instrumental variable (IV) analysis was used, with the program-level CHD testing rate in the year of the transplant as the IV. Analyses were stratified by study period, as the rate of CHD testing varied over time. A combination of US Renal Data System variables and Medicare claims was used to ascertain exposure, IV, covariates, and outcomes.Exposures: Receipt of nonurgent invasive or noninvasive CHD testing during the 12 months preceding kidney transplant.Main Outcomes and Measures: The primary outcome was a composite of death or acute MI within 30 days of after kidney transplant.Results: The cohort comprised 79 334 adult, first-time kidney transplant recipients (30 147 women [38%]; 25 387 [21%] Black and 48 394 [61%] White individuals; mean [SD] age of 56 [14] years during 2012 to 2014). The primary outcome occurred in 4604 patients (244 [5.3%]; 120 [2.6%] death, 134 [2.9%] acute MI). During the most recent study period (2012-2014), the CHD testing rate was 56% in patients in the most test-intensive transplant programs (fifth IV quintile) and 24% in patients at the least test-intensive transplant program (first IV quintile, P<.001); this pattern was similar across other study periods. In the main IV analysis, compared with no testing, CHD testing was not associated with a change in the rate of primary outcome (rate difference, 1.9%; 95% CI, 0%-3.5%). The results were similar across study periods, except for 2000 to 2003, during which CHD testing was associated with a higher event rate (rate difference, 6.8%; 95% CI, 1.8%-12.0%).Conclusions and Relevance: The results of this cohort study suggest that pretransplant CHD testing was not associated with a reduction in early posttransplant death or acute MI. The study findings potentially challenge the ubiquity of CHD testing before kidney transplant and should be confirmed in interventional studies.

  View details for DOI 10.1001/jamainternmed.2022.6069

  View details for PubMedID 36595271

• Is FFR dead? A conversation in cardiology. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions Kern, M. J., Cox, D., Fearon, W., Johnson, N., Klein, L., Krucoff, M., Moses, J., Naidu, S. S., Pinto, D., Ramee, S., Teirstein, P., Yeung, A. 2022

  View details for DOI 10.1002/ccd.30422

  View details for PubMedID 36273434

• Global Longitudinal Strain and Biomarkers of Cardiac Damage and Stress as Predictors of Outcomes After Transcatheter Aortic Valve Implantation. Journal of the American Heart Association Perry, A. S., Stein, E. J., Biersmith, M., Fearon, W. F., Elmariah, S., Kim, J. B., Clark, D. E., Patel, J. N., Gonzales, H., Baker, M., Piana, R. N., Mallugari, R. R., Kapadia, S., Kumbhani, D. J., Gillam, L., Whisenant, B., Quader, N., Zajarias, A., Welt, F. G., Bavry, A. A., Coylewright, M., Gupta, D. K., Vatterott, A., Jackson, N., Huang, S., Lindman, B. R. 2022: e026529

  Abstract

  Background Global longitudinal strain (GLS) is a sensitive measure of left ventricular function and a risk marker in severe aortic stenosis. We sought to determine whether biomarkers of cardiac damage (cardiac troponin) and stress (NT-proBNP [N-terminal pro-B-type natriuretic peptide]) could complement GLS to identify patients with severe aortic stenosis at highest risk. Methods and Results From a multicenter prospective cohort of patients with symptomatic severe aortic stenosis who underwent transcatheter aortic valve implantation, we measured absolute GLS (aGLS), cardiac troponin, and NT-proBNP at baseline in 499 patients. Left ventricular ejection fraction <50% was observed in 19% and impaired GLS (aGLS <15%) in 38%. Elevations in cardiac troponin and NT-proBNP were present in 79% and 89% of those with impaired GLS, respectively, as compared with 63% and 60% of those with normal GLS, respectively (P<0.001 for each). aGLS <15% was associated with increased mortality in univariable analysis (P=0.009), but, in a model with both biomarkers, aGLS, and clinical covariates included, aGLS was not associated with mortality; elevation in each biomarker was associated with an increased hazard of mortality (adjusted hazard ratio, >2; P≤0.002 for each) when the other biomarker was elevated, but not when the other biomarker was normal (interaction P=0.015). Conclusions Among patients with symptomatic severe aortic stenosis undergoing transcatheter aortic valve implantation, elevations in circulating cardiac troponin and NT-proBNP are more common as GLS worsens. Biomarkers of cardiac damage and stress are independently associated with mortality after transcatheter aortic valve implantation, whereas GLS is not. These findings may have implications for risk stratification of asymptomatic patients to determine optimal timing of valve replacement.

  View details for DOI 10.1161/JAHA.122.026529

  View details for PubMedID 36172966

• Comparison of Fractional Flow Reserve Alternatives: NonHyperemic Pressure Ratios and Imaging-Based Approach Li, W., Takahashi, T., Sehatbakhsh, S., Parikh, M., Fearon, W., Kobayashi, Y. ELSEVIER SCIENCE INC. 2022: B95-B96

  View details for Web of Science ID 000892594000222

• Differential Prognostic Impact of Conventional Surgical Risk Score on One-Year Mortality After Transcatheter Aortic Valve Replacement Among Asian and Non- Asian Populations: Insights From the Multinational Multicenter TP-TAVR Registry Kim, H., Kang, D., Ahn, J., Kim, J., Yeung, A., Fearon, W., Cantey, E., Flaherty, J., Davidson, C., Malaisrie, S., Kim, M., Lee, J., Park, J., Choi, Y., Park, S., Park, D. ELSEVIER SCIENCE INC. 2022: B208-B209

  View details for Web of Science ID 000892594000479

• Prognostic Value of Measuring Fractional Flow Reserve after Percutaneous Coronary Intervention in patients with Complex Coronary Artery Disease: Insights from the FAME 3 Trial. Circulation. Cardiovascular interventions Piroth, Z., Otsuki, H., Zimmermann, F. M., Ferenci, T., Keulards, D., Yeung, A. C., Pijls, N. H., De Bruyne, B., Fearon, W. F., FAME 3 Investigators 2022

  Abstract

  Background: We evaluate the prognostic value of measuring fractional flow reserve (FFR) after percutaneous coronary intervention (post-PCI FFR) and intravascular imaging in patients undergoing PCI for three-vessel coronary artery disease (CAD) in the FAME 3 trial. Methods: The FAME 3 trial is a multicenter, international, randomized study comparing FFR-guided PCI with coronary artery bypass grafting (CABG) in patients with multivessel CAD. PCI was not non-inferior with respect to the primary endpoint of death, myocardial infarction (MI), stroke or repeat revascularization at 1 year. Post-PCI FFR data were acquired on a patient and vessel-related basis. Intravascular imaging guidance was tracked. The primary end point is a comparison of target vessel failure (TVF) defined as a composite of cardiac death, target vessel MI and target vessel revascularization at one year based on post-PCI FFR values. Cox regression with robust standard errors was used for analysis. Results: Of the 757 patients randomized to PCI, 461 (61%) had post-PCI FFR measurement and 11.1% had intravascular imaging performed. The median post-PCI FFR was 0.89 [IQR 0.85-0.94]. On a vessel-level, post-PCI FFR was found to be a significant predictor of TVF univariately (HR=0.67 [95% CI:0.48-0.93] for 0.1 unit increase, p=0.0165). On a patient-level, the single lowest post-PCI FFR value was also found to be a significant predictor of TVF univariately (HR=0.65 [95% CI:0.48-0.89] for 0.1 unit increase, p=0.0074). Post-PCI FFR was an independent predictor of TVF in multivariable analysis adjusted for key clinical parameters. Outcomes were similar between patients who had intravascular imaging guidance and those who did not. Conclusions: Post-PCI FFR measurement was a significant predictor of TVF on a vessel and patient level and an independent predictor of outcomes in a population with complex three-vessel CAD eligible for CABG. The limited use of intravascular imaging did not affect outcomes.

  View details for DOI 10.1161/CIRCINTERVENTIONS.122.012542

  View details for PubMedID 36121706

• Impact of Serial Coronary Stenoses on Various Coronary Physiologic Indices. Circulation. Cardiovascular interventions Ahn, J. M., Nakayoshi, T., Hashikata, T., Kashiyama, K., Arashi, H., Kweon, J., Van't Veer, M., Lyons, J., Fearon, W. F. 2022; 15 (9): e012134

  Abstract

  Determining the functional significance of each individual coronary lesion in patients with serial coronary stenoses is challenging. It has been proposed that nonhyperemic pressure ratios, such as the instantaneous wave free ratio (iFR) and the ratio of resting distal to proximal coronary pressure (Pd/Pa) are more accurate than fractional flow reserve (FFR) because autoregulation should maintain stable resting coronary flow and avoid hemodynamic interdependence (cross-talk) that occurs during hyperemia. This study aimed to measure the degree of hemodynamic interdependence of iFR, resting Pd/Pa, and FFR in a porcine model of serial coronary stenosis.In 6 anesthetized female swine, 381 serial coronary stenoses were created in the left anterior descending artery using 2 balloon catheters. The degree of hemodynamic interdependence was calculated by measuring the absolute changes in iFR, resting Pd/Pa, and FFR across the fixed stenosis as the severity of the other stenosis varied.The hemodynamic interdependence of iFR, resting Pd/Pa, and FFR was 0.039±0.048, 0.021±0.026, and 0.034±0.034, respectively (all P<0.001). When the functional significance of serial stenoses was less severe (0.70-0.90 for each index), the hemodynamic interdependence was 0.009±0.020, 0.007±0.013, and 0.017±0.022 for iFR, resting Pd/Pa, and FFR, respectively (all P<0.001). However, in more severe serial coronary stenoses (<0.60 for each index), hemodynamic interdependence was 0.060±0.050, 0.037±0.030, and 0.051±0.037 for iFR, resting Pd/Pa, and FFR, respectively (all P<0.001).When assessing serial coronary stenoses, nonhyperemic pressure ratios are affected by hemodynamic interdependence. When the functional significance of serial coronary stenoses is severe, the effect is similar to that which is seen with FFR.

  View details for DOI 10.1161/CIRCINTERVENTIONS.122.012134

  View details for PubMedID 36126133

• Early Trends in Cardiac Allograft Vasculopathy After Implementation of the 2018 Donor Heart Allocation Policy in the United States: Short Title: CAV Trend After Allocation Policy Change. American heart journal Tehrani, D. M., Kim, J. S., Hsu, J. J., Nsair, A., Khush, K. K., Fearon, W. F., Parikh, R. V. 2022

  Abstract

  STUDY OBJECTIVE: To evaluate the impact of the new donor heart allocation system implemented in the United States in October 2018 on development of early cardiac allograft vasculopathy (CAV).DESIGN: Retrospective cohort study.PARTICIPANTS: Adult (≥ 18 years) heart transplant recipients registered in the United Network for Organ Sharing database between October 18, 2015 - October 17, 2018 (old system) and October 18, 2018 - May 31, 2020 (new system).MAIN OUTCOME MEASURE: Incidence of angiographic CAV at 1 year (accelerated CAV) in the overall transplant population and among the highest acuity subgroup-Status 1A (old) and Status 1 or 2 (new). We included recipient and donor demographic, cardiovascular, and transplant factors in multivariable logistic regression models to identify predictors of accelerated CAV.RESULTS: Of 10,375 transplant recipients, 6,660 (64%) and 3,715 (36%) were listed in the old and new allocation cohorts, respectively. The incidence of accelerated CAV was 521 (8%) in the old period compared with 272 (7%) in the new period (p = 0.36). Similar incidence rates were observed in the highest acuity subgroup-363 (8%) compared with 143 (7%), respectively (p = 0.13). In adjusted analyses of the high-acuity cohort, the new allocation system was not associated with a higher likelihood of accelerated CAV (odds ratio = 0.87, 95% confidence interval: 0.70-1.08, p = 0.20).CONCLUSIONS: The new donor heart allocation system is not associated with development of accelerated angiographic CAV at 1 year, including among recipients requiring the most urgent transplants.

  View details for DOI 10.1016/j.ahj.2022.08.002

  View details for PubMedID 35970399

• FFRCT Planner: The Next Tool in the Precision PCI Armamentarium? JACC. Cardiovascular imaging Fearon, W. F., Parikh, R. V. 2022; 15 (7): 1256-1258

  View details for DOI 10.1016/j.jcmg.2022.03.011

  View details for PubMedID 35798402

• Safety of Provocative Testing With Intracoronary Acetylcholine and Implications for Standard Protocols. Journal of the American College of Cardiology Takahashi, T., Samuels, B. A., Li, W., Parikh, M. A., Wei, J., Moses, J. W., Fearon, W. F., Henry, T. D., Tremmel, J. A., Kobayashi, Y., Microvascular Network 2022; 79 (24): 2367-2378

  Abstract

  BACKGROUND: Heterogeneity in diagnostic criteria and provocation protocols has posed challenges in understanding the safety of coronary provocation testing with intracoronary acetylcholine (ACh) for the contemporary diagnosis of epicardial and microvascular spasm.OBJECTIVES: We examined the safety of testing and subgroup differences in procedural risks based on ethnicity, diagnostic criteria, and provocation protocols.METHODS: PubMed and Embase were searched in November 2021 to identify original articles reporting procedural complications associated with intracoronary ACh administration. The primary outcome was the pooled estimate of the incidence of major complications including death, myocardial infarction, ventricular tachycardia/fibrillation, and shock.RESULTS: A total of 16 studies with 12,585 patients were included in the meta-analysis. The overall pooled estimate of the incidence of major complications was 0.5% (95%CI: 0.0%-1.3%) without any reports of death. Exploratory subgroup analyses revealed that the pooled incidence of major complications was significantly higher in the studies that followed the contemporary diagnosis criteria for epicardial spasm defined as≥90% diameter reduction (1.0%; 95%CI: 0.3%-2.0%) but significantly lower in Western populations (0.0%; 95%CI: 0.0%-0.45%). The rate of positive epicardial spasm and the incidence of major complications were similar between provocation protocols using the maximum ACh doses of 100mug and 200mug.CONCLUSIONS: Intracoronary ACh administration for the contemporary diagnosis of epicardial and microvascular spasm is a safe procedure. Moreover, excellent safety records are observed in Western populations primarily presenting with myocardial ischemia and/or infarction with nonobstructive coronary arteries. This study will help standardize ACh testing to improve clinical diagnosis and ensure procedural safety.

  View details for DOI 10.1016/j.jacc.2022.03.385

  View details for PubMedID 35710187

• What makes an ideal hyperemic drug? International journal of cardiology Zimmermann, F. M., Fearon, W. F. 2022

  View details for DOI 10.1016/j.ijcard.2022.06.005

  View details for PubMedID 35671899

• Untangling diffuse CAD: Light at the end of the tunnel? International journal of cardiology Stathogiannis, K., Fearon, W. F. 2022

  View details for DOI 10.1016/j.ijcard.2022.05.042

  View details for PubMedID 35609713

• Fractional Flow Reserve-Guided PCI as Compared with Coronary Bypass Surgery REPLY NEW ENGLAND JOURNAL OF MEDICINE Fearon, W. F., Zimmermann, F. M., Pijls, N. J. 2022; 386 (19): 1865-1866

  View details for Web of Science ID 000796390600025

• Trends in Coronary Artery Disease Screening before Kidney Transplantation. Kidney360 Cheng, X. S., Liu, S., Han, J., Stedman, M. R., Chertow, G. M., Tan, J. C., Fearon, W. F. 2022; 3 (3): 516-523

  Abstract

  Background: Coronary artery disease (CAD) screening in asymptomatic kidney transplant candidates is widespread but not well supported by contemporary cardiology literature. In this study we describe temporal trends in CAD screening before kidney transplant in the United States.Methods: Using the United States Renal Data System, we examined Medicare-insured adults who received a first kidney transplant from 2000 through 2015. We stratified analysis on the basis of whether the patient's comorbidity burden met guideline definitions of high risk for CAD. We examined temporal trends in nonurgent CAD tests within the year before transplant and the composite of death and nonfatal myocardial infarction in the 30 days after transplant.Results: Of 94,832 kidney transplant recipients, 37,139 (39%) underwent at least one nonurgent CAD test in the 1 year before transplant. From 2000 to 2015, the transplant program waitlist volume had increased as transplant volume stayed constant, whereas patients in the later eras had a slightly higher comorbidity burden (older, longer dialysis vintage, and a higher prevalence of diabetes mellitus and CAD). The likelihood of CAD test in the year before transplant increased from 2000 through 2003 and remained relatively stable thereafter. When stratified by CAD risk status, test rates decreased modestly in patients who were high risk but remained constant in patients who were low risk after 2008. Death or nonfatal myocardial infarction within 30 days after transplant decreased from 3% in 2000 to 2% in 2015. Nuclear perfusion scan was the most frequent modality of testing throughout the examined time periods.Conclusions: CAD testing rates before kidney transplantation have remained constant from 2000 through 2015, despite widespread changes in cardiology guidelines and practice.

  View details for DOI 10.34067/KID.0005282021

  View details for PubMedID 35582172

• Left Ventricular Hypertrophy and Biomarkers of Cardiac Damage and Stress in Aortic Stenosis. Journal of the American Heart Association Stein, E. J., Fearon, W. F., Elmariah, S., Kim, J. B., Kapadia, S., Kumbhani, D. J., Gillam, L., Whisenant, B., Quader, N., Zajarias, A., Welt, F. G., Bavry, A. A., Coylewright, M., Piana, R. N., Mallugari, R. R., Clark, D. E., Patel, J. N., Gonzales, H., Gupta, D. K., Vatterott, A., Jackson, N., Huang, S., Lindman, B. R. 2022: e023466

  Abstract

  Background Left ventricular hypertrophy (LVH) is associated with increased mortality risk and rehospitalization after transcatheter aortic valve replacement among those with severe aortic stenosis. Whether cardiac troponin (cTnT) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) risk stratify patients with aortic stenosis and without LVH is unknown. Methods and Results In a multicenter prospective registry of 923 patients with severe aortic stenosis undergoing transcatheter aortic valve replacement, we included 674 with core-laboratory-measured LV mass index, cTnT, and NT-proBNP. LVH was defined by sex-specific guideline cut-offs and elevated biomarker levels were based on age and sex cut-offs. Adjusted Cox proportional hazards models evaluated associations between LVH and biomarkers and all-cause death out to 5years. Elevated cTnT and NT-proBNP were present in 82% and 86% of patients with moderate/severe LVH, respectively, as compared with 66% and 69% of patients with no/mild LVH, respectively (P<0.001 for each). After adjustment, compared with no/mild LVH, moderate/severe LVH was associated with an increased hazard of mortality (adjusted hazard ratio [aHR], 1.34; 95% CI 1.01-1.77, P=0.043). cTnT and NT-proBNP each risk stratified patients with moderate/severe LVH (P<0.05). In a model with both biomarkers and LVH included, elevated cTnT (aHR, 2.08; 95% CI 1.45-3.00, P<0.001) and elevated NT-proBNP (aHR, 1.46; 95% CI 1.00-2.11, P=0.049) were each associated with increased mortality risk, whereas moderate/severe LVH was not (P=0.15). Conclusions Elevations in circulating cTnT and NT-proBNP are more common as LVH becomes more pronounced but are also observed in those with no/minimal LVH. As measures of maladaptive remodeling and cardiac injury, cTnT and NT-proBNP predict post-transcatheter aortic valve replacement mortality better than LV mass index. These findings may have important implications for risk stratification and treatment of patients with aortic stenosis.

  View details for DOI 10.1161/JAHA.121.023466

  View details for PubMedID 35301869

• Diagnostic performance of fractional flow reserve derived from coronary angiography, intravascular ultrasound, and optical coherence tomography; a meta-analysis. Journal of cardiology Takahashi, T., Shin, D., Kuno, T., Lee, J. M., Latib, A., Fearon, W. F., Maehara, A., Kobayashi, Y. 2022

  Abstract

  BACKGROUND: Little is known about the overall diagnostic performance of computational fractional flow reserve (FFR) derived from angiography (Angio-FFR), intravascular ultrasound (IVUS-FFR), and optical coherence tomography (OCT-FFR) to detect hemodynamically significant coronary artery disease. The present study aimed to evaluate the diagnostic performance of those novel physiologic indices using conventional FFR as the gold standard.METHODS: PubMed and Embase were searched in September 2021 for a systematic review and meta-analysis of studies assessing the diagnostic performance of invasive imaging-derived FFR. The primary outcomes were the summary sensitivity, specificity, correlation coefficients of each index.RESULTS: A total of 6572 records were initially identified and 49 studies were included in the final analysis (7010 lesions from 36 studies for Angio-FFR, 305 lesions from 5 studies for IVUS-FFR, and 667 lesions from 8 studies for OCT-FFR). Invasive imaging-derived FFR had a high diagnostic performance to detect functionally significant coronary lesions using conventional FFR as the gold standard [Angio-FFR, sensitivity 0.87 (95% CI 0.84-0.89), specificity 0.93 (95% CI 0.910.95); IVUS-FFR, sensitivity 0.90 (95% CI 0.84-0.94), specificity 0.95 (95% CI 0.90-0.98); OCT-FFR, sensitivity 0.85 (95% CI 0.78-0.91), specificity 0.93 (95% CI 0.89-0.95)]. The summary correlation coefficients of Angio-, IVUS-, and OCT-FFRs with wire-based FFR were 0.83 (95% CI 0.80-0.85), 0.85 (95% CI 0.79-0.91), and 0.80 (95% CI 0.74-0.86), respectively.CONCLUSIONS: This meta-analysis demonstrated that computational FFR derived from invasive coronary imaging has clinically acceptable diagnostic performances irrespective of modalities, supporting their applicability to clinical practice.

  View details for DOI 10.1016/j.jjcc.2022.02.015

  View details for PubMedID 35282944

• Inter-racial differences in patients undergoing transcatheter aortic valve implantation. Heart (British Cardiac Society) Kang, D., Ahn, J., Kim, J. B., Yeung, A., Nishi, T., Fearon, W., Cantey, E. P., Flaherty, J. D., Davidson, C. J., Malaisrie, S. C., Park, S. Y., Yun, S., Ko, E., Park, H., Lee, S., Kim, D., Kim, H. J., Kim, J. B., Choo, S. J., Park, D., Park, S. 1800

  Abstract

  OBJECTIVE: Little information exists about inter-racial differences in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). We investigated whether differences in baseline characteristics between Asian and non-Asian population may contribute to disparities in clinical outcomes after TAVI.METHODS: We performed a registry-based, multinational cohort study of patients with severe AS who underwent TAVI at two centres in the USA and one centre in South Korea. The primary outcome was a composite of death, stroke or rehospitalisation at 1year.RESULTS: Of 1412 patients, 581 patients were Asian and 831 were non-Asian (87.5% white, 1.7% black, 6.1% Hispanic or 4.7% others). There were substantial differences in baseline characteristics between two racial groups. The primary composite outcome was significantly lower in the Asian group than in the non-Asian group (26.0% vs 35.0%; HR 0.73; 95% CI 0.59 to 0.89; p=0.003). However, after adjustment of baseline covariates, the risk of primary composite outcome was not significantly different (HR 0.79; 95%CI 0.60 to 1.03; p=0.08). The all-cause mortality at 1year was significantly lower in the Asian group than the non-Asian group (7.4% vs 12.5%; HR 0.60; 95%CI 0.41 to 0.88; p=0.009). After multivariable adjustment, the risk of all-cause mortality was also similar (HR 1.17; 95%CI 0.73 to 1.88; p=0.52).CONCLUSIONS: There were significant differences in baseline and procedural factors among Asian and non-Asian patients who underwent TAVI. Observed inter-racial differences in clinical outcomes were largely explained by baseline differences in clinical, anatomical and procedural factors.TRIAL REGISTRATION NUMBER: NCT03826264 (https://wwwclinicaltrialsgov).

  View details for DOI 10.1136/heartjnl-2021-320364

  View details for PubMedID 35110384

• Clinical validation of a novel simplified offline tool for SYNTAX score calculation. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions Takahashi, T., Nishi, T., Zimmermann, F. M., Granada, J. F., Latib, A., Fearon, W. F., Kobayashi, Y. 1800

  View details for DOI 10.1002/ccd.30054

  View details for PubMedID 35084085

• Myocardial Microvascular Physiology in Acute and Chronic Coronary Syndromes, Aortic Stenosis, and Heart Failure JOURNAL OF INTERVENTIONAL CARDIOLOGY Larsen, A., Fearon, W. F., Anderson, T. J., Pijls, N. 2022; 2022

  View details for DOI 10.1155/2022/9846391

  View details for Web of Science ID 000832043600001

• Myocardial Microvascular Physiology in Acute and Chronic Coronary Syndromes, Aortic Stenosis, and Heart Failure. Journal of interventional cardiology Larsen, A. I., Fearon, W. F., Anderson, T. J., Pijls, N. 2022; 2022: 9846391

  View details for DOI 10.1155/2022/9846391

  View details for PubMedID 35935124

  View details for PubMedCentralID PMC9297731

• Fractional Flow Reserve and Instantaneous Wave-Free Ratio Predict Pathological Wall Shear Stress in Coronary Arteries: Implications for Understanding the Pathophysiological Impact of Functionally Significant Coronary Stenoses. Journal of the American Heart Association Wong, C. C., Javadzadegan, A., Ada, C., Lau, J. K., Bhindi, R., Fearon, W. F., Kritharides, L., Ng, M. K., Yong, A. S. 1800: e023502

  Abstract

  Background The pathophysiological mechanism behind adverse outcomes associated with ischemia-inducing epicardial coronary stenoses and microcirculatory dysfunction remains unclear. Wall shear stress (WSS) plays an important role in atherosclerotic plaque progression and vulnerability. We aimed to evaluate the relationship between WSS, functionally significant epicardial coronary stenoses, and microcirculatory dysfunction. Methods and Results Patients undergoing invasive coronary physiology testing were included. Fractional flow reserve, instantaneous wave-free ratio, and the index of microcirculatory resistance were measured. Quantitative coronary angiography was used to obtain the lesion percentage diameter stenosis. Computational fluid dynamics analysis was performed to calculate WSS parameters. Multiple regression analysis was performed to calculate the standardized regression coefficient (beta) for the coronary physiology indices. A total of 107 vessels from 88 patients were included. Fractional flow reserve independently predicted the total area of low WSS (beta=-0.44; 95% CI, -0.62 to -0.25; P<0.001) and maximum lesion WSS (beta=-0.53; 95% CI, -0.70 to -0.36; P<0.001) after adjusting for percentage diameter stenosis and index of microcirculatory resistance. Similarly, instantaneous wave-free ratio also independently predicted the total area of low WSS (beta=-0.45; 95% CI, -0.62 to -0.28; P<0.001) and maximum lesion WSS (beta=-0.58; 95% CI, -0.73 to -0.43; P<0.001). The index of microcirculatory resistance did not predict either low or high WSS. Conclusions Fractional flow reserve and instantaneous wave-free ratio independently predicted the total burden of low WSS and maximum lesion WSS in coronary arteries. No relationship was found between microcirculatory dysfunction and WSS.

  View details for DOI 10.1161/JAHA.121.023502

  View details for PubMedID 35043698

• Diagnostic performance and prognostic impact of coronary angiography-based Index of Microcirculatory Resistance assessment: A systematic review and meta-analysis. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions Li, W., Takahashi, T., Rios, S. A., Latib, A., Lee, J. M., Fearon, W. F., Kobayashi, Y. 1800

  Abstract

  BACKGROUND: The Index of Microcirculatory Resistance (IMR), measured with a pressure-thermistor tipped coronary guidewire has been established as a gold standard for coronary microvascular assessment. Angiography-based IMR (angio-IMR) is a novel method to derive IMR without intracoronary instrumentation or the need for adenosine.METHODS: PubMed and Embase databases were systemically searched in November 2021 for studies that measured angio-IMR. The primary outcomes were pooled sensitivity and specificity as well as the area under the curve (AUC) of the summary receiver operating characteristic curve using IMR as a reference standard.RESULTS: A total of 129 records were initially identified and 8 studies were included in the final analysis. Overall, 1653 lesions were included in this study, of which 733 were in patients presenting with ST-segment elevation myocardial infarction. Angio-IMR yielded high diagnostic performance predicting wire-based IMR with pooled sensitivity=0.81 (95% confidence interval: 0.76, 0.85), specificity=0.80 (0.72, 0.86), and AUC=0.86 (0.82, 0.88), which was similar irrespective of patient presentation. When the clinical outcome was compared between high versus low angio-IMR in patients presenting with myocardial infarction, high angio-IMR predicted an increased risk of major adverse cardiac events (MACE).CONCLUSION: Our study found that coronary angio-IMR has relatively high diagnostic performance as well as prognostic values predicting MACE, supporting its use in clinical practice.

  View details for DOI 10.1002/ccd.30076

  View details for PubMedID 35019220

• Variability in Coronary Artery Disease Testing for Patients With New-Onset Heart Failure. Journal of the American College of Cardiology Zheng, J., Heidenreich, P. A., Kohsaka, S., Fearon, W. F., Sandhu, A. T. 2022; 79 (9): 849-860

  Abstract

  Coronary artery disease (CAD) is the most common cause of new-onset heart failure (HF). Although guidelines recommend ischemic evaluation in this population, testing has historically been underutilized.This study aimed to identify contemporary trends in CAD testing for patients with new-onset HF, particularly after publication of the STICHES (Surgical Treatment for Ischemic Heart Failure Extension Study), and to characterize geographic and clinician-level variability in testing patterns.We determined the proportion of patients with incident HF who received CAD testing from 2004 to 2019 using an administrative claims database covering commercial insurance and Medicare. We identified demographic and clinical predictors of CAD testing during the 90 days before and after initial diagnosis. Patients were grouped by their county of residence to assess national variation. Patients were then linked to their primary care physician and/or cardiologist to evaluate variation across clinicians.Among 558,322 patients with new-onset HF, 34.8% underwent CAD testing and 9.3% underwent revascularization. After multivariable adjustment, patients who underwent CAD testing were more likely to be younger, male, diagnosed in an acute care setting, and have systolic dysfunction or recent cardiogenic shock. Incidence of CAD testing remained flat without significant change post-STICHES. Covariate-adjusted testing rates varied from 20% to 45% across counties. The likelihood of testing was higher among patients co-managed by a cardiologist (adjusted OR: 5.12; 95% CI: 4.98-5.27) but varied substantially across cardiologists (IQR: 50.9%-62.4%).Most patients with new-onset HF across inpatient and outpatient settings did not receive timely testing for CAD. Substantial variability in testing persists across regions and clinicians.

  View details for DOI 10.1016/j.jacc.2021.11.061

  View details for PubMedID 35241218

• Distance between valvular leaflet and coronary ostium predicting risk of coronary obstruction during TAVR. International journal of cardiology. Heart & vasculature Oh, J., Kobayashi, Y., Kang, G., Nishi, T., Willemink, M. J., Fearon, W. F., Fischbein, M., Fleishmann, D., Yeung, A. C., Kim, J. B. 1800; 37: 100917

  Abstract

  Background: The aim of this study was to evaluate the role of the distance between the aortic valve in projected position to the coronary ostium to determine risk of coronary artery obstruction after transcatheter aortic valve replacement (TAVR).Methods: An Expected Leaflet-to-ostium Distance (ELOD) was obtained on pre-TAVR planning computed tomography by subtracting leaflet thickness and the distances from the center to the annular rim at annulus level and from the center to the coronary ostium at mid-ostial level. Variables were compared between patients with and without coronary obstruction and the level of association between variables was assessed using log odds ratio (OR).Results: A total of 177 patients with 353 coronary arteries was analyzed. Mean annulus diameters (22.8±2.8mm and 23.4±1.0mm, p>0.05) and mean sinus of Valsalva (SOV) diameters (31.2±3.6mm and 31.9±3.6mm, p>0.05) were similar between patients with lower and higher coronary heights, respectively. There were three coronary obstruction cases. ELOD≤2mm in combination with leaflet length longer than mid-ostial height allowed for discrimination of cases with and without coronary obstruction. There was a significant association between coronary obstruction event and ELOD≤2mm (log OR=6.180, p<0.001).Conclusions: Our study showed that a combination of ELOD<2mm and a longer leaflet length than mid-ostial height may be associated with increased risk for coronary obstruction during TAVR.

  View details for DOI 10.1016/j.ijcha.2021.100917

  View details for PubMedID 34917750

• Racial Differences in the Incidence and Impact of Prosthesis-Patient MismatchAfter Transcatheter AorticValve Replacement. JACC. Cardiovascular interventions Park, H., Ahn, J., Kang, D., Kim, J. B., Yeung, A. C., Nishi, T., Fearon, W. F., Cantey, E. P., Flaherty, J. D., Davidson, C. J., Malaisrie, S. C., Kim, S., Yun, S., Ko, E., Lee, S., Kim, D., Kim, H. J., Kim, J. B., Choo, S. J., Park, D., Park, S. 2021

  Abstract

  OBJECTIVES: The aim of this study was to compare the incidence and prognostic significance of prosthesis-patient mismatch (PPM) after transcatheter aortic valve replacement (TAVR) according to racial groups.BACKGROUND: PPM after TAVR may be of more concern in Asian populations considering their relatively small annular and valve sizes compared with Western populations.METHODS: TP-TAVR (Transpacific TAVR Registry) was an international multicenter cohort study of patients with severe aortic stenosis who underwent TAVR in the United States and South Korea from January 2015 to November 2019. PPM was defined as moderate (0.65-0.85cm2/m2) or severe (<0.65cm2/m2) at the indexed effective orifice area. The primary outcome was a composite of death, stroke, or rehospitalization at 1 year.RESULTS: Among 1,101 eligible patients (533 Asian and 569 non-Asian), the incidence of PPM was significantly lower in the Asian population (33.6%; moderate, 26.5%; severe, 7.1%) than in the non-Asian population (54.5%; moderate, 29.8%; severe, 24.7%). The 1-year rate of the primary outcome was similar between the PPM and non-PPM groups (27.5% vs 28.1%; P=0.69); this pattern was consistent between Asian (25.4% vs 25.2%; P=0.31) and non-Asian (28.7% vs 32.1%; P=0.97) patients. After multivariable adjustment, the risk for the primary outcome did not significantly differ between the PPM and non-PPM groups in the overall population (HR: 0.95; 95% CI: 0.74-1.21), in Asian patients (HR: 1.07; 95%CI: 0.74-1.55), and in non-Asian patients (HR: 0.86; 95%CI: 0.63-1.19).CONCLUSIONS: In this study of patients with severe aortic stenosis who underwent TAVR, the incidence of PPM was significantly lower in Asian patients than in non-Asian patients. The 1-year risk for the primary composite outcome was similar between the PPM and non-PPM groups regardless of racial group. (Transpacific TAVR Registry [TP-TAVR]; NCT03826264).

  View details for DOI 10.1016/j.jcin.2021.08.038

  View details for PubMedID 34838464

• Resting Pd/Pa and the Instantaneous Wave-Free Ratio Are Not Immune to Hemodynamic Interdependence ("Crosstalk") in the Presence of Serial Coronary Stenoses Ahn, J., Hashikata, T., Nakayoshi, T., Kashiyama, K., Arashi, H., Kweon, J., Fearon, W. ELSEVIER SCIENCE INC. 2021: B65-B66

  View details for Web of Science ID 000715526900145

• Discordance Between the Index of Microcirculatory Resistance and Coronary Flow Reserve After Percutaneous Coronary Intervention JACC-CARDIOVASCULAR INTERVENTIONS Wong, C. Y., Nishi, T., Yong, A. C., Murai, T., Kakuta, T., Waseda, K., Amano, T., Hirohata, A., Barbato, E., Ng, M. C., Fearon, W. F. 2021; 14 (21): 2412-2414

  View details for DOI 10.1016/j.jcin.2021.07.053

  View details for Web of Science ID 000715082400023

  View details for PubMedID 34736742

• How Gold Is the Gold Standard for Machine Learning-Based CT-FFR? JACC. Cardiovascular imaging Yong, C. M., Fearon, W. F. 2021

  View details for DOI 10.1016/j.jcmg.2021.10.002

  View details for PubMedID 34801451

• Angiographic quantitative flow ratio-guided coronary intervention (FAVOR III China): a multicentre, randomised, sham-controlled trial. Lancet (London, England) Xu, B., Tu, S., Song, L., Jin, Z., Yu, B., Fu, G., Zhou, Y., Wang, J., Chen, Y., Pu, J., Chen, L., Qu, X., Yang, J., Liu, X., Guo, L., Shen, C., Zhang, Y., Zhang, Q., Pan, H., Fu, X., Liu, J., Zhao, Y., Escaned, J., Wang, Y., Fearon, W. F., Dou, K., Kirtane, A. J., Wu, Y., Serruys, P. W., Yang, W., Wijns, W., Guan, C., Leon, M. B., Qiao, S., Stone, G. W., FAVOR III China study group 2021

  Abstract

  BACKGROUND: Compared with visual angiographic assessment, pressure wire-based physiological measurement more accurately identifies flow-limiting lesions in patients with coronary artery disease. Nonetheless, angiography remains the most widely used method to guide percutaneous coronary intervention (PCI). In FAVOR III China, we aimed to establish whether clinical outcomes might be improved by lesion selection for PCI using the quantitative flow ratio (QFR), a novel angiography-based approach to estimate the fractional flow reserve.METHODS: FAVOR III China is a multicentre, blinded, randomised, sham-controlled trial done at 26 hospitals in China. Patients aged 18 years or older, with stable or unstable angina pectoris or patients who had a myocardial infarction at least 72 h before screening, who had at least one lesion with a diameter stenosis of 50-90% in a coronary artery with a reference vessel of at least 2·5 mm diameter by visual assessment were eligible. Patients were randomly assigned to a QFR-guided strategy (PCI performed only if QFR ≤0·80) or an angiography-guided strategy (PCI based on standard visual angiographic assessment). Participants and clinical assessors were masked to treatment allocation. The primary endpoint was the 1-year rate of major adverse cardiac events, a composite of death from any cause, myocardial infarction, or ischaemia-driven revascularisation. The primary analysis was done in the intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT03656848).FINDINGS: Between Dec 25, 2018, and Jan 19, 2020, 3847 patients were enrolled. After exclusion of 22 patients who elected not to undergo PCI or who were withdrawn by their physicians, 3825 participants were included in the intention-to-treat population (1913 in the QFR-guided group and 1912 in the angiography-guided group). The mean age was 62·7 years (SD 10·1), 2699 (70·6%) were men and 1126 (29·4%) were women, 1295 (33·9%) had diabetes, and 2428 (63·5%) presented with an acute coronary syndrome. The 1-year primary endpoint occurred in 110 (Kaplan-Meier estimated rate 5·8%) participants in the QFR-guided group and in 167 (8·8%) participants in the angiography-guided group (difference, -3·0% [95% CI -4·7 to -1·4]; hazard ratio 0·65 [95% CI 0·51 to 0·83]; p=0·0004), driven by fewer myocardial infarctions and ischaemia-driven revascularisations in the QFR-guided group than in the angiography-guided group.INTERPRETATION: In FAVOR III China, among patients undergoing PCI, a QFR-guided strategy of lesion selection improved 1-year clinical outcomes compared with standard angiography guidance.FUNDING: Beijing Municipal Science and Technology Commission, Chinese Academy of Medical Sciences, and the National Clinical Research Centre for Cardiovascular Diseases, Fuwai Hospital.

  View details for DOI 10.1016/S0140-6736(21)02248-0

  View details for PubMedID 34742368

• Can We Predict Rejection Early After Heart Transplantation? Circulation Fearon, W. F., Valantine, H. A. 2021; 144 (18): 1473-1475

  View details for DOI 10.1161/CIRCULATIONAHA.121.056808

  View details for PubMedID 34723641

• Age-related iFR/FFR discordance: does it matter? EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology Fearon, W. F. 2021; 17 (9): 704-705

  View details for DOI 10.4244/EIJV17I9A123

  View details for PubMedID 34665138

• Prognostic value of comprehensive intracoronary physiology assessment early after heart transplantation. European heart journal Ahn, J., Zimmermann, F. M., Arora, S., Solberg, O., Angeras, O., Rolid, K., Rafique, M., Aaberge, L., Karason, K., Okada, K., Luikart, H., Khush, K. K., Honda, Y., Pijls, N. H., Lee, S. E., Kim, J., Park, S., Gullestad, L., Fearon, W. F. 2021

  Abstract

  AIMS: We evaluated the long-term prognostic value of invasively assessing coronary physiology after heart transplantation in a large multicentre registry.METHODS AND RESULTS: Comprehensive intracoronary physiology assessment measuring fractional flow reserve (FFR), the index of microcirculatory resistance (IMR), and coronary flow reserve (CFR) was performed in 254 patients at baseline (a median of 7.2weeks) and in 240 patients at 1year after transplantation (199 patients had both baseline and 1-year measurement). Patients were classified into those with normal physiology, reduced FFR (FFR≤0.80), and microvascular dysfunction (either IMR≥25 or CFR≤2.0 with FFR>0.80). The primary outcome was the composite of death or re-transplantation at 10years. At baseline, 5.5% had reduced FFR; 36.6% had microvascular dysfunction. Baseline reduced FFR [adjusted hazard ratio (aHR) 2.33, 95% confidence interval (CI) 0.88-6.15; P=0.088] and microvascular dysfunction (aHR 0.88, 95% CI 0.44-1.79; P=0.73) were not predictors of death and re-transplantation at 10years. At 1year, 5.0% had reduced FFR; 23.8% had microvascular dysfunction. One-year reduced FFR (aHR 2.98, 95% CI 1.13-7.87; P=0.028) and microvascular dysfunction (aHR 2.33, 95% CI 1.19-4.59; P=0.015) were associated with significantly increased risk of death or re-transplantation at 10years. Invasive measures of coronary physiology improved the prognostic performance of clinical variables (chi2 improvement: 7.41, P=0.006). However, intravascular ultrasound-derived changes in maximal intimal thickness were not predictive of outcomes.CONCLUSION: Abnormal coronary physiology 1year after heart transplantation was common and was a significant predictor of death or re-transplantation at 10years.

  View details for DOI 10.1093/eurheartj/ehab568

  View details for PubMedID 34665224

• Microvascular Resistance Reserve forAssessment of Coronary MicrovascularFunction: JACC Technology Corner. Journal of the American College of Cardiology De Bruyne, B., Pijls, N. H., Gallinoro, E., Candreva, A., Fournier, S., Keulards, D. C., Sonck, J., Van't Veer, M., Barbato, E., Bartunek, J., Vanderheyden, M., Wyffels, E., De Vos, A., El Farissi, M., Tonino, P. A., Muller, O., Collet, C., Fearon, W. F. 2021; 78 (15): 1541-1549

  Abstract

  The need for a quantitative and operator-independent assessment of coronary microvascular function is increasingly recognized. We propose the theoretical framework of microvascular resistance reserve (MRR) as an index specific for the microvasculature, independent of autoregulation and myocardial mass, and based on operator-independent measurements of absolute values of coronary flow and pressure. In its general form, MRR equals coronary flow reserve (CFR) divided by fractional flow reserve (FFR) corrected for driving pressures. In 30 arteries, pressure, temperature, and flow velocity measurements were obtained simultaneously at baseline (BL), during infusion of saline at 10mL/min (rest) and 20mL/min (hyperemia). A strong correlation was found between continuous thermodilution-derived MRR and Doppler MRR (r=0.88; 95% confidence interval: 0.72-0.93; P< 0.001). MRR was independent from the epicardial resistance, the lower the FFR value, the greater the difference between MRR and CFR. Therefore, MRR is proposed as a specific, quantitative, and operator-independent metric to quantify coronary microvascular dysfunction.

  View details for DOI 10.1016/j.jacc.2021.08.017

  View details for PubMedID 34620412

• Association of microvascular dysfunction with clinical outcomes in patients with non-flow limiting fractional flow reserve after percutaneous coronary intervention. International journal of cardiology. Heart & vasculature Nishi, T., Murai, T., Waseda, K., Hirohata, A., Yong, A. S., Ng, M. K., Amano, T., Barbato, E., Kakuta, T., Fearon, W. F. 2021; 35: 100833

  Abstract

  Background: We sought to investigate prognostic implication of microvascular dysfunction as assessed by the index of microcirculatory index (IMR) in patients without residual obstructive CAD with non-flow limiting fractional flow reserve (FFR) (>0.80) following percutaneous coronary intervention (PCI).Methods: A total of 570 patients who had both post-PCI FFR and IMR values were included in the present analysis; of these, 65 patients had FFR≤0.80 and 505 had FFR>0.80. Of the 505 patients with FFR>0.80, 137 had high IMR and 368 had low IMR. The primary outcome of the present analysis is a composite of all-cause death, spontaneous myocardial infarction, or target-vessel revascularization. Impaired microvascular function was defined as IMR≥25 (high IMR).Results: During a median follow-up duration of 4.0years, those with FFR>0.80 and low IMR demonstrated lower rate or primary outcome event than those with FFR≤0.80 (hazard ratio 0.49 [95% confidence interval 0.27-0.92], p=0.026) and those with FFR>0.80 and high IMR (hazard ratio 1.60 [0.99-2.16], p=0.056). The patients with FFR>0.80 and IMR≥25 had similar rate of primary outcome event compared with those with FFR≤0.80 (p=0.49).Conclusion: Microvascular dysfunction following PCI is not rare and is associated with adverse events even in the setting of a non-flow limiting FFR; these results suggest that when performing coronary physiologic assessment following PCI, interrogating not only the epicardial vessel, but also the microvasculature is useful for the risk stratification in patients undergoing PCI.

  View details for DOI 10.1016/j.ijcha.2021.100833

  View details for PubMedID 34345649

• A Meta-Analysis of Recent Trials Comparing Revascularization With Medical Therapy Alone in Patients With Chronic Coronary Syndrome JACC-CARDIOVASCULAR INTERVENTIONS Fearon, W. F., Collet, C., da Costa, B., Mizukami, T., Barbato, E., Tonino, P. L., Pijls, N. J., Juni, P., De Bruyne, B. 2021; 14 (12): 1388-1390

  View details for DOI 10.1016/j.jcin.2021.04.021

  View details for Web of Science ID 000667656100026

  View details for PubMedID 34167686

• Physiology-Based Revascularization: A New Approach to Plan and Optimize Percutaneous Coronary Intervention. JACC. Asia Lee, J. M., Lee, S. H., Shin, D., Choi, K. H., van de Hoef, T. P., Kim, H. K., Samady, H., Kakuta, T., Matsuo, H., Koo, B. K., Fearon, W. F., Escaned, J. 2021; 1 (1): 14-36

  Abstract

  Coronary physiological assessment using fractional flow reserve or nonhyperemic pressure ratios has become a standard of care for patients with coronary atherosclerotic disease. However, most evidence has focused on the pre-interventional use of physiological assessment to aid revascularization decision-making, whereas post-interventional physiological assessment has not been well established. Although evidence for supporting the role of post-interventional physiological assessment to optimize immediate revascularization results and long-term prognosis has been reported, a more thorough understanding of these data is crucial in incorporating post-interventional physiological assessment into daily practice. Recent scientific efforts have also focused on the potential role of pre-interventional fractional flow reserve or nonhyperemic pressure ratio pullback tracings to characterize patterns of coronary atherosclerotic disease to better predict post-interventional physiological outcomes, and thereby identify the appropriate revascularization target. Pre-interventional pullback tracings with dedicated post-processing methods can provide characterization of focal versus diffuse disease or major gradient versus minor gradient stenosis, which would result in different post-interventional physiological results. This review provides a comprehensive look at the current evidence regarding the evolving role of physiological assessment as a functional optimization tool for the entire process of revascularization, and not merely as a pre-interventional tool for revascularization decision-making.

  View details for DOI 10.1016/j.jacasi.2021.03.002

  View details for PubMedID 36338358

  View details for PubMedCentralID PMC9627934

• Performance versus Risk Factor-Based Approaches to Coronary Artery Disease Screening in Waitlisted Kidney Transplant Candidates. Cardiorenal medicine Cheng, X. S., Watford, D. J., Arashi, H., Stedman, M. R., Chertow, G. M., Tan, J. C., Fearon, W. F. 2021: 1-11

  Abstract

  INTRODUCTION: Current screening algorithms for coronary artery disease (CAD) before kidney transplantation result in many tests but few interventions.OBJECTIVE: The aim of this study was to study the utility of 6-minute walk test (6MWT), an office-based test of cardiorespiratory fitness, for risk stratification in this setting.METHODS: We enrolled 360 patients who are near the top of the kidney transplant waitlist at our institution. All patients underwent CAD evaluation irrespective of 6MWT results. We examined the association between 6MWT and time to CAD-related events (defined as cardiac death, revascularization, nonfatal myocardial infarction, and removal from the waitlist for CAD), treating noncardiac death and waitlist removal for non-CAD reasons as competing events.RESULTS: The 6MWT-based approach designated approximately 45% of patients as "low risk," whereas a risk factor- or symptom-based approach designated 14 and 81% of patients as "low risk," respectively. The 6MWT-based approach was not significantly associated with CAD-related events within 1 year (subproportional hazard ratio [sHR] 1.00 [0.90-1.11] per 50 m) but was significantly associated with competing events (sHR 0.70 [0.66-0.75] per 50 m). In a companion analysis, removing waitlist status from consideration, 6MWT result was associated with the development of CAD-related events (sHR 0.92 [0.84-1.00] per 50 m).CONCLUSIONS: The 6MWT designates fewer patients as high risk and in need of further testing (compared to risk factor-based approaches), but its utility as a pure CAD risk stratification tool is modulated by the background waitlist removal rate. CAD screening before kidney transplant should be tailored according to a patient's actual chance of receiving a transplant.

  View details for DOI 10.1159/000516158

  View details for PubMedID 34034263

• STATIN ADHERENCE AFTER HEART TRANSPLANTATION: AN OUTCOMES ANALYSIS Li, K., Kalwani, N., Sandhu, A., Khush, K., Fearon, W. ELSEVIER SCIENCE INC. 2021: 569

  View details for Web of Science ID 000647487500568

• Deep learning for prediction of fractional flow reserve from resting coronary pressure curves EUROINTERVENTION Zimmermann, F. M., Mast, T. P., Johnson, N. P., Everts, I., Hennigan, B., Berry, C., Johnson, D. T., De Bruyne, B., Fearon, W. F., Oldroyd, K. G., Pijls, N. J., Tonino, P. L., van 't Veer, M. 2021; 17 (1): 51-+

  Abstract

  It would be ideal for a non-hyperaemic index to predict fractional flow reserve (FFR) more accurately, given FFR's extensive validation in a multitude of clinical settings.The aim of this study was to derive a novel non-hyperaemic algorithm based on deep learning and to validate it in an internal validation cohort against FFR.The ARTIST study is a post hoc analysis of three previously published studies. In a derivation cohort (random 80% sample of the total cohort) a deep neural network was trained (deep learning) with paired examples of resting coronary pressure curves and their FFR values. The resulting algorithm was validated against unseen resting pressure curves from a random 20% sample of the total cohort. The primary endpoint was diagnostic accuracy of the deep learning-derived algorithms against binary FFR ≤0.8. To reduce the variance in the precision, we used a fivefold cross-validation procedure.A total of 1,666 patients with 1,718 coronary lesions and 2,928 coronary pressure tracings were included. The diagnostic accuracy of our convolutional neural network (CNN) and recurrent neural networks (RNN) against binary FFR ≤0.80 was 79.6±1.9% and 77.6±2.3%, respectively. There was no statistically significant difference between the accuracy of our neural networks to predict binary FFR and the most accurate non-hyperaemic pressure ratio (NHPR).Compared to standard derivation of resting pressure ratios, we did not find a significant improvement in FFR prediction when resting data are analysed using artificial intelligence approaches. Our findings strongly suggest that a larger class of hidden information within resting pressure traces is not the main cause of the known disagreement between resting indices and FFR. Therefore, if clinicians want to use FFR for clinical decision making, hyperaemia induction should remain the standard practice. Visual summary. Development and validation of deep neural networks to predict fractional flow reserve (FFR) from resting coronary pressure curves. In a derivation cohort, a deep neural network was trained (deep learning) with examples of resting coronary pressure curves and matching FFR values. After the neural network was trained, its new algorithm was validated using different resting pressure curves. Deep learning-based algorithms did not improve the diagnos-tic accuracy of predicting FFR compared to other non-hyperae-mic indices in a clinically relevant way.

  View details for DOI 10.4244/EIJ-D-20-00648

  View details for Web of Science ID 000651622800009

  View details for PubMedID 32863244

• Atrial Fibrillation Is Associated With Mortality in Intermediate Surgical Risk Patients With Severe Aortic Stenosis: Analyses From the PARTNER 2A and PARTNER S3i Trials. Journal of the American Heart Association Brener, M. I., George, I., Kosmidou, I., Nazif, T., Zhang, Z., Dizon, J. M., Garan, H., Malaisrie, S. C., Makkar, R., Mack, M., Szeto, W. Y., Fearon, W. F., Thourani, V. H., Leon, M. B., Kodali, S., Biviano, A. B. 2021: e019584

  Abstract

  Background The impact of atrial fibrillation (AF) in intermediate surgical risk patients with severe aortic stenosis who undergo either transcatheter or surgical aortic valve replacement (AVR) is not well established. Methods and Results Data were assessed in 2663 patients from the PARTNER (Placement of Aortic Transcatheter Valve) 2A or S3i trials. Analyses grouped patients into 3 categories according to their baseline and discharge rhythms (ie, sinus rhythm [SR]/SR, SR/AF, or AF/AF). Among patients with transcatheter AVR (n=1867), 79.2% had SR/SR, 17.6% had AF/AF, and 3.2% had SR/AF. Among patients with surgical AVR (n=796), 71.7% had SR/SR, 14.1% had AF/AF, and 14.2% had SR/AF. Patients with transcatheter AVR in AF at discharge had increased 2-year mortality (SR/AF versus SR/SR; hazard ratio [HR], 2.73; 95% CI, 1.68-4.44; P<0.0001; AF/AF versus SR/SR; HR, 1.56; 95% CI, 1.16-2.09; P=0.003); patients with SR/AF also experienced increased 2-year mortality relative to patients with AF/AF (HR, 1.77; 95% CI, 1.04-3.00; P=0.03). For patients with surgicalAVR, the presence of AF at discharge was also associated with increased 2-year mortality (SR/AF versus SR/SR; HR, 1.93; 95% CI, 1.25-2.96; P=0.002; and AF/AF versus SR/SR; HR, 1.67; 95% CI, 1.06-2.63; P=0.027). Rehospitalization and persistent advanced heart failure symptoms were also more common among patients with transcatheter AVR and surgical AVR discharged in AF, and major bleeding was more common in the transcatheter AVR cohort. Conclusions The presence of AF at discharge in patients with intermediate surgical risk aortic stenosis was associated with worse outcomes-especially in patients with baseline SR-including increased all-cause mortality at 2-year follow-up. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01314313 and NCT03222128.

  View details for DOI 10.1161/JAHA.120.019584

  View details for PubMedID 33754803

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

  Abstract

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

  View details for DOI 10.1016/j.jcct.2021.03.004

  View details for PubMedID 33795188

• A real-world comparison of outcomes between fractional flow reserve-guided versus angiography-guided percutaneous coronary intervention. PloS one Wong, C. C., Ng, A. C., Ada, C., Chow, V., Fearon, W. F., Ng, M. K., Kritharides, L., Yong, A. S. 2021; 16 (12): e0259662

  Abstract

  Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) has been shown to be superior to angiography-guided PCI in randomized controlled studies. However, real-world data on the use and outcomes of FFR-guided PCI remain limited. Thus, we investigated the outcomes of patients undergoing FFR-guided PCI compared to angiography-guided PCI in a large, state-wide unselected cohort.All patients undergoing PCI between June 2017 and June 2018 in New South Wales, Australia, were included. The cohort was stratified into the FFR-guided group when concomitant FFR was performed, and the angiography-guided group when no FFR was performed. The primary outcome was a combined endpoint of death or myocardial infarction (MI). Secondary outcomes included all-cause death, cardiovascular (CVS) death, and MI. The cohort comprised 10,304 patients, of which 542 (5%) underwent FFR-guided PCI. During a mean follow-up of 12±4 months, the FFR-guided PCI group had reduced occurrence of the primary outcome (hazard ratio [HR] 0.34, 95% confidence intervals [CI] 0.20-0.56, P<0.001), all-cause death (HR 0.18, 95% CI 0.07-0.47, P = 0.001), CVS death (HR 0.21, 95% CI 0.07-0.66, P = 0.01), and MI (HR 0.46, 95% CI 0.25-0.84, P = 0.01) compared to the angiography-guided PCI group. Multivariable Cox regression analysis showed FFR-guidance to be an independent predictor of the primary outcome (HR 0.45, 95% CI 0.27-0.75, P = 0.002), all-cause death (HR 0.22, 95% CI 0.08-0.59, P = 0.003), and CVS death (HR 0.27, 95% CI 0.09-0.83, P = 0.02).In this real-world study of patients undergoing PCI, FFR-guidance was associated with lower rates of the primary outcome of death or MI, as well as the secondary outcomes of all-cause death and CVS death.

  View details for DOI 10.1371/journal.pone.0259662

  View details for PubMedID 34914720

• Global Fractional Flow Reserve Value Predicts 5-Year Outcomes in Patients With Coronary Atherosclerosis But Without Ischemia. Journal of the American Heart Association Fournier, S., Collet, C., Xaplanteris, P., Zimmermann, F. M., Toth, G. G., Tonino, P. A., Pijls, N. H., Colaiori, I., Di Gioia, G., Barbato, E., Juni, P., Fearon, W. F., De Bruyne, B. 2020: e017729

  Abstract

  Background Global fractional flow reserve (FFR) (ie, the sum of the FFR values in the 3 major coronary arteries) is a physiologic correlate of global atherosclerotic burden. The objective of the present study was to investigate the value of global FFR in predicting long-term clinical outcome of patients with stable coronary artery disease but no ischemia-inducing stenosis. Methods and Results We studied major adverse cardiovascular events (MACEs: all-cause death, myocardial infarction, and any revascularization) after 5years in 1122 patients without significant stenosis (all FFR >0.80; n=275) or with at least 1 significant stenosis successfully treated by percutaneous coronary intervention (ie, post-percutaneous coronary intervention FFR >0.80; n=847). The patients were stratified into low, mid, or high tertiles of global FFR (≤2.80, 2.80-2.88, and ≥2.88). Patients in the lowest tertile of global FFR showed the highest 5-year MACE rate compared with those in the mid or high tertile of global FFR (27.5% versus 22.0% and 20.9%, respectively; log-rank P=0.040). The higher 5-year MACE rate was mainly driven by a higher rate of revascularization in the low global FFR group (16.4% versus 11.3% and 11.8%, respectively; log-rank P=0.038). In a multivariable model, an increase in global FFR of 0.1 unit was associated with a significant reduction in the rates of MACE (hazard ratio [HR], 0.988; 95% CI, 0.977-0.998; P=0.023), myocardial infarction (HR, 0.982; 95% CI, 0.966-0.998; P=0.032), and revascularization (HR, 0.985; 95% CI, 0.972-0.999; P=0.040). Conclusions Even in the absence of ischemia-producing stenoses, patients with a low global FFR, physiologic correlate of global atherosclerotic burden, present a higher risk of MACE at 5-year follow-up.

  View details for DOI 10.1161/JAHA.120.017729

  View details for PubMedID 33283600

• Elective Percutaneous Coronary Intervention in Ambulatory Surgery Centers. JACC. Cardiovascular interventions Li, K., Kalwani, N. M., Heidenreich, P. A., Fearon, W. F. 2020

  Abstract

  OBJECTIVES: The aim of this study was to explore characteristics and outcomes of patients undergoing elective percutaneous coronary intervention (PCI) in ambulatory surgery centers (ASCs).BACKGROUND: Little is known about patients who underwent ASC PCI before Medicare reimbursement was instituted in2020.METHODS: Using commercial insurance claims from MarketScan, adults who underwent hospital outpatient department (HOPD) or ASC PCI for stable ischemic heart disease from 2007 to 2016 were studied. Propensity score analysis was used to measure the association between treatment setting and the primary composite outcome of 30-day myocardial infarction, bleeding complications, and hospital admission.RESULTS: The unmatched sample consisted of 95,492 HOPD and 849 ASC PCIs. Patients who underwent ASC PCI were more likely to be younger than 65 years, to live in the southern United States, and to have managed or consumer-driven health insurance. ASC PCI was also associated with decreased fractional flow reserve utilization (odds ratio [OR]: 0.31; 95% confidence interval [CI]: 0.20 to 0.48; p<0.001). In unmatched, multivariate analysis, ASC PCI was associated with increased odds of the primary outcome (OR: 1.25; 95%CI: 1.01 to 1.56; p=0.039) and bleeding complications (OR: 1.80; 95%CI: 1.11 to 2.90; p=0.016). In propensity-matched analysis, ASC PCI was not associated with the primary outcome (OR: 1.23; 95%CI: 0.94 to 1.60; p=0.124) but was significantly associated with increased bleeding complications (OR: 2.49; 95%CI: 1.25 to 4.95; p=0.009).CONCLUSIONS: Commercially insured patients undergoing ASC PCI were less likely to undergo fractional flow reserve testing and had higher odds of bleeding complications than HOPD-treated patients. Further study is warranted as Medicare ASC PCI volume increases.

  View details for DOI 10.1016/j.jcin.2020.10.015

  View details for PubMedID 33183992

• Association Between Sarcopenia and Mortality After Transcatheter Aortic Valve Replacement Neill, C., Fearon, W., Elmariah, S., Kim, B., Kapadia, S., Kumbhani, D., Gillam, L., Whisenant, B., Quader, N., Zajarias, A., Welt, F., Coylewright, M., Carr, J., Nair, S., Terry, J., Vatterott, A., Jackson, N., Huang, S., Lindman, B. ELSEVIER SCIENCE INC. 2020: B42

  View details for Web of Science ID 000597114500090

• Prognostic Impact of Discordance Between Coronary Flow Reserve and the Index of Microcirculatory Resistance After Percutaneous Coronary Intervention Wong, C., Nishi, T., Ng, M., Yong, A., Ada, C., Kakuta, T., Barbato, E., Waseda, K., Amano, T., Hirohata, A., Fearon, W. ELSEVIER SCIENCE INC. 2020: B168–B169

  View details for Web of Science ID 000597114500375

• Nonhyperemic Pressure Ratios and Their Relationship With Indices of Microvascular Function Ada, C., Wong, C., Svanerud, J., van 't Veer, M., Lo, S., Fearon, W., Yong, A. ELSEVIER SCIENCE INC. 2020: B140

  View details for Web of Science ID 000597114500309

• Physiology over Angiography to Determine Lesion Severity: the FAME Trials. Interventional cardiology clinics Parikh, R. V., Fearon, W. F. 2020; 9 (4): 409–18

  Abstract

  The "Achilles heel" of invasive coronary angiography is its inability to accurately localize which stenoses induce ischemia and warrant treatment. Fractional flow reserve (FFR) is a coronary wire-based physiologic index that measures the functional significance of epicardial stenoses, thereby overcoming this limitation. Over the past decade, the landmark FAME (Fractional Flow Reserve vs Angiography for Multivessel Evaluation) trials demonstrated the clinical utility of an FFR-guided strategy for percutaneous coronary intervention (PCI) compared with angiography-only PCI or medical therapy alone in patients with predominantly stable ischemic heart disease. These trials have spurred the current era of coronary-physiology-guided revascularization.

  View details for DOI 10.1016/j.iccl.2020.05.001

  View details for PubMedID 32921365

• When is Coronary Revascularization Complete? Circulation. Cardiovascular interventions Fearon, W. F., Ahn, J. 2020: CIRCINTERVENTIONS120009889

  View details for DOI 10.1161/CIRCINTERVENTIONS.120.009889

  View details for PubMedID 32895007

• Impact of cognitive behavioral therapy on depression symptoms after transcatheter aortic valve replacement: A randomized controlled trial. International journal of cardiology Edwards, K. S., Chow, E. K., Dao, C., Hossepian, D., Johnson, A. G., Desai, M., Shah, S., Lee, A., Yeung, A. C., Fischbein, M., Fearon, W. F. 2020

  Abstract

  BACKGROUND: Depression is a significant concern after cardiac surgery and has not been studied in patients undergoing transcatheter aortic valve replacement (TAVR). We sought to examine the prevalence of pre-procedure depression and anxiety symptoms and explore whether brief bedside cognitive behavioral therapy (CBT) could prevent post-TAVR psychological distress.METHODS: We prospectively recruited consecutive TAVR patients and randomized them to receive brief CBT or treatment as usual (TAU) during their hospitalization. Multi-level regression techniques were used to evaluate changes by treatment arm in depression, anxiety, and quality of life from baseline to 1 month post-TAVR adjusted for sex, race, DM, CHF, MMSE, and STS score.RESULTS: One hundred and forty six participants were randomized. The mean age was 82 years, and 43% were female. Self-reported depression and anxiety scores meeting cutoffs for clinical level distress were 24.6% and 23.2% respectively. Both TAU and CBT groups had comparable improvements in depressive symptoms at 1-month (31% reduction for TAU and 35% reduction for CBT, p = .83). Similarly, both TAU and CBT groups had comparable improvements in anxiety symptoms at 1-month (8% reduction for TAU and 11% reduction for CBT, p = .1). Quality of life scores also improved and were not significantly different between the two groups.CONCLUSIONS: Pre-procedure depression and anxiety may be common among patients undergoing TAVR. However, TAVR patients show spontaneous improvement in depression and anxiety scores at 1-month follow up, regardless of brief CBT. Further research is needed to determine whether more tailored CBT interventions may improve psychological and medical outcomes.

  View details for DOI 10.1016/j.ijcard.2020.08.007

  View details for PubMedID 32800909

• Fractional Flow Reserve and "Hard" Endpoints. Journal of the American College of Cardiology Fearon, W. F., Arashi, H. 2020; 75 (22): 2800–2803

  View details for DOI 10.1016/j.jacc.2020.04.042

  View details for PubMedID 32498807

• Diagnostic Accuracy of Nonhyperemic Pressure Ratios Using a Pressure Sensing Microcatheter The ACIST-FFR Study JACC-CARDIOVASCULAR INTERVENTIONS Arashi, H., Kobayashi, Y., Price, M. J., Nishi, T., Chambers, J. W., Seto, A. H., Sarembock, I. J., Raveendran, G., Jeremias, A., Fearon, W. F. 2020; 13 (10): 1272–75

  View details for DOI 10.1016/j.jcin.2020.02.031

  View details for Web of Science ID 000536575400026

  View details for PubMedID 32439000

• Dose-Response Relationship Between Intracoronary Acetylcholine and Minimal Lumen Diameter in Coronary Endothelial Function Testing of Women and Men With Angina and No Obstructive Coronary Artery Disease. Circulation. Cardiovascular interventions Pargaonkar, V. S., Lee, J. H., Chow, E. K., Nishi, T., Ball, R. L., Kobayashi, Y., Kimura, T., Lee, D. P., Stefanick, M. L., Fearon, W. F., Yeung, A. C., Tremmel, J. A. 2020; 13 (4): e008587

  Abstract

  BACKGROUND: Intracoronary acetylcholine (Ach) provocation testing is the gold standard for assessing coronary endothelial function. However, dosing regimens of Ach are quite varied in the literature, and there are limited data evaluating the optimal dose. We evaluated the dose-response relationship between Ach and minimal lumen diameter (MLD) by sex and studied whether incremental intracoronary Ach doses given during endothelial function testing improve its diagnostic utility.METHODS: We evaluated 65 men and 212 women with angina and no obstructive coronary artery disease who underwent endothelial function testing using the highest tolerable dose of intracoronary Ach, up to 200 mug. Epicardial endothelial dysfunction was defined as a decrease in MLD >20% after intracoronary Ach by quantitative coronary angiography. We used a linear mixed effects model to evaluate the dose-response relationship. Deming regression analysis was done to compare the %MLD constriction after incremental doses of intracoronary Ach.RESULTS: The mean age was 53.5 years. Endothelial dysfunction was present in 186 (68.1%). Among men with endothelial dysfunction, there was a significant decrease in MLD/10 g of Ach at doses above 50 mug and 100 g, while this decrease in MLD was not observed in women (P<0.001). The %MLD constriction at 20 mug versus 50 mug and 50 mug versus 100 mug were not equivalent while the %MLD constriction at 100 mug versus 200 mug were equivalent.CONCLUSIONS: Women and men appear to have different responses to Ach during endothelial function testing. In addition to having a greater response to intracoronary Ach at all doses, men also demonstrate an Ach-MLD dose-response relationship with doses up to 200 mug, while women have minimal change in MLD with doses above 50 g. An incremental dosing regimen during endothelial function testing appears to improve the diagnostic utility of the test and should be adjusted based on the sex of the patient.

  View details for DOI 10.1161/CIRCINTERVENTIONS.119.008587

  View details for PubMedID 32279562

• Fractional Flow Reserve to Guide Coronary Artery Bypass Graft Surgery. JACC. Cardiovascular interventions Fearon, W. F., Boyd, J. H. 2020

  View details for DOI 10.1016/j.jcin.2020.01.209

  View details for PubMedID 32222437

• Quantitative flow ratio-guided strategy versus angiography-guided strategy for percutaneous coronary intervention: Rationale and design of the FAVOR III China trial. American heart journal Song, L., Tu, S., Sun, Z., Wang, Y., Ding, D., Guan, C., Xie, L., Escaned, J., Fearon, W. F., Kirtane, A. J., Serruys, P. W., Wijns, W., Windecker, S., Leon, M. B., Stone, G. W., Qiao, S., Xu, B., FAVOR III China Investigators 2020; 223: 72–80

  Abstract

  BACKGROUND: Quantitative flow ratio (QFR) is a novel angiography-based approach enabling fast computation of fractional flow reserve without use of pressure wire or adenosine. The objective of this investigator-initiated, multicenter, patient- and clinical assessor-blinded randomized trial is to evaluate the efficacy and cost-effectiveness of a QFR-augmented angiography-guided (QFR-guided) strategy versus an angiography-only guided (angiography-guided) strategy for percutaneous coronary intervention (PCI) in patients with coronary artery disease.METHODS: Approximately 3,830 patients will be randomized in a 1:1 ratio to a QFR-guided or an angiography-guided strategy. Included subjects scheduled for coronary angiography have at least 1 lesion eligible for PCI with 50%-90% stenosis in an artery with ≥2.5 mm reference diameter. Subjects assigned to the QFR-guided strategy will have QFR measured in each interrogated vessel and undergo PCI when QFR ≤0.80, with deferral for lesions with QFR >0.80. Those assigned to the angiography-guided strategy will undergo PCI based on angiography. Optimal medical therapy will be administered to all treated and deferred patients. The primary end point is the 1-year rate of major adverse cardiac events (MACE), a composite of all-cause mortality, any myocardial infarction, or any ischemia-driven revascularization. The major secondary end point is 1-year MACE excluding periprocedural myocardial infarction. Other secondary end points include the individual components of MACE and cost-effectiveness end points. The sample size affords 85% power to demonstrate superiority of QFR guidance compared with angiography guidance.CONCLUSIONS: The FAVOR III China study will be the first randomized trial to examine the effectiveness and cost-effectiveness of a QFR-guided versus an angiography-guided PCI strategy in coronary artery disease patients.

  View details for DOI 10.1016/j.ahj.2020.02.015

  View details for PubMedID 32179258

• Diagnostic Performance of Angiogram-Derived Fractional Flow Reserve: A Pooled Analysis of 5 Prospective Cohort Studies. JACC. Cardiovascular interventions Witberg, G., De Bruyne, B., Fearon, W. F., Achenbach, S., Engstrom, T., Matsuo, H., Kornowski, R. 2020

  Abstract

  OBJECTIVES: The study sought to assess the diagnostic performance of FFRangio (CathWorks, Kfar Saba, Israel), an angiogram-derived fractional flow reserve (FFR) technology.BACKGROUND: Despite practice guidelines recommendations, the use of coronary physiologic assessment in daily practice remains low for patients undergoing coronary angiography. Angiogram-derived FFR technologies have the potential to promote the integration of physiologic assessment in daily practice.METHODS: The study performed an analysis of pooled patient- and lesion-level data from 5 prospective cohort studies that examined the diagnostic performance of FFRangio compared with the reference standard wire-based FFR.RESULTS: A total of 700 lesions from 588 patients were analyzed. Mean age was 65 years, 71% were men, and 40% presented with acute coronary syndromes. Mean FFR and FFRangio were 0.81 ± 0.12 and 0.81 ± 0.11, with 31.6% and 31.4% of lesions were in the 0.75 to 0.85 range, respectively. When using a binary cutoff FFR value of 0.80, FFRangio showed a sensitivity of 91%, a specificity of 94%, and a diagnostic accuracy of 93%. The mean difference between FFR and FFRangio was 0.00 ± 0.12. The correlation coefficient between FFR and FFRangio was 0.83 (p<0.001). The C-statistic for FFRangio was 0.95 (p<0.001). The accuracy of FFRangio was consistent across all subgroups examined.CONCLUSIONS: In the largest reported cohort examining the performance of angiogram-derived FFR technology, FFRangio showed excellent diagnostic performance, which was robust and consistent across all patient and lesion subgroups. Additional studies are needed allow FFRangio and fulfill its potential expand the implementation of functionalassessment of coronary lesions in routine clinical practice.

  View details for DOI 10.1016/j.jcin.2019.10.045

  View details for PubMedID 32007461

• Long-term clinical outcomes with use of an angiotensin-converting enzyme inhibitor early after heart transplantation. American heart journal Arashi, H., Sato, T., Kobashigawa, J., Luikart, H., Kobayashi, Y., Okada, K., Sinha, S., Honda, Y., Yeung, A. C., Khush, K., Fearon, W. F. 2020; 222: 30–37

  Abstract

  BACKGROUND: The safety and efficacy of angiotensin converting enzyme inhibition (ACEI) after heart transplantation (HT) is unknown. This study examined long-term clinical outcomes after ACEI in HT recipients.METHODS: The ACEI after HT study was a prospective, randomized trial that tested the efficacy of ACEI with ramipril after HT. In this study, long-term clinical outcomes were assessed in 91 patients randomized to either ramipril or placebo (median, 5.8 years). The primary endpoint was a composite of death, retransplantation, hospitalization for rejection or heart failure, and coronary revascularization.RESULTS: The primary endpoint occurred in 10 of 45 patients (22.2%) in the ramipril group and in 14 of 46 patients (30.4%) in the placebo group (Hazard ratio (HR), 0.68; 95% CI, 0.29-1.51; P = .34). When the analysis was restricted to comparing patients who remained on a renin-angiotensin system inhibitor beyond 1 year with those who did not, there was a trend to improved outcomes (HR, 0.54; 95% CI, 0.22-1.28, P = .16). There was no significant difference in creatinine, blood urea nitrogen, and potassium at 3 years after randomization. The cumulative incidence of the primary endpoint was significantly higher in patients in whom the index of microcirculatory resistance increased from baseline to 1 year compared with those in whom it did not (39.1 vs 17.4%, HR: 3.36; 95% CI, 1.07-12.7; P = .037).CONCLUSION: The use of ramipril after HT safely lowers blood pressure and is associated with favorable long-term clinical outcomes. Clinical Trial Registration-URL: https://www.clinicaltrials.gov. Unique identifier: NCT01078363.

  View details for DOI 10.1016/j.ahj.2020.01.003

  View details for PubMedID 32007823

• Individual Lesion-Level Meta-Analysis Comparing Various Doses of Intracoronary Bolus Injection of Adenosine With Intravenous Administration of Adenosine for Fractional Flow Reserve Assessment. Circulation. Cardiovascular interventions Wijntjens, G. W., van Uffelen, E. L., Echavarría-Pinto, M. n., Casadonte, L. n., Stegehuis, V. E., Murai, T. n., Marques, K. M., Yoon, M. H., Tahk, S. J., Casella, G. n., Leone, A. M., López Palop, R. n., Schlundt, C. n., Rivero, F. n., Petraco, R. n., Fearon, W. F., Johnson, N. P., Jeremias, A. n., Koo, B. K., Piek, J. J., van de Hoef, T. P. 2020; 13 (1): e007893

  Abstract

  Intravenous infusion of adenosine is considered standard practice for fractional flow reserve (FFR) assessment but is associated with adverse side-effects and is time-consuming. Intracoronary bolus injection of adenosine is better tolerated by patients, cheaper, and less time-consuming. However, current literature remains fragmented and modestly sized regarding the equivalence of intracoronary versus intravenous adenosine. We aim to investigate the relationship between intracoronary adenosine and intravenous adenosine to determine FFR.We performed a lesion-level meta-analysis to compare intracoronary adenosine with intravenous adenosine (140 µg/kg per minute) for FFR assessment. The search was conducted in accordance to the Preferred Reporting for Systematic Reviews and Meta-Analysis statement. Lesion-level data were obtained by contacting the respective authors or by digitization of scatterplots using custom-made software. Intracoronary adenosine dose was defined as; low: <40 µg, intermediate: 40 to 99 µg, and high: ≥100 µg.We collected 1972 FFR measurements (1413 lesions) comparing intracoronary with intravenous adenosine from 16 studies. There was a strong correlation (correlation coefficient =0.915; P<0.001) between intracoronary-FFR and intravenous-FFR. Mean FFR was 0.81±0.11 for intracoronary adenosine and 0.81±0.11 for intravenous adenosine (P<0.001). We documented a nonclinically relevant mean difference of 0.006 (limits of agreement: -0.066 to 0.078) between the methods. When stratified by the intracoronary adenosine dose, mean differences between intracoronary and intravenous-FFR amounted to 0.004, 0.011, or 0.000 FFR units for low-dose, intermediate-dose, and high-dose intracoronary adenosine, respectively.The present study documents clinically irrelevant differences in FFR values obtained with intracoronary versus intravenous adenosine. Intracoronary adenosine hence confers a practical and patient-friendly alternative for intravenous adenosine for FFR assessment.

  View details for DOI 10.1161/CIRCINTERVENTIONS.119.007893

  View details for PubMedID 31870178

• Cardiac Procedural Deferral during the Coronavirus (COVID-19) Pandemic. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions Yong, C. M., Ang, L. n., Welt, F. G., Gummidipundi, S. n., Henry, T. D., Pinto, D. S., Cox, D. n., Wang, P. n., Asch, S. n., Mahmud, E. n., Fearon, W. F. 2020

  Abstract

  We aimed to examine factors impacting variability in cardiac procedural deferral during the COVID-19 pandemic and assess cardiologists' perspectives regarding its implications.Unprecedented cardiac procedural deferral was implemented nationwide during the COVID-19 pandemic.A web-based survey was administered by SCAI and the ACC Interventional Council to cardiac catheterization laboratory (CCL) directors and interventional cardiologists across the United States during the COVID-19 pandemic.Among 414 total responses, 48 states and 360 unique cardiac catheterization laboratories were represented, with mean inpatient COVID-19 burden 16.4+21.9%. There was a spectrum of deferral by procedure type, varying by both severity of COVID-19 burden and procedural urgency (p<0.001). Percutaneous coronary intervention volumes dropped by 55% (p<0.0001) and transcatheter aortic valve replacement volumes dropped by 64%, (p=0.004), with cardiologists reporting an increase in late presenting ST-Elevation Myocardial Infarctions and deaths among patients waiting for transcatheter aortic valve replacement. Almost 1/3 of catheterization laboratories had at least one interventionalist testing positive for COVID-19. Salary reductions did not influence procedural deferral or speed of reinstituting normal volumes. Pandemic preparedness improved significantly over time, with the most pressing current problems focused on inadequate testing and staff health risks.During the COVID-19 pandemic, cardiac procedural deferrals were associated with procedural urgency and severity of hospital COVID-19 burden. Yet patients did not appear to be similarly influenced, with cardiologists reporting increases in late presenting ST-Elevation Myocardial Infarctions independent of local COVID-19 burden. The safety and importance of seeking healthcare during this pandemic deserves emphasis. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/ccd.29262

  View details for PubMedID 32882075

• A link between resting flow, coronary flow reserve and adverse outcomes. International journal of cardiology Fearon, W. F. 2020

  View details for DOI 10.1016/j.ijcard.2020.03.018

  View details for PubMedID 32192749

• Coronary Computed Tomography Angiography in Diagnosing Obstructive Coronary Artery Disease in Patients with Advanced Chronic Kidney Disease: A Systematic Review and Meta-Analysis. Cardiorenal medicine Cheng, X. S., Mohanty, S. n., Turner, V. n., Mastrodicasa, D. n., Winther, S. n., Fleischmann, D. n., Tan, J. C., Fearon, W. F. 2020: 1–8

  Abstract

  Coronary computed tomography angiography (CCTA) is emerging as an important noninvasive testing modality for coronary angiography. The performance characteristic of CCTA in patients with advanced kidney disease is unknown.We performed a systematic review and meta-analysis of studies specifically investigating the sensitivity and specificity of CCTA compared to coronary angiogram as a reference standard in patients with advanced kidney disease, defined as dialysis dependence or nearing kidney transplantation. Two independent investigators assessed studies for inclusion/exclusion, quality, and characteristics, while a third investigator adjudicated.We identified 4 studies including a total of 217 patients, of whom 159 were dialysis dependent. Three of the 4 studies had a high risk of bias in patient selection and study flow, while 1 study rated low in all areas of bias. The studies were heterogeneous in their patient selection and CCTA protocol but consistent in their definition of obstructive coronary artery disease. The pooled sensitivity and specificity for CCTA were 0.96 (0.87-0.99) and 0.66 (0.57-0.74), respectively. When we restricted the analysis to dialysis-dependent patients, the pooled sensitivity and specificity for CCTA were 0.99 (0.74-1.00) and 0.67 (0.49-0.82), respectively.Based on limited data, CCTA appears to have comparable sensitivity but lower specificity relative to the non-kidney disease population.

  View details for DOI 10.1159/000510402

  View details for PubMedID 33321489

• Health-Status Outcomes with Invasive or Conservative Care in Coronary Disease. The New England journal of medicine Spertus, J. A., Jones, P. G., Maron, D. J., O'Brien, S. M., Reynolds, H. R., Rosenberg, Y. n., Stone, G. W., Harrell, F. E., Boden, W. E., Weintraub, W. S., Baloch, K. n., Mavromatis, K. n., Diaz, A. n., Gosselin, G. n., Newman, J. D., Mavromichalis, S. n., Alexander, K. P., Cohen, D. J., Bangalore, S. n., Hochman, J. S., Mark, D. B. 2020

  Abstract

  In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients.We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency.At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina).In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

  View details for DOI 10.1056/NEJMoa1916370

  View details for PubMedID 32227753

• Initial Invasive or Conservative Strategy for Stable Coronary Disease. The New England journal of medicine Maron, D. J., Hochman, J. S., Reynolds, H. R., Bangalore, S. n., O'Brien, S. M., Boden, W. E., Chaitman, B. R., Senior, R. n., López-Sendón, J. n., Alexander, K. P., Lopes, R. D., Shaw, L. J., Berger, J. S., Newman, J. D., Sidhu, M. S., Goodman, S. G., Ruzyllo, W. n., Gosselin, G. n., Maggioni, A. P., White, H. D., Bhargava, B. n., Min, J. K., Mancini, G. B., Berman, D. S., Picard, M. H., Kwong, R. Y., Ali, Z. A., Mark, D. B., Spertus, J. A., Krishnan, M. N., Elghamaz, A. n., Moorthy, N. n., Hueb, W. A., Demkow, M. n., Mavromatis, K. n., Bockeria, O. n., Peteiro, J. n., Miller, T. D., Szwed, H. n., Doerr, R. n., Keltai, M. n., Selvanayagam, J. B., Steg, P. G., Held, C. n., Kohsaka, S. n., Mavromichalis, S. n., Kirby, R. n., Jeffries, N. O., Harrell, F. E., Rockhold, F. W., Broderick, S. n., Ferguson, T. B., Williams, D. O., Harrington, R. A., Stone, G. W., Rosenberg, Y. n. 2020

  Abstract

  Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain.We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction.Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32).Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

  View details for DOI 10.1056/NEJMoa1915922

  View details for PubMedID 32227755

• Diagnostic Performance of Angiography-based Fractional Flow Reserve in Various Subgroups: Report from the FAST-FFR Study. EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology Kobayashi, Y. n., Collet, C. n., Achenbach, S. n., Engstrøm, T. n., Assali, A. n., Shlofmitz, R. A., Fournier, S. n., Kirtane, A. J., Ali, Z. A., Kornowski, R. n., Leon, M. B., De Bruyne, B. n., Fearon, W. F., Jeremias, A. n., Greenberg, G. n., Jubeh, R. n., Kolansky, D. M., McAndrew, T. n., Dressler, O. n., Maehara, A. n., Matsumura, M. n. 2020

  Abstract

  A large, prospective, multicenter trial recently showed that fractional flow reserve (FFR) derived from coronary angiography (FFRangio) has an accuracy of 92% compared with conventional guide-wire based FFR (FFRwire); however, little is known whether specific patient/lesion characteristics affect the diagnostic performance.FFRangio was measured in a blinded fashion in 301 patients (319 vessels) who were undergoing FFRwire assessment. Using an FFRwire ≤0.80 as a reference, the diagnostic performance of FFRangio was compared in pre-specified subgroups. The mean FFRwire and FFRangio were 0.81 ± 0.13 and 0.80 ± 0.12. Overall, FFRangio had a sensitivity of 93.5% and specificity of 91.2% for predicting FFRwire. Patient characteristics including age, sex, clinical presentation, body mass index, and diabetes did not affect sensitivity or specificity (p>0.05 for all). Similarly, lesion characteristics including calcification, tortuosity did not affect sensitivity or specificity (p>0.05 for all), nor did lesion location (proximal, middle, versus distal). Sensitivity was equally high across all target vessels, while specificity was highest in the LAD and lower (~85%) in the RCA and LCx (p<0.05).FFRangio derived from coronary angiography has a high diagnostic performance regardless of patient and most lesion characteristics. The interaction of vessel on the specificity will need to be confirmed in larger cohorts.

  View details for DOI 10.4244/EIJ-D-19-00933

  View details for PubMedID 32364503

• Risk factors for early development of cardiac allograft vasculopathy by intravascular ultrasound. Clinical transplantation Moayedi, Y. n., Fan, C. P., Tremblay-Gravel, M. n., Miller, R. J., Kawana, M. n., Henricksen, E. n., Parizo, J. n., Wainwright, R. n., Fearon, W. F., Ross, H. J., Khush, K. K., Teuteberg, J. J. 2020: e14098

  Abstract

  Cardiac allograft vasculopathy (CAV) is the leading cause of late graft loss. While there are numerous post-transplant factors which may increase the risk of the development of CAV, there is a paucity of data on the impact of donor derived atherosclerosis (DA), early discontinuation of prednisone and early initiation of proliferation signal inhibitors (PSI) as assessed by intravascular ultrasound (IVUS).Retrospective single center study of all adult transplant patients (2008-2017) with serial IVUS at baseline and annually for 5 years. DA was defined as a baseline maximal intimal thickness (MIT) ≥ 0.5 mm, CAV development was defined as MIT ≥ 1 mm or an increase in MIT ≥ 0.5 mm at year 1 compared to baseline or an increase in 0.3 mm annually thereafter. Clinical risk factors for CAV were identified using multivariable hazard regression. Separate multistate models were applied to assess the association of prednisone discontinuation and PSI initiation and CAV.Of 282 patients screened, 186 patients had a 1-year angiogram. The mean age of those included in the cohort was 51±11 years, 70% were male, 58% were Caucasian and 27% were supported by a left ventricular assist device. Donor atherosclerosis was present in 40%. The cumulative incidence of CAV at 5 years is 41% in DA- vs. 59% in DA+(p=0.012). Donor age was a strong predictor of DA (p=0.016). Significant risk factors for CAV included male sex (HR= 4.141, p=0.001), non-Caucasian race (HR= 1.98, p= 0.011), BMI < 18 kg/m2 (HR=4.596, p=0.042), longer ischemic time (HR=1.374, p=0.028), older donor age (HR=1.158, p=0.009) and rejection with hemodynamic compromise within the first year (HR=2.858, p=0.043). Prednisone discontinuation within 1-year was associated with a lower risk of CAV (HR 0.58 p=0.047). Initiation of proliferation signal inhibitors (PSI) within 2 years resulted in fewer cases of CAV (HR 0.397 p<0.001).In patients with an angiogram at 1 year, those with DA were significantly more likely to develop CAV. Lower incidence of CAV by IVUS was seen in patients who discontinued prednisone in the first year or had initiation of a PSI within two years of transplantation. Knowledge of early IVUS may allow a more tailored approach to patient management.

  View details for DOI 10.1111/ctr.14098

  View details for PubMedID 32970884

• The Shifting Sands of Coronary Microvascular Dysfunction. Circulation Fearon, W. F., De Bruyne, B. 2019

  View details for DOI 10.1161/CIRCULATIONAHA.119.043952

  View details for PubMedID 31707789

• Association Between Current and Future Annual Hospital Percutaneous Coronary Intervention Mortality Rates JAMA CARDIOLOGY Sandhu, A. T., Kohsaka, S., Bhattacharya, J., Fearon, W. F., Harrington, R. A., Heidenreich, P. A. 2019; 4 (11): 1077–83

  View details for DOI 10.1001/jamacardio.2019.3221

  View details for Web of Science ID 000501300400005

• Nonhyperemic Coronary Pressure Ratiosto Assess Percutaneous CoronaryIntervention. JACC. Cardiovascular interventions Fearon, W. F. 2019; 12 (20): 2015–17

  View details for DOI 10.1016/j.jcin.2019.08.017

  View details for PubMedID 31648763

• Utility of High-Sensitivity and Conventional Troponin in Patients Undergoing Transcatheter Aortic Valve Replacement: Incremental Prognostic Value to B-type Natriuretic Peptide. Scientific reports Kobayashi, Y., Kim, J. B., Moneghetti, K. J., Fischbein, M., Lee, A., Watkins, C. A., Yeung, A. C., Liang, D., Ozen, M. O., Demirci, U., Bowen, R., Fearon, W. F., Haddad, F. 2019; 9 (1): 14936

  Abstract

  High-sensitivity Troponin (hs-Tn) has emerged as a useful marker for patients with myocardial injury or heart failure. However, few studies have compared intermediate and hs-Tn in patients undergoing transcatheter aortic valve replacement (TAVR). Moreover, there remains uncertainty of which thresholds are the most useful for discriminating ventricular dysfunction or outcome. In this study we prospectively enrolled 105 patients with severe aortic stenosis (AS) who underwent TAVR as well as blood sampling for high-sensitivity (hs-TnI) and conventional troponin I (EXL-LOCI and RXL) assessment. Patients underwent comprehensive pre-procedure echocardiography. Ventricular dysfunction was defined using left ventricular mass index (LVMI), LV global longitudinal strain (LVGLS) and LV end-diastolic pressure. The mean age was 84.0±8.7 years old and 60% were male sex with mean transaortic pressure gradient of 50.1±16.0mmHg and AVA of 0.63±0.19cm2. When using a threshold of 6ng/L, 77% had positive hs-TnI while 27% had positive hs-TnI using recommended thresholds (16ng/L for female and 34ng/L for male). Troponin levels were higher in the presence of abnormal LV phenotypes. The strongest correlate of troponin was LVMI. During median follow-up of 375 days, 21 patients (20%) died. Lower threshold of hs-TnI and EXL-TnI was more discriminatory for overall mortality (Log-rank P=0.03 for both), while higher threshold of hs-TnI (p=0.75) and RXL-TnI were not (p=0.30). Combining hs-TnI and BNP improved to predict long-term outcome (p=0.004). In conclusion, hs-TnI levels correlated with the degree of LV dysfunction phenotypes. Furthermore, applying a lower threshold for hs-TnI performed better for outcome prediction than a recommended threshold in patients undergoing TAVR. Combining hs-TnI with BNP helped better risk stratification.

  View details for DOI 10.1038/s41598-019-51371-x

  View details for PubMedID 31624275

• Diagnostic Performance of Angiogram-Derived Fractional Flow Reserve: A Pooled Analysis of 5 Prospective Cohort Studies Witberg, G., Fearon, W., Achenbach, S., Engstroem, T., Matsuo, H., Kornowski, R. ELSEVIER SCIENCE INC. 2019: B322

  View details for Web of Science ID 000487306300323

• Impact of Myocardial Bridging on Long-Term Outcomes After Heart Transplantation: Risk Stratification With IVUS-Determined Anatomical Properties Okada, K., Nishi, T., Tanaka, S., Luikart, H., Yock, P. G., Yeung, A. C., Hibi, K., Kimura, K., Schnittger, I., Khush, K., Fearon, W., Honda, Y. ELSEVIER SCIENCE INC. 2019: B342

  View details for Web of Science ID 000487306300343

• Aortic Lumen Area Modifies the Association Between Aortic Calcification and Mortality After Transcatheter Aortic Valve Replacement Rangavajla, G., Fearon, W., Elmariah, S., Kim, J., Gillam, L., Carr, J., Quader, N., Whisenant, B., Kapadia, S., Kumbhani, D., Bavry, A., Welt, F., Coylewright, M., Huang, S., Vatterott, A., Jackson, N., Lindman, B. ELSEVIER SCIENCE INC. 2019: B701

  View details for Web of Science ID 000487306300702

• Early invasive assessment of the coronary microcirculation predicts subsequent acute rejection after heart transplantation INTERNATIONAL JOURNAL OF CARDIOLOGY Okada, K., Honda, Y., Luikart, H., Yock, P. G., Fitzgerald, P. J., Yeung, A. C., Valantine, H. A., Khush, K. K., Fearon, W. F. 2019; 290: 27–32

  View details for DOI 10.1016/j.ijcard.2019.04.018

  View details for Web of Science ID 000470826500005

• Predictive factors of discordance between the instantaneous wave-free ratio and fractional flow reserve CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Derimay, F., Johnson, N. P., Zimmermann, F. M., Adjedj, J., Witt, N., Hennigan, B., Koo, B., Barbato, E., Esposito, G., Trimarco, B., Rioufol, G., Park, S., Baptista, S., Chrysant, G. S., Leone, A., Jeremias, A., Berry, C., De Bruyne, B., Oldroyd, K. G., Pijls, N. J., Fearon, W. F. 2019; 94 (3): 356–63

  View details for DOI 10.1002/ccd.28116

  View details for Web of Science ID 000484522100011

• Response by Fearon et al to Letter Regarding Article, "Accuracy of Fractional Flow Reserve Derived From Coronary Angiography". Circulation Fearon, W. F., Kornowski, R., De Bruyne, B. 2019; 140 (2): e96–e97

  View details for DOI 10.1161/CIRCULATIONAHA.119.040942

  View details for PubMedID 31283372

• Assessing Nonculprit Coronary Disease in ST-Segment Elevation Myocardial Infarction With Physiological Testing. JAMA cardiology Fearon, W. F. 2019

  View details for DOI 10.1001/jamacardio.2019.2217

  View details for PubMedID 31268484

• FFR-guided PCI in STEMI. EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology Nishi, T., Fearon, W. F. 2019; 15 (2): 134–36

  View details for DOI 10.4244/EIJV15I2A26

  View details for PubMedID 31217152

• The prognostic importance of silent ischemia. International journal of cardiology Fearon, W. F. 2019

  View details for DOI 10.1016/j.ijcard.2019.05.050

  View details for PubMedID 31155329

• Conversation in cardiology: Is there a need for clinical trials for the nonhyperemic pressure ratios? Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions Kern, M. J., Berry, C., deBruyne, B., Fearon, W., Jeremias, A., Johnson, N., Kandzari, D., Kirtane, A., Moses, J., Krucoff, M., Stone, G. 2019

  View details for DOI 10.1002/ccd.28336

  View details for PubMedID 31111644

• Optimal balloon positioning for the proximal optimization technique? An experimental bench study. International journal of cardiology Derimay, F., Rioufol, G., Nishi, T., Kobayashi, Y., Fearon, W. F., Veziers, J., Guerin, P., Finet, G. 2019

  Abstract

  AIMS: The proximal optimization technique (POT) in coronary bifurcation stenting improves apposition and side-branch obstruction. The POT balloon should be positioned with the distal radio-opaque marker at the carina cut plane. However, the real impact of positioning remains unknown.METHODS AND RESULTS: Synergy stents (Boston Scientific, USA) were implanted on left-main fractal bench models. Initial POT was performed in 3 positions according to distal shoulder position (loss of balloon parallelism) relative to the carina cut plane (n = 5/group): i) "proximal", 1 mm before carina; ii) "medium", just at carina; iii) "distal", 1 mm after carina. Results were quantified on 2D- and 3D-OCT. Compared to implantation, initial POT improved malapposition in all positions ("proximal": 61.5 ± 1.4% vs. 5.1 ± 2.7%; "medium": 60.2 ± 2.4% vs. 1.3 ± 0.6%; "distal": 60.5 ± 2.9% vs. 1.1 ± 1.8%, p < 0.05). However, residual malapposition was greater in "proximal" position (p < 0.05). "Proximal", unlike "medium" or "distal" POT, also failed to improve side-branch obstruction. Conversely, "distal" POT significantly overstretched the main-branch ostium, with stent/artery ratio 1.22 ± 0.04 vs. 1.11 ± 0.07 for "medium" POT (p < 0.05).CONCLUSION: Shoulder positioning is essential to optimize the mechanical benefit of POT without main-branch overstretch (too distal position). Experimentally, the best position is just at the carina cut plane ("medium").

  View details for DOI 10.1016/j.ijcard.2019.05.041

  View details for PubMedID 31130279

• Index of Microcirculatory Resistance and Infarct Size JACC-CARDIOVASCULAR IMAGING Fearon, W. F., Dash, R. 2019; 12 (5): 849–51

  View details for DOI 10.1016/j.jcmg.2018.04.004

  View details for Web of Science ID 000467057900012

• 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

• Diastolic pressure ratio: new approach and validation vs. the instantaneous wave-free ratio. European heart journal Johnson, N. P., Li, W., Chen, X., Hennigan, B., Watkins, S., Berry, C., Fearon, W. F., Oldroyd, K. G. 2019

  Abstract

  AIMS: The instantaneous wave-free ratio (iFR) and whole-cycle Pd/Pa investigate coronary physiology during non-hyperaemic conditions. To test for unique physiologic properties of the wave-free period when making resting coronary pressure measurements, we compared post hoc a diastolic pressure ratio (dPR) and Pd/Pa against iFR for numerical similarity and test/retest repeatability.METHODS AND RESULTS: Eight hundred and ninety-three lesions from 833 subjects were included from the VERIFY 2 and CONTRAST studies. Diastolic pressure ratio and a linear transform of Pd/Pa were compared against iFR for diagnostic performance. Mean difference between dPR and iFR [Delta = -0.006 ± 0.011, r2 = 0.993, area under receiver operating characteristic (ROC) curve (AUC) = 0.997] mirrored the difference of two iFR measurements repeated immediately (Delta = <0.001 ± 0.004, r2 = 0.998, AUC = 1.00). Minor variations in the definition of dPR changed its value by <1-2% over a broad range of the cardiac cycle. A linear transform of Pd/Pa showed very good diagnostic performance (Delta = -0.012 ± 0.031, r2 = 0.927, AUC = 0.979). Post hoc iFR values were validated against real-time iFR values and matched almost exactly (average Delta = <0.001 ± 0.004, 99.6% within ±0.01).CONCLUSIONS: Our dPR offers numerical equivalency to iFR. Despite different technical approaches for identifying the relevant period of diastole, the agreement between dPR and iFR and the insensitivity of dPR to minor variations in its definition further confirm numerical equivalency among resting metrics.

  View details for DOI 10.1093/eurheartj/ehz230

  View details for PubMedID 31329863

• Early invasive assessment of the coronary microcirculation predicts subsequent acute rejection after heart transplantation. International journal of cardiology Okada, K., Honda, Y., Luikart, H., Yock, P. G., Fitzgerald, P. J., Yeung, A. C., Valantine, H. A., Khush, K. K., Fearon, W. F. 2019

  Abstract

  BACKGROUND: Acute allograft rejection (AAR) plays an important role in patient and graft survival; therefore, more emphasis should be placed on its prediction. This study aimed to investigate baseline clinical and diagnostic variables associated with subsequent AAR during the first year post-transplant, especially focusing on early physiologic and anatomic measures.METHODS: This study enrolled 88 heart transplant patients who underwent fractional flow reserve (FFR), coronary flow reserve (CFR), the index of microcirculatory resistance (IMR) and intravascular ultrasound (IVUS) in the left anterior descending artery at baseline (within 8 weeks post-transplant). Cardiac index (CI), pulmonary capillary wedge pressure (PCWP), mean pulmonary artery pressure (mPAP), right atrial pressure and left ventricular ejection fraction were also evaluated. AAR was defined as acute cellular rejection of grade ≥2R and/or pathological antibody-mediated rejection of grade ≥pAMR2.RESULTS: During the first year post-transplant, 25.0% of patients experienced AAR. Patients with AAR during the first year showed higher rates of recipient obesity, lower rates of recipient-donor sex mismatch and rATG and tacrolimus uses, higher PCWP, mPAP and IMR, and lower CFR at baseline, compared with those without. In the multivariate analysis, only baseline IMR ≥ 16.0 was independently associated with AAR during the first year, demonstrating high negative predictive value (96.7%).CONCLUSIONS: Invasively assessing microvascular resistance (baseline IMR ≥ 16.0) in the early post-transplant period was an independent determinant of subsequent acute allograft rejection during the first year post-transplant, suggesting that early assessment of IMR may enhance patient risk stratification and target medical therapies to improve patient outcome.

  View details for PubMedID 30987835

• Association of Improvement in Fractional Flow Reserve With Outcomes, Including Symptomatic Relief, After Percutaneous Coronary Intervention JAMA CARDIOLOGY Fournier, S., Ciccarelli, G., Toth, G. G., Milkas, A., Xaplanteris, P., Tonino, P. L., Fearon, W. F., Pijls, N. J., Barbato, E., De Bruyne, B. 2019; 4 (4): 370–74

  View details for DOI 10.1001/jamacardio.2019.0175

  View details for Web of Science ID 000465123600012

• Combination of Mean Platelet Volume and Neutrophil to Lymphocyte Ratio Predicts Long-Term Major Adverse Cardiovascular Events After Percutaneous Coronary Intervention ANGIOLOGY Choi, D., Kobayashi, Y., Nishi, T., Kim, H., Ki, Y., Kim, S., Park, K., Song, H., Fearon, W. F. 2019; 70 (4): 345–51

  View details for DOI 10.1177/0003319718768658

  View details for Web of Science ID 000461553100009

• Combination of Mean Platelet Volume and Neutrophil to Lymphocyte Ratio Predicts Long-Term Major Adverse Cardiovascular Events After Percutaneous Coronary Intervention. Angiology Choi, D., Kobayashi, Y., Nishi, T., Kim, H. K., Ki, Y., Kim, S. S., Park, K., Song, H., Fearon, W. F. 2019; 70 (4): 345–51

  Abstract

  We hypothesized that the combination of a high neutrophil to lymphocyte ratio (NLR) and mean platelet volume (MPV) would be a stronger predictor of future cardiovascular events after percutaneous coronary intervention (PCI). Both NLR and MPV were measured in 364 consecutive patients undergoing PCI. The primary end point was the incidence of major adverse cardiovascular events (MACEs), including cardiac death, nonfatal myocardial infarction, and stent thrombosis. The median values of NLR and MPV were 2.8 and 8.2 fL, respectively. There were 26 MACEs during a median follow-up duration of 29.3 months. Kaplan-Meier analysis revealed that the higher NLR group had a significantly higher MACE rate than the lower NLR group and that the higher MPV group had a significantly higher MACE rate than the lower MPV group (log-rank: P = .0064 and P = .0004, respectively). The cumulative MACE-free survival can be further stratified by the combination of NLR and MPV. This value was especially useful in patients with acute coronary syndrome (ACS). By multivariate Cox proportional hazards model, the combination of high NLR and high MPV was independently associated with MACE ( P = .026). The combination of a high NLR and high MPV is an independent predictor of MACE after PCI, especially in patients with ACS.

  View details for PubMedID 29631419

• PERIARTERIAL NEOVASCULARIZATION AND ATTENUATED-SIGNAL PLAQUE PREDICT LONG-TERM MORTALITY AFTER HEART TRANSPLANTATION: RISK STRATIFICATION WITH IVUS-DETERMINED CORONARY INFLAMMATORY FINDINGS Kashiyama, K., Okada, K., Kitahara, H., Kameda, R., Hollak, M., Luikart, H., Yock, P., Yeung, A., Fitzgerald, P., Khush, K., Fearon, W., Honda, Y. ELSEVIER SCIENCE INC. 2019: 1428

  View details for Web of Science ID 000460565901440

• DIAGNOSTIC PERFORMANCE OF ANGIOGRAPHY-BASED FRACTIONAL FLOW RESERVE IN SUBGROUPS: REPORT FROM THE FAST-FFR STUDY Kobayashi, Y., Collet, C., Achenbach, S., Engstrom, T., Assali, A., Shlofmitz, R., Jeremias, A., Fournier, S., Kirtane, A., Kornowski, R., Greenberg, G., Jubeh, R., Kolansky, D., McAndrew, T., Dressler, O., Maehara, A., Matsumura, M., Leon, M., De Bruyne, B., Fearon, W. ELSEVIER SCIENCE INC. 2019: 1167

  View details for Web of Science ID 000460565901180

• Association of Improvement in Fractional Flow Reserve With Outcomes, Including Symptomatic Relief, After Percutaneous Coronary Intervention. JAMA cardiology Fournier, S., Ciccarelli, G., Toth, G. G., Milkas, A., Xaplanteris, P., Tonino, P. A., Fearon, W. F., Pijls, N. H., Barbato, E., De Bruyne, B. 2019

  Abstract

  Importance: Whether the improvement in myocardial perfusion provided by percutaneous coronary intervention (PCI) is associated with symptomatic relief or improved outcomes has not been well investigated.Objective: To investigate the prognostic value of the improvement in fractional flow reserve (FFR) after PCI (DeltaFFR) on patients' symptoms and 2-year outcomes.Design, Setting, and Participants: This study is a post hoc analysis of data from patients undergoing FFR-guided PCI in the randomized clinical trials Fractional Flow Reserve vs Angiography for Multivessel Evaluation (FAME) 1 (NCT00267774; 2009) and FAME 2 (NCT01132495; 2012), with inclusion of 2 years of follow-up data. The FAME 1 trial included patients with multivessel coronary artery disease from 20 medical centers in Europe and the United States. The FAME 2 trial included patients with stable coronary artery disease involving up to 3 vessels from 28 sites in Europe and North America. Lesions from the group in the FAME 1 trial from whom FFR was measured and the group in the FAME 2 trial who received FFR-guided PCI plus medical therapy were analyzed. Data analysis occurred from May 2017 to May 2018.Interventions: Measure of post-PCI FFR.Main Outcomes and Measures: Vessel-oriented clinical events at 2 years, a composite of cardiac death, target vessel-associated myocardial infarction, and target vessel revascularization.Results: This analysis included 639 patients from whom pre-PCI and post-PCI FFR values were available. Of their 837 lesions, 277 were classified into the lowest tertile (DeltaFFR≤0.18), 282 into the middle tertile (0.19≤DeltaFFR≤0.31), and 278 into the highest tertile (DeltaFFR>0.31). Vessel-oriented clinical events were significantly more frequent in the lowest tertile (n=25 of 277 [9.1%]) compared with the highest tertile (n=13 of 278 [4.7%]; hazard ratio, 2.01 [95% CI, 1.03-3.92]; P=.04). In addition, a significant association was observed between DeltaFFR and symptomatic relief (odds ratio, 1.33 [95% CI, 1.02-1.74]; P=.02).Conclusions and Relevance: In this analysis of 2 randomized clinical trials, the larger the improvement in FFR, the larger the symptomatic relief and the lower the event rate. This suggests that measuring FFR before and after PCI provides clinically useful information.

  View details for PubMedID 30840026

• Simultaneous Anatomic and Physiologic Assessment of Coronary Artery Disease With Coronary Angiography Alone: Seeing the Future. JACC. Cardiovascular interventions Kobayashi, Y., Fearon, W. F. 2019; 12 (3): 271–73

  View details for PubMedID 30732731

• Simultaneous Anatomic and Physiologic Assessment of Coronary Artery Disease With Coronary Angiography Alone Seeing the Future JACC-CARDIOVASCULAR INTERVENTIONS Kobayashi, Y., Fearon, W. F. 2019; 12 (3): 271–73

  View details for DOI 10.1016/j.jcin.2018.10.032

  View details for Web of Science ID 000457565300011

• Qualitative resting coronary pressure wave form analysis to predict fractional flow reserve EUROINTERVENTION Matsumura, M., Maehara, A., Johnson, N. P., Fearon, W. F., De Bruyne, B., Oldroyd, K. G., Pijls, N. J., Jenkins, P., Ali, Z. A., Mintz, G. S., Stone, G. W., Jeremias, A. 2019; 14 (15): E1601–E1608

  Abstract

  The aim of this study was to evaluate the predictability of resting distal coronary pressure wave forms for fractional flow reserve (FFR).Resting coronary wave forms were qualitatively evaluated for the presence of (i) dicrotic notch, (ii) diastolic dipping, and (iii) ventricularisation. In a development cohort (n=88), a scoring system was developed that was then applied to a validation cohort (n=428) using a multivariable linear regression model to predict FFR and receiver operating characteristics (ROC) to predict FFR ≤0.8. In the development cohort, all three qualitative parameters were independent predictors of FFR. However, in a multivariable linear regression model in the validation cohort, qualitative wave form analysis did not further improve the ability of resting distal coronary to aortic pressure ratio (Pd/Pa) (p=0.80) or instantaneous wave-free ratio (iFR) (p=0.26) to predict FFR. Using ROC, the area under the curve of resting Pd/Pa (0.86 versus 0.86, p=0.08) and iFR (0.86 versus 0.86, p=0.26) did not improve by adding qualitative analysis.Qualitative coronary wave form analysis showed moderate classification agreement in predicting FFR but did not add substantially to the resting pressure gradients Pd/Pa and iFR; however, when discrepancies between quantitative and qualitative analyses are observed, artefact or pressure drift should be considered.

  View details for DOI 10.4244/EIJ-D-17-01149

  View details for Web of Science ID 000458030000014

  View details for PubMedID 29581085

• Association of Endothelin-1 With Accelerated Cardiac Allograft Vasculopathy and Late Mortality Following Heart Transplantation JOURNAL OF CARDIAC FAILURE Parikh, R. V., Khush, K., Pargaonkar, V. S., Luikart, H., Grimm, D., Yu, M., Okada, K., Honda, Y., Yeung, A. C., Valantine, H., Fearon, W. F. 2019; 25 (2): 97–104

  View details for DOI 10.1016/j.cardfail.2018.12.001

  View details for Web of Science ID 000460190800004

• Predictive factors of discordance between the instantaneous wave-free ratio and fractional flow reserve. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions Derimay, F., Johnson, N. P., Zimmermann, F. M., Adjedj, J., Witt, N., Hennigan, B., Koo, B., Barbato, E., Esposito, G., Trimarco, B., Rioufol, G., Park, S., Baptista, S. B., Chrysant, G. S., Leone, A. M., Jeremias, A., Berry, C., De Bruyne, B., Oldroyd, K. G., Pijls, N. H., Fearon, W. F. 2019

  Abstract

  OBJECTIVES: To identify clinical, angiographic and hemodynamic predictors of discordance between instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR).BACKGROUND: The iFR was found to be non-inferior to the gold-standard FFR for guiding coronary revascularization, although it is discordant with FFR in 20% of cases. A better understanding of the causes of discordance may enhance application of these indices.METHODS: Both FFR and iFR were measured in the prospective multicenter CONTRAST study. Clinical, angiographic and hemodynamic variables were compared between patients with concordant values of FFR and iFR (cutoff ≤0.80 and ≤0.89, respectively).RESULTS: Out of the 587 patients included, in 466 patients (79.4%) FFR and iFR agreed: both negative, n=244 (41.6%), or positive, n=222 (37.8%). Compared with FFR, iFR was negative discordant (FFR+/iFR-) in 69 (11.8%) patients and positive discordant (FFR-/iFR+) in 52 (8.9%) patients. On multivariate regression, stenosis location (left main or proximal left anterior descending) (OR: 3.30[1.68;6.47]), more severe stenosis (OR: 1.77[1.35;2.30]), younger age (OR: 0.93[0.90;0.97]), and slower heart rate (OR: 0.59[0.42;0.75]) were predictors of a negative discordant iFR. Absence of a beta-blocker (OR: 0.41[0.22;0.78]), older age (OR: 1.04[1.00;1.07]), and less severe stenosis (OR: 0.69[0.53;0.89]) were predictors of a positive discordant iFR.CONCLUSIONS: During iFR acquisition, stenosis location, stenosis degree, heart rate, age and use of beta blockers influence concordance with FFR and should be taken into account when interpreting iFR.

  View details for PubMedID 30702186

• Fractional flow reserve-guided percutaneous coronary intervention vs. medical therapy for patients with stable coronary lesions: meta-analysis of individual patient data EUROPEAN HEART JOURNAL Zimmermann, F. M., Omerovic, E., Fournier, S., Kelbaek, H., Johnson, N. P., Rothenbuhler, M., Xaplanteris, P., Abdel-Wahab, M., Barbato, E., Hofsten, D., Tonino, P. L., Boxma-de Klerk, B. M., Fearon, W. F., Kober, L., Smits, P. C., De Bruyne, B., Pijls, N. J., Juni, P., Engstrom, T. 2019; 40 (2): 180-+

  View details for DOI 10.1093/eurheartj/ehy812

  View details for Web of Science ID 000459337100012

• Coronary microvascular dysfunction and clinical outcomes in patients with heart failure with preserved ejection fraction. Journal of cardiac failure Allan, T. n., Dryer, K. n., Fearon, W. F., Shah, S. J., Blair, J. E. 2019

  View details for DOI 10.1016/j.cardfail.2019.08.010

  View details for PubMedID 31487534

• Effect of Baseline Left Ventricular Ejection Fraction on 2-Year Outcomes After Transcatheter Aortic Valve Replacement: Analysis of the PARTNER 2 Trials. Circulation. Heart failure Furer, A. n., Chen, S. n., Redfors, B. n., Elmariah, S. n., Pibarot, P. n., Herrmann, H. C., Hahn, R. T., Kodali, S. n., Thourani, V. H., Douglas, P. S., Alu, M. C., Fearon, W. F., Passeri, J. n., Malaisrie, S. C., Crowley, A. n., McAndrew, T. n., Genereux, P. n., Ben-Yehuda, O. n., Leon, M. B., Burkhoff, D. n. 2019; 12 (8): e005809

  Abstract

  Impaired left ventricular function is associated with worse prognosis among patients with aortic stenosis treated medically or with surgical aortic valve replacement. It is unclear whether reduced left ventricular ejection fraction (LVEF) is an independent predictor of adverse outcomes after transcatheter aortic valve replacement.Patients who underwent transcatheter aortic valve replacement in the PARTNER 2 trials (Placement of Aortic Transcatheter Valves) and registries were stratified according to presence of reduced LVEF (<50%) at baseline, and 2-year risk of cardiovascular mortality was compared using Kaplan-Meier methods and multivariable Cox proportional hazards regression. Of 2991 patients, 839 (28%) had reduced LVEF. These patients were younger, more often males, and were more likely to have comorbidities, such as coronary disease, diabetes mellitus, and renal insufficiency. Compared with patients with normal LVEF, patients with low LVEF had higher crude rates of 2-year cardiovascular mortality (19.8% versus 12.0%, P<0.0001) and all-cause mortality (27.4% versus 19.2%, P<0.0001). Mean aortic valve gradient was not associated with clinical outcomes other than heart failure hospitalizations (hazard ratio [HR], 0.99; CI, 0.99-1.00; P=0.03). After multivariable adjustment, patients with reduced versus normal LVEF had significantly higher adjusted risk of cardiovascular death (adjusted HR, 1.42, 95% CI, 1.11-1.81; P=0.005), but not all-cause death (adjusted HR, 1.20; 95% CI, 0.99-1.47; P=0.07). When LVEF was treated as continuous variable, it was associated with increased 2-year risk of both cardiovascular mortality (adjusted HR per 10% decrease in LVEF, 1.16; 95% CI, 1.07-1.27; P=0.0006) and all-cause mortality (adjusted HR, 1.09; 95% CI, 1.01-1.16; P=0.02).In this patient-level pooled analysis of PARTNER 2 patients who underwent transcatheter aortic valve replacement, baseline LVEF was an independent predictor of 2-year cardiovascular mortality.URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01314313, NCT02184442, NCT03222128, and NCT02184441.

  View details for DOI 10.1161/CIRCHEARTFAILURE.118.005809

  View details for PubMedID 31525069

• Prognostic Value of Coronary Microvascular Function Measured Immediately After Percutaneous Coronary Intervention in Stable Coronary Artery Disease: An International Multicenter Study. Circulation. Cardiovascular interventions Nishi, T. n., Murai, T. n., Ciccarelli, G. n., Shah, S. V., Kobayashi, Y. n., Derimay, F. n., Waseda, K. n., Moonen, A. n., Hoshino, M. n., Hirohata, A. n., Yong, A. S., Ng, M. K., Amano, T. n., Barbato, E. n., Kakuta, T. n., Fearon, W. F. 2019; 12 (9): e007889

  Abstract

  The prognostic impact of coronary microvascular dysfunction after percutaneous coronary intervention (PCI) remains unclear in patients with stable coronary artery disease. This study sought to investigate the prognostic value of microvascular function measured immediately after PCI in patients with stable coronary artery disease.We enrolled 572 patients with stable coronary artery disease who underwent PCI and elective measurement of the index of microcirculatory resistance (IMR) immediately after PCI from 8 centers in 4 countries. Impaired microvascular function was defined as IMR≥25 (high IMR). Major adverse cardiac events, including death, myocardial infarction (MI) and target vessel revascularization, were evaluated.During a median follow-up duration of 4.0 years, the cumulative major adverse cardiac events rate was significantly higher in the high IMR group (n=66/148) compared with the low IMR group (n=128/424; hazard ratio [HR], 1.56; 95% CI, 1.16-2.105; P=0.001), primarily due to a higher rate of periprocedural MI (HR, 1.59; 95% CI, 1.11-2.28; P=0.004) but also due to higher rates of mortality (HR, 1.59; 95% CI, 0.76-3.35; P=0.22), spontaneous MI (HR, 2.10; 95% CI, 0.67-6.63; P=0.20) and target vessel revascularization (HR, 1.40; 95% CI, 0.77-2.54; P=0.27). Cumulative risk for death, spontaneous MI, and target vessel revascularization was higher in the high IMR group (HR, 1.55; 95% CI, 0.99-2.43; P=0.056), as was death and spontaneous MI alone (HR, 1.79; 95% CI, 0.96-3.36; P=0.065). On multivariable analysis, high IMR post-PCI was an independent predictor of major adverse cardiac events.IMR measured immediately after PCI predicts adverse events in patients with stable coronary artery disease.

  View details for DOI 10.1161/CIRCINTERVENTIONS.119.007889

  View details for PubMedID 31525096

• Safety and Efficacy of PCSK9 Inhibitors After Heart Transplantation. The Canadian journal of cardiology Moayedi, Y., Kozuszko, S., Knowles, J. W., Chih, S., Oro, G., Lee, R., Fearon, W. F., Ross, H. J., Teuteberg, J. J., Khush, K. K. 2019; 35 (1)

  Abstract

  Dyslipidemia is common in patients undergoing heart transplantation and is associated with the progression of cardiac allograft vasculopathy. Two monoclonal antibodies directed against PCSK9i-evolocumab and alirocumab-are currently available. However, their use, safety and efficacy in the post-transplant setting have not been studied. We present our experience with 6 heart transplant recipients treated with a PCSK9i. A > 70% reduction in LDL-cholesterol was observed after evolocumab therapy. PCSK9 inhibitors are a potentially lipid-lowering therapeutic option for heart transplant patients with suboptimal LDL despite maximal tolerated statin doses.

  View details for PubMedID 30595172

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

  Abstract

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

  View details for DOI 10.1148/ryct.2019190067

  View details for PubMedID 33778530

  View details for PubMedCentralID PMC7977784

• Safety and Efficacy of PCSK9 Inhibitors After Heart Transplantation CANADIAN JOURNAL OF CARDIOLOGY Moayedi, Y., Kozuszko, S., Knowles, J. W., Chih, S., Oro, G., Lee, R., Fearon, W. F., Ross, H. J., Teuteberg, J. J., Khush, K. K. 2019; 35 (1)

  View details for DOI 10.1016/j.cjca.2018.11.004

  View details for Web of Science ID 000454536800017

• Pivotal Clinical Study to Evaluate the Safety and Effectiveness of the MANTA Percutaneous Vascular Closure Device. Circulation. Cardiovascular interventions Wood, D. A., Krajcer, Z. n., Sathananthan, J. n., Strickman, N. n., Metzger, C. n., Fearon, W. n., Aziz, M. n., Satler, L. F., Waksman, R. n., Eng, M. n., Kapadia, S. n., Greenbaum, A. n., Szerlip, M. n., Heimansohn, D. n., Sampson, A. n., Coady, P. n., Rodriguez, R. n., Krishnaswamy, A. n., Lee, J. T., Ben-Dor, I. n., Moainie, S. n., Kodali, S. n., Chhatriwalla, A. K., Yadav, P. n., O'Neill, B. n., Kozak, M. n., Bacharach, J. M., Feldman, T. n., Guerrero, M. n., Nanjundappa, A. n., Bersin, R. n., Zhang, M. n., Potluri, S. n., Barker, C. n., Bernardo, N. n., Lumsden, A. n., Barleben, A. n., Campbell, J. n., Cohen, D. J., Dake, M. n., Brown, D. n., Maor, N. n., Nardone, S. n., Lauck, S. n., O'Neill, W. W., Webb, J. G. 2019; 12 (7): e007258

  Abstract

  Open surgical closure and small-bore suture-based preclosure devices have limitations when used for transcatheter aortic valve replacement, percutaneous endovascular abdominal aortic aneurysm repair, or percutaneous thoracic endovascular aortic aneurysm repair. The MANTA vascular closure device is a novel collagen-based technology designed to close large bore arteriotomies created by devices with an outer diameter ranging from 12F to 25F. In this study, we determined the safety and effectiveness of the MANTA vascular closure device.A prospective, single arm, multicenter investigation in patients undergoing transcatheter aortic valve replacement, percutaneous endovascular abdominal aortic aneurysm repair, or thoracic endovascular aortic aneurysm repair at 20 sites in North America. The primary outcome was time to hemostasis. The primary safety outcomes were accessed site-related vascular injury or bleeding complications. A total of 341 patients, 78 roll-in, and 263 in the primary analysis cohort, were entered in the study between November 2016 and September 2017. For the primary analysis cohort, transcatheter aortic valve replacement was performed in 210 (79.8%), and percutaneous endovascular abdominal aortic aneurysm repair or thoracic endovascular aortic aneurysm repair was performed in 53 (20.2%). The 14F MANTA was used in 42 cases (16%), and the 18F was used in 221 cases(84%). The mean effective sheath outer diameter was 22F (7.3 mm). The mean time to hemostasis was 65±157 seconds with a median time to hemostasis of 24 seconds. Technical success was achieved in 257 (97.7%) patients, and a single device was deployed in 262 (99.6%) of cases. Valve Academic Research Consortium-2 major vascular complications occurred in 11 (4.2%) cases: 4 received a covered stent (1.5%), 3 had access site bleeding (1.1%), 2 underwent surgical repair (0.8%), and 2 underwent balloon inflation (0.8%).In a selected population, this study demonstrated that the MANTA percutaneous vascular closure device can safely and effectively close large bore arteriotomies created by current generation transcatheter aortic valve replacement, percutaneous endovascular abdominal aortic aneurysm repair, and thoracic endovascular aortic aneurysm repair devices.URL: https://www.clinicaltrials.gov . Unique identifier: NCT02908880.

  View details for DOI 10.1161/CIRCINTERVENTIONS.119.007258

  View details for PubMedID 31296082

• Adrenomedullin and endothelin-1: Promising biomarkers of endothelial function, but not ready for prime time. International journal of cardiology Parikh, R. V., Fearon, W. F. 2019

  View details for DOI 10.1016/j.ijcard.2019.05.049

  View details for PubMedID 31155331

• Fractional flow reserve-guided percutaneous coronary intervention vs. medical therapy for patients with stable coronary lesions: meta-analysis of individual patient data. European heart journal Zimmermann, F. M., Omerovic, E., Fournier, S., Kelbak, H., Johnson, N. P., Rothenbuhler, M., Xaplanteris, P., Abdel-Wahab, M., Barbato, E., Hofsten, D. E., Tonino, P. A., Boxma-de Klerk, B. M., Fearon, W. F., Kober, L., Smits, P. C., De Bruyne, B., Pijls, N. H., Juni, P., Engstrom, T. 2018

  Abstract

  Aims: To assess the effect of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) with contemporary drug-eluting stents on the composite of cardiac death or myocardial infarction (MI) vs. medical therapy in patients with stable coronary lesions.Methods and results: We performed a systematic review and meta-analysis of individual patient data (IPD) of the three available randomized trials of contemporary FFR-guided PCI vs. medical therapy for patients with stable coronary lesions: FAME 2 (NCT01132495), DANAMI-3-PRIMULTI (NCT01960933), and Compare-Acute (NCT01399736). FAME 2 enrolled patients with stable coronary artery disease (CAD), while the other two focused on non-culprit lesions in stabilized patients after acute coronary syndrome. A total of 2400 subjects were recruited from 54 sites world-wide with 1056 randomly assigned to FFR-guided PCI and 1344 to medical therapy. The pre-specified primary outcome was a composite of cardiac death or MI. We included data from extended follow-ups for FAME 2 (up to 5.5years follow-up) and DANAMI-3-PRIMULTI (up to 4.7years follow-up). After a median follow-up of 35months (interquartile range 12-60months), a reduction in the composite of cardiac death or MI was observed with FFR-guided PCI as compared with medical therapy (hazard ratio 0.72, 95% confidence interval 0.54-0.96; P=0.02). The difference between groups was driven by MI.Conclusion: In this IPD meta-analysis of the three available randomized controlled trials to date, FFR-guided PCI resulted in a reduction of the composite of cardiac death or MI compared with medical therapy, which was driven by a decreased risk of MI.

  View details for PubMedID 30596995

• Association of Endothelin-1 with Accelerated Cardiac Allograft Vasculopathy and Late Mortality Following Heart Transplantation. Journal of cardiac failure Parikh, R. V., Khush, K., Pargaonkar, V. S., Luikart, H., Grimm, D., Yu, M., Akada, K., Honda, Y., Yeung, A. C., Valantine, H., Fearon, W. F. 2018

  Abstract

  BACKGROUND: Endothelin-1 (ET-1) has been implicated in the development of post-heart transplantation (HT) cardiac allograft vasculopathy (CAV), but has not been well-studied in humans.METHODS AND RESULTS: In 90 HT patients, plasma ET-1 was measured within 8 weeks of HT (baseline) via a competitive enzyme-linked immunosorbent assay. 3D volumetric intravascular ultrasound of the left anterior descending artery was performed at baseline and at 1 year. Accelerated CAV (lumen volume loss) was defined using the 75th percentile as a cutoff. Patients were followed beyond the first year post-HT for late death or re-transplantation. A receiver operative characteristic curve demonstrated that a baseline ET-1 concentration of 1.75 pg/mL provided the best accuracy for diagnosis of accelerated CAV at 1 year [area under the curve=0.69 (0.57-0.82), p=0.007]. In multivariate logistic regression, a higher baseline ET-1 concentration was independently associated with accelerated CAV [odds ratio (OR)=2.13, 95% confidence interval (CI): 1.15-3.94; p=0.01]; this relationship persisted when ET-1 was dichotomized at 1.75 pg/mL (OR=4.88, 95% CI: 1.69-14.10; p=0.003). Eighteen deaths occurred during a median follow-up period of 3.99 (2.51-9.95) years. Treated as a continuous variable, baseline ET-1 was not associated with late mortality in multivariate Cox regression [hazard ratio (HR)=1.22, 95% CI: 0.72-2.05; p=0.44]. However, ET-1 >1.75 pg/mL conferred a significantly lower cumulative event-free survival on Kaplan-Meier analysis (p=0.047), and was independently associated with late mortality (HR=2.94, 95% CI: 1.12-7.72; p=0.02).CONCLUSIONS: Elevated ET-1 early after HT is an independent predictor of accelerated CAV and late mortality, suggesting that ET-1 has durable prognostic value in the HT arena.

  View details for PubMedID 30543947

• Cardiac allograft vasculopathy: A review CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Lee, M. S., Tadwalkar, R. V., Fearon, W. F., Kirtane, A. J., Patel, A. J., Patel, C. B., Ali, Z., Rao, S. V. 2018; 92 (7): E527–E536

  View details for DOI 10.1002/ccd.27893

  View details for Web of Science ID 000452536900017

• Usefulness of Asymmetric Dimethylarginine to Predict Outcomes After Heart Transplantation AMERICAN JOURNAL OF CARDIOLOGY Parikh, R., Khush, K., Luikart, H., Sakarovitch, C., Lee, J., Desai, M., Valantine, H., Yeung, A. C., Fearon, W. F. 2018; 122 (10): 1707–11

  Abstract

  Asymmetric dimethylarginine (ADMA) is a key mediator of vascular homeostasis and an independent predictor of the development of accelerated cardiac allograft vasculopathy after heart transplantation. However, its association with clinical outcomes in heart transplant recipients has not been described. Plasma levels of ADMA were assayed within 8 weeks following transplantation (baseline) using a competitive enzyme-linked immunosorbent assay. The primary end point was the composite of nonfatal myocardial infarction, percutaneous coronary intervention, retransplantation, or death at 5-year follow-up. Kaplan-Meier curves were generated to assess the association between baseline ADMA levels (stratified at 0.70 µM, a previously established cutoff) and cumulative event-free survival. Multivariate Cox regression was performed to adjust for other candidate predictors. In 69 heart transplant recipients at Stanford, the primary end point occurred in 11 patients (16%)-4 percutaneous coronary intervention, 1 retransplant, and 6 deaths-during 5-years follow-up. Patients with baseline ADMA ≥0.70 µM had lower cumulative 5-year event-free survival (77% vs 93%, p = 0.059). In multivariate Cox analysis, baseline ADMA was the only significant predictor of the primary end point (hazard ratio 1.33, 95% confidence interval 1.03 to 1.72 per 0.1 µM; p = 0.031). This association remained significant even after restricting the end point to death or retransplantation (hazard ratio 1.48, 95% confidence interval 1.12 to 1.97 per 0.1 µM; p = 0.006). In conclusion, elevated baseline plasma levels of ADMA independently predicted 5-year clinical outcomes after heart transplantation, suggesting that ADMA has potential prognostic value in the heart transplant arena.

  View details for PubMedID 30220417

• Fractional flow reserve derived from routine coronary angiography INTERNATIONAL JOURNAL OF CARDIOLOGY Nishi, T., Fearon, W. F. 2018; 271: 51–52

  View details for DOI 10.1016/j.ijcard.2018.06.080

  View details for Web of Science ID 000444611600018

• Diagnostic Accuracy of Diastolic Pressure Ratio Using a Microcatheter: An Analysis of the ACIST-FFR Study Price, M., Yang, J., Chambers, J., Seto, A., Sarembock, I., Raveendran, G., Desai, M., Jeremias, A., Matsumura, M., Fearon, W. F. LIPPINCOTT WILLIAMS & WILKINS. 2018

  View details for Web of Science ID 000528619407186

• Impact of Myocardial Bridging on Long-Term Mortality After Heart Transplantation: Risk Stratification With Ivus-Determined Cardiac Allograft Vasculopathy Kameda, R., Okada, K., Tanaka, S., Luikart, H., Yock, P. G., Yeung, A. C., Schnittger, I., Fitzgerald, P. J., Khush, K. K., Fearon, W. F., Honda, Y. LIPPINCOTT WILLIAMS & WILKINS. 2018

  View details for Web of Science ID 000528619403405

• The Dose-Response Relationship Between Intracoronary Acetylcholine and Minimal Lumen Diameter in Endothelial Function Testing of Women and Men With Angina in the Absence of Obstructive Coronary Artery Disease Pargaonkar, V. S., Nishi, T., Lee, J., Chow, E. K., Ball, R. L., Kobayashi, Y., Kimura, T., Lee, D. P., Stefanick, M. L., Fearon, W. F., Yeung, A. C., Tremmel, J. A. LIPPINCOTT WILLIAMS & WILKINS. 2018

  View details for Web of Science ID 000528619406032

• Sex Differences in Clinical Outcomes and Quality of Life in Patients With Non-Obstructive CAD (a FAME 2 Substudy) Shah, S., Nishi, T., Kobayashi, Y., Barbato, E., Tonino, P., Juni, P., Pijls, H., De Bruyne, B., Fearon, W. LIPPINCOTT WILLIAMS & WILKINS. 2018

  View details for Web of Science ID 000528619403132

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

  View details for DOI 10.1016/j.ijcard.2018.05.020

  View details for Web of Science ID 000444609000021

• Is Post-Percutaneous Coronary Intervention Fractional Flow Reserve of Value in Chronic Total Occlusions? CIRCULATION-CARDIOVASCULAR INTERVENTIONS Tremmel, J. A., Fearon, W. F. 2018; 11 (11)

  View details for DOI 10.1161/CIRCINTERVENTIONS.118.007360

  View details for Web of Science ID 000450657500012

• Is Post-Percutaneous Coronary Intervention Fractional Flow Reserve of Value in Chronic Total Occlusions? Circulation. Cardiovascular interventions Tremmel, J. A., Fearon, W. F. 2018; 11 (11): e007360

  View details for DOI 10.1161/CIRCINTERVENTIONS.118.007360

  View details for PubMedID 30571221

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

  Abstract

  OBJECTIVE: Previous studies have suggested that cytokines and growth factors may predict ventricular recovery following aortic valve replacement (AVR). The primary objective of this study was to identify cytokines that predict ventricular recovery following transcatheter AVR (TAVR).METHODS: We prospectively enrolled 121 consecutive patients who underwent TAVR. Standard echocardiographic assessment at baseline, 1-month and 1-year after TAVR included left ventricular (LV) mass index (LVMI) and global longitudinal strain (GLS). Blood samples were obtained at the time of the procedure to measure cytokines using a 63-plex Luminex platform. Partial least squares-discriminant analysis was performed to identify cytokines associated with ventricular remodeling and function at baseline as well as 1 year after TAVR.RESULTS: The mean age was 84 ± 9 years, with a majority of male subjects (59%), a mean LVMI of 120.4 ± 45.1 g/m2 and LVGLS of -13.0 ± 3.2%. On average, LV mass decreased by 8.1% and GLS improved by 20.3% at 1 year following TAVR. Among cytokines assayed, elevated hepatocyte growth factor (HGF) emerged as a common factor significantly associated with worse baseline LVMI and GLS as well as reduced ventricular recovery (p < 0.005). Other factors associated with ventricular recovery included a select group of vascular growth factors, inflammatory mediators and tumor necrosis factors, including VEGF-D, ICAM-1, TNFbeta, and IL1beta.CONCLUSION: We identified a network of cytokines, including HGF, that are significantly correlated with baseline LVMI and GLS, and ventricular recovery following TAVR.

  View details for PubMedID 30219541

• Fractional Flow Reserve and Quality-of-Life Improvement After Percutaneous Coronary Intervention in Patients With Stable Coronary Artery Disease CIRCULATION Nishi, T., Piroth, Z., De Bruyne, B., Jagic, N., Mobius-Winkler, S., Kobayashi, Y., Derimay, F., Fournier, S., Barbato, E., Tonino, P., Juni, P., Pijls, N. J., Fearon, W. F. 2018; 138 (17): 1797–1804

  View details for DOI 10.1161/CIRCULATIONAHA.118.035263

  View details for Web of Science ID 000447973800011

• Predicting Outcomes After Percutaneous Coronary Intervention Using Relative Change in Fractional Flow Reserve JACC-CARDIOVASCULAR INTERVENTIONS Kobayashi, Y., Fearon, W. F. 2018; 11 (20): 2110–12

  View details for DOI 10.1016/j.jcin.2018.08.020

  View details for Web of Science ID 000447436200016

• High Coronary Shear Stress in Patients With Coronary Artery Disease Predicts Myocardial Infarction JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Kumar, A., Thompson, E. W., Lefieux, A., Molony, D. S., Davis, E. L., Chand, N., Fournier, S., Lee, H., Suh, J., Sato, K., Ko, Y., Molloy, D., Chandran, K., Hosseini, H., Gupta, S., Milkas, A., Gogas, B., Chang, H., Min, J. K., Fearon, W. F., Veneziani, A., Giddens, D. P., King, S. B., De Bruyne, B., Samady, H. 2018; 72 (16): 1926–35

  Abstract

  Coronary lesions with low fractional flow reserve (FFR) that are treated medically are associated with higher revascularization rates. High wall shear stress (WSS) has been linked with increased plaque vulnerability.This study investigated the prognostic value of WSS measured in the proximal segments of lesions (WSSprox) to predict myocardial infarction (MI) in patients with stable coronary artery disease (CAD) and hemodynamically significant lesions. The authors hypothesized that in patients with low FFR and stable CAD, higher WSSprox would predict MI.Among 441 patients in the FAME II (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation II) trial with FFR ≤0.80 who were randomized to medical therapy alone, 34 (8%) had subsequent MI within 3 years. Patients with vessel-related MI and adequate angiograms for 3-dimensional reconstruction (n = 29) were propensity matched to a control group with no MI (n = 29) by using demographic and clinical variables. Coronary lesions were divided into proximal, middle, and distal, along with 5-mm upstream and downstream segments. WSS was calculated for each segment.Median age was 62 years, and 46 (79%) were male. In the marginal Cox model, whereas lower FFR showed a trend (hazard ratio: 0.084; p = 0.064), higher WSSprox (hazard ratio: 1.234; p = 0.002, C-index = 0.65) predicted MI. Adding WSSprox to FFR resulted in a significant increase in global chi-square for predicting MI (p = 0.045), a net reclassification improvement of 0.69 (p = 0.005), and an integrated discrimination index of 0.11 (p = 0.010).In patients with stable CAD and hemodynamically significant lesions, higher WSS in the proximal segments of atherosclerotic lesions is predictive of MI and has incremental prognostic value over FFR.

  View details for PubMedID 30309470

• Remote Ischemic Preconditioning Acutely Improves Coronary Microcirculatory Function JOURNAL OF THE AMERICAN HEART ASSOCIATION Lau, J. K., Roy, P., Javadzadegan, A., Moshfegh, A., Fearon, W. F., Ng, M., Lowe, H., Brieger, D., Kritharides, L., Yong, A. S. 2018; 7 (19)

  View details for DOI 10.1161/JAHA.118.009058

  View details for Web of Science ID 000452823000012

• Remote Ischemic Preconditioning Acutely Improves Coronary Microcirculatory Function. Journal of the American Heart Association Lau, J. K., Roy, P., Javadzadegan, A., Moshfegh, A., Fearon, W. F., Ng, M., Lowe, H., Brieger, D., Kritharides, L., Yong, A. S. 2018; 7 (19): e009058

  Abstract

  Background Remote ischemic preconditioning (RIPC) attenuates myocardial damage during elective and primary percutaneous coronary intervention. Recent studies suggest that coronary microcirculatory function is an important determinant of clinical outcome. The aim of this study was to assess the effect of RIPC on markers of microcirculatory function. Methods and Results Patients referred for cardiac catheterization and fractional flow reserve measurement were randomized to RIPC or sham. Operators and patients were blinded to treatment allocation. Comprehensive physiological assessments were performed before and after RIPC/sham including the index of microcirculatory resistance and coronary flow reserve after intracoronary glyceryl trinitrate and during the infusion of intravenous adenosine. Thirty patients were included (87% male; mean age: 63.1±10.0years). RIPC and sham groups were similar with respect to baseline characteristics. RIPC decreased the calculated index of microcirculatory resistance (median, before RIPC: 22.6 [interquartile range [IQR]: 17.9-25.6]; after RIPC: 17.5 [IQR: 14.5-21.3]; P=0.007) and increased coronary flow reserve (2.6±0.9 versus 3.8±1.7, P=0.001). These RIPC-mediated changes were associated with a reduction in hyperemic transit time (median: 0.33 [IQR: 0.26-0.40] versus 0.25 [IQR: 0.20-0.30]; P=0.010). RIPC resulted in a significant decrease in the calculated index of microcirculatory resistance compared with sham (relative change with treatment [mean±SD] was -18.1±24.8% versus +6.1±37.5; P=0.047) and a significant increase in coronary flow reserve (+41.2% [IQR: 20.0-61.7] versus -7.8% [IQR: -19.1 to 10.3]; P<0.001). Conclusions The index of microcirculatory resistance and coronary flow reserve are acutely improved by remote ischemic preconditioning. This raises the possibility that RIPC confers cardioprotection during percutaneous coronary intervention as a result of an improvement in coronary microcirculatory function. Clinical Trial Registration URL: www.anzctr.org.au/ . Unique identifier: CTRN12616000486426.

  View details for PubMedID 30371329

• Cardiac allograft vasculopathy: A review. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions Lee, M. S., Tadwalkar, R. V., Fearon, W. F., Kirtane, A. J., Patel, A. J., Patel, C. B., Ali, Z., Rao, S. V. 2018

  Abstract

  Cardiac allograft vasculopathy (CAV) is a complex disease that remains a significant cause of morbidity and mortality after orthotopic heart transplantation (OHT). Originating as a result of inflammatory response, the development and progression of CAV is attributed to endothelial dysfunction, cellular infiltration, and a wide-range of genetic and patient factors. The detection of CAV remains a diagnostic challenge, as symptoms can be variable or absent. While coronary angiography remains the initial test of choice for the diagnosis and surveillance of CAV, intravascular imaging (either by ultrasound or optical coherence tomography) and physiologic assessments are useful adjuncts in the cardiac catheterization laboratory. Positron emission tomography, computed tomographic, and magnetic resonance imaging may have a role increasing the time interval between invasive screening tests for prognosis. Medical management should include a statin, vasodilator, and tailored immunosuppressive regimen that maximally decrease allograft rejection and CAV progression while causing minimal side effects. Patients that are less responsive to pharmacotherapy should be considered for invasive management with percutaneous coronary intervention. Although surgical revascularization is a poor option, repeat OHT is the only definitive treatment option but given its morbidity should be reserved for a highly selected patient population.

  View details for PubMedID 30265435

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

  View details for DOI 10.1016/j.jacc.2018.08.1809

  View details for Web of Science ID 000455137100602

• Prognostic Value of the Residual SYNTAX Score After Functionally Complete Revascularization in ACS JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Kobayashi, Y., Lonborg, J., Jong, A., Nishi, T., De Bruyne, B., Hofsten, D., Kelbaek, H., Layland, J., Nam, C., Pijls, N. J., Tonino, P. L., Warnoe, J., Oldroyd, K. G., Berry, C., Engstrom, T., Fearon, W. F., DANAMI-3-PRIMULTI Study Investigat, FAME Study Investigator, FAMOUS-NSTEMI Study Investigator 2018; 72 (12): 1321–29

  View details for DOI 10.1016/j.jacc.2018.06.069

  View details for Web of Science ID 000444236800001

• Sex Differences in Adenosine-Free Coronary Pressure Indexes A CONTRAST Substudy JACC-CARDIOVASCULAR INTERVENTIONS Shah, S. V., Zimmermann, F. M., Johnson, N. P., Nishi, T., Kobayashi, Y., Witt, N., Berry, C., Jeremias, A., Koo, B., Esposito, G., Rioufol, G., Park, S., Oldroyd, K. G., Barbato, E., Pijls, N. J., De Bruyne, B., Fearon, W. F., CONTRAST Study Investigators 2018; 11 (15): 1454–63

  View details for DOI 10.1016/j.jcin.2018.03.030

  View details for Web of Science ID 000440859800008

• Assessing the Coronary Microcirculation in Patients After Primary Percutaneous Coronary Intervention. Journal of the American Heart Association Yong, A. S., Fearon, W. F. 2018; 7 (15): e009828

  View details for PubMedID 30371235

• Assessing the Coronary Microcirculation in Patients After Primary Percutaneous Coronary Intervention JOURNAL OF THE AMERICAN HEART ASSOCIATION Yong, A. C., Fearon, W. F. 2018; 7 (15)

  View details for DOI 10.1161/JAHA.118.009828

  View details for Web of Science ID 000452701900035

• Focused update of expert consensus statement: Use of invasive assessments of coronary physiology and structure: A position statement of the society of cardiac angiography and interventions CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Lotfi, A., Davies, J. E., Fearon, W. F., Grines, C. L., Kern, M. J., Klein, L. W. 2018; 92 (2): 336–47

  View details for PubMedID 29968425

• Five-Year Outcomes with PCI Guided by Fractional Flow Reserve NEW ENGLAND JOURNAL OF MEDICINE Xaplanteris, P., Fournier, S., Pijls, N. J., Fearon, W. F., Barbato, E., Tonino, P. L., Engstrom, T., Kaab, S., Dambrink, J., Rioufol, G., Toth, G. G., Piroth, Z., Witt, N., Frobert, O., Kala, P., Linke, A., Jagic, N., Mates, M., Mavromatis, K., Samady, H., Irimpen, A., Oldroyd, K., Campo, G., Rothenbuhler, M., Juni, P., De Bruyne, B., FAME 2 Investigators 2018; 379 (3): 250–59

  View details for DOI 10.1056/NEJMoa1803538

  View details for Web of Science ID 000439063900008

• Sex Differences in Adenosine-Free Coronary Pressure Indexes: A CONTRAST Substudy. JACC. Cardiovascular interventions Shah, S. V., Zimmermann, F. M., Johnson, N. P., Nishi, T., Kobayashi, Y., Witt, N., Berry, C., Jeremias, A., Koo, B., Esposito, G., Rioufol, G., Park, S., Oldroyd, K. G., Barbato, E., Pijls, N. H., De Bruyne, B., Fearon, W. F., CONTRAST Study Investigators 2018

  Abstract

  OBJECTIVES: The goal of this study was to investigate sex differences in adenosine-free coronary pressure indexes.BACKGROUND: Several adenosine-free coronary pressure wire indexes have been proposed to assess the functional significance of coronary artery lesions; however, there is a theoretical concern that sex differences may affect diagnostic performance because of differences in resting flow and distal myocardial mass.METHODS: In this CONTRAST (Can Contrast Injection Better Approximate FFR Compared to Pure Resting Physiology?) substudy, contrast fractional flow reserve (cFFR), obtained during contrast-induced submaximal hyperemia, the instantaneous wave-free ratio (iFR), and distal/proximal coronary pressure ratio (Pd/Pa) were compared with fractional flow reserve (FFR) in 547 men and 216 women. Using FFR≤0.8 as a reference, the diagnostic performance of each index was compared.RESULTS: Men and women had similar diameter stenosis (p= 0.78), but women were less likely to have FFR≤0.80 than men (42.5% vs. 51.5%, p= 0.04). Sensitivity was similar among cFFR, iFR, and Pd/Pa when comparing women and men, respectively (cFFR, 77.5% vs. 75.3%, p= 0.69; iFR, 84.9% vs. 79.4%, p= 0.30; Pd/Pa, 78.8% vs. 77.3%, p= 0.78). cFFR was more specific than iFR or Pd/Pa regardless of sex (cFFR, 94.3% vs. 95.8%, p= 0.56; iFR, 75.6% vs. 80.1%, p= 0.38; Pd/Pa, 80.6% vs. 78.7%, p= 0.69). By receiver-operating characteristic curve analysis, cFFR provided better diagnostic accuracy than resting indexes irrespective of sex (p≤ 0.0001).CONCLUSIONS: Despite the theoretical concern, the diagnostic sensitivity and specificity of cFFR, iFR, and Pd/Pa did not differ between the sexes. Irrespective of sex, cFFR provides the best diagnostic performance.

  View details for PubMedID 30031722

• Fractional flow reserve derived from routine coronary angiography. International journal of cardiology Nishi, T., Fearon, W. F. 2018

  View details for PubMedID 29980365

• Standardized End Point Definitions for Coronary Intervention Trials EUROPEAN HEART JOURNAL Garcia-Garcia, H. M., McFadden, E. P., Farb, A., Mehran, R., Stone, G. W., Spertus, J., Onuma, Y., Morel, M., van Es, G., Zuckerman, B., Fearon, W. F., Taggart, D., Kappetein, A., Krucoff, M. W., Vranckx, P., Windecker, S., Cutlip, D., Serruys, P. W., Acad Res Consortium 2018; 39 (23): 2192–2207

  Abstract

  The Academic Research Consortium (ARC)-2 initiative revisited the clinical and angiographic end point definitions in coronary device trials, proposed in 2007, to make them more suitable for use in clinical trials that include increasingly complex lesion and patient populations and incorporate novel devices such as bioresorbable vascular scaffolds. In addition, recommendations for the incorporation of patient-related outcomes in clinical trials are proposed. Academic Research Consortium-2 is a collaborative effort between academic research organizations in the United States and Europe, device manufacturers, and European, US, and Asian regulatory bodies. Several in-person meetings were held to discuss the changes that have occurred in the device landscape and in clinical trials and regulatory pathways in the last decade. The consensus-based end point definitions in this document are endorsed by the stakeholders of this document and strongly advocated for clinical trial purposes. This Academic Research Consortium-2 document provides further standardization of end point definitions for coronary device trials, incorporating advances in technology and knowledge. Their use will aid interpretation of trial outcomes and comparison among studies, thus facilitating the evaluation of the safety and effectiveness of these devices.

  View details for PubMedID 29897428

• Standardized End Point Definitions for Coronary Intervention Trials The Academic Research Consortium-2 Consensus Document CIRCULATION Garcia-Garcia, H. M., McFadden, E. P., Farb, A., Mehran, R., Stone, G. W., Spertus, J., Onuma, Y., Morel, M., van Es, G., Zuckerman, B., Fearon, W. F., Taggart, D., Kappetein, A., Krucoff, M. W., Vranckx, P., Windecker, S., Cutlip, D., Serruys, P. W., Acad Res Consortium 2018; 137 (24): 2635–50

  Abstract

  The Academic Research Consortium (ARC)-2 initiative revisited the clinical and angiographic end point definitions in coronary device trials, proposed in 2007, to make them more suitable for use in clinical trials that include increasingly complex lesion and patient populations and incorporate novel devices such as bioresorbable vascular scaffolds. In addition, recommendations for the incorporation of patient-related outcomes in clinical trials are proposed. Academic Research Consortium-2 is a collaborative effort between academic research organizations in the United States and Europe, device manufacturers, and European, US, and Asian regulatory bodies. Several in-person meetings were held to discuss the changes that have occurred in the device landscape and in clinical trials and regulatory pathways in the last decade. The consensus-based end point definitions in this document are endorsed by the stakeholders of this document and strongly advocated for clinical trial purposes. This Academic Research Consortium-2 document provides further standardization of end point definitions for coronary device trials, incorporating advances in technology and knowledge. Their use will aid interpretation of trial outcomes and comparison among studies, thus facilitating the evaluation of the safety and effectiveness of these devices.

  View details for PubMedID 29891620

• Coronary microvascular dysfunction in patients with heart failure with preserved ejection fraction AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Dryer, K., Gajjar, M., Narang, N., Lee, M., Paul, J., Shah, A. P., Nathan, S., Butler, J., Davidson, C. J., Fearon, W. F., Shah, S. J., Blair, G. A. 2018; 314 (5): H1033–H1042

  Abstract

  There are multiple proposed mechanisms for the pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF). We hypothesized that coronary microvascular dysfunction is common in these patients. In a prospective, observational study, patients undergoing cardiac catheterization with HFpEF [left ventricular (LV) ejection fraction ≥ 50% and with clinical HF] were compared with similar patients without HFpEF. Patients with ≥50% stenosis were excluded, and coronary flow reserve (CFR) and the index of microvascular resistance (IMR) were measured after adenosine administration using a guidewire, with CFR ≤ 2 and IMR ≥ 23 being abnormal. Baseline characteristics and CFR and IMR were compared in 30 HFpEF patients and 14 control subjects. Compared with control subjects, HFpEF patients were older (65.4 ± 9.6 vs. 55.1 ± 3.1 yr, P < 0.01), had higher numbers of comorbidities (4.4 ± 1.5 vs. 2.6 ± 1.9, P = 0.002), had higher median B-type natriuretic peptide [161 (interquartile range: 75-511) pg/dl vs. 37 (interquartile range: 18.5-111) pg/dl, P < 0.01], and had higher LV end-diastolic pressure (17.8 ± 4.2 vs. 8.4 ± 4.2, P < 0.01). HFpEF patients had lower CFR (2.55 ± 1.60 vs. 3.84 ± 1.89, P = 0.024) and higher IMR (26.7 ± 10.3 vs. 19.7 ± 9.7 units, P = 0.037) than control subjects. Most (71.4%) control subjects had normal coronary physiology, whereas 36.7% of HFpEF patients had both abnormal CFR and IMR and another 36.7% had either abnormal CFR or IMR. In conclusion, this is the first study that has reported invasively determined CFR and IMR in HFpEF patients. We demonstrated the presence of four distinct coronary physiology groups in HFpEF patients. Investigation into the potential mechanisms for these findings is needed. NEW & NOTEWORTHY In this prospective observational study of patients with heart failure with preserved ejection fraction (HFpEF), we found that patients with HFpEF had more abnormalities of coronary flow and resistance than asymptomatic control patients, indicating that coronary microvascular dysfunction may play a role in the HFpEF disease process.

  View details for PubMedID 29424571

• Index of Microcirculatory Resistance and Infarct Size. JACC. Cardiovascular imaging Fearon, W. F., Dash, R. 2018

  View details for PubMedID 29680353

• Angiography Versus Hemodynamics to Predict the Natural History of Coronary Stenoses Fractional Flow Reserve Versus Angiography in Multivessel Evaluation 2 Substudy CIRCULATION Ciccarelli, G., Barbato, E., Toth, G. G., Gahl, B., Xaplanteris, P., Fournier, S., Milkas, A., Bartunek, J., Vanderheyden, M., Pijls, N., Tonino, P., Fearon, W. F., Juni, P., De Bruyne, B. 2018; 137 (14): 1475–85

  Abstract

  Among patients with documented stable coronary artery disease and in whom no revascularization was performed, we compared the respective values of angiographic diameter stenosis (DS) and fractional flow reserve (FFR) in predicting natural history.The present analysis included the 607 patients from the FAME 2 trial (Fractional Flow Reserve Versus Angiography in Multivessel Evaluation 2) in whom no revascularization was performed. FFR varied from 0.20 to 1.00 (average 0.74±0.16), and DS (by quantitative coronary analysis) varied from 8% to 98% (average 53±15). The primary end point, defined as vessel-oriented clinical end point (VOCE) at 2 years, was a composite of prospectively adjudicated cardiac death, vessel-related myocardial infarction, vessel-related urgent, and not urgent revascularization. The stenoses were divided into 4 groups according to FFR and %DS values: positive concordance (FFR≤0.80; DS≥50%), negative concordance (FFR>0.80; DS<50%), positive mismatch (FFR≤0.80; DS<50%), and negative mismatch (FFR>0.80; DS≥50%).The rate of VOCE was highest in the positive concordance group (log rank: X2=80.96; P=0.001) and lowest in the negative concordance group. The rate of VOCE was higher in the positive mismatch group than in the negative mismatch group (hazard ratio, 0.38; 95% confidence interval, 0.21-0.67; P=0.001). There was no significant difference in VOCE between the positive concordance and positive mismatch groups (FFR≤0.80; hazard ratio, 0.77; 95% confidence interval, 0.57-1.09; P=0.149) and no significant difference in rate of VOCE between the negative mismatch and negative concordance groups (FFR>0.80; hazard ratio, 1.89; 95% confidence interval, 0.96-3.74; P=0.067).In patients with stable coronary disease, physiology (FFR) is a more important determinant of the natural history of coronary stenoses than anatomy (DS).URL: https://clinicaltrials.gov. Unique identifier: NCT01132495.

  View details for PubMedID 29162610

• The ratio of circulating regulatory cluster of differentiation 4 T cells to endothelial progenitor cells predicts clinically significant acute rejection after heart transplantation JOURNAL OF HEART AND LUNG TRANSPLANTATION Choi, D., Chmura, S. A., Ramachandran, V., Dionis-Petersen, K. Y., Kobayashi, Y., Nishi, T., Luikart, H., Dimbil, S., Kobashigawa, J., Khush, K., Lewis, D. B., Fearon, W. F. 2018; 37 (4): 496–502

  View details for DOI 10.1016/j.healun.2017.10.012

  View details for Web of Science ID 000429915500012

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

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

  View details for Web of Science ID 000429659703241

• IMPACT OF ENDOTHELIN-1 ON CARDIAC ALLOGRAFT VASCULOPATHY, LATE MORTALITY AND RE-TRANSPLANTATION FOLLOWING HEART TRANSPLANTATION Parikh, R., Khush, K., Luikart, H., Grimm, D., Yu, M., Yeung, A., Valantine, H., Fearon, W. ELSEVIER SCIENCE INC. 2018: 2667

  View details for DOI 10.1016/S0735-1097(18)33208-X

  View details for Web of Science ID 000429659705117

• SEX DIFFERENCES AND ADENOSINE FREE CORONARY PRESSURE INDICES: A CONTRAST SUBSTUDY Shah, S., Zimmermann, F. M., Johnson, N., Nishi, T., Kobayashi, Y., Witt, N., Berry, C., Jeremias, A., Koo, B., Esposito, G., Rioufol, G., Park, S., Oldroyd, K., Barbato, E., Pijls, N., De Bruyne, B., Fearon, W. ELSEVIER SCIENCE INC. 2018: 1183

  View details for DOI 10.1016/S0735-1097(18)31724-8

  View details for Web of Science ID 000429659702433

• THE PROGNOSTIC VALUE OF COMPUTED TOMOGRAPHY FRAILTY MEASURES FOR PROLONGED HOSPITAL STAY AFTER TAVR IN 429 PATIENTS Maret, E., Willemink, M., Moneghetti, K., Kim, J., Haddad, F., Kobayashi, Y., Miller, C., Yeung, A., Fishbein, M., Fearon, W., Fleischmann, D. ELSEVIER SCIENCE INC. 2018: 1414

  View details for DOI 10.1016/S0735-1097(18)31955-7

  View details for Web of Science ID 000429659703064

• PROGNOSTIC VALUE OF THE INDEX OF MICROCIRCULATORY RESISTANCE AFTER PERCUTANEOUS CORONARY INTERVENTION IN PATIENTS WITH STABLE CORONARY ARTERY DISEASE Nishi, T., Murai, T., Ciccarelli, G., Kobayashi, Y., Waseda, K., Hirohata, A., Amano, T., Barbato, E., Kakuta, T., Fearon, W. ELSEVIER SCIENCE INC. 2018: 1173

  View details for DOI 10.1016/S0735-1097(18)31714-5

  View details for Web of Science ID 000429659702423

• Invasive physiological indices to determine the functional significance of coronary stenosis IJC HEART & VASCULATURE AL-Obaidi, F. R., Fearon, W. F., Yong, A. C. 2018; 18: 39–45

  View details for DOI 10.1016/j.ijcha.2018.02.003

  View details for Web of Science ID 000432566900008

• Invasive physiological indices to determine the functional significance of coronary stenosis. International journal of cardiology. Heart & vasculature Al-Obaidi, F. R., Fearon, W. F., Yong, A. S. 2018; 18: 39-45

  Abstract

  Physiological measurements are now commonly used to assess coronary lesions in the cardiac catheterisation laboratory, and this practice is evidence-based and supported by clinical guidelines. Fractional flow reserve is currently the gold standard method to determine whether coronary lesions are functionally significant, and is used to guide revascularization. There are however several other physiological measurements that have been proposed as alternatives to the fractional flow reserve. This review aims to comprehensively discuss physiological indices that can be used in the cardiac catheterisation laboratory to determine the functional significance of coronary lesions. We will focus on their advantages and disadvantages, and the current evidence supporting their use.

  View details for DOI 10.1016/j.ijcha.2018.02.003

  View details for PubMedID 29876502

  View details for PubMedCentralID PMC5988484

• Response by Kobayashi et al to Letter Regarding Article, "Three-Vessel Assessment of Coronary Microvascular Dysfunction in Patients with Clinical Suspicion of Ischemia: Prospective Observation Study With the Index of Microcirculatory Resistance" CIRCULATION-CARDIOVASCULAR INTERVENTIONS Kobayashi, Y., Fearon, W. F., Nishi, T., Choi, D., Lee, J., Lee, J., Zimmermann, F. M., Jung, J., Lee, H., Doh, J., Nam, C., Shin, E., Koo, B. 2018; 11 (2)

  View details for DOI 10.1161/CIRCINTERVENTIONS.117.006302

  View details for Web of Science ID 000435565000015

• Change in lymphocyte to neutrophil ratio predicts acute rejection after heart transplantation INTERNATIONAL JOURNAL OF CARDIOLOGY Choi, D., Kobayashi, Y., Nishi, T., Luikart, H., Dimbil, S., Kobashigawa, J., Khush, K., Fearon, W. F. 2018; 251: 58–64

  View details for DOI 10.1016/j.ijcard.2017.10.060

  View details for Web of Science ID 000416951600017

• Change in lymphocyte to neutrophil ratio predicts acute rejection after heart transplantation. International journal of cardiology Choi, D. H., Kobayashi, Y. n., Nishi, T. n., Luikart, H. n., Dimbil, S. n., Kobashigawa, J. n., Khush, K. n., Fearon, W. F. 2018; 251: 58–64

  Abstract

  Most immunosuppressive drugs provide targeted immunosuppression by selective inhibition of lymphocyte activation and proliferation. This study evaluated whether a change in the lymphocyte to neutrophil ratio (LNR) is related to acute rejection.In 74 cardiac transplant recipients peripheral blood lymphocyte and neutrophil counts were measured soon after (baseline) and three, six, and 12months after heart transplantation. The primary endpoint was the incidence of acute rejection.Significant acute rejection after heart transplantation occurred in 20 patients (27%) during a median follow-up of 49.4 [IQR 37.4-61.1] months. LNR significantly increased over time (0.1149±0.1354 at baseline, 0.2330±0.2266 at 3months, 0.2961±0.2849 at 6months, and 0.3521±0.2383 at 12months; P<0.001), especially during the first 3months in the group without acute rejection. The area under the curve of the change in LNR during the first three months (ΔLNR) for acute rejection was 0.565 (95% CI 0.420 to 0.710, P=0.380) on ROC curve analysis. The best cutoff value of Δ LNR to differentiate those with and without acute rejection was ≤0.046 by ROC curve analysis. Kaplan-Meier analysis revealed that the low ΔLNR group (≤0.046) had a significantly higher rate of acute rejection than the high ΔLNR group (>0.046) (37.5% vs. 19.0%, log-rank: P=0.0358). The low ΔLNR for the first 3months was an independent predictor of clinically significant acute rejection after adjusting for cytomegalovirus donor seropositive and recipient seronegative.The results of this study suggest that ΔLNR over the first 3months after heart transplantation is a strong and independent predictor of acute rejection after heart transplantation. ΔLNR can be used as an early biomarker for predicting of acute rejection after heart transplantation.

  View details for PubMedID 29074043

• Predicting Outcomes After Percutaneous Coronary Intervention Using Relative Change in Fractional Flow Reserve. JACC. Cardiovascular interventions Kobayashi, Y. n., Fearon, W. F. 2018; 11 (20): 2110–12

  View details for PubMedID 30336815

• Accuracy of non-invasive stress testing in women and men with angina in the absence of obstructive coronary artery disease. International journal of cardiology Pargaonkar, V. S., Kobayashi, Y. n., Kimura, T. n., Schnittger, I. n., Chow, E. K., Froelicher, V. F., Rogers, I. S., Lee, D. P., Fearon, W. F., Yeung, A. C., Stefanick, M. L., Tremmel, J. A. 2018

  Abstract

  While >20% of patients presenting to the cardiac catheterization laboratory with angina have no obstructive coronary artery disease (CAD), a majority (77%) have an occult coronary abnormality (endothelial dysfunction, microvascular dysfunction (MVD), and/or a myocardial bridge (MB)). There are little data regarding the ability of noninvasive stress testing to identify these occult abnormalities in patients with angina in the absence of obstructive CAD.We retrospectively evaluated 155 patients (76.7% women) with angina and no obstructive CAD who underwent stress echocardiography and/or electrocardiography before angiography. We evaluated Duke treadmill score, heart rate recovery (HRR), metabolic equivalents, and blood pressure response. During angiography, patients underwent invasive testing for endothelial dysfunction (decrease in epicardial coronary artery diameter >20% after intracoronary acetylcholine), MVD (index of microcirculatory resistance ≥25), and intravascular ultrasound for the presence of an MB.Stress echocardiography and electrocardiography were positive in 58 (43.6%) and 57 (36.7%) patients, respectively. Endothelial dysfunction was present in 96 (64%), MVD in 32 (20.6%), and an MB in 83 (53.9%). On multivariable logistic regression, stress echo was not associated with any abnormality, while stress ECG was associated with endothelial dysfunction. An abnormal HRR was associated with endothelial dysfunction and MVD, but not an MB.Conventional stress testing is insufficient for identifying occult coronary abnormalities that are frequently present in patients with angina in the absence of obstructive CAD. A normal stress test does not rule out a non-obstructive coronary etiology of angina, nor does it negate the need for comprehensive invasive testing.

  View details for DOI 10.1016/j.ijcard.2018.10.073

  View details for PubMedID 30527992

• Long-term prognostic value of invasive and non-invasive measures early after heart transplantation. International journal of cardiology Kobayashi, Y. n., Kobayashi, Y. n., Yang, H. M., Bouajila, S. n., Luikart, H. n., Nishi, T. n., Choi, D. H., Schnittger, I. n., Valantine, H. A., Khush, K. K., Yeung, A. C., Haddad, F. n., Fearon, W. F. 2018; 260: 31–35

  Abstract

  Invasively assessed coronary microvascular resistance early after heart transplantation predicts worse long-term outcome; however, little is known about the relationship between microvascular resistance, left ventricular function and outcomes in this setting.A total of 100 cardiac transplant recipients had fractional flow reserve (FFR) and the index of microcirculatory resistance (IMR) measured in the left anterior descending artery and echocardiographic assessment of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) at 1 year after heart transplantation. The primary endpoint was the composite of death and retransplantation occurring beyond the first post-operative year.The mean FFR, IMR, LVEF, and GLS values at 1 year were 0.87 ± 0.06, 21.3 ± 17.3, 60.4 ± 5.4%, and 14.2 ± 2.4%, respectively. FFR and IMR had no significant correlation with LVEF and GLS. During a mean follow-up of 6.7 ± 4.2 years, the primary endpoint occurred in 24 patients (24.0%). By ROC curve analysis, IMR = 19.3 and GLS = 13.3% were the best cutoff values for predicting death or retransplantation. Cumulative event-free survival was significantly lower in patients with higher IMR (log-rank p = 0.02) and lower GLS (log-rank p < 0.001). Cumulative event-free survival can be further stratified by the combination of IMR and GLS (long-rank p < 0.001). By multivariable Cox proportional hazards model, higher IMR and lower GLS were independently associated with long-term death or retransplantation (elevated IMR, hazard ratio = 2.50, p = 0.04 and reduced GLS, hazard ratio = 3.79, p = 0.003, respectively).Invasively assessed IMR does not correlate with GLS at 1 year after heart transplantation. IMR and GLS determined at 1 year may be used as independent predictors of late death or retransplantation.

  View details for PubMedID 29622448

• Response by Kobayashi et al to Letter Regarding Article, "Three-Vessel Assessment of Coronary Microvascular Dysfunction in Patients with Clinical Suspicion of Ischemia: Prospective Observation Study With the Index of Microcirculatory Resistance". Circulation. Cardiovascular interventions Kobayashi, Y. n., Fearon, W. F., Nishi, T. n., Choi, D. H., Lee, J. M., Lee, J. H., Zimmermann, F. M., Jung, J. H., Lee, H. J., Doh, J. H., Nam, C. W., Shin, E. S., Koo, B. K. 2018; 11 (2): e006302

  View details for PubMedID 29386190

• Should We Just Go With the Flow? JACC-CARDIOVASCULAR INTERVENTIONS Chacko, Y., Fearon, W. F. 2017; 10 (24): 2525–27

  View details for PubMedID 29268882

• Physiological Predictors of Acute Coronary Syndromes Emerging Insights From the Plaque to the Vulnerable Patient JACC-CARDIOVASCULAR INTERVENTIONS Ford, T. J., Berry, C., De Bruyne, B., Yong, A. C., Barlis, P., Fearon, W. F., Ng, M. C. 2017; 10 (24): 2539–47

  Abstract

  In this review, the authors explore the evolving evidence linking physiological assessment of coronary artery disease with plaque progression and vulnerability. Reducing adverse clinical events remains the ultimate goal for diagnostic tests, and this review highlights evidence supporting the prognostic value of physiological metrics in predicting outcomes. Historical and contemporary studies support synergy among lesion severity, ischemia, plaque vulnerability, and patient prognosis. Ischemia contributes to clinical events through association with plaque burden, but this review addresses the emerging concept that it associates with atherothrombosis via disturbed lesion hemodynamics. Biomechanical pathophysiological forces including endothelial shear stress-the frictional force generated by blood flow on the vessel wall-are increasingly linked with atherogenesis, vulnerable plaque morphology, and platelet and leukocyte activation. The authors conclude by transitioning from the model of the vulnerable plaque to the concept of the "vulnerable patient," looking more broadly at physiological contributors to Virchow's triad underpinning acute coronary syndrome.

  View details for PubMedID 29268883

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

  Abstract

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

  View details for PubMedID 29217004

• ACIST-FFR Study (Assessment of Catheter-Based Interrogation and Standard Techniques for Fractional Flow Reserve Measurement). Circulation. Cardiovascular interventions Fearon, W. F., Chambers, J. W., Seto, A. H., Sarembock, I. J., Raveendran, G., Sakarovitch, C., Yang, L., Desai, M., Jeremias, A., Price, M. J., ACIST-FFR Study Investigators 2017; 10 (12)

  Abstract

  BACKGROUND: Measurement of fractional flow reserve (FFR) to guide coronary revascularization lags despite robust supportive data, partly because of the handling characteristics of traditional coronary pressure wires. An optical pressure-monitoring microcatheter, which can be advanced over a traditional coronary guidewire, facilitates FFR assessment but may underestimate pressure wire-derived FFR.METHODS AND RESULTS: In this prospective, multicenter trial, 169 patients underwent FFR assessment with a pressure wire alone and with a pressure microcatheter over the pressure wire. An independent core laboratory performed quantitative coronary angiography and evaluated all pressure tracings. The primary end point was the bias or difference between the microcatheter FFR and the pressure wire FFR, as assessed by Bland-Altman analysis. The mean difference between the microcatheter and the pressure wire-derived FFR values was -0.022 (95% confidence interval, -0.029 to -0.015). On multivariable analysis, reference vessel diameter (P=0.027) and lesion length (P=0.044) were independent predictors of bias between the 2 FFR measurements. When the microcatheter FFR was added to this model, it was the only independent predictor of bias (P<0.001). The mean FFR value from the microcatheter was significantly lower than from the pressure wire (0.81 versus 0.83; P<0.001). In 3% of cases (95% confidence interval, 1.3%-6.7%), there was clinically meaningful diagnostic discordance, with the FFR from the pressure wire >0.80 and that from the microcatheter <0.75. These findings were similar when including all 210 patients with site-reported paired FFR data.CONCLUSIONS: An optical, pressure-monitoring microcatheter measures lower FFR compared with a pressure wire, but the diagnostic impact appears to be minimal in most cases.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02577484.

  View details for PubMedID 29246917

• ACIST-FFR Study (Assessment of Catheter-Based Interrogation and Standard Techniques for Fractional Flow Reserve Measurement) CIRCULATION-CARDIOVASCULAR INTERVENTIONS Fearon, W. F., Chambers, J. W., Seto, A. H., Sarembock, I. J., Raveendran, G., Sakarovitch, C., Yang, L., Desai, M., Jeremias, A., Price, M. J., ACIST-FFR Study Investigators 2017; 10 (12)

  View details for DOI 10.1161/CIRCINTERVENTIONS.117.005905

  View details for Web of Science ID 000418461700011

• The Prognostic Value of Residual Coronary Stenosis After "Functionally" Complete Revascularization in Acute Coronary Syndrome: Insights from the DANAMI-3-PRIMULTI, FAME, and FAMOUS-NSTEMI Kobayashi, Y., Lonborg, J., Jong, A., Nishi, T., De Bruyne, B., Hofsten, D., Kelbaek, H., Layland, J., Nam, C., Pijls, N., Tonino, P., Warnoe, J., Oldroyd, K., Berry, C., Engstroem, T., Fearon, W. ELSEVIER SCIENCE INC. 2017: B301–B302

  View details for Web of Science ID 000413459200738

• Long-Term Prognostic Value of Invasive and Non-Invasive Measures Early after Heart Transplantation Kobayashi, Y., Kobayashi, Y., Luikart, H., Nishi, T., Choi, D., Schnittger, I., Fearon, W. ELSEVIER SCIENCE INC. 2017: B273

  View details for Web of Science ID 000413459200664

• Brief Cognitive Behavioral Therapy for Patients Undergoing TAVR: A Randomized Controlled Trial Edwards, K., Hossepian, D., Johnson, A., Dao, C., Shah, S., Fearon, W. ELSEVIER SCIENCE INC. 2017: B174

  View details for Web of Science ID 000413459200423

• Atrial Fibrillation is Associated with Increased Mortality in Intermediate-Risk Patients Undergoing TAVR or SAVR: Insights From the PARTNER 2A and PARTNER 2 S3i Trials Biviano, A., Nazif, T., Dizon, J., Garan, H., Crowley, A., Malaisrie, S., Makkar, R., Thourani, V., Mack, M., Szeto, W. Y., Fearon, W., Leon, M., Kodali, S. ELSEVIER SCIENCE INC. 2017: B46–B47

  View details for Web of Science ID 000413459200107

• The Myocardial Contraction Fraction Predicts Adverse Events after Aortic Valve Replacement: An Analysis of 3,259 Patients from the Pooled PARTNER 2 Database Madhavan, M., Maurer, M., Redfors, B., Jaber, W., Pibarot, P., Douglas, P., Makkar, R., Thourani, V., Herrmann, H., Desai, N., Mack, M., Elmariah, S., Fearon, W., Lindman, B., Blanke, P., Leipsic, J., Zhang, Y., McAndrew, T., Alu, M., Kodali, S., Leon, M., Hahn, R. ELSEVIER SCIENCE INC. 2017: B158

  View details for Web of Science ID 000413459200383

• Response by Piroth et al to Letter Regarding Article, "Prognostic Value of Fractional Flow Reserve Measured Immediately After Drug-Eluting Stent Implantation". Circulation. Cardiovascular interventions Piroth, Z., Toth, G. G., Tonino, P. A., Barbato, E., Aghlmandi, S., Curzen, N., Rioufol, G., Pijls, N. H., Fearon, W. F., Jüni, P., De Bruyne, B. 2017; 10 (10)

  View details for DOI 10.1161/CIRCINTERVENTIONS.117.005973

  View details for PubMedID 29038228

• Response by Pirothet al to Letter Regarding Article, "Prognostic Value of Fractional Flow Reserve Measured Immediately After Drug-Eluting Stent Implantation" CIRCULATION-CARDIOVASCULAR INTERVENTIONS Piroth, Z., Toth, G. G., Tonino, P. L., Barbato, E., Aghlmandi, S., Curzen, N., Rioufol, G., Pijls, N. J., Fearon, W. F., Juni, P., De Bruyne, B. 2017; 10 (10)

  View details for DOI 10.1161/CIRCINTERVENTIONS.117.005973

  View details for Web of Science ID 000413088100014

• The effect of negative remodeling on fractional flow reserve after cardiac transplantation INTERNATIONAL JOURNAL OF CARDIOLOGY Fearon, W. F., Felix, R., Hirohata, A., Sakurai, R., Jose, P. O., Yamasaki, M., Nakamura, M., Fitzgerald, P. J., Valantine, H. A., Yock, P. G., Yeung, A. C. 2017; 241: 283–87

  Abstract

  Negative remodeling is a common occurrence early after cardiac transplantation. Its impact on the development of myocardial ischemia is not well documented. The aim of this study is to investigate the impact of negative remodeling on fractional flow reserve after cardiac transplantation.Thirty-four cardiac transplant recipients underwent intravascular ultrasound (IVUS) and fractional flow reserve (FFR) assessment soon after transplantation and one year later. Patients were divided into those with and without negative remodeling based on IVUS, and the impact on FFR was assessed. In the 19 patients with negative remodeling, there was no significant change in plaque volume (119.3±82.0 to 131.3±91.2mm3, p=0.21), but vessel volume (775.6±212.0 to 621.9±144.1mm3, p<0.0001) and lumen volume (656.3±169.1 to 490.7±132.0mm3, p<0.0001) decreased significantly and FFR likewise decreased significantly (0.88±0.06 to 0.84±0.07, p=0.04). In the 15 patients without negative remodeling, vessel volume did not change (711.7±217.6 to 745.7±198.5, p=0.28), but there was a significant increase in plaque volume (126.8±88.3 to 194.4±92.7, p<0.001) and a resultant significant decrease in FFR (0.89±0.05 to 0.85±0.05, p=0.01).Negative remodeling itself, without any change in plaque volume can cause a significant decrease in fractional flow reserve after cardiac transplantation and appears to be another possible mechanism for myocardial ischemia.

  View details for PubMedID 28413112

• Prognostic Value of Fractional Flow Reserve Measured Immediately After Drug-Eluting Stent Implantation CIRCULATION-CARDIOVASCULAR INTERVENTIONS Piroth, Z., Toth, G. G., Tonino, P. L., Barbato, E., Aghlmandi, S., Curzen, N., Rioufol, G., Pijls, N. J., Fearon, W. F., Juni, P., De Bruyne, B. 2017; 10 (8)

  Abstract

  The predictive value of fractional flow reserve (FFR) measured immediately after percutaneous coronary intervention (PCI) with drug-eluting stent placement has not been prospectively investigated. We investigated the potential of post-PCI FFR measurements to predict clinical outcome in patients from FAME 1 and 2 trials (Fractional Flow Reserve or Angiography for Multivessel Evaluation).All patients of FAME 1 and FAME 2 who had post-PCI FFR measurement were included. The primary outcome was vessel-oriented composite end point at 2 years, defined as vessel-related cardiovascular death, vessel-related spontaneous myocardial infarction, and ischemia-driven target vessel revascularization. Eight hundred thirty-eight vessels in 639 patients were analyzed. Baseline FFR values did not differ between vessels with versus without vessel-oriented composite end point (0.66±0.11 versus 0.63±0.14, respectively; P=0.207). Post-PCI FFR was significantly lower in vessels with vessel-oriented composite end point (0.88±0.06 versus 0.90±0.06, respectively; P=0.019). Comparing the 2-year outcome of lower and upper tertiles of post-PCI FFR significant difference was found favoring upper tertile in terms of overall vessel-oriented composite end point (9.2% versus 3.8%, respectively; hazard ratio, 1.46; 95% confidence interval, 1.02-2.08; P=0.037) and target vessel revascularization (7.0% versus 2.4%, respectively; hazard ratio, 1.59; 95% confidence interval, 1.03-2.46; P=0.037). When adjusted to sex, hypertension, diabetes mellitus, target vessel, serial stenosis, and baseline percentage diameter stenosis, a strong trend was preserved in terms of target vessel revascularization (harzard ratio, 1.55; 95% confidence interval, 0.97-2.46; P=0.066), favoring the upper tertile. Post-PCI FFR of 0.92 was found to have the highest diagnostic accuracy; however, the positive likelihood ratio remained low (<1.4).A higher post-PCI FFR value is associated with a better vessel-related outcome. However, its predictive value is too low to advocate its use as a surrogate clinical end point.

  View details for PubMedID 28790165

• The relationship between coronary artery distensibility and fractional flow reserve PLOS ONE Yong, A. C., Javadzadegan, A., Fearon, W. F., Moshfegh, A., Lau, J. K., Nicholls, S., Ng, M. C., Kritharides, L. 2017; 12 (7): e0181824

  Abstract

  Discordance between angiography-based anatomical assessment of coronary stenosis severity and fractional flow reserve (FFR) has been attributed to several factors including lesion length and irregularity, and the myocardial territory supplied by the target vessel. We sought to examine if coronary arterial distensibility is an independent contributor to this discordance. There were two parts to this study. The first consisted of "in silico" models of 26 human coronary arteries. Computational fluid dynamics-derived FFR was calculated for fully rigid, partially distensible and fully distensible models of the 26 arteries. The second part of the study consisted of 104 patients who underwent coronary angiography and FFR measurement. Distensibility at the lesion site (DistensibilityMLA) and for the reference vessel (DistensibilityRef) was determined by analysing three-dimensional angiography images during end-systole and end-diastole. Computational fluid dynamics-derived FFR was 0.67±0.19, 0.70±0.18 and 0.75±0.17 (P<0.001) in the fully rigid, partially distensible and fully distensible models respectively. FFR correlated with both DistensibilityMLA (r = 0.36, P<0.001) and DistensibilityRef (r = 0.44, P<0.001). Two-way ANCOVA analysis revealed that DistensibilityMLA (F (1, 100) = 4.17, p = 0.031) and percentage diameter stenosis (F (1, 100) = 60.30, p < 0.01) were both independent predictors of FFR. Coronary arterial distensibility is a novel, independent determinant of FFR, and an important factor contributing to the discordance between anatomical and functional assessment of stenosis severity.

  View details for PubMedID 28742827

• Accuracy of Fractional Flow Reserve Measurements in Clinical Practice Observations From a Core Laboratory Analysis JACC-CARDIOVASCULAR INTERVENTIONS Matsumura, M., Johnson, N. P., Fearon, W. F., Mintz, G. S., Stone, G. W., Oldroyd, K. G., De Bruyne, B., Pijls, N. J., Maehara, A., Jeremias, A. 2017; 10 (14): 1392–1401

  Abstract

  The aim of this study was to compare site-reported measurements of fractional flow reserve (FFR) with FFR analysis by an independent core laboratory (CL).FFR is an index of coronary stenosis severity that has been validated in multiple trials and is widely used in clinical practice. However, the incidence of suboptimal FFR measurements is unknown.Patients undergoing FFR assessment within the CONTRAST (Can Contrast Injection Better Approximate FFR Compared to Pure Resting Physiology) study had paired, repeated measurements of multiple physiological metrics per local practice. An independent central physiology CL analyzed blinded pressure tracings off-line in a standardized fashion for comparison.A total of 763 patients were included in the study; 4,946 distal coronary artery pressure/aortic pressure (nonhyperemic) and FFR tracings were analyzed by the CL (mean 6.5 tracings per patient). Pull-back data were available for 616 patients (80.7%), of whom 108 (17.5%) had signal drift, defined as distal coronary artery pressure/aortic pressure (nonhyperemic) <0.97 or >1.03. Among the remaining 4,217 tracings without evidence of signal drift, 222 (5.3%) were noted to have ventricularization of the aortic waveform, and 168 (4.0%) had aortic waveform distortion. Excluding cases with signal drift and waveform distortion, there was excellent agreement between CL-calculated and site-reported FFR, with a mean difference of 0.003 ± 0.02. Predictors of distorted waveforms were smaller guiding catheter size (odds ratio: 6.30; 95% confidence interval: 3.22 to 12.32; p < 0.001) and intracoronary adenosine use (odds ratio: 0.13; 95% confidence interval: 0.05 to 0.33; p < 0.001).This FFR CL analysis showed that almost 10% of tracings demonstrated waveform artifacts, and an additional 17.5% had signal drift. Among adequate tracings, there was a close correlation between site-reported and CL-analyzed FFR values. Attention to detail is critical for FFR studies to ensure adequate technique and optimal results.

  View details for PubMedID 28728652

• Atrial Fibrillation is Associated with Increased Pacemaker Implantation Rates in the Placement of AoRTic Transcatheter Valve (PARTNER) Trial. Journal of atrial fibrillation Biviano, A. B., Nazif, T., Dizon, J., Garan, H., Abrams, M., Fleitman, J., Hassan, D., Kapadia, S., Babaliaros, V., Xu, K., Rodes-Cabau, J., Szeto, W. Y., Fearon, W. F., Dvir, D., Dewey, T., Williams, M., Kindsvater, S., Mack, M. J., Webb, J. G., Craig Miller, D., Smith, C. R., Leon, M. B., Kodali, S. 2017; 10 (1): 1494

  Abstract

  Atrial fibrillation (AF) is associated with worse outcomes in many cardiovascular diseases. There are few data examining pacemaker implantation rates and indications in patients with AF who undergo transcatheter aortic valve replacement (TAVR). To examine the impact of AF on the incidence of and indications for pacemakers in patients undergoing TAVR, we evaluated data of 1723 patients without pre-existing pacemakers who underwent TAVR in the Placement of AoRTic TraNscathetER Valve (PARTNER) trial. Permanent pacemaker implantation rates and indications were compared in groups based on baseline and discharge heart rhythm: sinus rhythm (SR) vs. AF. 1211 patients manifested SR at baseline/SR at discharge (SR/SR), 105 SR baseline/AF discharge (SR/AF), and 407 AF baseline/AF discharge (AF/AF). Patients who developed and were discharged with AF (SR/AF) had the highest rates of pacemaker implantation at 30 days (13.7% SR/AF vs. 5.4% SR/SR, p=0.0008 and 5.9% AF/AF, p=0.008) and 1 year (17.7% SR/AF vs. 7.1% SR/SR, p=0.0002 and 8.1% AF/AF, p=0.0034). Conversion from SR to AF by discharge was an independent predictor of increased pacemaker implantation at 30 days (HR 2.19 vs. SR/SR, 95% CI 1.23-3.93, p=0.008) and 1 year (HR 1.91 vs. SR/SR, 95% CI 1.33-3.80). Pacemaker indications differed between groups, with relatively more implanted in the AF groups for sick sinus syndrome (SSS) versus AV block. In conclusion, conversion to AF is an independent predictor of permanent pacemaker implantation in TAVR patients. Indications differ depending on heart rhythm, with patients in AF manifesting clinically significant tachy-brady syndrome versus AV block.

  View details for PubMedID 29250217

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

  Abstract

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

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

  View details for PubMedID 28516313

• Adjuvant Antithrombotic Therapy in TAVR CURRENT CARDIOLOGY REPORTS O'Malley, R. G., Mahaffey, K. W., Fearon, W. F. 2017; 19 (5)

  Abstract

  Transcatheter aortic valve replacement (TAVR) has developed into an important alternative to surgical aortic valve replacement (SAVR) for patients with severe aortic stenosis (AS). Adjuvant antithrombotic therapies are commonly used during and after TAVR to decrease the risk of valve thrombosis and thromboembolic cerebrovascular events (CVEs) but consequently increase the risk of bleeding. This article reviews the past and current clinical data regarding adjuvant antithrombotic therapies in TAVR.Cerebrovascular and bleeding events during and after TAVR are associated with substantial morbidity and mortality. Bivalirudin, a direct thrombin inhibitor, has been shown to be safe alternative to unfractionated heparin (UFH) as procedural anticoagulation during TAVR; however, sparse evidence exists to guide use of antiplatelet and anticoagulant therapies in patients after TAVR. Multiple studies comparing different antithrombotic regimens in the post-TAVR setting are currently underway. Current guidelines recommend intra-procedural anticoagulation with UFH for during TAVR and with dual antiplatelet therapy (DAPT) after TAVR. There is a need to better understand the role of adjuvant antithrombotic therapies in TAVR. The results of ongoing studies are needed to develop evidence-based guidance for the use of adjuvant antithrombotic therapies after TAVR.

  View details for DOI 10.1007/s11886-017-0850-1

  View details for PubMedID 28391560

• Collateral Damage Sufficient Coronary Collaterals Provide Important, Yet Limited, Protection in Chronic Total Occlusions JACC-CARDIOVASCULAR INTERVENTIONS Parikh, R. V., Fearon, W. F. 2017; 10 (6): 594–96

  View details for PubMedID 28335896

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

  View details for Web of Science ID 000397342301562

• SEX DIFFERENCES IN THE RISK FACTORS FOR ENDOTHELIAL AND MICROVASCULAR DYSFUNCTION IN PATIENTS WITH ANGINA IN THE ABSENCE OF OBSTRUCTIVE CORONARY ARTERY DISEASE Pargaonkar, V., Kobayashi, Y., Kimura, T., Lee, D., Stefanick, M., Fearon, W., Yeung, A., Tremmel, J. ELSEVIER SCIENCE INC. 2017: 1749

  View details for Web of Science ID 000397342302471

• Diabetes does not impact the diagnostic performance of contrast-based fractional flow reserve: insights from the CONTRAST study CARDIOVASCULAR DIABETOLOGY Gargiulo, G., Stabile, E., Ferrone, M., Barbato, E., Zimmermann, F. M., Adjedj, J., Hennigan, B., Matsumura, M., Johnson, N. P., Fearon, W. F., Jeremias, A., Trimarco, B., Esposito, G. 2017; 16

  Abstract

  Adenosine-free coronary pressure wire metrics have been proposed to test the functional significance of coronary artery lesions, but it is unexplored whether their diagnostic performance might be altered in patients with diabetes.We performed a post-hoc analysis of the CONTRAST study, which prospectively enrolled an international cohort of patients undergoing routine fractional flow reserve (FFR) assessment for standard indications. Paired, repeated measurements of all physiology metrics (Pd/Pa, iFR, contrast-based FFR, and FFR) were made. A central core laboratory analyzed blinded pressure tracings in a standardized fashion.Of 763 subjects enrolled at 12 international centers, 219 (29%) had diabetes. The two groups were well-balanced for age, clinical presentation (stable or unstable), coronary vessel studied, volume and type of intracoronary contrast, and volume of intracoronary adenosine. A binary threshold of cFFR ≤ 0.83 produced an accuracy superior to both Pd/Pa and iFR when compared with FFR ≤ 0.80 in the absence of significant interaction with diabetes status; indeed, accuracy in subgroups of patients with or without diabetes was similar for cFFR (86.7 vs 85.4% respectively; p = 0.76), iFR (84.2 vs 80.0%, p = 0.29) and Pd/Pa (81.3 vs 78.9%, p = 0.55). There was no significant heterogeneity between patients with or without diabetes in terms of sensitivity and specificity of all metrics. The area under the receiver operating characteristic (ROC) curve was largest for cFFR compared with Pd/Pa and iFR which were equivalent (cFFR 0.961 and 0.928; Pd/Pa 0.916 and 0.870; iFR 0.911 and 0.861 in diabetic and non-diabetic patients respectively).cFFR provides superior diagnostic performance compared with Pd/Pa or iFR for predicting FFR irrespective of diabetes (clinicaltrials.gov identifier NCT02184117).

  View details for DOI 10.1186/s12933-016-0494-2

  View details for PubMedID 28086778

• Clinical value of post-percutaneous coronary intervention fractional flow reserve value: A systematic review and meta-analysis AMERICAN HEART JOURNAL Rimac, G., Fearon, W. F., De Bruyne, B., Ikeno, F., Matsuo, H., Piroth, Z., Costerousse, O., Bertrand, O. F. 2017; 183: 1-9

  Abstract

  Fractional flow reserve (FFR) prior to percutaneous coronary intervention (PCI) is useful to guide treatment. Whether post-PCI FFR assessment might have clinical impact is controversial. The aim of this study is to evaluate the range of post-PCI FFR values and analyze the relationship between post-PCI FFR and clinical outcomes.We systematically searched the PubMed, EMBASE, and Cochrane Library databases with cross-referencing of articles reporting post-PCI FFR and correlating post-PCI FFR values and clinical outcomes. The outcomes of interest were the immediate post-PCI FFR values and the correlations between post-PCI FFR and the incidence of repeat intervention and major adverse cardiac events (MACE).From 1995 to 2015, a total of 105 studies (n = 7470) were included, with 46 studies reporting post-PCI FFR and 59 studies evaluating relationship between post-PCI and clinical outcomes up to 30 months after PCI. Overall, post-PCI FFR values demonstrated a normal distribution with a mean value of 0.90 ± 0.04. There was a positive correlation between the percentage of stent use and post-PCI FFR (P < .0001). Meta-regression analysis indicated that higher post-PCI FFR values were associated with reduced rates of repeat intervention (P < .0001) and MACE (P = .0013). A post-PCI FFR ≥0.90 was associated with significantly lower risk of repeat PCI (odds ratio 0.43, 95% CI 0.34-0.56, P < .0001) and MACE (odds ratio 0.71, 95% CI 0.59-0.85, P = .0003).FFR measurement after PCI was associated with prognostic significance. Further investigation is required to assess the role of post-PCI FFR and validate cutoff values in contemporary clinical practice.

  View details for DOI 10.1016/j.ahj.2016.10.005

  View details for PubMedID 27979031

• Moving Beyond Linear Formulas for Left Ventricular Mass in Aortic Valve Replacement Structural Heart Moneghetti , K. J., Bouajila, S., Kobayashi, Y., Kim, J., Fearon, W., Haddad, F. 2017

  View details for DOI 10.1080/24748706.2017.1377364

• Agreement of the Resting Distal to Aortic Coronary Pressure With the Instantaneous Wave-Free Ratio. Journal of the American College of Cardiology Kobayashi, Y. n., Johnson, N. P., Zimmermann, F. M., Witt, N. n., Berry, C. n., Jeremias, A. n., Koo, B. K., Esposito, G. n., Rioufol, G. n., Park, S. J., Nishi, T. n., Choi, D. H., Oldroyd, K. G., Barbato, E. n., Pijls, N. H., De Bruyne, B. n., Fearon, W. F. 2017; 70 (17): 2105–13

  Abstract

  Recently, 2 randomized controlled trials showed that the instantaneous wave-free ratio (iFR), a resting coronary physiological index, is noninferior to fractional flow reserve for guiding revascularization. The resting distal to aortic coronary pressure (Pd/Pa) measured at rest is another adenosine-free index widely available in the cardiac catheterization laboratory; however, little is known about the agreement of Pd/Pa using iFR as a reference standard.The goal of this study was to investigate the agreement of Pd/Pa with iFR.A total of 763 patients were prospectively enrolled from 12 institutions. iFR and Pd/Pa were measured under resting conditions. Using iFR ≤0.89 as a reference standard, the agreement of Pd/Pa and its best cutoff value were assessed.According to the independent core laboratory analysis, iFR and Pd/Pa were analyzable in 627 and 733 patients (82.2% vs. 96.1%; p < 0.001), respectively. The median iFR and Pd/Pa were 0.90 (interquartile range: 0.85 to 0.94) and 0.92 (interquartile range: 0.88 to 0.95), and the 2 indices were highly correlated (R(2) = 0.93; p < 0.001; iFR = 1.31 * Pd/Pa -0.31). According to the receiver-operating characteristic curve analysis, Pd/Pa showed excellent agreement (area under the curve: 0.98; 95% confidence interval: 0.97 to 0.99; p < 0.001) with a best cutoff value of Pd/Pa ≤0.91. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 93.0%, 91.4%, 94.4%, 93.3%, and 92.7%, respectively. These results were similar in patients with acute coronary syndrome and stable angina.Pd/Pa was analyzable in a significantly higher number of patients than iFR. Pd/Pa showed excellent agreement with iFR, suggesting that it could be applied clinically in a similar fashion. (Can Contrast Injection Better Approximate FFR Compared to Pure Resting Physiology? [CONTRAST]; NCT02184117).

  View details for PubMedID 29050557

• Impact of Asymmetric Dimethylarginine on Coronary Physiology Early After Heart Transplantation. The American journal of cardiology Parikh, R. V., Khush, K. K., Luikart, H. n., Pargaonkar, V. S., Kobayashi, Y. n., Lee, J. H., Sinha, S. n., Cohen, G. n., Valantine, H. A., Yeung, A. C., Fearon, W. F. 2017

  Abstract

  Cardiac allograft vasculopathy is a major cause of long-term graft failure following heart transplantation. Asymmetric dimethylarginine (ADMA), a marker of endothelial dysfunction, has been mechanistically implicated in the development of cardiac allograft vasculopathy, but its impact on coronary physiology early after transplantation is unknown. Invasive indices of coronary physiology, namely, fractional flow reserve (FFR), the index of microcirculatory resistance, and coronary flow reserve, were measured with a coronary pressure wire in the left anterior descending artery within 8 weeks (baseline) and 1 year after transplant. Plasma levels of ADMA were concurrently assayed using high-performance liquid chromatography. In 46 heart transplant recipients, there was a statistically significant correlation between elevated ADMA levels and lower FFR values at baseline (r = -0.33; p = 0.024); this modest association persisted 1 year after transplant (r = -0.39; p = 0.0085). Patients with a baseline FFR <0.90 (a prognostically validated cutoff) had significantly higher baseline ADMA levels (0.63 ± 0.16 vs 0.54 ± 0.12 µM; p = 0.034). Baseline ADMA (odds ratio 1.80 per 0.1 µM; 95% confidence interval 1.07 to 3.03; p = 0.027) independently predicted a baseline FFR <0.90 after multivariable adjustment. Even after dichotomizing ADMA (≥0.60 µM, provides greatest diagnostic accuracy by receiver operating characteristic curve), this association remained significant (odds ratio 7.52, 95% confidence interval 1.74 to 32.49; p = 0.006). No significant relationship between ADMA and index of microcirculatory resistance or coronary flow reserve was detected. In conclusion, baseline ADMA was a strong independent predictor of FFR <0.90, suggesting that elevated ADMA levels are associated with abnormal epicardial function soon after heart transplantation.

  View details for PubMedID 28754566

• Coronary Endothelial Dysfunction and the Index of Microcirculatory Resistance as a Marker of Subsequent Development of Cardiac Allograft Vasculopathy. Circulation Lee, J. H., Okada, K. n., Khush, K. n., Kobayashi, Y. n., Sinha, S. n., Luikart, H. n., Valantine, H. n., Yeung, A. C., Honda, Y. n., Fearon, W. F. 2017; 135 (11): 1093–95

  View details for PubMedID 28289008

• Angiotensin-Converting Enzyme Inhibition Early After Heart Transplantation. Journal of the American College of Cardiology Fearon, W. F., Okada, K. n., Kobashigawa, J. A., Kobayashi, Y. n., Luikart, H. n., Sana, S. n., Daun, T. n., Chmura, S. A., Sinha, S. n., Cohen, G. n., Honda, Y. n., Pham, M. n., Lewis, D. B., Bernstein, D. n., Yeung, A. C., Valantine, H. A., Khush, K. n. 2017; 69 (23): 2832–41

  Abstract

  Cardiac allograft vasculopathy (CAV) remains a leading cause of mortality after heart transplantation (HT). Angiotensin-converting enzyme inhibitors (ACEIs) may retard the development of CAV but have not been well studied after HT.This study tested the safety and efficacy of the ACEI ramipril on the development of CAV early after HT.In this prospective, multicenter, randomized, double-blind, placebo-controlled trial, 96 HT recipients were randomized to undergo ramipril or placebo therapy. They underwent coronary angiography, endothelial function testing; measurements of fractional flow reserve (FFR) and coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR); and intravascular ultrasonography (IVUS) of the left anterior descending coronary artery, within 8 weeks of HT. At 1 year, the invasive assessment was repeated. Circulating endothelial progenitor cells (EPCs) were quantified at baseline and 1 year.Plaque volumes at 1 year were similar between the ramipril and placebo groups (162.1 ± 70.5 mm(3) vs. 177.3 ± 94.3 mm(3), respectively; p = 0.73). Patients receiving ramipril had improvement in microvascular function as shown by a significant decrease in IMR (21.4 ± 14.7 to 14.4 ± 6.3; p = 0.001) and increase in CFR (3.8 ± 1.7 to 4.8 ± 1.5; p = 0.017), from baseline to 1 year. This did not occur with IMR (17.4 ± 8.4 to 21.5 ± 20.0; p = 0.72) or CFR (4.1 ± 1.8 to 4.1 ± 2.2; p = 0.60) in the placebo-treated patients. EPCs decreased significantly at 1 year in the placebo group but not in the ramipril group.Ramipril does not slow development of epicardial plaque volume but does stabilize levels of endothelial progenitor cells and improve microvascular function, which have been associated with improved long-term survival after HT. (Angiotensin Converting Enzyme [ACE] Inhibition and Cardiac Allograft Vasculopathy; NCT01078363).

  View details for PubMedID 28595700

• Three-Vessel Assessment of Coronary Microvascular Dysfunction in Patients With Clinical Suspicion of Ischemia: Prospective Observational Study With the Index of Microcirculatory Resistance. Circulation. Cardiovascular interventions Kobayashi, Y. n., Lee, J. M., Fearon, W. F., Lee, J. H., Nishi, T. n., Choi, D. H., Zimmermann, F. M., Jung, J. H., Lee, H. J., Doh, J. H., Nam, C. W., Shin, E. S., Koo, B. K. 2017; 10 (11)

  Abstract

  Difficulty directly visualizing the coronary microvasculature as opposed to the epicardial coronary artery makes its assessment challenging. The goal of this study is to measure the index of microcirculatory resistance (IMR) in all 3 major coronary vessels to identify the clinical and angiographic predictors of an abnormal IMR.Ninety-three patients who underwent coronary physiological assessment in all 3 major coronary vessels were prospectively enrolled (59.8±9.4 years with 77.4% men). IMR was corrected using Yong's formula and coronary microvascular dysfunction (CMD) was defined using vessel-specific cutoffs. A global IMR was calculated as the sum of the IMR in all 3 major epicardial vessels. Angiographic epicardial disease severity was assessed with vessel-specific and overall SYNTAX score. Median IMR and fractional flow reserve was 17.2 (Q1-Q3: 13.3-22.9) and 0.92 (0.85-0.97). The majority of patients (59.1%) had no CMD, 23.7% had 1-vessel CMD, 14.0% had 2-vessel CMD, and 3.2% had 3-vessel CMD. CMD was observed at a similar rate in the territories supplied by all 3 major coronary vessels (left anterior descending coronary artery 28.0%, left circumflex artery 19.4%, and right coronary artery 23.7%; P=0.39). Fractional flow reserve had a weak, positive correlation with IMR (ρ=0.16; P<0.01). The SYNTAX score had no significant correlation with IMR, both at a patient level (ρ=-0.002; P=0.99) and a vessel-specific level (ρ=-0.06; P=0.36). By multivariable ordinal logistic regression analysis, no variable was left as an independent predictor of an abnormal IMR.Clinical factors and epicardial coronary disease severity are not predictors of the extent of CMD.URL: https://www.clinicaltrials.gov. Unique identifier: NCT01621438.

  View details for PubMedID 29146670

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

  Abstract

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

  View details for PubMedID 29222133

• The ratio of circulating regulatory cluster of differentiation 4 T cells to endothelial progenitor cells predicts clinically significant acute rejection after heart transplantation. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Choi, D. H., Chmura, S. A., Ramachandran, V. n., Dionis-Petersen, K. Y., Kobayashi, Y. n., Nishi, T. n., Luikart, H. n., Dimbil, S. n., Kobashigawa, J. n., Khush, K. n., Lewis, D. B., Fearon, W. F. 2017

  Abstract

  The aim of this study was to determine the value of the ratio of the percentage of circulating regulatory cluster of differentiation 4 T cells (%Tregs) to the percentage of endothelial progenitor cells (%EPCs; Treg/EPC ratio) for predicting clinically significant acute rejection.Peripheral blood %Tregs and %EPCs were quantified in 91 cardiac transplant recipients using flow cytometry at a mean of 42 ± 13 days after transplant. The primary end point was clinically significant acute rejection, defined as an event that led to an acute augmentation of immunosuppression in conjunction with an International Society for Heart and Lung Transplantation grade ≥ 2R in a right ventricular endomyocardial biopsy specimen or non-cellular rejection (specimen-negative rejection) with hemodynamic compromise (decrease in left ventricular ejection fraction by > 25%).Significant rejection occurred in 27 recipients (29.7%) during a median of 49.4 months (interquartile range, 37.0-62.0 months). The mean %Tregs and %EPCs were not significantly different between those with and without an episode of significant rejection, but the mean Treg/EPC ratio was significantly lower in recipients with significant rejection (44.9 vs 106.7, p = 0.001). Receiver operating characteristic curve analysis showed an area under the curve value for significant rejection for a Treg/EPC ratio of 0.712. The best cutoff value of the Treg/EPC ratio that distinguished between those with or without significant rejection was ≤ 18 by receiver operating characteristic curve analysis. Kaplan-Meier analysis revealed that patients with a Treg/EPC ratio of ≤ 18 had a significantly higher rate of rejection than those with a Treg/EPC ratio > 18 (61.5% vs 16.9%, log-rank p < 0.0001). A low Treg/EPC ratio was an independent predictor of significant rejection.A low Treg/EPC ratio measured soon after heart transplantation is an independent predictor of acute rejection. The Treg/EPC ratio has potential as an early biomarker after heart transplantation for predicting acute rejection.

  View details for PubMedID 29198869

• Incremental Value of Deformation Imaging and Hemodynamics Following Heart Transplantation: Insights From Graft Function Profiling. JACC. Heart failure Kobayashi, Y. n., Sudini, N. L., Rhee, J. W., Aymami, M. n., Moneghetti, K. J., Bouajila, S. n., Kobayashi, Y. n., Kim, J. B., Schnittger, I. n., Teuteberg, J. J., Khush, K. K., Fearon, W. F., Haddad, F. n. 2017; 5 (12): 930–39

  Abstract

  This study investigated to define graft dysfunction and to determine its incremental association with long-term outcome after heart transplantation (HT).Although graft failure is an established cause of late mortality after HT, few studies have analyzed the prognostic value of graft dysfunction at 1- and 5-year follow-up of HT.Patients who underwent HT and completed their first annual evaluation with right heart catheterization and echocardiography at Stanford University between January 1999 and December 2011 were included in the study. Hierarchical clustering was used to identify modules to capture independent features of graft dysfunction at 1 year. The primary endpoint for analysis consisted of the composite of cardiovascular mortality, re-transplantation, or heart failure hospitalization within 5 years of HT. The study further explored whether changes in graft dysfunction between 1 and 5 years were associated with 10-year all-cause mortality.A total of 215 HT recipients were included in the study. Using hierarchical clustering, 3 functional modules were identified; among them, left ventricular global longitudinal strain (LVGLS), stroke volume index, and right atrial pressure (RAP) or pulmonary capillary wedge pressure (PCWP) captured key features of graft function. Graft dysfunction based on pre defined LVGLS in absolute value <14%, stroke volume index <35 ml/m2, RAP >10 mm Hg, or PCWP >15 mm Hg were present in 41%, 36%, and 27%, respectively. The primary endpoint at 5 years occurred in 52 patients (24%), whereas 10-year all-cause mortality occurred in 30 (27%) of 110 patients alive at 5 years. On multivariate analysis, RAP (standardized hazard ratio: 1.63), LVGLS (standardized hazard ratio: 1.39), and a history of hemodynamically compromising rejection within 1 year (hazard ratio: 2.18) were independent predictors of 5-year outcome. RAP at 5 years, as well as change in RAP from 1 to 5 years, was predictive of 10-year all-cause mortality.RAP and LVGLS at the first annual evaluation provide complementary prognostic information in predicting 5-year outcome after HT.

  View details for PubMedID 29191301

• Influence of Contrast Media Dose and Osmolality on the Diagnostic Performance of Contrast Fractional Flow Reserve. Circulation. Cardiovascular interventions Nishi, T. n., Johnson, N. P., De Bruyne, B. n., Berry, C. n., Gould, K. L., Jeremias, A. n., Oldroyd, K. G., Kobayashi, Y. n., Choi, D. H., Pijls, N. H., Fearon, W. F. 2017; 10 (10)

  Abstract

  Contrast fractional flow reserve (cFFR) is a method for assessing functional significance of coronary stenoses, which is more accurate than resting indices and does not require adenosine. However, contrast media volume and osmolality may affect the degree of hyperemia and therefore diagnostic performance.cFFR, instantaneous wave-free ratio, distal pressure/aortic pressure at rest, and FFR were measured in 763 patients from 12 centers. We compared the diagnostic performance of cFFR between patients receiving low or iso-osmolality contrast (n=574 versus 189) and low or high contrast volume (n=341 versus 422) using FFR≤0.80 as a reference standard. The sensitivity, specificity, and overall accuracy of cFFR for the low versus iso-osmolality groups were 73%, 93%, and 85% versus 87%, 90%, and 89%, and for the low versus high contrast volume groups were 69%, 99%, and 83% versus 82%, 93%, and 88%. By receiver operating characteristics (ROC) analysis, cFFR provided better diagnostic performance than resting indices regardless of contrast osmolality and volume (P<0.001 for all groups). There was no significant difference between the area under the curve of cFFR in the low- and iso-osmolality groups (0.938 versus 0.957; P=0.40) and in the low- and high-volume groups (0.939 versus 0.949; P=0.61). Multivariable logistic regression analysis showed that neither contrast osmolality nor volume affected the overall accuracy of cFFR; however, both affected the sensitivity and specificity.The overall accuracy of cFFR is greater than instantaneous wave-free ratio and distal pressure/aortic pressure and not significantly affected by contrast volume and osmolality. However, contrast volume and osmolality do affect the sensitivity and specificity of cFFR.URL: https://www.clinicaltrials.gov. Unique identifier: NCT02184117.

  View details for PubMedID 29042397

• The Influence of Lesion Location on the Diagnostic Accuracy of Adenosine-Free Coronary Pressure Wire Measurements JACC-CARDIOVASCULAR INTERVENTIONS Kobayashi, Y., Johnson, N. P., Berry, C., De Bruyne, B., Gould, K. L., Jeremias, A., Oldroyd, K. G., Pijls, N. H., Fearon, W. F. 2016; 9 (23): 2390-2399

  Abstract

  This work compares the diagnostic performance of adenosine-free coronary pressure wire indices based on lesion location.Several adenosine-free coronary pressure wire indices have been proposed to assess the functional significance of coronary artery lesions; however, there is a theoretical concern that lesion location and the mass of perfused myocardium may affect diagnostic performance.A total of 763 patients were prospectively enrolled from 12 institutions. Fractional flow reserve (FFR) and contrast-based FFR (cFFR) were obtained during adenosine-induced maximal hyperemia and contrast-induced submaximal hyperemia respectively, whereas the instantaneous wave-free ratio (iFR) and distal pressure/aortic pressure (Pd/Pa) were obtained at rest. Using an FFR of ≤0.80 as a reference standard, the diagnostic accuracy of each index was compared based on lesion location (left main or proximal left anterior descending artery [LM/pLAD] compared with other lesion locations).The median FFR, cFFR, iFR, and Pd/Pa were 0.81 (interquartile range [IQR]: 0.74 to 0.87), 0.86 (IQR: 0.79 to 0.91), 0.90 (IQR: 0.85 to 0.94), and 0.92 (IQR: 0.88 to 0.95), respectively. The cFFR, iFR, and Pd/Pa were less accurate in LM/pLAD compared with other lesion locations (cFFR: 80.3% vs. 87.8%; iFR: 73.3% vs. 81.8%; Pd/Pa: 71.4% vs. 81.1%, respectively). By receiver-operating characteristics curve analysis, cFFR provided better diagnostic accuracy than resting indices regardless of lesion location (p ≤0.0001 vs. iFR and Pd/Pa for both groups).The cFFR, iFR, and Pd/Pa are less accurate in LM/pLAD compared with other lesion locations, likely related to the larger amount of myocardium supplied by LM/pLAD. Nevertheless, cFFR provides the best diagnostic accuracy among the adenosine-free indices, regardless of lesion location.

  View details for DOI 10.1016/j.jcin.2016.08.041

  View details for PubMedID 27838269

• Non-invasive FFRCT revealing severe inducible ischaemia in an anomalous right coronary artery. European heart journal Zimmermann, F. M., Kobayashi, Y., Mullen, W. L., Fearon, W. F. 2016

  View details for PubMedID 27941015

• A Prospective Natural History Study of Coronary Atherosclerosis Using Fractional Flow Reserve JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Barbato, E., Toth, G. G., Johnson, N. P., Pijls, N. H., Fearon, W. F., Tonino, P. A., Curzen, N., Piroth, Z., Rioufol, G., Juni, P., De Bruyne, B. 2016; 68 (21): 2247-2255

  Abstract

  In patients with coronary artery disease, clinical outcome depends on the extent of reversible myocardial ischemia. Whether the outcome also depends on the severity of the stenosis as determined by fractional flow reserve (FFR) remains unknown.This study sought to investigate the relationship between FFR values and vessel-related clinical outcome.We prospectively studied major adverse cardiovascular events (MACE) at 2 years in 607 patients in whom all stenoses were assessed by FFR and who were treated with medical therapy alone. The relationship between FFR and 2-year MACE was assessed as a continuous function. Logistic and Cox proportional hazards regression models were used to calculate the average decrease in the risk of MACE per 0.05-U increase in FFR.MACE occurred in 272 (26.5%) of 1,029 lesions. Target lesions with diameter stenosis ≥70% were more often present in the MACE group (p < 0.01). Median FFR was significantly lower in the MACE group versus the non-MACE group (0.68 [interquartile range: 0.54 to 0.77] vs. 0.80 [interquartile range: 0.70 to 0.88]; p < 0.01). The cumulative incidence of MACE significantly increased with increasing FFR quartiles. An average decrease in MACE per 0.05-unit increase in FFR was statistically significant even after adjustment for all clinical and angiographic features (odds ratio: 0.81; 95% confidence interval: 0.76 to 0.86]). The strongest increase in MACE occurred for FFR values between 0.80 and 0.60. In multivariable Cox regression analysis, FFR was significantly associated with MACE up to 2 years (hazard ratio: 0.87; 95% confidence interval: 0.83 to 0.91]).In patients with stable coronary disease, stenosis severity as assessed by FFR is a major and independent predictor of lesion-related outcome. (FAME II - Fractional Flow Reserve [FFR] Guided Percutaneous Coronary Intervention [PCI] Plus Optimal Medical Treatment [OMT] Verses OMT; NCT01132495).

  View details for DOI 10.1016/j.jacc.2016.08.055

  View details for PubMedID 27884241

• The Independence of Coronary Microvascular Dysfunction from Epicardial Disease Severity: Three-Vessel Invasive Coronary Physiologic Study Kobayashi, Y., Lee, J., Fearon, W., Lee, J., Zimmermann, F., Jung, J., Lee, H., Doh, J., Nam, C., Shin, E., Koo, B. ELSEVIER SCIENCE INC. 2016: B210–B211

  View details for DOI 10.1016/j.jacc.2016.09.659

  View details for Web of Science ID 000398590400049

• Frailty in Intermediate Risk Patients Undergoing Transcatheter or Surgical Aortic Valve Replacement, Cut Points and Relationship With Outcomes: An Analysis of the Placement of Aortic Transcatheter Valves (PARTNER) 2 Cohort A Randomized Trial Green, P., Russo, M., Arnold, S., Doshi, D., Pichard, A., Szeto, W., Makkar, R., Babaliaros, V., Fearon, W., Svensson, L., Webb, J., Nazif, T., Zajarias, A., Quader, N., Parvataneni, R., Kirtane, A., Cohen, D., Mack, M., Leon, M. ELSEVIER SCIENCE INC. 2016: B15

  View details for DOI 10.1016/j.jacc.2016.09.058

  View details for Web of Science ID 000397332900037

• Qualitative Resting Wave Form Analysis to Predict an Abnormal Fractional Flow Reserve (FFR): A CONTRAST FFR Sub-Study Matsumura, M., Maehara, A., Johnson, N., Fearon, W., De Bruyne, B., Oldroyd, K., Pijls, N., Jenkins, P., Mintz, G., Stone, G., Jeremias, A. ELSEVIER SCIENCE INC. 2016: B209–B210

  View details for DOI 10.1016/j.jacc.2016.09.657

  View details for Web of Science ID 000398590400047

• Early Left Ventricular Dysfunction is Associated with Cardiac Allograft Vasculopathy and Late Mortality After Heart Transplantation Okada, K., Honda, Y., Luikart, H., Yock, P. G., Fitzgerald, P. J., Yeung, A. C., Valantine, H., Khush, K., Fearon, W. ELSEVIER SCIENCE INC. 2016: B331

  View details for DOI 10.1016/j.jacc.2016.09.909

  View details for Web of Science ID 000398590400337

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

  View details for DOI 10.1016/j.jacc.2016.09.150

  View details for Web of Science ID 000398590400257

• Pulling the RIPCORD FFRCT to Improve Interpretation of Coronary CT Angiography JACC-CARDIOVASCULAR IMAGING Fearon, W. F., Lee, J. 2016; 9 (10): 1195–97

  View details for PubMedID 27568112

• Fractional Flow Reserve in Acute Coronary Syndromes JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Fearon, W. F., De Bruyne, B., Pijls, N. J. 2016; 68 (11): 1192–94

  View details for PubMedID 27609681

• Attenuated-Signal Plaque Progression Predicts Long-Term Mortality After Heart Transplantation: IVUS Assessment of Cardiac Allograft Vasculopathy. Journal of the American College of Cardiology Okada, K., Fearon, W. F., Luikart, H., Kitahara, H., Otagiri, K., Tanaka, S., Kimura, T., Yock, P. G., Fitzgerald, P. J., Yeung, A. C., Valantine, H. A., Khush, K. K., Honda, Y. 2016; 68 (4): 382-392

  Abstract

  Although cardiac allograft vasculopathy (CAV) is typically characterized by diffuse coronary intimal thickening with pathological vessel remodeling, plaque instability may also play an important role in CAV. Previous studies of native coronary atherosclerosis have demonstrated associations between attenuated-signal plaque (ASP), plaque instability, and adverse clinical events.This study's aim was to characterize the association between ASP and long-term mortality post-heart transplantation.In 105 heart transplant recipients, serial (baseline and 1-year post-transplant) intravascular ultrasound was performed in the first 50 mm of the left anterior descending artery. The ASP score was calculated by grading the measured angle of attenuation from grades 0 to 4 (specifically, 0°, 1° to 90°, 91° to 180°, 181° to 270°, and >270°) at 1-mm intervals. The primary endpoint was all-cause death or retransplantation.At 1-year post-transplant, 10.5% of patients demonstrated ASP progression (newly developed or increased ASP). Patients with ASP progression had a higher incidence of acute cellular rejection during the first year (63.6% vs. 22.3%; p = 0.006) and tendency for greater intimal growth (percent intimal volume: 9.2 ± 9.3% vs. 4.4 ± 5.3%; p = 0.07) than those without. Over a median follow-up of 4.6 years, there was a significantly lower event-free survival rate in patients with ASP progression at 1-year post-transplant compared with those without. In contrast, maximum intimal thickness did not predict long-term mortality.ASP progression appears to reflect chronic inflammation related to acute cellular rejection and is an independent predictor of long-term mortality after heart transplantation. Serial assessments of plaque instability may enhance identification of high-risk patients who may benefit from closer follow-up and targeted medical therapies.

  View details for DOI 10.1016/j.jacc.2016.05.028

  View details for PubMedID 27443435

• Fractional Flow Reserve and Coronary Computed Tomographic Angiography A Review and Critical Analysis CIRCULATION RESEARCH Hecht, H. S., Narula, J., Fearon, W. F. 2016; 119 (2): 300–316

  Abstract

  Invasive fractional flow reserve (FFR) is now the gold standard for intervention. Noninvasive functional imaging analyses derived from coronary computed tomographic angiography (CTA) offer alternatives for evaluating lesion-specific ischemia. CT-FFR, CT myocardial perfusion imaging, and transluminal attenuation gradient/corrected contrast opacification have been studied using invasive FFR as the gold standard. CT-FFR has demonstrated significant improvement in specificity and positive predictive value compared with CTA alone for predicting FFR of ≤0.80, as well as decreasing the frequency of nonobstructive invasive coronary angiography. High-risk plaque characteristics have also been strongly implicated in abnormal FFR. Myocardial computed tomographic perfusion is an alternative method with promising results; it involves more radiation and contrast. Transluminal attenuation gradient/corrected contrast opacification is more controversial and may be more related to vessel diameter than stenosis. Important considerations remain: (1) improvement of CTA quality to decrease unevaluable studies, (2) is the diagnostic accuracy of CT-FFR sufficient? (3) can CT-FFR guide intervention without invasive FFR confirmation? (4) what are the long-term outcomes of CT-FFR-guided treatment and how do they compare with other functional imaging-guided paradigms? (5) what degree of stenosis on CTA warrants CT-FFR? (6) how should high-risk plaque be incorporated into treatment decisions? (7) how will CT-FFR influence other functional imaging test utilization, and what will be the effect on the practice of cardiology? (8) will a workstation-based CT-FFR be mandatory? Rapid progress to date suggests that CTA-based lesion-specific ischemia will be the gatekeeper to the cardiac catheterization laboratory and will transform the world of intervention.

  View details for PubMedID 27390333

• Impact of Age on the Functional Significance of Intermediate Epicardial Artery Disease CIRCULATION JOURNAL Jin, X., Lim, H., Tahk, S., Yang, H., Yoon, M., Choi, S., Choi, B., Yong, A. S., Fearon, W. F., Sheen, S. S., Seo, K., Shin, J. 2016; 80 (7): 1583-1589

  Abstract

  The functional significance of an intermediate coronary lesion is crucial for determining the treatment strategy, but age-related changes in cardiovascular function could affect the functional significance of an epicardial stenosis. The aim of this study was therefore to investigate the impact of age on fractional flow reserve (FFR) measurements in patients with intermediate coronary artery disease (CAD).Intracoronary pressure measurements and intravascular ultrasound (IVUS) were performed in 178 left anterior descending coronary arteries with intermediate stenosis. The morphological characteristics and FFR of 91 lesions in patients <65 years old were compared with those of 87 patients ≥65 years old. There was no difference in lesion location, diameter stenosis, minimum lumen area, plaque burden, or lesion length between the 2 age groups. Elderly patients had higher FFR (0.81±0.06 vs. 0.79±0.06, P=0.004) and lower ∆FFR, defined as the difference between resting Pd/Pa and FFR (0.13±0.05 vs. 0.15±0.05, P=0.014). Age, along with the location and degree of stenosis, was independently associated with FFR and ∆FFR (β=0.162, P=0.008; β=-0.131, P=0.043, respectively).Elderly patients with intermediate CAD are more likely to have higher FFR and lower ∆FFR, despite a similar degree of epicardial stenosis, compared with younger patients. (Circ J 2016; 80: 1583-1589).

  View details for DOI 10.1253/circj.CJ-15-1402

  View details for Web of Science ID 000379609200019

  View details for PubMedID 27194466

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

  Abstract

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

  View details for DOI 10.1111/jocs.12750

  View details for PubMedID 27109017

• Outcomes of a Dedicated Stent in Coronary Bifurcations with Large Side Branches: A Subanalysis of the Randomized TRYTON Bifurcation Study CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Genereux, P., Kini, A., Lesiak, M., Kumsars, I., Fontos, G., Slagboom, T., Ungi, I., Metzger, D. C., Wykrzykowska, J. J., Stella, P. R., Bartorelli, A. L., Fearon, W. F., Lefevre, T., Feldman, R. L., Tarantini, G., Bettinger, N., Ayele, G. M., Lasalle, L., Francese, D. P., Onuma, Y., Grundeken, M. J., Garcia-Garcia, H. M., Laak, L. L., Cutlip, D. E., Kaplan, A. V., Serruys, P. W., Leon, M. B. 2016; 87 (7): 1231-1241

  Abstract

  To examine the benefit of the Tryton dedicated side branch (SB) stent compared with provisional stenting in the treatment of complex bifurcation lesions involving large SBs.The TRYTON Trial was designed to evaluate the utility of a dedicated SB stent to treat true bifurcation lesions involving large (≥2.5 mm by visual estimation) SBs. Patient enrolled in the trial had smaller SB diameters than intended (59% SB ≤2.25 mm by Core Lab QCA). The TRYTON Trial did not meet its primary endpoint due to an increased rate of peri-procedural myocardial infarctions (MIs).The TRYTON Trial randomized 704 patients to the Tryton SB stent with main vessel DES versus provisional SB treatment with main vessel DES. The rates of the primary end point of target vessel failure and the secondary powered end point of angiographic percent diameter stenosis in the SB at 9 months were assessed and compared between the two treatment strategies among patients with a SB ≥2.25 mm diameter at baseline determined by Core Lab QCA.Among the 704 patients enrolled in the TRYTON Trial, 289 patients (143 provisional and 146 Tryton stent; 41% of entire cohort) had a SB ≥2.25 mm. The primary end point of TVF was numerically lower in the Tryton group compared with the provisional group (11.3% vs. 15.6%, P = 0.38), and was within the non-inferiority margin. No difference among the rates of clinically driven target vessel revascularization (3.5% vs. 4.3% P = 0.77) or cardiac death (0% both groups) were seen. In-segment percent diameter stenosis of the SB was significantly lower in the Tryton group compared with the provisional group (30.4% vs. 40.6%, P = 0.004).Analysis of the TRYTON Trial cohort of SB ≥2.25 mm supports the safety and efficacy of the Tryton SB stent compared with a provisional stenting strategy in the treatment of bifurcation lesions involving large SBs. © 2015 Wiley Periodicals, Inc.

  View details for DOI 10.1002/ccd.26240

  View details for PubMedID 26397982

• Association of periarterial neovascularization with progression of cardiac allograft vasculopathy and long-term clinical outcomes in heart transplant recipients JOURNAL OF HEART AND LUNG TRANSPLANTATION Kitahara, H., Okada, K., Tanaka, S., Yang, H., Miki, K., Kobayashi, Y., Kimura, T., Luikart, H., Yock, P. G., Yeung, A. C., Fitzgerald, P. J., Khush, K. K., Fearon, W. F., Honda, Y. 2016; 35 (6): 752-759

  Abstract

  This study investigated the relationship between periarterial neovascularization, development of cardiac allograft vasculopathy (CAV), and long-term clinical outcomes after heart transplantation. Proliferation of the vasa vasorum is associated with arterial inflammation. The contribution of angiogenesis to the development of CAV has been suggested.Serial (baseline and 1-year post-transplant) intravascular ultrasound was performed in 102 heart transplant recipients. Periarterial small vessels (PSV) were defined as echolucent luminal structures <1 mm in diameter, located ≤2 mm outside of the external elastic membrane. The signal void structures were excluded when they connected to the coronary lumen (considered as side branches) or could not be followed in ≥3 contiguous frames. The number of PSV was counted at 1-mm intervals throughout the first 50 mm of the left anterior descending artery, and the PSV score was calculated as the sum of cross-sectional values. Patients with a PSV score increase of ≥ 4 between baseline and 1-year post-transplant were classified as the "proliferative" group. Maximum intimal thickness was measured for the entire analysis segment.During the first year post-transplant, the proliferative group showed a greater increase in maximum intimal thickness (0.33 ± 0.36 mm vs 0.10 ± 0.28 mm, p < 0.001) and had a higher incidence of acute cellular rejection (50.0% vs 23.9%, p = 0.025) than the non-proliferative group. On Kaplan-Meier analysis, cardiac death-free survival rate over a median of 4.7 years was significantly lower in the proliferative group than in the non-proliferative group (hazard ratio, 3.10; p = 0.036).The increase in PSV, potentially representing an angioproliferative response around the coronary arteries, was associated with early CAV progression and reduced survival after heart transplantation.

  View details for DOI 10.1016/j.healun.2016.02.002

  View details for PubMedID 27068036

• Invasive Assessment of Coronary Physiology Predicts Late Mortality After Heart Transplantation CIRCULATION Yang, H., Khush, K., Luikart, H., Okada, K., Lim, H., Kobayashi, Y., Honda, Y., Yeung, A. C., Valantine, H., Fearon, W. F. 2016; 133 (20): 1945-1950

  Abstract

  -The aim of this study is to determine the prognostic value of invasively assessing coronary physiology early after heart transplantation.-Seventy-four cardiac transplant recipients had fractional flow reserve (FFR), coronary flow reserve (CFR), the index of microcirculatory resistance (IMR) and intravascular ultrasound (IVUS) performed down the left anterior descending coronary artery soon after (baseline) and 1 year after heart transplantation. The primary endpoint was the cumulative survival free of death or retransplantation at a mean follow-up of 4.5±3.5 years. The cumulative event-free survival was significantly lower in patients with an FFR<0.90 at baseline (42 vs 79%, p=0.01) or an IMR≥20 measured one year after heart transplantation (39 vs. 69%, p=0.03). Patients in whom IMR decreased or did not change from baseline to 1 year had higher event-free survival compared to those patients with an increase in IMR (66 vs. 36%, p=0.03). FFR<0.90 at baseline (hazards ratio [HR] 0.13, 95% confidence interval [CI] 0.02-0.81, p=0.03), IMR ≥20 at 1 year (HR 3.93, 95% CI 1.08-14.27, p=0.04) and rejection during the first year (HR 6.00, 95% CI 1.56-23.09, p=0.009) were independent predictors of death/retransplantation, while IVUS parameters were not.-Invasive measures of coronary physiology (FFR and IMR) determined early after heart transplantation are significant predictors of late death or retransplantation.

  View details for DOI 10.1161/CIRCULATIONAHA.115.018741

  View details for PubMedID 27143679

• Continuum of Vasodilator Stress From Rest to Contrast Medium to Adenosine Hyperemia for Fractional Flow Reserve Assessment JACC-CARDIOVASCULAR INTERVENTIONS Johnson, N. P., Jeremias, A., Zimmermann, F. M., Adjedj, J., Witt, N., Hennigan, B., Koo, B., Maehara, A., Matsumura, M., Barbato, E., Esposito, G., Trimarco, B., Rioufol, G., Park, S., Yang, H., Baptista, S. B., Chrysant, G. S., Leone, A. M., Berry, C., De Bruyne, B., Gould, K. L., Kirkeeide, R. L., Oldroyd, K. G., Pijls, N. H., Fearon, W. F. 2016; 9 (8): 757-767

  Abstract

  This study compared the diagnostic performance with adenosine-derived fractional flow reserve (FFR) ≤0.8 of contrast-based FFR (cFFR), resting distal pressure (Pd)/aortic pressure (Pa), and the instantaneous wave-free ratio (iFR).FFR objectively identifies lesions that benefit from medical therapy versus revascularization. However, FFR requires maximal vasodilation, usually achieved with adenosine. Radiographic contrast injection causes submaximal coronary hyperemia. Therefore, intracoronary contrast could provide an easy and inexpensive tool for predicting FFR.We recruited patients undergoing routine FFR assessment and made paired, repeated measurements of all physiology metrics (Pd/Pa, iFR, cFFR, and FFR). Contrast medium and dose were per local practice, as was the dose of intracoronary adenosine. Operators were encouraged to perform both intracoronary and intravenous adenosine assessments and a final drift check to assess wire calibration. A central core lab analyzed blinded pressure tracings in a standardized fashion.A total of 763 subjects were enrolled from 12 international centers. Contrast volume was 8 ± 2 ml per measurement, and 8 different contrast media were used. Repeated measurements of each metric showed a bias <0.005, but a lower SD (less variability) for cFFR than resting indexes. Although Pd/Pa and iFR demonstrated equivalent performance against FFR ≤0.8 (78.5% vs. 79.9% accuracy; p = 0.78; area under the receiver-operating characteristic curve: 0.875 vs. 0.881; p = 0.35), cFFR improved both metrics (85.8% accuracy and 0.930 area; p < 0.001 for each) with an optimal binary threshold of 0.83. A hybrid decision-making strategy using cFFR required adenosine less often than when based on either Pd/Pa or iFR.cFFR provides diagnostic performance superior to that of Pd/Pa or iFR for predicting FFR. For clinical scenarios or health care systems in which adenosine is contraindicated or prohibitively expensive, cFFR offers a universal technique to simplify invasive coronary physiological assessments. Yet FFR remains the reference standard for diagnostic certainty as even cFFR reached only ∼85% agreement.

  View details for DOI 10.1016/j.jcin.2015.12.273

  View details for PubMedID 27101902

• HIGHER LEVELS OF ASYMMETRIC DIMETHYLARGININE ARE ASSOCIATED WITH LOWER FRACTIONAL FLOW RESERVE AFTER ORTHOTOPIC HEART TRANSPLANTATION Parikh, R., Khush, K., Luikart, H., Pargaonkar, V., Kobayashi, Y., Lee, J., Sinha, S., Cohen, G., Valantine, H., Yeung, A., Fearon, W. ELSEVIER SCIENCE INC. 2016: 1355

  View details for DOI 10.1016/S0735-1097(16)31356-0

  View details for Web of Science ID 000375188702201

• CLINICAL PRESENTATION, MANAGEMENT AND PROGNOSIS OF PATIENTS WITH SPONTANEOUS CORONARY ARTERY DISSECTION Pargaonkar, V., Khandelwal, A., Krishnan, G., Sears, K., Hoover, V., Fearon, W., Lee, D., Yeung, A., Tsai, S., Nejedly, M., Naderi, S., Tremmel, J. ELSEVIER SCIENCE INC. 2016: 53

  View details for DOI 10.1016/S0735-1097(16)30054-7

  View details for Web of Science ID 000375188700054

• INFLUENCE OF LESION LOCATION ON THE DIAGNOSTIC ACCURACY OF ADENOSINE-FREE CORONARY PRESSURE WIRE MEASUREMENTS: THE CONTRAST (CAN CONTRAST INJECTION BETTER APPROXIMATE FFR COMPARED TO PURE RESTING PHYSIOLOGY?) SUBSTUDY Kobayashi, Y., Johnson, N., Berry, C., De Bruyne, B., Gould, K., Jeremias, A., Oldroyd, K., Pijls, N., Fearon, W., CONTRAST Study Investigators ELSEVIER SCIENCE INC. 2016: 30

  View details for DOI 10.1016/S0735-1097(16)30031-6

  View details for Web of Science ID 000375188700031

• FRACTIONAL FLOW RESERVE IN PATIENTS WITH ANGINA IN THE ABSENCE OF OBSTRUCTIVE CORONARY ARTERY DISEASE: IS THERE SUCH A THING AS NORMAL CORONARY ARTERIES? Kimura, T., Fearon, W., Kobayashi, Y., Okada, K., Miki, K., Pargaonkar, V., Yock, P., Fitzgerald, P., Honda, Y., Yeung, A., Tremmel, J. ELSEVIER SCIENCE INC. 2016: 375

  View details for DOI 10.1016/S0735-1097(16)30376-X

  View details for Web of Science ID 000375188701219

• ENDOTHELIUM DEPENDENT AND INDEPENDENT VASODILATOR RESPONSES AFTER HEART TRANSPLANTATION: GEOGRAPHIC DISTRIBUTION AND ASSOCIATION WITH PROGRESSION OF CARDIAC ALLOGRAFT VASCULOPATHY Okada, K., Kimura, T., Miki, K., Yock, P., Yeung, A., Fitzgerald, P., Luikart, H., Khush, K., Honda, Y., Fearon, W. ELSEVIER SCIENCE INC. 2016: 254

  View details for DOI 10.1016/S0735-1097(16)30255-8

  View details for Web of Science ID 000375188701098

• THE IMPACT OF ANGIOTENSIN CONVERTING ENZYME INHIBITORS ON ASYMMETRIC DIMETHYLARGININE IN ORTHOTOPIC HEART TRANSPLANTATION RECIPIENTS: A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL Parikh, R., Khush, K., Sana, S., Daun, T., Luikart, H., Pargaonkar, V., Sinha, S., Cohen, G., Valantine, H., Yeung, A., Kobashigawa, J., Fearon, W. ELSEVIER SCIENCE INC. 2016: 1356

  View details for DOI 10.1016/S0735-1097(16)31357-2

  View details for Web of Science ID 000375188702202

• ANGIOTENSIN-CONVERTING ENZYME INHIBITION EARLY AFTER CARDIAC TRANSPLANTATION: A MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND TRIAL COMPARING RAMIPRIL VERSUS PLACEBO Kobayashi, Y., Okada, K., Khush, K., Sana, S., Daun, T., Sinha, S., Cohen, G., Honda, Y., Luikart, H., Valantine, H., Yeung, A., Kobashigawa, J., Fearon, W. ELSEVIER SCIENCE INC. 2016: 1445

  View details for DOI 10.1016/S0735-1097(16)31446-2

  View details for Web of Science ID 000375188702291

• EARLY CORONARY ENDOTHELIAL DYSFUNCTION PREDICTS ACCELERATED PLAQUE PROGRESSION 1 YEAR AFTER CARDIAC TRANSPLANTATION: SERIAL VOLUMETRIC EVALUATION BY INTRAVASCULAR ULTRASOUND Lee, J., Okada, K., Khush, K., Kobayashi, Y., Sinha, S., Luikart, H., Valantine, H., Yeung, A., Honda, Y., Fearon, W. ELSEVIER SCIENCE INC. 2016: 364

  View details for DOI 10.1016/S0735-1097(16)30365-5

  View details for Web of Science ID 000375188701208

• Coronary Artery Bypass Surgery Is Not Underutilized! CIRCULATION Fearon, W. F., Harrington, R. A. 2016; 133 (10): 1027–35

  View details for PubMedID 26951822

• The impact of left ventricular ejection fraction on fractional flow reserve: Insights from the FAME (Fractional flow reserve versus Angiography for Multivessel Evaluation) trial INTERNATIONAL JOURNAL OF CARDIOLOGY Kobayashi, Y., Tonino, P. A., De Bruyne, B., Yang, H., Lim, H., Pijls, N. H., Fearon, W. F. 2016; 204: 206-210

  Abstract

  Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) significantly improves outcomes compared with angio-guided PCI in patients with multivessel coronary artery disease. However, there is a theoretical concern that in patients with reduced left ventricular ejection fraction (EF) FFR may be less accurate and FFR-guided PCI less beneficial.From the FAME (Fractional flow reserve versus Angiography for Multivessel Evaluation) trial database, we compared FFR values between patients with reduced EF (both ≤40%, n=90 and ≤50%, n=252) and preserved EF (>40%, n=825 and >50%, n=663) according to the angiographic stenosis severity. We also compared differences in 1year outcomes between FFR- vs. angio-guided PCI in patients with reduced and preserved EF.Both groups had similar FFR values in lesions with 50-70% stenosis (p=0.49) and with 71-90% stenosis (p=0.89). The reduced EF group had a higher mean FFR compared to the preserved EF group across lesions with 91-99% stenosis (0.55 vs. 0.50, p=0.02), although the vast majority of FFR values remained ≤0.80. There was a similar reduction in the composite end point of death, nonfatal myocardial infarction, and repeat revascularization with FFR-guided compared to angio-guided PCI for both the reduced (14.5% vs. 19.0%, relative risk=0.76, p=0.34) and the preserved EF group (13.8 vs. 17.0%, relative risk=0.81, p=0.25). The results were similar with an EF cutoff of 40%.Reduced EF has no influence on the FFR value unless the stenosis is very tight, in which case a theoretically explainable, but clinically irrelevant overestimation might occur. As a result, FFR-guided PCI remains beneficial regardless of EF.

  View details for DOI 10.1016/j.ijcard.2015.11.169

  View details for PubMedID 26670174

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

  Abstract

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

  View details for DOI 10.1161/CIRCINTERVENTIONS.115.002766

  View details for Web of Science ID 000368611900001

  View details for PubMedCentralID PMC4704130

• Invasive Assessment of the Coronary Microcirculation. JACC. Cardiovascular interventions Fearon, W. F., Kobayashi, Y. n. 2016

  View details for PubMedID 27017372

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

  Abstract

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

  View details for DOI 10.1161/CIRCINTERVENTIONS.115.002766

  View details for PubMedID 26733582

  View details for PubMedCentralID PMC4704130

• Paradoxical Vessel Remodeling of the Proximal Segment of the Left Anterior Descending Artery Predicts Long-Term Mortality After Heart Transplantation JACC-HEART FAILURE Okada, K., Kitahara, H., Yang, H., Tanaka, S., Kobayashi, Y., Kimura, T., Luikart, H., Yock, P. G., Yeung, A. C., Valantine, H. A., Fitzgerald, P. J., Khush, K. K., Honda, Y., Fearon, W. F. 2015; 3 (12): 942-952

  Abstract

  This study investigated the association between arterial remodeling and geographic distribution of cardiac allograft vasculopathy (CAV), and outcomes after heart transplantation.CAV is characterized by a combination of coronary intimal thickening and pathological vessel remodeling, which varies at different locations in coronary arteries.In 100 transplant recipients, serial volumetric intravascular ultrasonography (IVUS) was performed at baseline and 1 year post-transplantation in the first 50 mm of the left anterior descending artery (LAD). IVUS indices were evaluated in the entire segment and 3 equally divided LAD segments. Paradoxical vessel remodeling was defined as [Δvessel volume/Δintimal volume <0].After 1 year, death or re-transplantation occurred in 20 patients over a median follow-up period of 4.7 years. Paradoxical vessel remodeling was observed in 57%, 41%, 50%, and 40% for the entire vessel, proximal, middle, and distal LAD segments, respectively. Kaplan-Meier analysis revealed a significantly lower event-free rate of survival in patients with paradoxical vessel remodeling involving the proximal LAD segment, which was not present when involving the entire LAD or mid and distal LAD segments. In multivariate analysis, paradoxical vessel remodeling of the proximal LAD segment was independently associated with death or re-transplantation (hazard ratio [HR]: 11.18; 95% confidence interval [CI]: 2.39 to 83.23; p = 0.0015).Despite the diffuse nature of CAV, paradoxical vessel remodeling of the proximal LAD segment at 1 year was the primary determinant of long-term mortality or re-transplantation. Assessment of arterial remodeling combined with coronary intimal thickening may enhance identification of high-risk patients who may benefit from closer follow-up and targeted medical therapies.

  View details for DOI 10.1016/j.jchf.2015.07.013

  View details for Web of Science ID 000366949300002

• Paradoxical Vessel Remodeling of the Proximal Segment of the Left Anterior Descending Artery Predicts Long-Term Mortality After Heart Transplantation. JACC. Heart failure Okada, K., Kitahara, H., Yang, H., Tanaka, S., Kobayashi, Y., Kimura, T., Luikart, H., Yock, P. G., Yeung, A. C., Valantine, H. A., Fitzgerald, P. J., Khush, K. K., Honda, Y., Fearon, W. F. 2015; 3 (12): 942-952

  Abstract

  This study investigated the association between arterial remodeling and geographic distribution of cardiac allograft vasculopathy (CAV), and outcomes after heart transplantation.CAV is characterized by a combination of coronary intimal thickening and pathological vessel remodeling, which varies at different locations in coronary arteries.In 100 transplant recipients, serial volumetric intravascular ultrasonography (IVUS) was performed at baseline and 1 year post-transplantation in the first 50 mm of the left anterior descending artery (LAD). IVUS indices were evaluated in the entire segment and 3 equally divided LAD segments. Paradoxical vessel remodeling was defined as [Δvessel volume/Δintimal volume <0].After 1 year, death or re-transplantation occurred in 20 patients over a median follow-up period of 4.7 years. Paradoxical vessel remodeling was observed in 57%, 41%, 50%, and 40% for the entire vessel, proximal, middle, and distal LAD segments, respectively. Kaplan-Meier analysis revealed a significantly lower event-free rate of survival in patients with paradoxical vessel remodeling involving the proximal LAD segment, which was not present when involving the entire LAD or mid and distal LAD segments. In multivariate analysis, paradoxical vessel remodeling of the proximal LAD segment was independently associated with death or re-transplantation (hazard ratio [HR]: 11.18; 95% confidence interval [CI]: 2.39 to 83.23; p = 0.0015).Despite the diffuse nature of CAV, paradoxical vessel remodeling of the proximal LAD segment at 1 year was the primary determinant of long-term mortality or re-transplantation. Assessment of arterial remodeling combined with coronary intimal thickening may enhance identification of high-risk patients who may benefit from closer follow-up and targeted medical therapies.

  View details for DOI 10.1016/j.jchf.2015.07.013

  View details for PubMedID 26577615

• Response to Letters Regarding Article, "Invasive Evaluation of Patients With Angina in the Absence of Obstructive Coronary Artery Disease" CIRCULATION Tremmel, J. A., Fearon, W. F., Lee, B., Lim, H., Yong, A. S., Yamada, R., Tanaka, S., Lee, D. P., Yeung, A. C. 2015; 132 (20): E244

  View details for PubMedID 26572677

• Clinical Relevance of Myocardial Injury After Transcatheter Aortic Valve Replacement JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Fearon, W. F., Yeung, A. C. 2015; 66 (19): 2089–91

  View details for PubMedID 26541918

• Fractional flow reserve versus angiography for guidance of PCI in patients with multivessel coronary artery disease (FAME): 5-year follow-up of a randomised controlled trial LANCET van Nunen, L. X., Zimmermann, F. M., Tonino, P. A., Barbato, E., Baumbach, A., Engstrom, T., Klauss, V., MacCarthy, P. A., Manoharan, G., Oldroyd, K. G., Lee, P. N., van't Veer, M., Fearon, W. F., De Bruyne, B., Pijls, N. H. 2015; 386 (10006)

  Abstract

  In the Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) study, fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) improved outcome compared with angiography-guided PCI for up to 2 years of follow-up. The aim in this study was to investigate whether the favourable clinical outcome with the FFR-guided PCI in the FAME study persisted over a 5-year follow-up.The FAME study was a multicentre trial done in Belgium, Denmark, Germany, the Netherlands, Sweden, the UK, and the USA. Patients (aged ≥ 18 years) with multivessel coronary artery disease were randomly assigned to undergo angiography-guided PCI or FFR-guided PCI. Before randomisation, stenoses requiring PCI were identified on the angiogram. Patients allocated to angiography-guided PCI had revascularisation of all identified stenoses. Patients allocated to FFR-guided PCI had FFR measurements of all stenotic arteries and PCI was done only if FFR was 0·80 or less. No one was masked to treatment assignment. The primary endpoint was major adverse cardiac events at 1 year, and the data for the 5-year follow-up are reported here. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00267774.After 5 years, major adverse cardiac events occurred in 31% of patients (154 of 496) in the angiography-guided group versus 28% (143 of 509 patients) in the FFR-guided group (relative risk 0·91, 95% CI 0·75-1·10; p=0·31). The number of stents placed per patient was significantly higher in the angiography-guided group than in the FFR-guided group (mean 2·7 [SD 1·2] vs 1·9 [1·3], p<0·0001).The results confirm the long-term safety of FFR-guided PCI in patients with multivessel disease. A strategy of FFR-guided PCI resulted in a significant decrease of major adverse cardiac events for up to 2 years after the index procedure. From 2 years to 5 years, the risks for both groups developed similarly. This clinical outcome in the FFR-guided group was achieved with a lower number of stented arteries and less resource use. These results indicate that FFR guidance of multivessel PCI should be the standard of care in most patients.St Jude Medical, Friends of the Heart Foundation, and Medtronic.

  View details for DOI 10.1016/S0140-6736(15)00057-4

  View details for Web of Science ID 000364194700036

• Fractional flow reserve versus angiography for guidance of PCI in patients with multivessel coronary artery disease (FAME): 5-year follow-up of a randomised controlled trial. Lancet (London, England) van Nunen, L. X., Zimmermann, F. M., Tonino, P. A., Barbato, E., Baumbach, A., Engstrøm, T., Klauss, V., MacCarthy, P. A., Manoharan, G., Oldroyd, K. G., Ver Lee, P. N., Van't Veer, M., Fearon, W. F., De Bruyne, B., Pijls, N. H. 2015; 386 (10006): 1853-60

  Abstract

  In the Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) study, fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) improved outcome compared with angiography-guided PCI for up to 2 years of follow-up. The aim in this study was to investigate whether the favourable clinical outcome with the FFR-guided PCI in the FAME study persisted over a 5-year follow-up.The FAME study was a multicentre trial done in Belgium, Denmark, Germany, the Netherlands, Sweden, the UK, and the USA. Patients (aged ≥ 18 years) with multivessel coronary artery disease were randomly assigned to undergo angiography-guided PCI or FFR-guided PCI. Before randomisation, stenoses requiring PCI were identified on the angiogram. Patients allocated to angiography-guided PCI had revascularisation of all identified stenoses. Patients allocated to FFR-guided PCI had FFR measurements of all stenotic arteries and PCI was done only if FFR was 0·80 or less. No one was masked to treatment assignment. The primary endpoint was major adverse cardiac events at 1 year, and the data for the 5-year follow-up are reported here. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00267774.After 5 years, major adverse cardiac events occurred in 31% of patients (154 of 496) in the angiography-guided group versus 28% (143 of 509 patients) in the FFR-guided group (relative risk 0·91, 95% CI 0·75-1·10; p=0·31). The number of stents placed per patient was significantly higher in the angiography-guided group than in the FFR-guided group (mean 2·7 [SD 1·2] vs 1·9 [1·3], p<0·0001).The results confirm the long-term safety of FFR-guided PCI in patients with multivessel disease. A strategy of FFR-guided PCI resulted in a significant decrease of major adverse cardiac events for up to 2 years after the index procedure. From 2 years to 5 years, the risks for both groups developed similarly. This clinical outcome in the FFR-guided group was achieved with a lower number of stented arteries and less resource use. These results indicate that FFR guidance of multivessel PCI should be the standard of care in most patients.St Jude Medical, Friends of the Heart Foundation, and Medtronic.

  View details for DOI 10.1016/S0140-6736(15)00057-4

  View details for PubMedID 26333474

• Integrated Physiologic Assessment of Ischemic Heart Disease in Real-World Practice Using Index of Microcirculatory Resistance and Fractional Flow Reserve: Insights From the International Index of Microcirculatory Resistance Registry. Circulation. Cardiovascular interventions Lee, J. M., Layland, J., Jung, J., Lee, H., Echavarria-Pinto, M., Watkins, S., Yong, A. S., Doh, J., Nam, C., Shin, E., Koo, B., Ng, M. K., Escaned, J., Fearon, W. F., Oldroyd, K. G. 2015; 8 (11): e002857

  Abstract

  The index of microcirculatory resistance (IMR) is a quantitative and specific index for coronary microcirculation. However, the distribution and determinants of IMR have not been fully investigated in patients with ischemic heart disease (IHD).Consecutive patients who underwent elective measurement of both fractional flow reserve (FFR) and IMR were enrolled from 8 centers in 5 countries. Patients with acute myocardial infarction were excluded. To adjust for the influence of collateral flow, IMR values were corrected with Yong's formula (IMRcorr). High IMR was defined as greater than the 75th percentile in each of the major coronary arteries. FFR≤0.80 was defined as an ischemic value. 1096 patients with 1452 coronary arteries were analyzed (mean age 61.1, male 71.2%). Mean FFR was 0.84 and median IMRcorr was 16.6 U (Q1, Q3 12.4 U, 23.0 U). There was no correlation between IMRcorr and FFR values (r=0.01, P=0.62), and the categorical agreement of FFR and IMRcorr was low (kappa value=-0.04, P=0.10). There was no correlation between IMRcorr and angiographic % diameter stenosis (r=-0.03, P=0.25). Determinants of high IMR were previous myocardial infarction (odds ratio [OR] 2.16, 95% confidence interval [CI] 1.24-3.74, P=0.01), right coronary artery (OR 2.09, 95% CI 1.54-2.84, P<0.01), female (OR 1.67, 95% CI 1.18-2.38, P<0.01), and obesity (OR 1.80, 95% CI 1.31-2.49, P<0.01). Determinants of FFR ≤0.80 were left anterior descending coronary artery (OR 4.31, 95% CI 2.92-6.36, P<0.01), angiographic diameter stenosis ≥50% (OR 5.16, 95% CI 3.66-7.28, P<0.01), male (OR 2.15, 95% CI 1.38-3.35, P<0.01), and age (per 10 years, OR 1.21, 95% CI 1.01-1.46, P=0.04).IMR showed no correlation with FFR and angiographic lesion severity, and the predictors of high IMR value were different from those for ischemic FFR value. Therefore, integration of IMR into FFR measurement may provide additional insights regarding the relative contribution of macro- and microvascular disease in patients with ischemic heart disease.URL: http://www.clinicaltrials.gov. Unique identifier: NCT02186093.

  View details for DOI 10.1161/CIRCINTERVENTIONS.115.002857

  View details for PubMedID 26499500

• How Can We Further Optimize the Invasive Evaluation of Coronary Physiology? JACC-CARDIOVASCULAR INTERVENTIONS Fearon, W. F., Tremmel, J. A. 2015; 8 (13): 1692–94

  View details for PubMedID 26585619

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

  View details for DOI 10.1016/j.jacc.2015.08.664

  View details for Web of Science ID 000363329000588

• The Prognostic Value of the Residual SYNTAX Score after "Functionally" Complete Revascularization: Insights from the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) Trial Kobayashi, Y., Nam, C., Tonino, P. A., De Bruyne, B., Pijls, N. H., Fearon, W. F. ELSEVIER SCIENCE INC. 2015: B16

  View details for DOI 10.1016/j.jacc.2015.08.084

  View details for Web of Science ID 000363329000038

• Accuracy of Fractional Flow Reserve (FFR) Measurements in Clinical Practice - Observations from a Core Laboratory Analysis Matsumura, M., Maehara, A., Fearon, W. F., Johnson, N. P., Jeremias, A. ELSEVIER SCIENCE INC. 2015: B121

  View details for DOI 10.1016/j.jacc.2015.08.320

  View details for Web of Science ID 000363329000265

• 2-Year Clinical Follow-up of the TRYTON IDE Randomized Trial Comparing a Dedicated Bifurcation Stent to Provisional Stenting in the Treatment of Coronary Bifurcations Kumsars, I., Genereux, P., Kini, A., Lesiak, M., Fontos, G., Slagboom, T., Ungi, I., Metzger, D., Wykrzykowska, J. J., Stella, P. R., Bartorelli, A. L., Fearon, W. F., Lefevre, T., Feldman, R. L., Tarantini, G., Laak, L. L., Cutlip, D., Kaplan, A., Serruys, P. W., Leon, M. ELSEVIER SCIENCE INC. 2015: B161

  View details for DOI 10.1016/j.jacc.2015.08.1016

  View details for Web of Science ID 000363329000351

• 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

• Landmark Fractional Flow Reserve Trials. Interventional cardiology clinics Lynch, D. R., Fearon, W. F. 2015; 4 (4): 435–41

  Abstract

  Fractional flow reserve (FFR) has become widely used for physiologic assessment of intermediate coronary lesions. The Fractional Flow Reserve to Determine Appropriateness of Angioplasty in Moderate Coronary Stenoses (DEFER) trial established the safety of deferring angioplasty for moderate lesions that are not functionally significant. DEFER and Fractional Flow Reserve versus Angiography for Multivessel Evaluation 1 trials established the feasibility of FFR-guided intervention in stable and unstable patients with moderate coronary lesions, translating to improved clinical outcome and reduced number of unnecessary stents. This article reviews the trials establishing FFR as an important tool for on-the-table functional assessment of coronary lesions.

  View details for PubMedID 28581930

• Chronic pacing and adverse outcomes after transcatheter aortic valve implantation HEART Dizon, J. M., Nazif, T. M., Hess, P. L., Biviano, A., Garan, H., Douglas, P. S., Kapadia, S., Babaliaros, V., Herrmann, H. C., Szeto, W. Y., Jilaihawi, H., Fearon, W. F., Tuzcu, E. M., Pichard, A. D., Makkar, R., Williams, M., Hahn, R. T., Xu, K., Smith, C. R., Leon, M. B., Kodali, S. K. 2015; 101 (20): 1665-1671

  Abstract

  Many patients undergoing transcatheter aortic valve implantation (TAVI) have a pre-existing, permanent pacemaker (PPM) or receive one as a consequence of the procedure. We hypothesised that chronic pacing may have adverse effects on TAVI outcomes.Four groups of patients undergoing TAVI in the Placement of Aortic Transcatheter Valves (PARTNER) trial and registries were compared: prior PPM (n=586), new PPM (n=173), no PPM (n=1612), and left bundle branch block (LBBB)/no PPM (n=160). At 1 year, prior PPM, new PPM and LBBB/no PPM had higher all-cause mortality than no PPM (27.4%, 26.3%, 27.7% and 20.0%, p<0.05), and prior PPM or new PPM had higher rehospitalisation or mortality/rehospitalisation (p<0.04). By Cox regression analysis, new PPM (HR 1.38, 1.00 to 1.89, p=0.05) and prior PPM (HR 1.31, 1.08 to 1.60, p=0.006) were independently associated with 1-year mortality. Surviving prior PPM, new PPM and LBBB/no PPM patients had lower LVEF at 1 year relative to no PPM (50.5%, 55.4%, 48.9% and 57.6%, p<0.01). Prior PPM had worsened recovery of LVEF after TAVI (Δ=10.0 prior vs 19.7% no PPM for baseline LVEF <35%, p<0.0001; Δ=4.1 prior vs 7.4% no PPM for baseline LVEF 35-50%, p=0.006). Paced ECGs displayed a high prevalence of RV pacing (>88%).In the PARTNER trial, prior PPM, along with new PPM and chronic LBBB patients, had worsened clinical and echocardiographic outcomes relative to no PPM patients, and the presence of a PPM was independently associated with 1-year mortality. Ventricular dyssynchrony due to chronic RV pacing may be mechanistically responsible for these findings.(ClinicalTrials.gov NCT00530894).

  View details for DOI 10.1136/heartjnl-2015-307666

  View details for PubMedID 26261157

• Effect of Sex Differences on Invasive Measures of Coronary Microvascular Dysfunction in Patients With Angina in the Absence of Obstructive Coronary Artery Disease. JACC. Cardiovascular interventions Kobayashi, Y., Fearon, W. F., Honda, Y., Tanaka, S., Pargaonkar, V., Fitzgerald, P. J., Lee, D. P., Stefanick, M., Yeung, A. C., Tremmel, J. A. 2015; 8 (11): 1433-41

  Abstract

  This study investigated sex differences in coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) in patients with angina in the absence of obstructive coronary artery disease.Coronary microvascular dysfunction is associated with worse long-term outcomes, especially in women. Coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) are 2 methods of assessing the coronary microcirculation.We prospectively enrolled 117 women and 40 men with angina in the absence of obstructive coronary artery disease. We performed CFR, IMR, fractional flow reserve, and quantitative coronary angiography in the left anterior descending artery. Coronary flow was assessed with a thermodilution method by obtaining mean transit time (Tmn) (an inverse correlate to absolute flow) at rest and hyperemia.All patients had minimal atherosclerosis by quantitative coronary angiography (% diameter stenosis: 23.2 ± 12.3%), and epicardial disease was milder in women (fractional flow reserve: 0.88 ± 0.04 vs. 0.87 ± 0.04; p = 0.04). IMR was similar between the sexes (20.7 ± 9.8 vs. 19.1 ± 8.0; p = 0.45), but CFR was lower in women (3.8 ± 1.6 vs. 4.8 ± 1.9; p = 0.004). This was primarily due to a shorter resting Tmn in women (p = 0.005), suggesting increased resting coronary flow, whereas hyperemic Tmn was identical (p = 0.79). In multivariable analysis, female sex was an independent predictor of lower CFR and shorter resting Tmn.Despite similar microvascular function in women and men by IMR, CFR is lower in women. This discrepancy appears to be due to differences in resting coronary flow between the sexes. The effect of sex differences should be considered in interpretation of physiological indexes using resting coronary flow.

  View details for DOI 10.1016/j.jcin.2015.03.045

  View details for PubMedID 26404195

• Effect of Sex Differences on Invasive Measures of Coronary Microvascular Dysfunction in Patients With Angina in the Absence of Obstructive Coronary Artery Disease JACC-CARDIOVASCULAR INTERVENTIONS Kobayashi, Y., Fearon, W. F., Honda, Y., Tanaka, S., Pargaonkar, V., Fitzgerald, P. J., Lee, D. P., Stefanick, M., Yeung, A. C., Tremmel, J. A. 2015; 8 (11): 1433-1441

  Abstract

  This study investigated sex differences in coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) in patients with angina in the absence of obstructive coronary artery disease.Coronary microvascular dysfunction is associated with worse long-term outcomes, especially in women. Coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) are 2 methods of assessing the coronary microcirculation.We prospectively enrolled 117 women and 40 men with angina in the absence of obstructive coronary artery disease. We performed CFR, IMR, fractional flow reserve, and quantitative coronary angiography in the left anterior descending artery. Coronary flow was assessed with a thermodilution method by obtaining mean transit time (Tmn) (an inverse correlate to absolute flow) at rest and hyperemia.All patients had minimal atherosclerosis by quantitative coronary angiography (% diameter stenosis: 23.2 ± 12.3%), and epicardial disease was milder in women (fractional flow reserve: 0.88 ± 0.04 vs. 0.87 ± 0.04; p = 0.04). IMR was similar between the sexes (20.7 ± 9.8 vs. 19.1 ± 8.0; p = 0.45), but CFR was lower in women (3.8 ± 1.6 vs. 4.8 ± 1.9; p = 0.004). This was primarily due to a shorter resting Tmn in women (p = 0.005), suggesting increased resting coronary flow, whereas hyperemic Tmn was identical (p = 0.79). In multivariable analysis, female sex was an independent predictor of lower CFR and shorter resting Tmn.Despite similar microvascular function in women and men by IMR, CFR is lower in women. This discrepancy appears to be due to differences in resting coronary flow between the sexes. The effect of sex differences should be considered in interpretation of physiological indexes using resting coronary flow.

  View details for DOI 10.1016/j.jcin.2015.03.045

  View details for Web of Science ID 000361757600013

• REPLY: True Fractional Flow Reserve of Left Main Coronary Artery Stenosis in the Presence of Downstream Coronary Stenoses JACC-CARDIOVASCULAR INTERVENTIONS Fearon, W. F., Yong, A. S., Lenders, G., Toth, G. G., Dao, C., Daniels, D. V., Pijls, N. J., De Bruyne, B. 2015; 8 (9): 1273

  View details for DOI 10.1016/j.jcin.2015.06.012

  View details for Web of Science ID 000360016600030

  View details for PubMedID 26292600

• Assessment of left main artery stenosis with fractional flow reserve is affected by downstream stenosis in the left anterior descending artery. Coronary artery disease Bing, R., Yong, A. S., Fearon, W. F. 2015; 26: e35-7

  View details for DOI 10.1097/MCA.0000000000000202

  View details for PubMedID 26247268

• Assessment of left main artery stenosis with fractional flow reserve is affected by downstream stenosis in the left anterior descending artery CORONARY ARTERY DISEASE Bing, R., Yong, A. C., Fearon, W. F. 2015; 26: E35-E37

  View details for DOI 10.1097/MCA.0000000000000202

  View details for Web of Science ID 000846865300006

• The index of microcirculatory resistance in the physiologic assessment of the coronary microcirculation CORONARY ARTERY DISEASE Martinez, G. J., Yong, A. C., Fearon, W. F., Ng, M. C. 2015; 26: E15-E26

  View details for DOI 10.1097/MCA.0000000000000213

  View details for Web of Science ID 000846865300004

• The index of microcirculatory resistance in the physiologic assessment of the coronary microcirculation. Coronary artery disease Martinez, G. J., Yong, A. S., Fearon, W. F., Ng, M. K. 2015; 26 Suppl 1: e15–26

  Abstract

  The coronary microcirculation plays a critical role in normal cardiac physiology as well as in many disease states. However, methods to evaluate the function of the coronary microvessels have been limited by technical and theoretical issues. Recently, the index of microcirculatory resistance (IMR) has been proposed and validated as a simple and specific invasive method of assessing the coronary microcirculation. By relying on the thermodilution theory and using a pressure-temperature sensor guidewire, IMR provides a measurement of the minimum achievable microcirculatory resistance in a target coronary artery territory, enabling a quantitative assessment of the microvascular integrity. Unlike indices such as coronary flow reserve, IMR is highly reproducible and independent of hemodynamic changes. In ST-elevation myocardial infarction, IMR predicts myocardial recovery and long-term mortality, whereas in patients with stable coronary artery disease, preintervention IMR predicts the occurrence of periprocedural myocardial infarction. Increasingly, research has focused on IMR-guided interventions of the microcirculation, with the aim of preventing and/or treating the microcirculatory dysfunction that commonly accompanies the epicardial coronary disease. In the present review, we will discuss the theoretical and practical basis for IMR, the clinical studies supporting it, and the future lines of research using this novel tool.

  View details for PubMedID 26247265

• Repeatability of Fractional Flow Reserve Despite Variations in Systemic and Coronary Hemodynamics JACC-CARDIOVASCULAR INTERVENTIONS Johnson, N. P., Johnson, D. T., Kirkeeide, R. L., Berry, C., De Bruyne, B., Fearon, W. F., Oldroyd, K. G., Pijls, N. H., Gould, K. L. 2015; 8 (8): 1018-1027

  Abstract

  This study classified and quantified the variation in fractional flow reserve (FFR) due to fluctuations in systemic and coronary hemodynamics during intravenous adenosine infusion.Although FFR has become a key invasive tool to guide treatment, questions remain regarding its repeatability and stability during intravenous adenosine infusion because of systemic effects that can alter driving pressure and heart rate.We reanalyzed data from the VERIFY (VERification of Instantaneous Wave-Free Ratio and Fractional Flow Reserve for the Assessment of Coronary Artery Stenosis Severity in EverydaY Practice) study, which enrolled consecutive patients who were infused with intravenous adenosine at 140 μg/kg/min and measured FFR twice. Raw phasic pressure tracings from the aorta (Pa) and distal coronary artery (Pd) were transformed into moving averages of Pd/Pa. Visual analysis grouped Pd/Pa curves into patterns of similar response. Quantitative analysis of the Pd/Pa curves identified the "smart minimum" FFR using a novel algorithm, which was compared with human core laboratory analysis.A total of 190 complete pairs came from 206 patients after exclusions. Visual analysis revealed 3 Pd/Pa patterns: "classic" (sigmoid) in 57%, "humped" (sigmoid with superimposed bumps of varying height) in 39%, and "unusual" (no pattern) in 4%. The Pd/Pa pattern repeated itself in 67% of patient pairs. Despite variability of Pd/Pa during the hyperemic period, the "smart minimum" FFR demonstrated excellent repeatability (bias -0.001, SD 0.018, paired p = 0.93, r(2) = 98.2%, coefficient of variation = 2.5%). Our algorithm produced FFR values not significantly different from human core laboratory analysis (paired p = 0.43 vs. VERIFY; p = 0.34 vs. RESOLVE).Intravenous adenosine produced 3 general patterns of Pd/Pa response, with associated variability in aortic and coronary pressure and heart rate during the hyperemic period. Nevertheless, FFR - when chosen appropriately - proved to be a highly reproducible value. Therefore, operators can confidently select the "smart minimum" FFR for patient care. Our results suggest that this selection process can be automated, yet comparable to human core laboratory analysis.

  View details for DOI 10.1016/j.jcin.2015.01.039

  View details for Web of Science ID 000358261300008

• Repeatability of Fractional Flow Reserve Despite Variations in Systemic and Coronary Hemodynamics. JACC. Cardiovascular interventions Johnson, N. P., Johnson, D. T., Kirkeeide, R. L., Berry, C., De Bruyne, B., Fearon, W. F., Oldroyd, K. G., Pijls, N. H., Gould, K. L. 2015; 8 (8): 1018-27

  Abstract

  This study classified and quantified the variation in fractional flow reserve (FFR) due to fluctuations in systemic and coronary hemodynamics during intravenous adenosine infusion.Although FFR has become a key invasive tool to guide treatment, questions remain regarding its repeatability and stability during intravenous adenosine infusion because of systemic effects that can alter driving pressure and heart rate.We reanalyzed data from the VERIFY (VERification of Instantaneous Wave-Free Ratio and Fractional Flow Reserve for the Assessment of Coronary Artery Stenosis Severity in EverydaY Practice) study, which enrolled consecutive patients who were infused with intravenous adenosine at 140 μg/kg/min and measured FFR twice. Raw phasic pressure tracings from the aorta (Pa) and distal coronary artery (Pd) were transformed into moving averages of Pd/Pa. Visual analysis grouped Pd/Pa curves into patterns of similar response. Quantitative analysis of the Pd/Pa curves identified the "smart minimum" FFR using a novel algorithm, which was compared with human core laboratory analysis.A total of 190 complete pairs came from 206 patients after exclusions. Visual analysis revealed 3 Pd/Pa patterns: "classic" (sigmoid) in 57%, "humped" (sigmoid with superimposed bumps of varying height) in 39%, and "unusual" (no pattern) in 4%. The Pd/Pa pattern repeated itself in 67% of patient pairs. Despite variability of Pd/Pa during the hyperemic period, the "smart minimum" FFR demonstrated excellent repeatability (bias -0.001, SD 0.018, paired p = 0.93, r(2) = 98.2%, coefficient of variation = 2.5%). Our algorithm produced FFR values not significantly different from human core laboratory analysis (paired p = 0.43 vs. VERIFY; p = 0.34 vs. RESOLVE).Intravenous adenosine produced 3 general patterns of Pd/Pa response, with associated variability in aortic and coronary pressure and heart rate during the hyperemic period. Nevertheless, FFR - when chosen appropriately - proved to be a highly reproducible value. Therefore, operators can confidently select the "smart minimum" FFR for patient care. Our results suggest that this selection process can be automated, yet comparable to human core laboratory analysis.

  View details for DOI 10.1016/j.jcin.2015.01.039

  View details for PubMedID 26205441

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

  Abstract

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

  View details for DOI 10.1161/CIRCULATIONAHA.114.012525

  View details for PubMedID 25832034

• The evolution of temporary percutaneous mechanical circulatory support devices: a review of the options and evidence in cardiogenic shock. Current cardiology reports Abnousi, F., Yong, C. M., Fearon, W., Banerjee, D. 2015; 17 (6): 40-?

  Abstract

  Temporary percutaneous mechanical circulatory support (MCS) devices were introduced in the 1960s and have developed into a diverse portfolio of options currently available for left, right, and biventricular support. Patients undergoing high-risk percutaneous coronary interventions (PCI), patients with acute myocardial infarction (AMI), and patients with cardiogenic shock in particular may benefit from these options. In this review, we will discuss the currently available devices and the evidence supporting their use in cardiogenic shock.

  View details for DOI 10.1007/s11886-015-0594-8

  View details for PubMedID 25899658

• The Evolution of Temporary Percutaneous Mechanical Circulatory Support Devices: a Review of the Options and Evidence in Cardiogenic Shock CURRENT CARDIOLOGY REPORTS Abnousi, F., Yong, C. M., Fearon, W., Banerjee, D. 2015; 17 (6)

  Abstract

  Temporary percutaneous mechanical circulatory support (MCS) devices were introduced in the 1960s and have developed into a diverse portfolio of options currently available for left, right, and biventricular support. Patients undergoing high-risk percutaneous coronary interventions (PCI), patients with acute myocardial infarction (AMI), and patients with cardiogenic shock in particular may benefit from these options. In this review, we will discuss the currently available devices and the evidence supporting their use in cardiogenic shock.

  View details for DOI 10.1007/s11886-015-0594-8

  View details for Web of Science ID 000353514800004

  View details for PubMedID 25899658

• Prevalence and Prognostic Role of Right Ventricular Involvement in Stress-Induced Cardiomyopathy JOURNAL OF CARDIAC FAILURE Finocchiaro, G., Kobayashi, Y., Magavern, E., Zhou, J. Q., Ashley, E., Sinagra, G., Schnittger, I., Knowles, J. W., Fearon, W. F., Haddad, F., Tremmel, J. A. 2015; 21 (5): 419-425

  Abstract

  Stress-induced cardiomyopathy (SCM) is a reversible cardiomyopathy observed in patients without significant coronary disease. The aim of this study was to assess the incidence and clinical significance of right ventricular (RV) involvement in SCM.We retrospectively analyzed echocardiograms from 40 consecutive patients who presented with SCM at Stanford University Medical Center from September 2000 to November 2010. The primary end point was overall mortality. RV involvement was observed in 20 patients (50%; global RV hypokinesia in 15 patients and focal RV apical akinesia in 5 patients). The independent correlates of RV involvement were older age (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.02-1.7two, P = .01) and LVEF (per 10% decrease: OR 3.60, CI 1.77-7.32; P = .02). At a mean follow-up of 44 ± 32 months, 12 patients (30%) died (in-hospital death in 3 patients). At multivariate analysis, the presence of an RV fractional area change <35% emerged as an independent predictor of death (OR 3.6, CI 1.06-12.41; P = .04).RV involvement is a common finding in SCM, and may present as either global or focal RV apical involvement. Both older age and lower LVEF are associated with a higher risk of RV involvement, which appears to be a major predictor of death.

  View details for DOI 10.1016/j.cardfail.2015.02.001

  View details for PubMedID 25704104

• Invasive Evaluation of Patients With Angina in the Absence of Obstructive Coronary Artery Disease CIRCULATION Lee, B., Lim, H., Fearon, W. F., Yong, A. S., Yamada, R., Tanaka, S., Lee, D. P., Yeung, A. C., Tremmel, J. A. 2015; 131 (12): 1054-1060

  Abstract

  More than 20% of patients presenting to the cardiac catheterization laboratory with angina have no angiographic evidence of coronary artery disease. Despite a "normal" angiogram, these patients often have persistent symptoms, recurrent hospitalizations, a poor functional status, and adverse cardiovascular outcomes, without a clear diagnosis.In 139 patients with angina in the absence of obstructive coronary artery disease (no diameter stenosis >50%), endothelial function was assessed; the index of microcirculatory resistance, coronary flow reserve, and fractional flow reserve were measured; and intravascular ultrasound was performed. There were no complications. The average age was 54.0±11.4 years, and 107 (77%) were women. All patients had at least some evidence of atherosclerosis based on an intravascular ultrasound examination of the left anterior descending artery. Endothelial dysfunction (a decrease in luminal diameter of >20% after intracoronary acetylcholine) was present in 61 patients (44%). Microvascular impairment (an index of microcirculatory resistance ≥25) was present in 29 patients (21%). Seven patients (5%) had a fractional flow reserve ≤0.80. A myocardial bridge was present in 70 patients (58%). Overall, only 32 patients (23%) had no coronary explanation for their angina, with normal endothelial function, normal coronary physiological assessment, and no myocardial bridging.The majority of patients with angina in the absence of obstructive coronary artery disease have occult coronary abnormalities. A comprehensive invasive assessment of these patients at the time of coronary angiography can be performed safely and provides important diagnostic information that may affect treatment and outcomes.

  View details for DOI 10.1161/CIRCULATIONAHA.114.012636

  View details for PubMedID 25712205

• PARADOXICAL ARTERIAL REMODELING OF THE PROXIMAL SEGMENT OF THE LEFT ANTERIOR DESCENDING ARTERY PREDICTS LONG-TERM MORTALITY AFTER HEART TRANSPLANTATION Okada, K., Kitahara, H., Yang, H., Tanaka, S., Kobayashi, Y., Luikart, H., Yock, P., Yeung, A., Fitzgerald, P., Khush, K., Honda, Y., Fearon, W. ELSEVIER SCIENCE INC. 2015: A1740

  View details for DOI 10.1016/S0735-1097(15)61740-5

  View details for Web of Science ID 000375328802062

• SEX DIFFERENCES IN CORONARY PATHOPHYSIOLOGY IN PATIENTS WITH ANGINA IN THE ABSENCE OF OBSTRUCTIVE CORONARY ARTERY DISEASE Pargaonkar, V., Kobayashi, Y., Tanaka, S., Mathur, M. B., Nguyen, P., Lee, D., Fearon, W., Yeung, A., Tremmel, J. ELSEVIER SCIENCE INC. 2015: A1859

  View details for DOI 10.1016/S0735-1097(15)61859-9

  View details for Web of Science ID 000375328802181

• INVASIVE CORONARY PHYSIOLOGY AT ONE YEAR PREDICTS LATE MORTALITY AFTER HEART TRANSPLANTATION Yang, H., Okada, K., Cohen, G., Strehl, C., Luikart, H., Valantine, H., Honda, Y., Khush, K., Fearon, W. ELSEVIER SCIENCE INC. 2015: A1685

  View details for DOI 10.1016/S0735-1097(15)61685-0

  View details for Web of Science ID 000375328802007

• THE IMPACT OF EJECTION FRACTION ON FRACTIONAL FLOW RESERVE: INSIGHTS FROM THE FAME (FRACTIONAL FLOW RESERVE VERSUS ANGIOGRAPHY FOR MULTIVESSEL EVALUATION) TRIAL Kobayashi, Y., Tonino, P., De Bruyne, B., Yang, H., Lim, H., Pijls, N., Fearon, W. ELSEVIER SCIENCE INC. 2015: A1720

  View details for DOI 10.1016/S0735-1097(15)61720-X

  View details for Web of Science ID 000375328802042

• ASSOCIATION OF PERIARTERIAL NEOVASCULARIZATION WITH PROGRESSION OF CARDIAC ALLOGRAFT VASCULOPATHY AND LONG-TERM CLINICAL OUTCOMES IN HEART TRANSPLANT RECIPIENTS Kitahara, H., Okada, K., Tanaka, S., Yang, H., Kobayashi, Y., Kimura, T., Luikart, H., Yock, P., Yeung, A., Fitzgerald, P., Khush, K., Fearon, W., Honda, Y. ELSEVIER SCIENCE INC. 2015: A1710

  View details for DOI 10.1016/S0735-1097(15)61710-7

  View details for Web of Science ID 000375328802032

• REPRODUCIBILITY AND HEMODYNAMIC DEPENDENCE OF CORONARY PHYSIOLOGIC INDICES Yang, H., van't Veer, M., Ng, M. C., Kobayashi, Y., Yeung, A., Pijis, N., Fearon, W. ELSEVIER SCIENCE INC. 2015: A1915

  View details for DOI 10.1016/S0735-1097(15)61915-5

  View details for Web of Science ID 000375328802237

• IMPACT OF MYOCARDIAL BRIDGING ON CORONARY ARTERY PLAQUE FORMATION AND LONG-TERM MORTALITY AFTER HEART TRANSPLANTATION Tanaka, S., Okada, K., Kitahara, H., Kobayashi, Y., Luikart, H., Yock, P., Yeung, A., Schnittger, I., Fitzgerald, P., Khush, K., Fearon, W., Honda, Y. ELSEVIER SCIENCE INC. 2015: A1741

  View details for DOI 10.1016/S0735-1097(15)61741-7

  View details for Web of Science ID 000375328802063

• Transcatheter aortic valve replacement and standard therapy in inoperable patients with aortic stenosis and low EF HEART Passeri, J. J., Elmariah, S., Xu, K., Inglessis, I., Baker, J. N., Alu, M., Kodali, S., Leon, M. B., Svensson, L. G., Pibarot, P., Fearon, W. F., Kirtane, A. J., Vlahakes, G. J., Palacios, I. F., Douglas, P. S. 2015; 101 (6): 463-471

  Abstract

  The aims of this study were to evaluate the effect of left ventricular (LV) dysfunction on clinical outcomes after transcatheter aortic valve replacement (TAVR) and standard therapy for severe aortic stenosis (AS) and to assess LV ejection fraction (LVEF) recovery and its impact on subsequent clinical outcomes.Cohort B of the Placement of AoRtic TraNscathetER Valves trial randomised 342 inoperable patients with severe AS to TAVR or standard therapy. We defined LV dysfunction as an LVEF <50% and LVEF improvement as an absolute increase in LVEF ≥10% at 30 days.Baseline LV dysfunction did not affect survival after TAVR but was associated with increased cardiac mortality at 1 year with standard therapy (59.3% vs 45.8% with normal LVEF; HR=1.71 (95% CI 1.08 to 2.71); p=0.02). In those with LV dysfunction, LVEF improvement occurred in 48.7% and 30.4% of TAVR and standard therapy patients, respectively (p=0.08), and was independently predicted by relative wall thickness and receipt of TAVR. LVEF improvement with standard therapy portended reduced all-cause mortality at 1 year (28.6% vs 65.6% without LVEF improvement; HR=0.32 (95% CI 0.11 to 0.93); p=0.03) but not at 2 years.In inoperable patients with severe AS, mild-to-moderate LV dysfunction is associated with higher cardiac mortality with standard therapy but not TAVR. A subset of patients undergoing standard therapy with LV dysfunction demonstrates LVEF improvement and favourable 1-year but not 2-year survival. TAVR improves survival and should be considered the standard of care for inoperable patients with AS and LVEF >20%.ClinicalTrials.gov Unique Identifier #NCT00530894.

  View details for DOI 10.1136/heartjnl-2014-306737

  View details for PubMedID 25586156

• The Impact of Downstream Coronary Stenosis on Fractional Flow Reserve Assessment of Intermediate Left Main Coronary Artery Disease Human Validation JACC-CARDIOVASCULAR INTERVENTIONS Fearon, W. F., Yong, A. S., Lenders, G., Toth, G. G., Dao, C., Daniels, D. V., Pijls, N. H., De Bruyne, B. 2015; 8 (3): 398-403

  Abstract

  The aim of this study was to determine the impact of downstream coronary stenosis in the left anterior descending coronary artery (LAD) or left circumflex coronary artery (LCx) on the assessment of fractional flow reserve (FFR) across an intermediate left main coronary artery (LMCA) stenosis in humans with the pressure wire positioned in the nondiseased downstream vessel.Accurate assessment of intermediate LMCA disease is critical for guiding decisions regarding revascularization. In theory, FFR across an intermediate LMCA stenosis will be affected by downstream disease, even if the pressure wire is positioned in the nondiseased downstream vessel.After percutaneous coronary intervention of the LAD, LCx, or both, an intermediate LMCA stenosis was created with a deflated balloon catheter. FFR was measured in the LAD and LCx coronary arteries before and after creation of downstream stenosis by inflating an angioplasty balloon within the newly placed stent. The true FFR (FFRtrue) of the LMCA, measured in the nondiseased downstream vessel in the absence of stenosis in the other vessel, was compared with the apparent FFR (FFRapp) measured in the presence of stenosis.In 25 patients, 91 pairs of measurements were made, 71 with LAD stenosis and 20 with LCx stenosis. FFRtrue of the LMCA was significantly lower than FFRapp (0.81 ± 0.08 vs. 0.83 ± 0.08, p < 0.001), although the numerical difference was small. This difference correlated with the severity of the downstream disease (r = 0.35, p < 0.001). In all cases in which FFRapp was >0.85, FFRtrue was >0.80.In most cases, downstream disease does not have a clinically significant impact on the assessment of FFR across an intermediate LMCA stenosis with the pressure wire positioned in the nondiseased vessel.

  View details for DOI 10.1016/j.jcin.2014.09.027

  View details for PubMedID 25790763

• A Randomized Trial of a Dedicated Bifurcation Stent Versus Provisional Stenting in the Treatment of Coronary Bifurcation Lesions JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Genereux, P., Kumsars, I., Lesiak, M., Kini, A., Fontos, G., Slagboom, T., Ungi, I., Metzger, D. C., Wykrzykowska, J. J., Stella, P. R., Bartorelli, A. L., Fearon, W. F., Lefevre, T., Feldman, R. L., Lasalle, L., Francese, D. P., Onuma, Y., Grundeken, M. J., Garcia-Garcia, H. M., Laak, L. L., Cutlip, D. E., Kaplan, A. V., Serruys, P. W., Leon, M. B. 2015; 65 (6): 533-543

  Abstract

  Bifurcation lesions are frequent among patients with symptomatic coronary disease treated by percutaneous coronary intervention. Current evidence recommends a conservative (provisional) approach when treating the side branch (SB).The TRYTON (Prospective, Single Blind, Randomized Controlled Study to Evaluate the Safety & Effectiveness of the Tryton Side Branch Stent Used With DES in Treatment of de Novo Bifurcation Lesions in the Main Branch & Side Branch in Native Coronaries) bifurcation trial sought to compare treatment of de novo true bifurcation lesions using a dedicated bifurcation stent or SB balloon angioplasty.We randomly assigned patients with true bifurcation lesions to a main vessel stent plus provisional stenting or the bifurcation stent. The primary endpoint (powered for noninferiority) was target vessel failure (TVF) (cardiac death, target vessel myocardial infarction, and target vessel revascularization). The secondary angiographic endpoint (powered for superiority) was in-segment percent diameter stenosis of the SB at 9 months.We randomized 704 patients with bifurcation coronary lesions at 58 centers (30 from Europe and 28 from the United States). At 9 months, TVF was 17.4% in the bifurcation stent group compared with 12.8% in the provisional group (p = 0.11), mainly because of a higher periprocedural myocardial infarction rate (13.6% vs. 10.1%, p = 0.19). The TVF difference of +4.6% (2-sided 95% confidence interval: -1.0 to 10.3; upper limit of the 1-sided 95% confidence interval: 10.3) was not within the pre-specified noninferiority margin of 5.5% (p = 0.42 for noninferiority). The SB in-segment diameter stenosis among the angiographic cohort was lower in the bifurcation stent group compared with the provisional group (31.6% vs. 38.6%, p = 0.002 for superiority), with no difference in binary restenosis rates (diameter stenosis ≥50%) at 9 months follow-up (22.6% vs. 26.8%, p = 0.44).Provisional stenting should remain the preferred strategy for treatment of non-left main true coronary bifurcation lesions. (Prospective, Single Blind, Randomized Controlled Study to Evaluate the Safety & Effectiveness of the Tryton Side Branch Stent Used With DES in Treatment of de Novo Bifurcation Lesions in the Main Branch & Side Branch in Native Coronaries [TRYTON]; NCT01258972).

  View details for DOI 10.1016/j.jacc.2014.11.031

  View details for PubMedID 25677311

• Fractional flow reserve-guided PCI. New England journal of medicine De Bruyne, B., Fearon, W. F., Jüni, P. 2015; 372 (1): 95-?

  View details for DOI 10.1056/NEJMc1412894

  View details for PubMedID 25551539

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

  Abstract

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

  View details for DOI 10.1016/j.jtcvs.2014.04.006

  View details for PubMedID 24820191

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

  Abstract

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

  View details for DOI 10.1016/j.jtcvs.2014.04.006

  View details for Web of Science ID 000345686100086

  View details for PubMedID 24820191

• The impact of age on fractional flow reserve-guided percutaneous coronary intervention: a FAME (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) trial substudy. International journal of cardiology Lim, H., Tonino, P. A., De Bruyne, B., Yong, A. S., Lee, B., Pijls, N. H., Fearon, W. F. 2014; 177 (1): 66-70

  Abstract

  Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) improved outcomes compared with an angiography-guided strategy in patients with multivessel coronary artery disease (CAD). However, the effect of age on FFR has not been well-studied. We aimed to evaluate the impact of age on the favorable results of routine FFR-guided PCI for multivessel CAD.We compared 1 year outcomes between FFR-guided PCI and angiography-guided PCI in the 512 patients enrolled in the FAME study <65 years old compared to the 493 patients ≥ 65 years old. We also evaluated the effect of age on the FFR result of varying degrees of visually estimated coronary stenosis.The 1-year rate of death, myocardial infarction or repeat revascularization in the angiography-guided group tended to be higher than in the FFR-guided group for both those patients <65 (17.2% vs. 12.0%, P = 0.098) and those ≥ 65 years old (19.7% vs. 14.3%, P = 0.111) with no significant interaction based on age (P = 0.920). Older patients had higher FFR in vessels with 50% to 70% stenosis (0.83 ± 0.11 vs. 0.80 ± 0.13, P = 0.028) and in vessels with 71% to 90% stenosis (0.69 ± 0.15 vs. 0.65 ± 0.16, P = 0.002). The proportion of functionally significant lesions (FFR ≤ 0.80) in vessels with 71% to 90% stenosis was significantly lower in elderly compared to younger patients (75.3% vs. 84.1%, P = 0.013).FFR-guided PCI is beneficial regardless of age, however, older patients have fewer functionally significant lesions, despite a similar angiographic appearance.

  View details for DOI 10.1016/j.ijcard.2014.09.010

  View details for PubMedID 25499342

• Outcomes After Transfemoral Transcatheter Aortic Valve Replacement A Comparison of the Randomized PARTNER (Placement of AoRTic TraNscathetER Valves) Trial With the NRCA (Nonrandomized Continued Access) Registry JACC-CARDIOVASCULAR INTERVENTIONS Fearon, W. F., Kodali, S., Doshi, D., Fischbein, M. P., Yeung, A. C., Tuzcu, E. M., Rihal, C. S., Babaliaros, V., Zajarias, A., Herrmann, H. C., Brown, D. L., Mack, M., Teirstein, P. S., Whisenant, B. K., Makkar, R., Kapadia, S., Leon, M. B. 2014; 7 (11): 1245-1251

  Abstract

  This study sought to determine whether outcomes for transfemoral (TF) transcatheter aortic valve replacement (TAVR) differ between the randomized controlled trial (RCT) and the subsequent NRCA (Nonrandomized Continued Access) registry of the PARTNER (Placement of AoRTic TraNscathetER Valves) trial.The PARTNER RCT demonstrated that TAVR with the Edwards Sapien valve (Edwards Lifesciences, Irvine, California) is noninferior to surgery in high-risk patients and superior to standard therapy for inoperable patients.The inclusion and exclusion criteria, data collection, monitoring, and core laboratories were the same for the RCT and NRCA registry. Baseline characteristics, procedural results, and 1-year outcomes were compared between patients undergoing TF-TAVR as part of the RCT and as part of the NRCA registry.In the RCT, 415 patients underwent TF-TAVR, whereas in the NRCA, 1,023 patients did. At 30 days, death, cardiac death, stroke, and transient ischemic attacks were not different in the NRCA registry than in the RCT. Major vascular complications (8.0% vs. 15.7%, p < 0.0001) and major bleeding (6.8% vs. 15.3%, p < 0.0001) were significantly lower in the NRCA registry. At 1 year, death rates were significantly lower in the NRCA cohort (19.0% vs. 25.3%, p = 0.009) and cardiac death tended to be lower (8.4% vs. 11.1%, p = 0.12). Stroke or transient ischemic attack (6.2% vs. 8.7%, p = 0.10) and stroke alone (5.0% vs. 7.1%, p = 0.13) also tended to be lower.The large NRCA registry demonstrates further improvement in procedural and longer-term outcomes after TF-TAVR when compared with the favorable results from the PARTNER RCT. (THE PARTNER TRIAL: Placement of AoRTic TraNscathetER Valve Trial; NCT00530894).

  View details for DOI 10.1016/j.jcin.2014.05.033

  View details for Web of Science ID 000345288400013

• Outcomes after transfemoral transcatheter aortic valve replacement: a comparison of the randomized PARTNER (Placement of AoRTic TraNscathetER Valves) trial with the NRCA (Nonrandomized Continued Access) registry. JACC. Cardiovascular interventions Fearon, W. F., Kodali, S., Doshi, D., Fischbein, M. P., Yeung, A. C., Tuzcu, E. M., Rihal, C. S., Babaliaros, V., Zajarias, A., Herrmann, H. C., Brown, D. L., Mack, M., Teirstein, P. S., Whisenant, B. K., Makkar, R., Kapadia, S., Leon, M. B. 2014; 7 (11): 1245-1251

  Abstract

  This study sought to determine whether outcomes for transfemoral (TF) transcatheter aortic valve replacement (TAVR) differ between the randomized controlled trial (RCT) and the subsequent NRCA (Nonrandomized Continued Access) registry of the PARTNER (Placement of AoRTic TraNscathetER Valves) trial.The PARTNER RCT demonstrated that TAVR with the Edwards Sapien valve (Edwards Lifesciences, Irvine, California) is noninferior to surgery in high-risk patients and superior to standard therapy for inoperable patients.The inclusion and exclusion criteria, data collection, monitoring, and core laboratories were the same for the RCT and NRCA registry. Baseline characteristics, procedural results, and 1-year outcomes were compared between patients undergoing TF-TAVR as part of the RCT and as part of the NRCA registry.In the RCT, 415 patients underwent TF-TAVR, whereas in the NRCA, 1,023 patients did. At 30 days, death, cardiac death, stroke, and transient ischemic attacks were not different in the NRCA registry than in the RCT. Major vascular complications (8.0% vs. 15.7%, p < 0.0001) and major bleeding (6.8% vs. 15.3%, p < 0.0001) were significantly lower in the NRCA registry. At 1 year, death rates were significantly lower in the NRCA cohort (19.0% vs. 25.3%, p = 0.009) and cardiac death tended to be lower (8.4% vs. 11.1%, p = 0.12). Stroke or transient ischemic attack (6.2% vs. 8.7%, p = 0.10) and stroke alone (5.0% vs. 7.1%, p = 0.13) also tended to be lower.The large NRCA registry demonstrates further improvement in procedural and longer-term outcomes after TF-TAVR when compared with the favorable results from the PARTNER RCT. (THE PARTNER TRIAL: Placement of AoRTic TraNscathetER Valve Trial; NCT00530894).

  View details for DOI 10.1016/j.jcin.2014.05.033

  View details for PubMedID 25459036

• Prognostic Value of Fractional Flow Reserve Linking Physiologic Severity to Clinical Outcomes JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Johnson, N. P., Toth, G. G., Lai, D., Zhu, H., Acar, G., Agostoni, P., Appelman, Y., Arslan, F., Barbato, E., Chen, S., Di Serafino, L., Dominguez-Franco, A. J., Dupouy, P., Esen, A. M., Esen, O. B., Hamilos, M., Iwasaki, K., Jensen, L. O., Jimenez-Navarro, M. F., Katritsis, D. G., Kocaman, S. A., Koo, B., Lopez-Palop, R., Lorin, J. D., Miller, L. H., Muller, O., Nam, C., Oud, N., Puymirat, E., Rieber, J., Rioufol, G., Rodes-Cabau, J., Sedlis, S. P., Takeishi, Y., Tonino, P. A., Van Belle, E., Verna, E., Werner, G. S., Fearon, W. F., Pijls, N. H., De Bruyne, B., Gould, K. L. 2014; 64 (16): 1641-1654

  Abstract

  Fractional flow reserve (FFR) has become an established tool for guiding treatment, but its graded relationship to clinical outcomes as modulated by medical therapy versus revascularization remains unclear.The study hypothesized that FFR displays a continuous relationship between its numeric value and prognosis, such that lower FFR values confer a higher risk and therefore receive larger absolute benefits from revascularization.Meta-analysis of study- and patient-level data investigated prognosis after FFR measurement. An interaction term between FFR and revascularization status allowed for an outcomes-based threshold.A total of 9,173 (study-level) and 6,961 (patient-level) lesions were included with a median follow-up of 16 and 14 months, respectively. Clinical events increased as FFR decreased, and revascularization showed larger net benefit for lower baseline FFR values. Outcomes-derived FFR thresholds generally occurred around the range 0.75 to 0.80, although limited due to confounding by indication. FFR measured immediately after stenting also showed an inverse relationship with prognosis (hazard ratio: 0.86, 95% confidence interval: 0.80 to 0.93; p < 0.001). An FFR-assisted strategy led to revascularization roughly half as often as an anatomy-based strategy, but with 20% fewer adverse events and 10% better angina relief.FFR demonstrates a continuous and independent relationship with subsequent outcomes, modulated by medical therapy versus revascularization. Lesions with lower FFR values receive larger absolute benefits from revascularization. Measurement of FFR immediately after stenting also shows an inverse gradient of risk, likely from residual diffuse disease. An FFR-guided revascularization strategy significantly reduces events and increases freedom from angina with fewer procedures than an anatomy-based strategy.

  View details for DOI 10.1016/j.jacc.2014.07.973

  View details for Web of Science ID 000343489900001

• Prognostic value of fractional flow reserve: linking physiologic severity to clinical outcomes. Journal of the American College of Cardiology Johnson, N. P., Tóth, G. G., Lai, D., Zhu, H., Açar, G., Agostoni, P., Appelman, Y., Arslan, F., Barbato, E., Chen, S., Di Serafino, L., Domínguez-Franco, A. J., Dupouy, P., Esen, A. M., Esen, O. B., Hamilos, M., Iwasaki, K., Jensen, L. O., Jiménez-Navarro, M. F., Katritsis, D. G., Kocaman, S. A., Koo, B., López-Palop, R., Lorin, J. D., Miller, L. H., Muller, O., Nam, C., Oud, N., Puymirat, E., Rieber, J., Rioufol, G., Rodés-Cabau, J., Sedlis, S. P., Takeishi, Y., Tonino, P. A., Van Belle, E., Verna, E., Werner, G. S., Fearon, W. F., Pijls, N. H., De Bruyne, B., Gould, K. L. 2014; 64 (16): 1641-1654

  Abstract

  Fractional flow reserve (FFR) has become an established tool for guiding treatment, but its graded relationship to clinical outcomes as modulated by medical therapy versus revascularization remains unclear.The study hypothesized that FFR displays a continuous relationship between its numeric value and prognosis, such that lower FFR values confer a higher risk and therefore receive larger absolute benefits from revascularization.Meta-analysis of study- and patient-level data investigated prognosis after FFR measurement. An interaction term between FFR and revascularization status allowed for an outcomes-based threshold.A total of 9,173 (study-level) and 6,961 (patient-level) lesions were included with a median follow-up of 16 and 14 months, respectively. Clinical events increased as FFR decreased, and revascularization showed larger net benefit for lower baseline FFR values. Outcomes-derived FFR thresholds generally occurred around the range 0.75 to 0.80, although limited due to confounding by indication. FFR measured immediately after stenting also showed an inverse relationship with prognosis (hazard ratio: 0.86, 95% confidence interval: 0.80 to 0.93; p < 0.001). An FFR-assisted strategy led to revascularization roughly half as often as an anatomy-based strategy, but with 20% fewer adverse events and 10% better angina relief.FFR demonstrates a continuous and independent relationship with subsequent outcomes, modulated by medical therapy versus revascularization. Lesions with lower FFR values receive larger absolute benefits from revascularization. Measurement of FFR immediately after stenting also shows an inverse gradient of risk, likely from residual diffuse disease. An FFR-guided revascularization strategy significantly reduces events and increases freedom from angina with fewer procedures than an anatomy-based strategy.

  View details for DOI 10.1016/j.jacc.2014.07.973

  View details for PubMedID 25323250

• Appropriate Intravascular Ultrasound Measurement Intervals for Assessment of Cardiac Allograft Vasculopathy after Heart Transplantation Okada, K., Kitahara, H., Otagiri, K., Tanaka, S., Kobayashi, Y., Yock, P., Yeung, A., Fitzgerald, P. J., Valantine, H. A., Khush, K. K., Fearon, W. F., Honda, Y. ELSEVIER SCIENCE INC. 2014: B105

  View details for DOI 10.1016/j.jacc.2014.07.407

  View details for Web of Science ID 000359649700355

• Impact of Coronary Artery Size on Physiologic Microcirculatory Indices: A Volumetric Intravascular Ultrasound Study with Coronary Flow Assessment Kobayashi, Y., Honda, Y., Fearon, W. F., Tanaka, S., Fitzgerald, P., Yeung, A., Tremmel, J. A. ELSEVIER SCIENCE INC. 2014: B91

  View details for DOI 10.1016/j.jacc.2014.07.362

  View details for Web of Science ID 000359649700312

• Attenuated-Signal Plaque and Cardiac Allograft Vasculopathy: A Serial Volumetric IVUS Study of Heart Transplant Recipients Okada, K., Kitahara, H., Otagiri, K., Tanaka, S., Kobayashi, Y., Yock, P., Yeung, A., Fitzgerald, P., Valantine, H. A., Khush, K. K., Fearon, W. F., Honda, Y. ELSEVIER SCIENCE INC. 2014: B102

  View details for DOI 10.1016/j.jacc.2014.07.398

  View details for Web of Science ID 000359649700346

• Functional assessment of multivessel coronary artery disease: ischemia-guided percutaneous coronary intervention CORONARY ARTERY DISEASE Schwartz, J. G., Fearon, W. F. 2014; 25 (6): 521-528

  Abstract

  Invasive evaluation and treatment of coronary artery disease (CAD) has traditionally been based upon coronary angiography to determine the need for and the success of revascularization. However, coronary angiography augmented with fractional flow reserve (FFR) creates a paradigm shift, providing a more complete functional assessment of coronary lesions. Measuring FFR to identify ischemic lesions and guide revascularization results in fewer adverse outcomes, including persistent angina, myocardial infarction, and mortality. An ischemic lesion identified by FFR is more likely to lead to adverse events when compared with an angiographically similar lesion with nonischemic FFR when both are treated medically. Although the mechanism explaining this is unclear, it is likely multifactorial, including the impact of mechanical forces, upregulation of inflammatory mediators, and the amount of distal myocardial tissue at risk. Using both anatomic and ischemia-guided assessments (such as the Functional SYNTAX Score) aids in the therapeutic decision-making process in patients with multivessel CAD. This review focuses on the evidence for FFR-guided management of multivessel CAD.

  View details for DOI 10.1097/MCA.0000000000000153

  View details for PubMedID 25072658

• Fractional flow reserve and the index of microvascular resistance in patients with acute coronary syndromes EUROINTERVENTION Hennigan, B., Layland, J., Fearon, W. F., Oldroyd, K. G. 2014; 10: T55-T63

  Abstract

  The aim of this article is to review what is currently known about fractional flow reserve (FFR) and related coronary physiological indices in patients with acute coronary syndrome (ACS) including non-ST-elevation (NSTEMI) and ST-elevation myocardial infarction (STEMI) with a view to making recommendations for daily practice.We explored all relevant publications to date including literature reviews, clinical trials and registries. We identified sufficient data on FFR in the setting of NSTEMI to confirm it to be a reliable and useful tool for lesion-level decision making with certain pitfalls as outlined below. There was limited published literature on FFR in STEMI. However, there is some evidence that, in patients who are stable after culprit lesion intervention, FFR may be of value for assessing the functional significance of non-culprit lesions. When measured in the culprit artery of patients with STEMI, the index of myocardial resistance (IMR) predicts long-term clinical outcomes.In patients with ACS, there is an increasing evidence base to support the role of FFR to guide revascularisation and of IMR to predict outcome.

  View details for DOI 10.4244/EIJV10STA10

  View details for Web of Science ID 000343376600010

  View details for PubMedID 25256535

• Response to letter regarding article, "Cost-effectiveness of percutaneous coronary intervention in patients with stable coronary artery disease and abnormal fractional flow reserve". Circulation Fearon, W. F., Shilane, D., Pijls, N. H., Boothroyd, D. B., Tonino, P. A., Barbato, E., Juni, P., De Bruyne, B., Hlatky, M. A. 2014; 129 (25)

  View details for DOI 10.1161/CIRCULATIONAHA.114.009349

  View details for PubMedID 24958760

• Clinical implications of new-onset left bundle branch block after transcatheter aortic valve replacement: analysis of the PARTNER experience EUROPEAN HEART JOURNAL Nazif, T. M., Williams, M. R., Hahn, R. T., Kapadia, S., Babaliaros, V., Rodes-Cabau, J., Szeto, W. Y., Jilaihawi, H., Fearon, W. F., Dvir, D., Dewey, T. M., Makkar, R. R., Xu, K., Dizon, J. M., Smith, C. R., Leon, M. B., Kodali, S. K. 2014; 35 (24): 1599-U19

  Abstract

  Cardiac conduction disturbances, including a left bundle branch block (LBBB), occur frequently following transcatheter aortic valve replacement (TAVR) and may be associated with adverse clinical events. This analysis examines the incidence and implications of new onset, persistent LBBB in patients undergoing TAVR with a balloon-expandable valve.Patients undergoing TAVR in the Placement of Aortic Transcatheter Valves (PARTNER) trial and continued access registries with baseline and discharge/7-day electrocardiograms were included. Prior permanent pacemaker implantation (PPI) and baseline intraventricular conduction abnormalities were exclusion criteria. Predictors of new LBBB were identified and outcomes compared between patients with and without new LBBB. New LBBB occurred in 121 of 1151 (10.5%) patients and persisted in more than half at 6 months to 1 year. The only predictor of new LBBB was prior coronary artery bypass grafting. New LBBB was not associated with significant differences in 1-year mortality, cardiovascular mortality, repeat hospitalization, stroke, or myocardial infarction. However, it was associated with increased PPI during hospitalization (8.3 vs 2.8%, P = 0.005) and from discharge to 1 year (4.7 vs. 1.5%, P = 0.01). The ejection fraction failed to improve after TAVR in patients with new LBBB and remained lower at 6 months to 1 year (52.8 vs. 58.1%, P < 0.001).Persistent, new-onset LBBB occurred in 10.5% of patients without intraventricular baseline conduction who underwent TAVR in the PARTNER experience. New LBBB was not associated with death, repeat hospitalization, stroke, or myocardial infarction at 1 year, but was associated with a higher rate of PPI and failure of left ventricular ejection fraction to improve.

  View details for DOI 10.1093/eurheartj/eht376

  View details for Web of Science ID 000338629900009

  View details for PubMedID 24179072

• Percutaneous coronary intervention should be guided by fractional flow reserve measurement. Circulation Fearon, W. F. 2014; 129 (18): 1860-70

  View details for DOI 10.1161/CIRCULATIONAHA.113.004300

  View details for PubMedID 24799502

  View details for PubMedCentralID PMC5544937

• Invasive Coronary Microcirculation Assessment - Current Status of Index of Microcirculatory Resistance CIRCULATION JOURNAL Kobayashi, Y., Fearon, W. F. 2014; 78 (5): 1021-1028

  Abstract

  Assessment of the coronary microvasculature in the clinical setting is a key issue, given that microvascular dysfunction itself has a predictive value for cardiovascular events. The index of microcirculatory resistance (IMR) is an invasive method of interrogating the microvasculature and provides further insight into the physiology of cardiovascular diseases. It is simple and readily applicable in the cardiac catheterization laboratory where many patients first present for evaluation of their coronary circulation. In contrast to other invasive and non-invasive tests, this method is known to be stable and reproducible under various hemodynamics and even in the presence of epicardial coronary artery stenosis. IMR has been shown to have prognostic value in patients with ST-segment elevation myocardial infarction; therefore it can be a surrogate marker of cardiovascular events. At the same time, it has the potential to be a therapeutic as well as an investigational tool in the physiology of cardiovascular diseases. This review summarizes the development of IMR, tips and tricks for its measurement, and its usefulness in various clinical settings.

  View details for DOI 10.1253/circj.CJ-14-0364

  View details for Web of Science ID 000335382900001

• Invasive coronary microcirculation assessment--current status of index of microcirculatory resistance. Circulation journal : official journal of the Japanese Circulation Society Kobayashi, Y., Fearon, W. F. 2014; 78 (5): 1021-8

  Abstract

  Assessment of the coronary microvasculature in the clinical setting is a key issue, given that microvascular dysfunction itself has a predictive value for cardiovascular events. The index of microcirculatory resistance (IMR) is an invasive method of interrogating the microvasculature and provides further insight into the physiology of cardiovascular diseases. It is simple and readily applicable in the cardiac catheterization laboratory where many patients first present for evaluation of their coronary circulation. In contrast to other invasive and non-invasive tests, this method is known to be stable and reproducible under various hemodynamics and even in the presence of epicardial coronary artery stenosis. IMR has been shown to have prognostic value in patients with ST-segment elevation myocardial infarction; therefore it can be a surrogate marker of cardiovascular events. At the same time, it has the potential to be a therapeutic as well as an investigational tool in the physiology of cardiovascular diseases. This review summarizes the development of IMR, tips and tricks for its measurement, and its usefulness in various clinical settings.

  View details for PubMedID 24739222

• Multicenter Core Laboratory Comparison of the Instantaneous Wave-Free Ratio and Resting P-d/P-a With Fractional Flow Reserve JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Jeremias, A., Maehara, A., Genereux, P., Asrress, K. N., Berry, C., De Bruyne, B., Davies, J. E., Escaned, J., Fearon, W. F., Gould, K. L., Johnson, N. P., Kirtane, A. J., Koo, B., Marques, K. M., Nijjer, S., Oldroyd, K. G., Petraco, R., Piek, J. J., Pijls, N. H., Redwood, S., Siebes, M., Spaan, J. A., van 't Veer, M., Mintz, G. S., Stone, G. W. 2014; 63 (13): 1253-1261

  Abstract

  This study sought to examine the diagnostic accuracy of the instantaneous wave-free ratio (iFR) and resting distal coronary artery pressure/aortic pressure (Pd/Pa) with respect to hyperemic fractional flow reserve (FFR) in a core laboratory-based multicenter collaborative study.FFR is an index of the severity of coronary stenosis that has been clinically validated in 3 prospective randomized trials. iFR and Pd/Pa are nonhyperemic pressure-derived indices of the severity of stenosis with discordant reports regarding their accuracy with respect to FFR.iFR, resting Pd/Pa, and FFR were measured in 1,768 patients from 15 clinical sites. An independent physiology core laboratory performed blinded off-line analysis of all raw data. The primary objectives were to determine specific iFR and Pd/Pa thresholds with ≥90% accuracy in predicting ischemic versus nonischemic FFR (on the basis of an FFR cut point of 0.80) and the proportion of patients falling beyond those thresholds.Of 1,974 submitted lesions, 381 (19.3%) were excluded because of suboptimal acquisition, leaving 1,593 for final analysis. On receiver-operating characteristic analysis, the optimal iFR cut point for FFR ≤0.80 was 0.90 (C statistic: 0.81 [95% confidence interval: 0.79 to 0.83]; overall accuracy: 80.4%) and for Pd/Pa was 0.92 (C statistic: 0.82 [95% confidence interval: 0.80 to 0.84]; overall accuracy: 81.5%), with no significant difference between these resting measures. iFR and Pd/Pa had ≥90% accuracy to predict a positive or negative FFR in 64.9% (62.6% to 67.3%) and 48.3% (45.6% to 50.5%) of lesions, respectively.This comprehensive core laboratory analysis comparing iFR and Pd/Pa with FFR demonstrated an overall accuracy of ~80% for both nonhyperemic indices, which can be improved to ≥90% in a subset of lesions. Clinical outcome studies are required to determine whether the use of iFR or Pd/Pa might obviate the need for hyperemia in selected patients.

  View details for DOI 10.1016/j.jacc.2013.09.060

  View details for Web of Science ID 000333804300005

• Multicenter core laboratory comparison of the instantaneous wave-free ratio and resting Pd/Pa with fractional flow reserve: the RESOLVE study. Journal of the American College of Cardiology Jeremias, A., Maehara, A., Généreux, P., Asrress, K. N., Berry, C., De Bruyne, B., Davies, J. E., Escaned, J., Fearon, W. F., Gould, K. L., Johnson, N. P., Kirtane, A. J., Koo, B., Marques, K. M., Nijjer, S., Oldroyd, K. G., Petraco, R., Piek, J. J., Pijls, N. H., Redwood, S., Siebes, M., Spaan, J. A., van 't Veer, M., Mintz, G. S., Stone, G. W. 2014; 63 (13): 1253-1261

  Abstract

  This study sought to examine the diagnostic accuracy of the instantaneous wave-free ratio (iFR) and resting distal coronary artery pressure/aortic pressure (Pd/Pa) with respect to hyperemic fractional flow reserve (FFR) in a core laboratory-based multicenter collaborative study.FFR is an index of the severity of coronary stenosis that has been clinically validated in 3 prospective randomized trials. iFR and Pd/Pa are nonhyperemic pressure-derived indices of the severity of stenosis with discordant reports regarding their accuracy with respect to FFR.iFR, resting Pd/Pa, and FFR were measured in 1,768 patients from 15 clinical sites. An independent physiology core laboratory performed blinded off-line analysis of all raw data. The primary objectives were to determine specific iFR and Pd/Pa thresholds with ≥90% accuracy in predicting ischemic versus nonischemic FFR (on the basis of an FFR cut point of 0.80) and the proportion of patients falling beyond those thresholds.Of 1,974 submitted lesions, 381 (19.3%) were excluded because of suboptimal acquisition, leaving 1,593 for final analysis. On receiver-operating characteristic analysis, the optimal iFR cut point for FFR ≤0.80 was 0.90 (C statistic: 0.81 [95% confidence interval: 0.79 to 0.83]; overall accuracy: 80.4%) and for Pd/Pa was 0.92 (C statistic: 0.82 [95% confidence interval: 0.80 to 0.84]; overall accuracy: 81.5%), with no significant difference between these resting measures. iFR and Pd/Pa had ≥90% accuracy to predict a positive or negative FFR in 64.9% (62.6% to 67.3%) and 48.3% (45.6% to 50.5%) of lesions, respectively.This comprehensive core laboratory analysis comparing iFR and Pd/Pa with FFR demonstrated an overall accuracy of ~80% for both nonhyperemic indices, which can be improved to ≥90% in a subset of lesions. Clinical outcome studies are required to determine whether the use of iFR or Pd/Pa might obviate the need for hyperemia in selected patients.

  View details for DOI 10.1016/j.jacc.2013.09.060

  View details for PubMedID 24211503

• VOLUMETRIC VERSUS PLANAR INTRAVASCULAR ULTRASOUND ANALYSIS TO ASSESS SEVERITY OF CARDIAC ALLOGRAFT VASCULOPATHY Okada, K., Kitahara, H., Otagiri, K., Tanaka, S., Kobayashi, Y., Yock, P., Yeung, A., Valantine, H., Khush, K., Fearon, W., Fitzgerald, P., Honda, Y. ELSEVIER SCIENCE INC. 2014: A1765

  View details for DOI 10.1016/S0735-1097(14)61768-X

  View details for Web of Science ID 000359579102523

• CORONARY PHYSIOLOGICAL INDICES IN PATIENTS WITH MYOCARDIAL BRIDGING Tanaka, S., Honda, Y., Yamada, R., Kobayashi, Y., Schnittger, I., Yock, P., Yeung, A., Fitzgerald, P., Fearon, W., Tremmel, J. ELSEVIER SCIENCE INC. 2014: A1691

  View details for DOI 10.1016/S0735-1097(14)61694-6

  View details for Web of Science ID 000359579102449

• Expert Consensus Statement on the Use of Fractional Flow Reserve, Intravascular Ultrasound, and Optical Coherence Tomography: A Consensus Statement of the Society of Cardiovascular Angiography and Interventions CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Lotfi, A., Jeremias, A., Fearon, W. F., Feldman, M. D., Mehran, R., Messenger, J. C., Grines, C. L., Dean, L. S., Kern, M. J., Klein, L. W. 2014; 83 (4): 509-518

  View details for Web of Science ID 000331444200001

  View details for PubMedID 24227282

• Response to letter regarding article, "Prognostic value of the index of microcirculatory resistance measured after primary percutaneous coronary intervention". Circulation Fearon, W. F., Low, A. F., Yong, A. C., McGeoch, R., Berry, C., Shah, M. G., Ho, M., Kim, H., Loh, J. P., Oldroyd, K. G. 2014; 129 (7)

  View details for DOI 10.1161/CIRCULATIONAHA.113.007271

  View details for PubMedID 24550557

• Intracoronary and retrograde coronary venous myocardial delivery of adipose-derived stem cells in swine infarction lead to transient myocardial trapping with predominant pulmonary redistribution. Catheterization and cardiovascular interventions Hong, S. J., Hou, D., Brinton, T. J., Johnstone, B., Feng, D., Rogers, P., Fearon, W. F., Yock, P., March, K. L. 2014; 83 (1): E17-25

  Abstract

  To examine the comparative fate of adipose-derived stem cells (ASCs) as well as their impact on coronary microcirculation following either retrograde coronary venous (RCV) or arterial delivery.Local delivery of ASCs to the heart has been proposed as a practical approach to limiting the extent of myocardial infarction. Mouse models of mesenchymal stem cell effects on the heart have also demonstrated significant benefits from systemic (intravenous) delivery, prompting a question about the advantage of local delivery. There has been no study addressing the extent of myocardial vs. systemic disposition of ASCs in large animal models following local delivery to the myocardium.In an initial experiment, dose-dependent effects of ASC delivery on coronary circulation in normal swine were evaluated to establish a tolerable ASC dosing range for intracoronary (IC) delivery. In a set of subsequent experiments, an anterior acute myocardial infarction (AMI) was created by balloon occlusion of the proximal left anterior descending (LAD) artery, followed by either IC or RCV infusion of 10(7) (111)Indium-labeled autologous ASCs 6 days following AMI. Indices of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were measured before sacrifices to collect tissues for analysis at 1 or 24 hr after cell delivery.IC delivery of porcine ASCs to normal myocardium was well tolerated up to a cumulative dose of 14 × 10(6) cells (approximately 0.5 × 10(6) cells/kg). There was evidence suggesting microcirculatory trapping of ASC: at unit doses of 50 × 10(6) ASCs, IMR and CFR were found to be persistently altered in the target LAD distribution at 7 days following delivery, whereas at 10 × 10(6) ASCs, only CFR was altered. In the context of recent MI, a significantly higher percentage of ASCs was retained at 1 hr with IC delivery compared with RCV delivery (57.2 ± 12.7% vs. 17.9 ± 1.6%, P = 0.037) but this initial difference was not apparent at 24 hr (22.6 ± 5.5% vs. 18.7 ± 8.6%; P = 0.722). In both approaches, most ASC redistributed to the pulmonary circulation by 24 hr postdelivery. There were no significant differences in CFR or IMR following ASC delivery to infarcted tissue by either route.Selective intravascular delivery of ASC by coronary arterial and venous routes leads to similarly limited myocardial cell retention with predominant redistribution of cells to the lungs. IC arterial delivery of ASC leads to only transiently greater myocardial retention, which is accompanied by obstruction of normal regions of coronary microcirculation at higher doses. The predominant intrapulmonary localization of cells following local delivery via both methods prompts the notion that systemic delivery of ASC might provide similarly beneficial outcomes while avoiding risks of inadvertent microcirculatory compromise.

  View details for DOI 10.1002/ccd.24659

  View details for PubMedID 22972685

• Intracoronary and Retrograde Coronary Venous Myocardial Delivery of Adipose-Derived Stem Cells in Swine Infarction Lead to Transient Myocardial Trapping with Predominant Pulmonary Redistribution CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Hong, S. J., Hou, D., Brinton, T. J., Johnstone, B., Feng, D., Rogers, P., Fearon, W. F., Yock, P., March, K. L. 2014; 83 (1): E17-E25

  Abstract

  To examine the comparative fate of adipose-derived stem cells (ASCs) as well as their impact on coronary microcirculation following either retrograde coronary venous (RCV) or arterial delivery.Local delivery of ASCs to the heart has been proposed as a practical approach to limiting the extent of myocardial infarction. Mouse models of mesenchymal stem cell effects on the heart have also demonstrated significant benefits from systemic (intravenous) delivery, prompting a question about the advantage of local delivery. There has been no study addressing the extent of myocardial vs. systemic disposition of ASCs in large animal models following local delivery to the myocardium.In an initial experiment, dose-dependent effects of ASC delivery on coronary circulation in normal swine were evaluated to establish a tolerable ASC dosing range for intracoronary (IC) delivery. In a set of subsequent experiments, an anterior acute myocardial infarction (AMI) was created by balloon occlusion of the proximal left anterior descending (LAD) artery, followed by either IC or RCV infusion of 10(7) (111)Indium-labeled autologous ASCs 6 days following AMI. Indices of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were measured before sacrifices to collect tissues for analysis at 1 or 24 hr after cell delivery.IC delivery of porcine ASCs to normal myocardium was well tolerated up to a cumulative dose of 14 × 10(6) cells (approximately 0.5 × 10(6) cells/kg). There was evidence suggesting microcirculatory trapping of ASC: at unit doses of 50 × 10(6) ASCs, IMR and CFR were found to be persistently altered in the target LAD distribution at 7 days following delivery, whereas at 10 × 10(6) ASCs, only CFR was altered. In the context of recent MI, a significantly higher percentage of ASCs was retained at 1 hr with IC delivery compared with RCV delivery (57.2 ± 12.7% vs. 17.9 ± 1.6%, P = 0.037) but this initial difference was not apparent at 24 hr (22.6 ± 5.5% vs. 18.7 ± 8.6%; P = 0.722). In both approaches, most ASC redistributed to the pulmonary circulation by 24 hr postdelivery. There were no significant differences in CFR or IMR following ASC delivery to infarcted tissue by either route.Selective intravascular delivery of ASC by coronary arterial and venous routes leads to similarly limited myocardial cell retention with predominant redistribution of cells to the lungs. IC arterial delivery of ASC leads to only transiently greater myocardial retention, which is accompanied by obstruction of normal regions of coronary microcirculation at higher doses. The predominant intrapulmonary localization of cells following local delivery via both methods prompts the notion that systemic delivery of ASC might provide similarly beneficial outcomes while avoiding risks of inadvertent microcirculatory compromise.

  View details for DOI 10.1002/ccd.24659

  View details for Web of Science ID 000328631400006

  View details for PubMedID 22972685

• Outcomes of Transcatheter and Surgical Aortic Valve Replacement in High-Risk Patients With Aortic Stenosis and Left Ventricular Dysfunction Results From the Placement of Aortic Transcatheter Valves (PARTNER) Trial (Cohort A) CELL BIOLOGY INTERNATIONAL Elmariah, S., Palacios, I. F., McAndrew, T., Hueter, I., Inglessis, I., Baker, J. N., Kodali, S., Leon, M. B., Svensson, L., Pibarot, P., Douglas, P. S., Fearon, W. F., Kirtane, A. J., Maniar, H. S., Passeri, J. J. 2014; 38 (1): 604-614

  View details for DOI 10.1161/CIRCINTERVENTIONS.113.000650

  View details for Web of Science ID 000328511600007

• Assessing Intermediate Coronary Lesions More Than Meets the Eye CIRCULATION Fearon, W. F. 2013; 128 (24): 2551–53

  View details for PubMedID 24141254

  View details for PubMedCentralID PMC5544935

• Outcomes of Transcatheter and Surgical Aortic Valve Replacement in High-Risk Patients With Aortic Stenosis and Left Ventricular Dysfunction Results From the Placement of Aortic Transcatheter Valves (PARTNER) Trial (Cohort A) CIRCULATION-CARDIOVASCULAR INTERVENTIONS Elmariah, S., Palacios, I. F., McAndrew, T., Hueter, I., Inglessis, I., Baker, J. N., Kodali, S., Leon, M. B., Svensson, L., Pibarot, P., Douglas, P. S., Fearon, W. F., Kirtane, A. J., Maniar, H. S., Passeri, J. J. 2013; 6 (6): 604-614

  Abstract

  The Placement of Aortic Transcatheter Valves (PARTNER) trial demonstrated similar survival after transcatheter and surgical aortic valve replacement (TAVR and SAVR, respectively) in high-risk patients with symptomatic, severe aortic stenosis. The aim of this study was to evaluate the effect of left ventricular (LV) dysfunction on clinical outcomes after TAVR and SAVR and the impact of aortic valve replacement technique on LV function.The PARTNER trial randomized high-risk patients with severe aortic stenosis to TAVR or SAVR. Patients were stratified by the presence of LV ejection fraction (LVEF) <50%. All-cause mortality was similar for TAVR and SAVR at 30-days and 1 year regardless of baseline LV function and valve replacement technique. In patients with LV dysfunction, mean LVEF increased from 35.7±8.5% to 48.6±11.3% (P<0.0001) 1 year after TAVR and from 38.0±8.0% to 50.1±10.8% after SAVR (P<0.0001). Higher baseline LVEF (odds ratio, 0.90 [95% confidence interval, 0.86, 0.95]; P<0.0001) and previous permanent pacemaker (odds ratio, 0.34 [95% confidence interval, 0.15, 0.81]) were independently associated with reduced likelihood of ≥10% absolute LVEF improvement by 30 days; higher mean aortic valve gradient was associated with increased odds of LVEF improvement (odds ratio, 1.04 per 1 mm Hg [95% confidence interval, 1.01, 1.08]). Failure to improve LVEF by 30 days was associated with adverse 1-year outcomes after TAVR but not SAVR.In high-risk patients with severe aortic stenosis and LV dysfunction, mortality rates and LV functional recovery were comparable between valve replacement techniques. TAVR is a feasible alternative for patients with symptomatic severe aortic stenosis and LV dysfunction who are at high risk for SAVR.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894.

  View details for DOI 10.1161/CIRCINTERVENTIONS.113.000650

  View details for PubMedID 24221391

• Elevated Right Ventricular Operant Diastolic Elastance Strongly Predicts Increased Risk of Mortality Following Heart Transplantation Rhee, J., Sudini, N. L., Pham, M., Fearon, W., Lee, D., Beygui, R. E., Montoya, J. G., Wu, J. C., Vrtovec, B., Hunt, S. A., Haddad, F. LIPPINCOTT WILLIAMS & WILKINS. 2013

  View details for Web of Science ID 000332162907319

• Relation Between Periarterial Neovascularization and Progression of Coronary Allograft Vasculopathy: A Serial IVUS Study of Cardiac Transplant Patients Kitahara, H., Yamada, R., Sakamoto, K., Waseda, K., Yock, P. G., Yeung, A. C., Valantine, H. A., Fearon, W., Fitzgerald, P. J., Honda, Y. LIPPINCOTT WILLIAMS & WILKINS. 2013

  View details for Web of Science ID 000332162905312

• Invasive Evaluation of Chest Pain in Patients With Angiographically Normal Coronary Arteries Lee, B., Yong, A. C., Fearon, W. F., Lim, H., Nguyen, P. K., Yeung, A. C., Tremmel, J. A. LIPPINCOTT WILLIAMS & WILKINS. 2013

  View details for Web of Science ID 000332162908129

• Does High Dose Atorvastatin Pre-treatment Prevent Microvascular Dysfunction After Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome? : A Randomized Comparison Study Using the Index of Microcirculatory Resistance Lee, B., Choi, W., Nam, C., Doh, J., Chung, W., Fearon, W. F., Koo, B. ELSEVIER SCIENCE INC. 2013: B186

  View details for DOI 10.1016/j.jacc.2013.08.1361

  View details for Web of Science ID 000329845600607

• Fractional Flow Reserve Assessment of Left Main Stenosis in the Presence of Downstream Coronary Stenoses: Validation in Humans Yong, A. S., Toth, G., Lenders, G., De Bruyne, B., Dao, C., Daniels, D. V., Pijls, N., Fearon, W. F. ELSEVIER SCIENCE INC. 2013: B188

  View details for DOI 10.1016/j.jacc.2013.08.1366

  View details for Web of Science ID 000329845600612

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

  View details for DOI 10.1016/j.jacc.2013.08.841

  View details for Web of Science ID 000329845600109

• Does Age Affect Fractional Flow Reserve-Guided Percutaneous Coronary Intervention? A FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) Trial Substudy Lim, H., De Bruyne, B., Fearon, W. F., Lee, B., Pijls, N., Tonino, P. A., Yong, A. S. ELSEVIER SCIENCE INC. 2013: B25

  View details for DOI 10.1016/j.jacc.2013.08.811

  View details for Web of Science ID 000329845600074

• Variability in quantitative and qualitative analysis of intravascular ultrasound and frequency domain optical coherence tomography. Catheterization and cardiovascular interventions Abnousi, F., Waseda, K., Kume, T., Otake, H., Kawarada, O., Yong, C. M., Fitzgerald, P. J., Honda, Y., Yeung, A. C., Fearon, W. F. 2013; 82 (3): E192-9

  Abstract

  BACKGROUND: Frequency-domain optical coherence tomography (FD-OCT) is an intravascular imaging technique now available in the United States. However, the importance of level of training required for analysis using intravascular ultrasound (IVUS) and FD-OCT is unclear. The aim of this study was to evaluate inter- and intra-observer variability between expert and beginner analysts interpreting IVUS and FD-OCT images. METHODS AND RESULTS: Two independent expert analysts and two independent beginner analysts evaluated a total of 226 ± 2 stent cross-sections with IVUS and 232 ± 2 stent cross-sections with FD-OCT in 14 patients after stenting. Inter- and intra-observer variability for determining stent volume index (VI), as well as identifying incomplete stent apposition and dissection were assessed. The inter- and intra-observer variability of stent VI was minimal for both beginner and expert analysts regardless of imaging technology (random variability: 0.38 vs. 0.05 mm(3) /mm for IVUS, 0.26 vs. 0.08 mm(3) /mm for FD-OCT). Although qualitative IVUS analysis at the patient level revealed no significant difference between beginners and experts, this was not the case for FD-OCT. The number of overall qualitative findings noted by beginner and expert analysts were more variable (overestimated or underestimated) with FD-OCT. CONCLUSION: Despite varying levels of training, the increased resolution of FD-OCT compared to IVUS provides better detection and less variability in quantitative image analysis. On the contrary, this increased resolution not only increases the rate but also the variability of detection of qualitative image analysis, especially for beginner analysts. © 2013 Wiley Periodicals, Inc.

  View details for DOI 10.1002/ccd.24871

  View details for PubMedID 23412754

• Variability in quantitative and qualitative analysis of intravascular ultrasound and frequency domain optical coherence tomography CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Abnousi, F., Waseda, K., Kume, T., Otake, H., Kawarada, O., Yong, C. M., Fitzgerald, P. J., Honda, Y., Yeung, A. C., Fearon, W. F. 2013; 82 (3): E192-E199

  Abstract

  BACKGROUND: Frequency-domain optical coherence tomography (FD-OCT) is an intravascular imaging technique now available in the United States. However, the importance of level of training required for analysis using intravascular ultrasound (IVUS) and FD-OCT is unclear. The aim of this study was to evaluate inter- and intra-observer variability between expert and beginner analysts interpreting IVUS and FD-OCT images. METHODS AND RESULTS: Two independent expert analysts and two independent beginner analysts evaluated a total of 226 ± 2 stent cross-sections with IVUS and 232 ± 2 stent cross-sections with FD-OCT in 14 patients after stenting. Inter- and intra-observer variability for determining stent volume index (VI), as well as identifying incomplete stent apposition and dissection were assessed. The inter- and intra-observer variability of stent VI was minimal for both beginner and expert analysts regardless of imaging technology (random variability: 0.38 vs. 0.05 mm(3) /mm for IVUS, 0.26 vs. 0.08 mm(3) /mm for FD-OCT). Although qualitative IVUS analysis at the patient level revealed no significant difference between beginners and experts, this was not the case for FD-OCT. The number of overall qualitative findings noted by beginner and expert analysts were more variable (overestimated or underestimated) with FD-OCT. CONCLUSION: Despite varying levels of training, the increased resolution of FD-OCT compared to IVUS provides better detection and less variability in quantitative image analysis. On the contrary, this increased resolution not only increases the rate but also the variability of detection of qualitative image analysis, especially for beginner analysts. © 2013 Wiley Periodicals, Inc.

  View details for DOI 10.1002/ccd.24871

  View details for Web of Science ID 000323454100008

• Response to letter regarding article, "fractional flow reserve assessment of left main stenosis in the presence of downstream coronary stenoses". Circulation. Cardiovascular interventions Yong, A. S., Daniels, D., Kim, H., Ikeno, F., Lyons, J., Fearon, W. F., Pijls, N. H., De Bruyne, B. 2013; 6 (4)

  View details for DOI 10.1161/CIRCINTERVENTIONS.113.000507

  View details for PubMedID 23963582

• Granulocyte colony-stimulating factor therapy is associated with a reduced incidence of acute rejection episodes or allograft vasculopathy in heart transplant recipients. Transplantation proceedings Vrtovec, B., Haddad, F., Pham, M., Deuse, T., Fearon, W. F., Schrepfer, S., Leon, S., Vu, T., Valantine, H., Hunt, S. A. 2013; 45 (6): 2406-2409

  Abstract

  We evaluated the potential effects of granulocyte colony-simulating factor (G- CSF) on the incidence of rejection and allograft vasculopathy in heart transplant recipients.Of 247 patients undergoing heart transplantation from 2000 to 2007, 52 (21%) developed leukopenia (white blood cell [WBC] <2.5 × 10(9)cells/L) in the absence of active infection, rejection, or malignancy. In 24 (46%) patients a clinical decision was made to treat the leukopenia with G-CSF (G-CSF group), and 28 (54%) Patients received no G-CSF (non-GCSF group). Patients followed up for 1 year after the period of leukopenia were assessed for allograft vasculopathy and acute rejection incidence.At baseline, the G-CSF group and the non-GCSF group did not differ in age, gender, race, heart failure etiology, creatinine, left ventricular ejection fraction (LVEF) or immunosupressive regimen. During 1-year follow-up there were no deaths in the G-CSF group, and 1 death in the non-GCSF group (P = .34). The incidence of rejection or progressive allograft vasculopathy was lower in the G-CSF group when compared with the non-GCSF group (2 [8%] vs 15 [53%]; P < .01). Multivariate analysis identified both prior rejection episodes and G-CSF therapy as factors associated with the combined end-point of rejection or progressive allograft vasculopathy (odds ratio [OR] = 7.89 [1.67-37.2] and OR = 0.09 [0.02-0.52], respectively).G-CSF therapy appears to be associated with a decreased incidence of acute rejection episodes or allograft vasculopathy in heart transplant recipients, suggesting a potential immunomodulatory effect of G-CSF.

  View details for DOI 10.1016/j.transproceed.2013.01.106

  View details for PubMedID 23953556

• Coronary Microvascular Dysfunction After ST-Segment-Elevation Myocardial Infarction: Local or Global Phenomenon? Circulation. Cardiovascular interventions Yong, A. S., Fearon, W. F. 2013; 6 (3): 201-203

  View details for DOI 10.1161/CIRCINTERVENTIONS.113.000462

  View details for PubMedID 23780293

• Functional assessment of coronary stenoses: can we live without it? EUROPEAN HEART JOURNAL Pijls, N. H., Tanaka, N., Fearon, W. F. 2013; 34 (18): 1335-1344

  Abstract

  When selecting coronary stenoses for interventional treatment, assessment of reversible ischaemia is paramount from a symptomatic as well as prognostic point of view. Fractional flow reserve (FFR) is now considered the gold standard for invasive assessment of ischaemia. By measuring FFR in the catheterization laboratory, one can accurately identify which lesions should be stented resulting in improved patient outcome in most elective clinical and angiographic conditions. Recently, in the European Society of Cardiology guidelines on coronary revascularization, FFR was upgraded to an IA classification in multivessel percutaneous coronary intervention. In this review paper, the rationale for routine measurement of FFR will be reviewed and studies supporting its integration into everyday practice will be highlighted.

  View details for DOI 10.1093/eurheartj/ehs436

  View details for Web of Science ID 000318807700010

  View details for PubMedID 23257950

• Does the Instantaneous Wave-Free Ratio Approximate the Fractional Flow Reserve? JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Johnson, N. P., Kirkeeide, R. L., Asrress, K. N., Fearon, W. F., Lockie, T., Marques, K. M., Pyxaras, S. A., Rolandi, M. C., van 't Veer, M., De Bruyne, B., Piek, J. J., Pijls, N. H., Redwood, S., Siebes, M., Spaan, J. A., Gould, K. L. 2013; 61 (13): 1428-1435

  Abstract

  This study sought to examine the clinical performance of and theoretical basis for the instantaneous wave-free ratio (iFR) approximation to the fractional flow reserve (FFR).Recent work has proposed iFR as a vasodilation-free alternative to FFR for making mechanical revascularization decisions. Its fundamental basis is the assumption that diastolic resting myocardial resistance equals mean hyperemic resistance.Pressure-only and combined pressure-flow clinical data from several centers were studied both empirically and by using pressure-flow physiology. A Monte Carlo simulation was performed by repeatedly selecting random parameters as if drawing from a cohort of hypothetical patients, using the reported ranges of these physiologic variables.We aggregated observations of 1,129 patients, including 120 with combined pressure-flow data. Separately, we performed 1,000 Monte Carlo simulations. Clinical data showed that iFR was +0.09 higher than FFR on average, with ±0.17 limits of agreement. Diastolic resting resistance was 2.5 ± 1.0 times higher than mean hyperemic resistance in patients. Without invoking wave mechanics, classic pressure-flow physiology explained clinical observations well, with a coefficient of determination of >0.9. Nearly identical scatter of iFR versus FFR was seen between simulation and patient observations, thereby supporting our model.iFR provides both a biased estimate of FFR, on average, and an uncertain estimate of FFR in individual cases. Diastolic resting myocardial resistance does not equal mean hyperemic resistance, thereby contravening the most basic condition on which iFR depends. Fundamental relationships of coronary pressure and flow explain the iFR approximation without invoking wave mechanics.

  View details for DOI 10.1016/j.jacc.2012.09.064

  View details for Web of Science ID 000317191200010

  View details for PubMedID 23395077

• VERIFY (VERification of Instantaneous Wave-Free Ratio and Fractional Flow Reserve for the Assessment of Coronary Artery Stenosis Severity in EverydaY Practice) JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Berry, C., van 't Veer, M., Witt, N., Kala, P., Bocek, O., Pyxaras, S. A., McClure, J. D., Fearon, W. F., Barbato, E., Tonino, P. A., De Bruyne, B., Pijls, N. H., Oldroyd, K. G. 2013; 61 (13): 1421-1427

  Abstract

  This study sought to compare fractional flow reserve (FFR) with the instantaneous wave-free ratio (iFR) in patients with coronary artery disease and also to determine whether the iFR is independent of hyperemia.FFR is a validated index of coronary stenosis severity. FFR-guided percutaneous coronary intervention (PCI) improves clinical outcomes compared to angiographic guidance alone. iFR has been proposed as a new index of stenosis severity that can be measured without adenosine.We conducted a prospective, multicenter, international study of 206 consecutive patients referred for PCI and a retrospective analysis of 500 archived pressure recordings. Aortic and distal coronary pressures were measured in duplicate in patients under resting conditions and during intravenous adenosine infusion at 140 μg/kg/min.Compared to the FFR cut-off value of ≤0.80, the diagnostic accuracy of the iFR value of ≤0.80 was 60% (95% confidence interval [CI]: 53% to 67%) for all vessels studied and 51% (95% CI: 43% to 59%) for those patients with FFR in the range of 0.60 to 0.90. iFR was significantly influenced by the induction of hyperemia: mean ± SD iFR at rest was 0.82 ± 0.16 versus 0.64 ± 0.18 with hyperemia (p < 0.001). Receiver operating characteristics confirmed that the diagnostic accuracy of iFR was similar to resting Pd/Pa and trans-stenotic pressure gradient and significantly inferior to hyperemic iFR. Analysis of our retrospectively acquired dataset showed similar results.iFR correlates weakly with FFR and is not independent of hyperemia. iFR cannot be recommended for clinical decision making in patients with coronary artery disease.

  View details for DOI 10.1016/j.jacc.2012.09.065

  View details for Web of Science ID 000317191200009

• VERIFY (VERification of Instantaneous Wave-Free Ratio and Fractional Flow Reserve for the Assessment of Coronary Artery Stenosis Severity in EverydaY Practice): a multicenter study in consecutive patients. Journal of the American College of Cardiology Berry, C., van 't Veer, M., Witt, N., Kala, P., Bocek, O., Pyxaras, S. A., McClure, J. D., Fearon, W. F., Barbato, E., Tonino, P. A., De Bruyne, B., Pijls, N. H., Oldroyd, K. G. 2013; 61 (13): 1421-1427

  Abstract

  This study sought to compare fractional flow reserve (FFR) with the instantaneous wave-free ratio (iFR) in patients with coronary artery disease and also to determine whether the iFR is independent of hyperemia.FFR is a validated index of coronary stenosis severity. FFR-guided percutaneous coronary intervention (PCI) improves clinical outcomes compared to angiographic guidance alone. iFR has been proposed as a new index of stenosis severity that can be measured without adenosine.We conducted a prospective, multicenter, international study of 206 consecutive patients referred for PCI and a retrospective analysis of 500 archived pressure recordings. Aortic and distal coronary pressures were measured in duplicate in patients under resting conditions and during intravenous adenosine infusion at 140 μg/kg/min.Compared to the FFR cut-off value of ≤0.80, the diagnostic accuracy of the iFR value of ≤0.80 was 60% (95% confidence interval [CI]: 53% to 67%) for all vessels studied and 51% (95% CI: 43% to 59%) for those patients with FFR in the range of 0.60 to 0.90. iFR was significantly influenced by the induction of hyperemia: mean ± SD iFR at rest was 0.82 ± 0.16 versus 0.64 ± 0.18 with hyperemia (p < 0.001). Receiver operating characteristics confirmed that the diagnostic accuracy of iFR was similar to resting Pd/Pa and trans-stenotic pressure gradient and significantly inferior to hyperemic iFR. Analysis of our retrospectively acquired dataset showed similar results.iFR correlates weakly with FFR and is not independent of hyperemia. iFR cannot be recommended for clinical decision making in patients with coronary artery disease.

  View details for DOI 10.1016/j.jacc.2012.09.065

  View details for PubMedID 23395076

• Fractional flow reserve assessment of left main stenosis in the presence of downstream coronary stenoses. Circulation. Cardiovascular interventions Yong, A. S., Daniels, D., De Bruyne, B., Kim, H., Ikeno, F., Lyons, J., Pijls, N. H., Fearon, W. F. 2013; 6 (2): 161-165

  Abstract

  Several studies have shown that fractional flow reserve (FFR) measurement can aid in the assessment of left main coronary stenosis. However, the impact of downstream epicardial stenosis on left main FFR assessment with the pressure wire in the nonstenosed downstream vessel remains unknown.Variable stenoses were created in the left main coronary arteries and downstream epicardial vessels in 6 anaesthetized male sheep using balloon catheters. A total of 220 pairs of FFR assessments of the left main stenosis were obtained, before and after creation of a stenosis in a downstream epicardial vessel, by having a pressure-sensor wire in the other nonstenosed downstream vessel. The apparent left main FFR in the presence of downstream stenosis (FFR(app)) was significantly higher compared with the true FFR in the absence of downstream stenosis (FFR(true); 0.80±0.05 versus 0.76±0.05; estimate of the mean difference, 0.035; P<0.001). The difference between FFR(true) and FFR(app) correlated with composite FFR of the left main plus stenosed artery (r=-0.31; P<0.001) indicating that this difference was greater with increasing epicardial stenosis severity. Among measurements with FFR(app) >0.80, 9% were associated with an FFR(true) of <0.75. In all instances, the epicardial lesion was in the proximal portion of the stenosed vessel, and the epicardial FFR (combined FFR of the left main and downstream stenosed vessel) was ≤0.50.A clinically relevant effect on the FFR assessment of left main disease with the pressure wire in a nonstenosed downstream vessel occurs only when the stenosis in the other vessel is proximal and very severe.

  View details for DOI 10.1161/CIRCINTERVENTIONS.112.000104

  View details for PubMedID 23549643

• ST-Elevation Myocardial Infarction Following Heart Transplantation as an Unusual Presentation of Coronary Allograft Vasculopathy: A Case Report TRANSPLANTATION PROCEEDINGS Peter, S., HULME, O., Deuse, T., Vrtovec, B., Fearon, W. F., Hunt, S., Haddad, F. 2013; 45 (2): 787-791

  Abstract

  The presentation, mechanisms, and incidence of ST elevation myocardial infarction (STEMI) in heart transplant recipients have been characterized only to a limited degree in the current literature. Herein, we present a unique case of STEMI years after heart transplantation with a focus on the salient features of its diagnosis and interventions. We also provide a review of the epidemiology of this phenomenon.A 33-year-old woman who was status post cardiac transplantation for dilated cardiomyopathy presented to the clinic with mild nonspecific fatigue and concern after having noticed relative bradycardia compared with her posttransplantation baseline heart rate. Electrocardiogram (ECG) showed junctional rhythm and inferior ST elevations, likely reflecting nodal ischemia. Troponins were grossly positive and echocardiogram showed marked right ventricular dysfunction.Successful percutaneous coronary intervention (PCI) with aspiration thrombectomy and drug-eluting stent placement was emergently performed. The heart's rhythm soon returned to sinus tachycardia. Right ventricular wall-motion abnormalities resolved. The patient suffered no clinical sequelae of her STEMI.This case illustrated that "classic" symptoms of STEMI may not occur at all in the setting of heart transplantation. To our knowledge, this is the first case of posttransplantation STEMI presenting as asymptomatic bradycardia, and highlights the importance of maintaining high clinical suspicion for ischemia in transplant recipients with subtle changes. In reviewing the epidemiology of this case, we locate and bundle different types of studies that have directly or indirectly looked at STEMI in heart transplantation. For a variety of putative pathophysiological reasons, STEMI is indeed a rare manifestation of the common transplant phenomenon of coronary artery vasculopathy (CAV).

  View details for DOI 10.1016/j.transproceed.2012.08.021

  View details for PubMedID 23498821

• Physiologic approach for coronary intervention. The Korean journal of internal medicine Fearon, W. F. 2013; 28 (1): 1-7

  Abstract

  When invasively assessing coronary artery disease, the primary goal should be to determine whether the disease is causing a patient's symptoms and whether it is likely to cause future cardiac events. The presence of myocardial ischemia is our best gauge of whether a lesion is responsible for symptoms and likely to result in a future cardiac event. In the catheterization laboratory, fractional flow reserve (FFR) measured with a coronary pressure wire is the reference standard for identifying ischemia-producing lesions. Its spatial resolution is unsurpassed with it not only being vessel-specific, but also lesion-specific. There is now a wealth of data supporting the accuracy of measuring FFR to identify ischemia-producing lesions. FFR-guided percutaneous coronary intervention of these lesions results in improved outcomes and saves resources. Non-hemodynamically significant lesions can be safely managed medically with a low rate of subsequent cardiac events.

  View details for DOI 10.3904/kjim.2013.28.1.1

  View details for PubMedID 23345989

• Calculation of the Index of Microcirculatory Resistance Without Coronary Wedge Pressure Measurement in the Presence of Epicardial Stenosis JACC-CARDIOVASCULAR INTERVENTIONS Yong, A. S., Layland, J., Fearon, W. F., Ho, M., Shah, M. G., Daniels, D., Whitbourn, R., MacIsaac, A., Kritharides, L., Wilson, A., Ng, M. K. 2013; 6 (1): 53-58

  Abstract

  This study sought to investigate a novel method to calculate the index of microcirculatory resistance (IMR) in the presence of significant epicardial stenosis without the need for balloon dilation to measure the coronary wedge pressure (P(w)).The IMR provides a quantitative measure of coronary microvasculature status. However, in the presence of significant epicardial stenosis, IMR calculation requires incorporation of the coronary fractional flow reserve (FFR(cor)), which requires balloon dilation within the coronary artery for P(w) measurement.A method to calculate IMR by estimating FFR(cor) from myocardial FFR (FFR(myo)), which does not require P(w) measurement, was developed from a derivation cohort of 50 patients from a single institution. This method to calculate IMR was then validated in a cohort of 72 patients from 2 other different institutions. Physiology measurements were obtained with a pressure-temperature sensor wire before coronary intervention in both cohorts.From the derivation cohort, a strong linear relationship was found between FFR(cor) and FFR(myo) (FFR(cor) = 1.34 × FFR(myo) - 0.32, r(2) = 0.87, p < 0.001) by regression analysis. With this equation to estimate FFR(cor) in the validation cohort, there was no significant difference between IMR calculated from estimated FFR(cor) and measured FFR(cor) (21.2 ± 12.9 U vs. 20.4 ± 13.6 U, p = 0.161). There was good correlation (r = 0.93, p < 0.001) and agreement by Bland-Altman analysis between calculated and measured IMR.The FFR(cor), and, by extension, microcirculatory resistance can be derived without the need for P(w). This method enables assessment of coronary microcirculatory status before or without balloon inflation, in the presence of epicardial stenosis.

  View details for DOI 10.1016/j.jcin.2012.08.019

  View details for PubMedID 23347861

• Clinical and Functional Correlates of Early Microvascular Dysfunction After Heart Transplantation CIRCULATION-HEART FAILURE Haddad, F., Khazanie, P., Deuse, T., Weisshaar, D., Zhou, J., Nam, C. W., Vu, T. A., Gomari, F. A., Skhiri, M., Simos, A., Schnittger, I., Vrotvec, B., Hunt, S. A., Fearon, W. F. 2012; 5 (6): 759-768

  Abstract

  Microvascular dysfunction is emerging as a strong predictor of outcome in heart transplant recipients. At this time, the determinants and consequences of early microvascular dysfunction are not well established. The objective of the study was to determine the risk factors and functional correlates associated with early microvascular dysfunction in heart transplant recipients.Sixty-three heart transplant recipients who had coronary physiology assessment, right heart catheterization, and echocardiography performed at the time of their first annual evaluation were included in the study. Microvascular dysfunction was assessed using the recently described index of microcirculatory resistance. The presence of microvascular dysfunction, predefined by an index of microcirculatory resistance >20, was observed in 46% of patients at 1 year. A history of acute rejection and undersized donor hearts were associated with microvascular dysfunction at 1 year, with odds ratio of 4.0 (1.3-12.8) and 3.6 (1.2-11.1), respectively. Patients with microvascular dysfunction had lower cardiac index (3.1±0.7 versus 3.5±0.7 L/min per m(2); P=0.02) and mild graft dysfunction measured by echocardiography-derived left and right myocardial performance indices ([0.54±0.09 versus 0.43±0.09; P<0.01] and [0.47±0.14 versus 0.32±0.05; P<0.01], respectively). Microvascular dysfunction was also associated with a higher likelihood of death, graft failure, or allograft vasculopathy at 5 years after transplant (hazard ratio, 2.52 [95% CI, 1.04-5.91]).A history of acute rejection during the first year and smaller donor hearts were identified as risk factors for early microvascular dysfunction. Microvascular dysfunction assessed using index of microcirculatory resistances at 1 year was also associated with worse graft function and possibly worse clinical outcomes.

  View details for DOI 10.1161/CIRCHEARTFAILURE.111.962787

  View details for PubMedID 22933526

• The Impact of Downstream Coronary Stenoses on Fractional Flow Reserve Assessment of Intermediate Left Main Disease JACC-CARDIOVASCULAR INTERVENTIONS Daniels, D. V., van't Veer, M., Pijls, N. H., van der Horst, A., Yong, A. S., De Bruyne, B., Fearon, W. F. 2012; 5 (10): 1021-1025

  Abstract

  The aim of this study was to assess the validity of measuring fractional flow reserve (FFR) of the left main (LM) coronary artery in the setting of concomitant left anterior descending (LAD) or left circumflex (LCX) stenoses.The theoretical impact of a stenosis in the LAD on the FFR assessment of intermediate LM disease with the pressure wire in an unobstructed LCX is currently unknown.A previously validated in vitro model of the coronary circulation was used to create a fixed intermediate stenosis of the LM and a variable downstream LAD or LCX stenosis. The true LM FFR (FFR(LM true)), with no concomitant downstream disease, was compared to the apparent LM FFR (FFR(LM apparent)), with concomitant downstream disease measured with different degrees of LAD or LCX disease. Additionally, an equation based on a resistors model was derived to predict the effect of downstream stenosis on LM FFR (FFR(LM predicted)).In the setting of isolated moderate LM disease (FFR 0.72 ± 0.08), mild to moderate proximal LAD or LCX lesions did not significantly affect LM FFR. Lesions with a composite FFR (LM + downstream disease) ≥0.65 resulted in an FFR(LM apparent) that was not significantly different from FFR(LM true) (0.76 ± 0.06 vs. 0.76 ± 0.05, p = 0.124). Our equation for FFR(LM predicted) accurately modeled the effects of concomitant disease (r = 0.95, p < 0.001).These data suggest that in the presence of proximal mild to moderate LAD or LCX disease, LM FFR can be reliably measured with the pressure wire placed in the uninvolved epicardial artery.

  View details for DOI 10.1016/j.jcin.2012.07.005

  View details for PubMedID 23078730

• The Impact of Sex Differences on Fractional Flow Reserve-Guided Percutaneous Coronary Intervention A FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) Substudy JACC-CARDIOVASCULAR INTERVENTIONS Kim, H., Tonino, P. A., De Bruyne, B., Yong, A. S., Tremmel, J. A., Pijls, N. H., Fearon, W. F. 2012; 5 (10): 1037-1042

  Abstract

  This study sought to evaluate the impact of sex differences on fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI).The FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study demonstrated that FFR-guided PCI improves outcomes compared with an angiography-guided strategy. The role of FFR-guided PCI in women versus men has not been evaluated.We analyzed 2-year data from the FAME study in the 744 men and 261 women with multivessel coronary disease, who were randomized to angiography- or FFR-guided PCI. Statistical comparisons based on sex were stratified by treatment method.Although women were older and had significantly higher rates of hypertension than men did, there were no differences in the rates of major adverse cardiac events (20.3% vs. 20.2%, p = 0.923) and its individual components at 2 years. FFR values were significantly higher in women than in men (0.75 ± 0.18 vs. 0.71 ± 0.17, p = 0.001). The proportion of functionally significant lesions (FFR ≤ 0.80) was lower in women than in men for lesions with 50% to 70% stenosis (21.1% vs. 39.5%, p < 0.001) and for lesions with 70% to 90% stenosis (71.9% vs. 82.0%, p = 0.019). An FFR-guided strategy resulted in similar relative risk reductions for death, myocardial infarction, and repeat revascularization in men and in women. There were no interactions between sex and treatment method for any outcome variables.In comparison with men, angiographic lesions of similar severity are less likely to be ischemia-producing in women. An FFR-guided PCI strategy is equally beneficial in women as it is in men.

  View details for DOI 10.1016/j.jcin.2012.06.016

  View details for PubMedID 23078733

• Vascular Complications After Transcatheter Aortic Valve Replacement JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Genereux, P., Webb, J. G., Svensson, L. G., Kodali, S. K., Satler, L. F., Fearon, W. F., Davidson, C. J., Eisenhauer, A. C., Makkar, R. R., Bergman, G. W., Babaliaros, V., Bavaria, J. E., Velazquez, O. C., Williams, M. R., Hueter, I., Xu, K., Leon, M. B. 2012; 60 (12): 1043-1052

  Abstract

  This study sought to identify incidence, predictors, and impact of vascular complications (VC) after transfemoral (TF) transcatheter aortic valve replacement (TAVR).VC after TF-TAVR are frequent and may be associated with unfavorable prognosis.From the randomized controlled PARTNER (Placement of AoRTic TraNscathetER Valve) trial, a total of 419 patients (177 from cohort B [inoperable] and 242 from cohort A [operable high-risk]) were randomly assigned to TF-TAVR and actually received the designated treatment. First-generation Edwards-Sapien valves and delivery systems were used, via a 22- or 24-F sheath. The 30-day rates of major and minor VC (modified Valve Academic Research Consortium definitions), predictors, and effect on 1-year mortality were assessed.Sixty-four patients (15.3%) had major VC and 50 patients (11.9%) had minor VC within 30 days of the procedure. Among patients with major VC, vascular dissection (62.8%), perforation (31.3%), and access-site hematoma (22.9%) were the most frequent modes of presentation. Major VC, but not minor VC, were associated with significantly higher 30-day rates of major bleeding, transfusions, and renal failure requiring dialysis, and with a significantly higher rate of 30-day and 1-year mortality. The only identifiable independent predictor of major VC was female gender (hazard ratio [HR]: 2.31 [95% confidence interval (CI): 1.08 to 4.98], p = 0.03). Major VC (HR: 2.31 [95% CI: 1.20 to 4.43], p = 0.012), and renal disease at baseline (HR: 2.26 [95% CI: 1.34 to 3.81], p = 0.002) were identified as independent predictors of 1-year mortality.Major VC were frequent after TF-TAVR in the PARTNER trial using first-generation devices and were associated with high mortality. However, the incidence and impact of major VC on 1-year mortality decreased with lower-risk populations.

  View details for DOI 10.1016/j.jacc.2012.07.003

  View details for Web of Science ID 000308746100003

• Vascular complications after transcatheter aortic valve replacement: insights from the PARTNER (Placement of AoRTic TraNscathetER Valve) trial. Journal of the American College of Cardiology Généreux, P., Webb, J. G., Svensson, L. G., Kodali, S. K., Satler, L. F., Fearon, W. F., Davidson, C. J., Eisenhauer, A. C., Makkar, R. R., Bergman, G. W., Babaliaros, V., Bavaria, J. E., Velazquez, O. C., Williams, M. R., Hueter, I., Xu, K., Leon, M. B. 2012; 60 (12): 1043-1052

  Abstract

  This study sought to identify incidence, predictors, and impact of vascular complications (VC) after transfemoral (TF) transcatheter aortic valve replacement (TAVR).VC after TF-TAVR are frequent and may be associated with unfavorable prognosis.From the randomized controlled PARTNER (Placement of AoRTic TraNscathetER Valve) trial, a total of 419 patients (177 from cohort B [inoperable] and 242 from cohort A [operable high-risk]) were randomly assigned to TF-TAVR and actually received the designated treatment. First-generation Edwards-Sapien valves and delivery systems were used, via a 22- or 24-F sheath. The 30-day rates of major and minor VC (modified Valve Academic Research Consortium definitions), predictors, and effect on 1-year mortality were assessed.Sixty-four patients (15.3%) had major VC and 50 patients (11.9%) had minor VC within 30 days of the procedure. Among patients with major VC, vascular dissection (62.8%), perforation (31.3%), and access-site hematoma (22.9%) were the most frequent modes of presentation. Major VC, but not minor VC, were associated with significantly higher 30-day rates of major bleeding, transfusions, and renal failure requiring dialysis, and with a significantly higher rate of 30-day and 1-year mortality. The only identifiable independent predictor of major VC was female gender (hazard ratio [HR]: 2.31 [95% confidence interval (CI): 1.08 to 4.98], p = 0.03). Major VC (HR: 2.31 [95% CI: 1.20 to 4.43], p = 0.012), and renal disease at baseline (HR: 2.26 [95% CI: 1.34 to 3.81], p = 0.002) were identified as independent predictors of 1-year mortality.Major VC were frequent after TF-TAVR in the PARTNER trial using first-generation devices and were associated with high mortality. However, the incidence and impact of major VC on 1-year mortality decreased with lower-risk populations.

  View details for DOI 10.1016/j.jacc.2012.07.003

  View details for PubMedID 22883632

• The Index of Microcirculatory Resistance Predicts Myocardial Infarction Related to Percutaneous Coronary Intervention CIRCULATION-CARDIOVASCULAR INTERVENTIONS Ng, M. K., Yong, A. S., Ho, M., Shah, M. G., Chawantanpipat, C., O'Connell, R., Keech, A., Kritharides, L., Fearon, W. F. 2012; 5 (4): 515-522

  Abstract

  Periprocedural myocardial infarction (MI) occurs in a significant proportion of patients undergoing percutaneous coronary intervention (PCI) and portends poor outcomes. Currently, no clinically applicable method predicts periprocedural MI in the cardiac catheterization laboratory before it occurs. We hypothesized that impaired baseline coronary microcirculatory reserve, which reduces the ability to tolerate ischemic insults, is a risk for periprocedural MI and that the index of microcirculatory resistance (IMR) measured during PCI can predict occurrence of periprocedural MI.Consecutive patients undergoing elective PCI of a single lesion in the left anterior descending coronary artery were recruited. A pressure-temperature sensor wire was used to measure IMR before PCI. Of the 50 patients studied, 10 had periprocedural MI. From binary logistic regression analyses of all clinical, procedural, and physiological parameters, univariable predictors of periprocedural MI were pre-PCI IMR (P=0.003) and the number of stents used (P=0.039). Pre-PCI IMR was the only independent predictor in bivariable regression analyses performed by adjusting for each available covariate one at a time (all P≤0.02). Pre-PCI IMR ≥27 U had 80.0% sensitivity and 85.0% specificity for predicting periprocedural MI (C statistic, 0.80; P=0.003). Pre-PCI IMR ≥27 U was independently associated with a 23-fold risk of developing periprocedural MI (odds ratio, 22.7; 95% CI, 3.8-133.9).These data suggest that the status of the coronary microcirculation plays a role in determining susceptibility toward periprocedural MI at the time of elective PCI. The IMR can predict subsequent risk of developing myocardial necrosis and may guide adjunctive prevention strategies.

  View details for DOI 10.1161/CIRCINTERVENTIONS.112.969048

  View details for Web of Science ID 000313575600014

  View details for PubMedID 22874078

• Most accurate definition of a high femoral artery puncture: Aiming to better predict retroperitoneal hematoma in percutaneous coronary intervention CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Tremmel, J. A., Tibayan, Y. D., O'Loughlin, A. J., Chan, T., Fearon, W. F., Yeung, A. C., Lee, D. P. 2012; 80 (1): 37-42

  Abstract

  Retroperitoneal hematoma (RPH) increases morbidity and mortality in percutaneous coronary intervention (PCI). High femoral arteriotomy is an independent predictor of RPH, but the optimal angiographic criterion for defining a high puncture is unknown.We retrospectively identified 557 consecutive PCI cases with femoral angiograms. Arteriotomy sites were categorized as high based on three angiographic criteria: at or above the proximal third of the femoral head (criterion A), at or above the most inferior border of the inferior epigastric artery (criterion B), and at or above the origin of the inferior epigastric artery (criterion C). Cases of RPH were then identified.Of the 557 PCI patients, 26 had a high femoral arteriotomy by criterion A, 17 by criterion B, and 6 by criterion C. Among these patients with a high arteriotomy, RPH occurred in four with criterion A, in three with criterion B, and in one with criterion C. Of the three criteria, criterion A most strongly correlated with RPH (odds ratio [OR] 96, 95% confidence interval [CI] 10.3-898.4; p < 0.0001) compared with criterion B (OR 58, 95% CI 8.9 to 372.6; p < 0.0001) or C (OR 27, 95% CI 2.6 to 290.1; p = 0.053). All criteria had high specificity (A, 96%; B, 97%; C, 99%), but the sensitivity was higher with criterion A (80%) than criterion B (60%) or C (20%), and statistically, the use of criterion A led to the most accurate risk-stratification for RPH (A, κ = 0.79; B, κ = 0.59; C, κ = 0.19).Among the three common definitions of high arteriotomy, femoral artery puncture at or above the proximal third of the femoral head is the landmark that most accurately risk stratifies PCI patients for development of RPH.

  View details for DOI 10.1002/ccd.23175

  View details for PubMedID 22511409

• Feasibility and Safety of the Second-Generation, Frequency Domain Optical Coherence Tomography (FD-OCT): A Multicenter Study JOURNAL OF INVASIVE CARDIOLOGY Yoon, J. H., Di Vito, L., Moses, J. W., Fearon, W. F., Yeung, A. C., Zhang, S., Bezerra, H. G., Costa, M. A., Jang, I. 2012; 24 (5): 206-209

  Abstract

  This study sought to assess the effectiveness and safety of the second-generation frequency-domain optical coherence tomography (FD-OCT) system.The second-generation FD-OCT was recently developed, with simplified imaging technique and faster acquisition time compared to the first-generation time-domain OCT. However, the safety and effectiveness of the FD-OCT has not been evaluated, and this study was conceived as a preapproval study for Food and Drug Administration clearance for clinical use in the United States.A total of 50 patients were enrolled from 3 institutions. Following stent implantation, the FD-OCT was performed with contrast injection through the guiding catheter to acquire pullback images with the pressure-triggered automatic pullback device. The primary endpoint was to achieve a median clear image length of more than 24 mm. Serious procedure-related or postprocedural adverse events (death, myocardial infarction, or ventricular arrhythmia) were recorded to assess safety of the device.The primary endpoint of obtaining >24 mm of median clear image length (CIL) was achieved in 94% of the subjects (47 out of 50), with measured CIL of 43.2 mm. In 5 patients (10.6%), a second attempt was necessary due to suboptimal image quality of the first pullback. In 36 patients (76.6%), a full stent length was obtained during the first attempt. There were no serious procedure-related or postprocedural adverse events.The new second-generation FD-OCT system provides fast and reliable resolution images of the coronary artery. The pullback can be safely performed over long segments of the artery without serious adverse events.

  View details for Web of Science ID 000304669300011

  View details for PubMedID 22562913

• Feasibility and Safety of the Second Generation, Frequency Domain Optical Coherence Tomography: A Multi-Center Study 17th Annual Interventional Vascular Therapeutics Angioplasty Summit-Transcatheter Cardiovascular Therapeutics Asia Pacific Symposium Yoon, J. H., Di Vito, L., Moses, J., Fearon, W., Yeung, A., Zhang, S., Bezerra, H., Costa, M., Jang, I. EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2012: 121S–122S

  View details for Web of Science ID 000302111800248

• PROGNOSTIC VALUE OF THE INDEX OF MICROCIRCULATORY RESISTANCE AFTER PRIMARY PERCUTANEOUS CORONARY INTERVENTION 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC)/Conference on ACC-i2 with TCT Yong, A., Loh, J., McGeoch, R., Shah, M., Ho, M., Daniels, D., Berry, C., Low, A., Oldroyd, K., Fearon, W. ELSEVIER SCIENCE INC. 2012: E48–E48

  View details for Web of Science ID 000302326700049

• THE IMPACT OF SEX DIFFERENCES ON FRACTIONAL FLOW RESERVE-GUIDED PERCUTANEOUS CORONARY INTERVENTION: A FAME SUBSTUDY Kim, H., Tonino, P., De Bruyne, B., Yong, A., Tremmel, J., Pijls, N., Fearon, W. ELSEVIER SCIENCE INC. 2012: E305

  View details for DOI 10.1016/S0735-1097(12)60306-4

  View details for Web of Science ID 000302326700306

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

  View details for Web of Science ID 000302326701306

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

  View details for Web of Science ID 000302326701310

• Coronary Microcirculatory Resistance Is Independent of Epicardial Stenosis CIRCULATION-CARDIOVASCULAR INTERVENTIONS Yong, A. S., Ho, M., Shah, M. G., Ng, M. K., Fearon, W. F. 2012; 5 (1): 103-U180

  Abstract

  Recent studies show that coronary microcirculatory impairment is an independent predictor of poor outcomes in patients with cardiovascular disease. However, controversy exists over whether microcirculatory resistance, a measure of coronary microcirculatory status, is dependent on epicardial stenosis severity. Previous studies demonstrating that microcirculatory resistance is dependent on epicardial stenosis severity have not accounted for collateral flow in their measurement of microcirculatory resistance. We investigated whether the index of microcirculatory resistance is independent of epicardial stenosis by comparing the index of microcirculatory resistance (IMR) levels in patients before and after percutaneous coronary intervention (PCI).Consecutive patients undergoing elective PCI of the left anterior descending artery were recruited. Patients who developed periprocedural myocardial infarction were excluded. A pressure-temperature sensor wire was used to measure the apparent IMR (IMR(app)), which does not adjust for collateral flow, and the true IMR (IMR(true)), which incorporates wedge pressure measurement to account for collateral flow, before and after PCI. In 43 patients, there was no difference between pre- and post-PCI IMR(true) (mean difference=0.8±11.7, P=0.675). IMR(app) was higher pre-PCI compared with post-PCI (mean difference=10.0±14.5, P<0.001). IMR(app) was higher than IMR(true) (mean difference=9.3±14.2, P<0.001), and the difference between the IMR(app) and IMR(true) became greater with decreasing fractional flow reserve and increasing coronary wedge pressure. Pre-PCI fractional flow reserve correlated modestly with IMR(app) (r=-0.33, P=0.03), but not IMR(true) (r=0.26, P=0.10).Coronary microcirculatory resistance is independent of functional epicardial stenosis severity when collateral flow is taken into account.

  View details for DOI 10.1161/CIRCINTERVENTIONS.111.966556

  View details for PubMedID 22298800

• Comparison of the Frequency of Coronary Artery Disease in Alcohol-Related Versus Non-Alcohol-Related Endstage Liver Disease AMERICAN JOURNAL OF CARDIOLOGY Patel, S., Kiefer, T. L., Ahmed, A., Ali, Z. A., Tremmel, J. A., Lee, D. P., Yeung, A. C., Fearon, W. F. 2011; 108 (11): 1552-1555

  Abstract

  There are conflicting data as to the prevalence of coronary artery disease (CAD) in patients with end-stage liver disease (ESLD) being assessed for liver transplantation (LT). The aims of this study were to compare the prevalence of CAD in patients with alcohol-related versus non-alcohol-related ESLD and to assess the diagnostic utility of dobutamine stress echocardiography (DSE) in predicting angiographically important CAD. Consecutive patients with ESLD being assessed for LT (n = 420, mean age 56 ± 8 years) were identified and divided into groups of those with alcohol-related ESLD (n = 125) and non-alcohol-related ESLD (n = 295). Demographic characteristics, CAD risk factors, results of DSE, and coronary angiographic characteristics were recorded. There were no significant differences in age or CAD risk factors between groups. The incidence of severe CAD (>70% diameter stenosis) was 2% in the alcohol-related ESLD group and 13% in the non-alcohol-related ESLD group (p <0.005). In the 2 groups, the presence of ≥1 CAD risk factor was associated with significant CAD (p <0.05 for all). Absence of cardiac risk factors was highly predictive in ruling out angiographically significant disease (negative predictive value 100% for alcohol-related ESLD and 97% for non-alcohol-related ESLD). DSE was performed in 205 patients. In the 2 groups, DSE had poor predictive value for diagnosing significant CAD but was useful in ruling out patients without significant disease (negative predictive value 89% for alcohol-related ESLD and 80% for non-alcohol-related ESLD). In conclusion, there was a significantly lower prevalence of severe CAD in patients with alcohol-related ESLD. These findings suggest that invasive coronary angiography may not be necessary in this subgroup, particularly in the absence of CAD risk factors and negative results on DSE.

  View details for DOI 10.1016/j.amjcard.2011.07.013

  View details for PubMedID 21890080

• Is a Myocardial Infarction More Likely to Result From a Mild Coronary Lesion or an Ischemia-Producing One? CIRCULATION-CARDIOVASCULAR INTERVENTIONS Fearon, W. F. 2011; 4 (6): 539-541

  View details for DOI 10.1161/CIRCINTERVENTIONS.111.966416

  View details for Web of Science ID 000300549500003

  View details for PubMedID 22186104

• Quantitative Comparison of Microcirculatory Dysfunction in Patients With Stress Cardiomyopathy and ST-Segment Elevation Myocardial Infarction JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Kim, H., Tremmel, J. A., Nam, C., Zhou, J., Haddad, F., Vagelos, R. H., Lee, D. P., Yeung, A. C., Fearon, W. F. 2011; 58 (23): 2430-2431

  View details for DOI 10.1016/j.jacc.2011.08.046

  View details for Web of Science ID 000297319700016

  View details for PubMedID 22115653

• Assessment of the Left Main (LM) with Fractional Flow Reserve (FFR): The Influence Of Concomitant Proximal Epicardial Coronary Disease Daniels, D., van 't Veer, M., van der Horst, A., Pijls, N. H., Fearon, W. F. ELSEVIER SCIENCE INC. 2011: B14

  View details for Web of Science ID 000296891900070

• Fractional Flow Reserve in Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction Experience From the FAME (Fractional flow reserve versus Angiography for Multivessel Evaluation) Study JACC-CARDIOVASCULAR INTERVENTIONS Sels, J. E., Tonino, P. A., Siebert, U., Fearon, W. F., van't Veer, M., De Bruyne, B., Pijls, N. H. 2011; 4 (11): 1183-1189

  Abstract

  The aim of this study was to study whether there is a difference in benefit of fractional flow reserve (FFR) guidance for percutaneous coronary intervention (PCI) in multivessel coronary disease in patients with unstable angina (UA) or non-ST-segment elevation myocardial infarction (NSTEMI), compared with stable angina (SA).The use of FFR to guide PCI has been well established for patients with SA. Its use in patients with UA or NSTEMI has not been investigated prospectively.In the FAME (Fractional flow reserve versus Angiography for Multivessel Evaluation) study 1,005 patients with multivessel disease amenable to PCI were included and randomized to either angiography-guided PCI of all lesions ≥50% or FFR-guided PCI of lesions with an FFR ≤0.80. Patients admitted for UA or NSTEMI with positive troponin but total creatine kinase <1,000 U/l were eligible for inclusion. We determined 2-year major adverse cardiac event rates of these patients and compared it with stable patients.Of 1,005 patients, 328 had UA or NSTEMI. There was no evidence for heterogeneity among the subgroups for any of the outcome variables (all p values >0.05). Using FFR to guide PCI resulted in similar risk reductions of major adverse cardiac events and its components in patients with UA or NSTEMI, compared with patients with SA (absolute risk reduction of 5.1% vs. 3.7%, respectively, p = 0.92). In patients with UA or NSTEMI, the number of stents was reduced without increase in hospital stay or procedure time and with less contrast use, in similarity to stable patients.The benefit of using FFR to guide PCI in multivessel disease does not differ between patients with UA or NSTEMI, compared with patients with SA.

  View details for DOI 10.1016/j.jcin.2011.08.008

  View details for Web of Science ID 000297662100004

  View details for PubMedID 22115657

• Health-Related Quality of Life After Transcatheter Aortic Valve Replacement in Inoperable Patients With Severe Aortic Stenosis CIRCULATION Reynolds, M. R., Magnuson, E. A., Lei, Y., Leon, M. B., Smith, C. R., Svensson, L. G., Webb, J. G., Babaliaros, V. C., Bowers, B. S., Fearon, W. F., Herrmann, H. C., Kapadia, S., Kodali, S. K., Makkar, R. R., Pichard, A. D., Cohen, D. J. 2011; 124 (18): 1964-1972

  Abstract

  Background- Transcatheter aortic valve replacement (TAVR) has been shown to improve survival compared with standard therapy in patients with severe aortic stenosis who cannot have surgery. The effects of TAVR on health-related quality of life have not been reported from a controlled study. Methods and Results- The Placement of Aortic Transcatheter Valves (PARTNER) trial randomized patients with symptomatic, severe aortic stenosis who were not candidates for surgical valve replacement to TAVR (n=179) or standard therapy (n=179). Health-related quality of life was assessed at baseline and at 1, 6, and 12 months with the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the 12-item Short Form-12 General Health Survey (SF-12). The primary end point was the KCCQ overall summary score (range, 0-100; higher=better). At baseline, mean KCCQ summary scores (35±20) and SF-12 physical summary scores (28±7) were markedly depressed. Although the KCCQ summary score improved from baseline in both groups, the extent of improvement was greater after TAVR compared with control at 1 month (mean between-group difference, 13 points; 95% confidence interval, 8-19; P<0.001) with larger benefits at 6 months (mean difference, 21 points; 95% confidence interval, 15-27; P<0.001) and 12 months (mean difference, 26 points; 95% confidence interval, 19-33; P<0.001). At 12 months, TAVR patients also reported higher SF-12 physical and mental health scores with mean differences compared with standard care of 5.7 and 6.4 points, respectively (P<0.001 for both comparisons). Conclusions- Among inoperable patients with severe aortic stenosis, compared with standard care, TAVR resulted in significant improvements in health-related quality of life that were maintained for at least 1 year. Clinical Trials Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894.

  View details for DOI 10.1161/CIRCULATIONAHA.111.040022

  View details for Web of Science ID 000296593800019

  View details for PubMedID 21969017

• Discrepancy in the Assessment of Jailed Side Branch Lesions by Visual Estimation and Quantitative Coronary Angiographic Analysis: Comparison With Fractional Flow Reserve CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Shin, D., Koo, B., Waseda, K., Park, K. W., Kim, H., Corral, M., Lansky, A., Honda, Y., Fearon, W. F., Fitzgerald, P. J. 2011; 78 (5): 720-726

  Abstract

  We sought to evaluate the variability in the assessment of jailed side branch (SB) lesions by visual estimation and quantitative coronary angiography (QCA) and to compare those results with fractional flow reserve (FFR).Twenty jailed SB lesions with available FFR (median 0.76; range, 0.39-0.94) were selected from the PRESSURE trial. Lesions were assessed by three independent QCA core laboratories with different QCA systems and by three different cardiologist groups (five European bifurcation club members, five Korean experts, and five trainees). Agreements of the continuous measurements were expressed as the intraclass correlation coefficient (ICC) and average coefficient of variance (CV), and those of the categorical values as kappa.Mean minimum lumen diameter (MLD) and % diameter stenosis differed among the three QCA systems up to 0.30 mm and 9.65%, respectively (P < 0.001). Three QCA systems showed fair agreement for the measurements of reference diameter, % diameter stenosis, MLD, and lesion length (ICC 0.346-0.686, CV 8.7-29.5%), and a poor agreement on stenosis of 75% or more (Fleiss κ 0.14 and mean κ 0.18). Agreements of visual estimation among the three groups were poor to fair (Fleiss κ 0.167-0.367). Sensitivity and specificity for predicting ischemia-inducible lesion (FFR < 0.75) were 64.7% and 48.0% for visual estimation and 56.6% and 56.6% by QCA, respectively. Visual estimation overestimated the % diameter stenosis and functional significance of the lesions compared with QCA (P < 0.001) and FFR (P = 0.036).Angiographic assessment of jailed SB lesions by both QCA and visual estimation showed variability. Visual estimation tended to overestimate the severity of jailed SB lesions compared to FFR and QCA.

  View details for DOI 10.1002/ccd.23049

  View details for Web of Science ID 000296412800012

  View details for PubMedID 22025472

• Comparison of Drug-Eluting Versus Bare Metal Stents in Cardiac Allograft Vasculopathy AMERICAN JOURNAL OF CARDIOLOGY Tremmel, J. A., Ng, M. K., Ikeno, F., Hunt, S. A., Lee, D. P., Yeung, A. C., Fearon, W. F. 2011; 108 (5): 665-668

  Abstract

  Although not a definitive treatment, percutaneous coronary intervention offers a palliative benefit to patients with cardiac allograft vasculopathy. Given the superior outcomes with drug-eluting stents (DESs) over bare metal stents (BMSs) in native coronary artery disease, similar improvements might be expected in transplant patients; however, the results have been mixed. Consecutive cardiac transplantation recipients at a single center receiving a stent for de novo cardiac allograft vasculopathy from 1997 to 2009 were retrospectively analyzed according to receipt of a DES versus a BMS. The angiographic and clinical outcomes were subsequently evaluated at 1 year. The baseline clinical and procedural characteristics were similar among those receiving DESs (n = 18) and BMSs (n = 16). Quantitative coronary angiography revealed no difference in the reference diameter, lesion length, or pre-/postprocedural minimal luminal diameter. At the 12-month angiographic follow-up visit, the mean lumen loss was significantly lower in the DES group than in the BMS group (0.19 ± 0.73 mm vs 0.76 ± 0.97 mm, p = 0.02). The DES group also had a lower rate of in-stent restenosis (12.5% vs 33%, p = 0.18), as well as a significantly lower rate of target lesion revascularization (0% vs 19%, p = 0.03). At 1 year, DESs were associated with a lower composite rate of cardiac death and nonfatal myocardial infarction (12% vs 38%, p = 0.04). In conclusion, DESs are safe and effective in the suppression of neointimal hyperplasia after percutaneous coronary intervention for cardiac allograft vasculopathy, resulting in significantly lower rates of late lumen loss and target lesion revascularization, as well as a reduced combined rate of cardiac death and nonfatal myocardial infarction.

  View details for DOI 10.1016/j.amjcard.2011.04.014

  View details for PubMedID 21684511

• Saphenous Vein Graft Intervention JACC-CARDIOVASCULAR INTERVENTIONS Lee, M. S., Park, S., Kandzari, D. E., Kirtane, A. J., Fearon, W. F., Brilakis, E. S., Vermeersch, P., Kim, Y., Waksman, R., Mehilli, J., Mauri, L., Stone, G. W. 2011; 4 (8): 831-843

  Abstract

  Saphenous vein grafts are commonly used conduits for surgical revascularization of coronary arteries but are associated with poor long-term patency rates. Percutaneous revascularization of saphenous vein grafts is associated with worse clinical outcomes including higher rates of in-stent restenosis, target vessel revascularization, myocardial infarction, and death compared with percutaneous coronary intervention of native coronary arteries. Use of embolic protection devices is a Class I indication according to the American College of Cardiology/American Heart Association guidelines to decrease the risk of distal embolization, no-reflow, and periprocedural myocardial infarction. Nonetheless, these devices are underused in clinical practice. Various pharmacological agents are available that may also reduce the risk of or mitigate the consequences of no-reflow. Covered stents do not decrease the rates of periprocedural myocardial infarction and restenosis. Most available evidence supports treatment with drug-eluting stents in this high-risk lesion subset to reduce angiographic and clinical restenosis, although large, randomized trials comparing drug-eluting stents and bare-metal stents are needed.

  View details for DOI 10.1016/j.jcin.2011.05.014

  View details for Web of Science ID 000294147500001

  View details for PubMedID 21851895

• Impact of Donor-Transmitted Atherosclerosis on Early Cardiac Allograft Vasculopathy: New Findings by Three-Dimensional Intravascular Ultrasound Analysis TRANSPLANTATION Yamasaki, M., Sakurai, R., Hirohata, A., Honda, Y., Bonneau, H. N., Luikart, H., Yock, P. G., Fitzgerald, P. J., Yeung, A. C., Valantine, H. A., Fearon, W. F. 2011; 91 (12): 1406-1411

  Abstract

  The influence of donor-transmitted coronary atherosclerosis (DA) on plaque progression during the first year after cardiac transplantation (Tx) is unknown.Serial 3-dimensional intravascular ultrasound (IVUS) studies were performed within 8 weeks (baseline; BL) and at 1 year after Tx in 38 recipients. On the basis of maximum intimal thickness (MIT) at BL, recipients were divided into DA group (DA+; MIT≥0.5 mm, n=23) or non-DA group (DA-; MIT<0.5 mm, n=15). Plaque, lumen, and vessel volume indexes were calculated by volume/measured length (mm/mm) in the left anterior descending artery. Univariate and multivariate regression analyses were attempted to reveal clinical predictors of change in coronary dimensions.During the first year after Tx, plaque volume index increased significantly in DA+ group, but did not change in DA- Group (DA+, 3.0±1.5 to 4.1±1.5 mm/mm, P<0.0001: DA-, 1.2±0.4 to 1.3±0.5 mm/mm, P=0.53). In both groups vessel volume index decreased significantly (DA+, 16.3±3.6 to 14.6±3.3 mm/mm, P=0.003: DA-, 13.5±4.1 to 12.0±3.3 mm/mm, P=0.01), as did lumen volume index (DA+, 13.2±3.1 to 10.5±2.7 mm/mm, P<0.0001: DA-, 12.2±3.7 to 10.7±3.0 mm/mm, P=0.004). Univariate and multivariate regression analyses revealed that DA was one of the strongest predictors for plaque progression.DA was associated with significant plaque progression during the first year after Tx, and in conjunction with negative remodeling, may be an important determinant of cardiac allograft vasculopathy.

  View details for DOI 10.1097/TP.0b013e31821ab91b

  View details for PubMedID 21512436

• Relation of Fractional Flow Reserve After Drug-Eluting Stent Implantation to One-Year Outcomes AMERICAN JOURNAL OF CARDIOLOGY Nam, C., Hur, S., Cho, Y., Park, H., Yoon, H., Kim, H., Chung, I., Kim, Y., Kim, K., Doh, J., Koo, B., Tahk, S., Fearon, W. F. 2011; 107 (12): 1763-1767

  Abstract

  Patients still present with drug-eluting stent (DES) failure despite an angiographically successful implantation. The aim of the present study was to investigate the relation between the fractional flow reserve (FFR) measured after DES implantation and the clinical outcomes at 1 year. A total of 80 patients (mean age 62 years, 74% men, 99 DESs) underwent coronary pressure measurement at maximum hyperemia after successful DES implantation. The composite of major adverse cardiac events (MACE), including death, myocardial infarction, and ischemia-driven target vessel revascularization was evaluated at 1 year. The patients were divided into 2 groups (low-FFR group, FFR ≤0.90 and high-FFR group, FFR >0.90) according to the median FFR. The mean poststent percent diameter stenosis was 11 ± 5% in the low-FFR group and 12 ± 3% in the high-FFR group (p = 0.31). Left anterior descending coronary artery lesions were more frequent in the low-FFR group than in the high-FFR group (82% vs 55%, p = 0.02). The mean stent length was greater in the low-FFR group than in the high-FFR group (38 ± 18 vs 28 ± 13 mm, p = 0.01). Six cases (7.5%) of MACE occurred during the 1-year follow-up. The rate of MACE was 12.5% in the low-FFR group and 2.5% in the high-FFR group (p <0.01). Receiver operating characteristic curves revealed 0.90 as the best cutoff of FFR after DES implantation for the prediction of 1-year MACE. In conclusion, a poststent FFR of ≤0.90 correlated with a greater adverse event rate at 1 year.

  View details for DOI 10.1016/j.amjcard.2011.02.329

  View details for Web of Science ID 000291754900010

  View details for PubMedID 21481828

• Fractional Flow Reserve Versus Angiography in Left Circumflex Ostial Intervention After Left Main Crossover Stenting KOREAN CIRCULATION JOURNAL Nam, C., Hur, S., Koo, B., Doh, J. H., Cho, Y., Park, H., Yoon, H., Kim, H., Chung, I., Kim, Y., Fearon, W. F., Tahk, S., Kim, K. 2011; 41 (6): 304-307

  Abstract

  Discrepancy between angiographic percent (%) diameter stenosis and fractional flow reserve (FFR) exists in non-left main bifurcation lesions. The aim of this study was to compare angiographic stenosis severity and FFR in jailed ostial left circumflex artery (LCX) lesions after left main (LM)-to-left anterior descending artery (LAD) crossover stenting.Twenty-nine (n=29) patients with distal LM or ostial LAD lesions treated by LM-to-LAD crossover stenting were consecutively enrolled. After successful stenting, FFR was measured at the jailed LCX. Additional intervention was performed in lesions with FFR <0.8.The mean reference diameter of LCX was 3.1±0.4 mm, and percent diameter stenosis after crossover stenting was 56±21%. Angiographically significant stenosis (>50%) at the ostial LCX occurred in 59% (17/29) of cases. Among them, only five (29%) lesions had functional significance, and underwent additional procedure. During follow-up, three patients in the deferral group and two patients in the additional intervention group had target lesion revascularization.There was a discrepancy between angiographic percent diameter stenosis and FFR in jailed LCX lesions after LM crossover stenting.

  View details for DOI 10.4070/kcj.2011.41.6.304

  View details for Web of Science ID 000209078700004

  View details for PubMedCentralID PMC3132691

• THE FRACTIONAL FLOW RESERVE-GUIDED SYNTAX SCORE FOR RISK ASSESSMENT IN MULTI-VESSEL CORONARY ARTERY DISEASE Nam, C., Mangiacapra, F., Entjes, R., Chung, I., Tonino, P. L., De Bruyne, B., Pijls, N. J., Fearon, W. F. ELSEVIER SCIENCE INC. 2011: E1090

  View details for DOI 10.1016/S0735-1097(11)61090-5

  View details for Web of Science ID 000291695101093

• Letter by Fearon Regarding Article, "Primary Coronary Microvascular Dysfunction: Clinical Presentation, Pathophysiology, and Management" CIRCULATION Fearon, W. F. 2011; 123 (4): E212

  View details for DOI 10.1161/CIRCULATIONAHA.110.977058

  View details for Web of Science ID 000286727900003

  View details for PubMedID 21282519

  View details for PubMedCentralID PMC5546229

• The Index of Microcirculatory Resistance (IMR) in Takotsubo Cardiomyopathy CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Daniels, D. V., Fearon, W. F. 2011; 77 (1): 128-131

  Abstract

  We report a patient who presents with acute chest pain and positive cardiac enzymes clinically consistent with an acute coronary syndrome (ACS). Coronary angiography revealed normal epicardial arteries and the left ventriculogram was notable for apical ballooning. This was strongly suggestive of takotsubo cardiomyopathy. Pressure wire measurements of Fractional flow reserve (FFR) and IMR demonstrated a normal FFR, but significant microcirculatory dysfunction. This is the first such case that documents this abnormality invasively using the IMR, which unlike CFR is specific for the microcirculation and reproducible through a range of hemodynamic states.

  View details for DOI 10.1002/ccd.22599

  View details for PubMedID 20506131

• CCR2 Antagonist Inhibits Neointimal Proliferation Post CoronaryStent Deployment Teramoto, T., Ikeno, F., Nakatani, D., Otake, H., Lyons, J. K., Sullivan, T., Jaen, J., Schall, T., Tio, F., Yeung, A. C., Fearon, W. F. LIPPINCOTT WILLIAMS & WILKINS. 2010

  View details for Web of Science ID 000208231602333

• Impaired Baseline Coronary Microcirculatory Reserve Predicts Peri-percutaneous Coronary Intervention Myocardial Necrosis. Yong, A., Ho, M., Shah, M., Kritharides, L., Fearon, W. F., Ng, M. K. LIPPINCOTT WILLIAMS & WILKINS. 2010

  View details for Web of Science ID 000208231600851

• Does an Epicardial Coronary Stenosis Affect Microvascular Resistance? Ho, M. Y., Yong, A. S., Shah, M. G., Ng, M. K., Fearon, W. F. LIPPINCOTT WILLIAMS & WILKINS. 2010

  View details for Web of Science ID 000208231603013

• Long-Term Outcomes After Percutaneous Coronary Intervention of Left Main Coronary Artery for Treatment of Cardiac Allograft Vasculopathy After Orthotopic Heart Transplantation AMERICAN JOURNAL OF CARDIOLOGY Lee, M. S., Yang, T., Fearon, W. F., Ho, M., Tarantini, G., Xhaxho, J., Gerosa, G., Weston, M., Ehdaie, A., Rabbani, L., Kirtane, A. J. 2010; 106 (8): 1086-1089

  Abstract

  The present study evaluated the safety and efficacy of percutaneous coronary intervention (PCI) of the unprotected left main coronary artery (ULMCA) for the treatment of cardiac allograft vasculopathy (CAV) in consecutive unselected patients with orthotopic heart transplantation (OHT). PCI in patients with OHT and develop CAV has been associated with greater restenosis rates compared to PCI in patients with native coronary artery disease. A paucity of short- and long-term data is available from patients with OHT who have undergone PCI for ULMCA disease. The present retrospective, multicenter, international registry included 21 patients with OHT and CAV who underwent ULMCA PCI from 1997 to 2009. Angiographic success was achieved in all patients. Drug-eluting stents were used in 14 of the 21 patients. No major adverse cardiac events or repeat OHT occurred within the first 30 days. At a mean follow-up of 4.9 ± 3.2 years, 3 patients (14%) had died, myocardial infarction had occurred in 1 patient (5%), and target lesion revascularization had been required in 4 patients (19%). Follow-up angiography was performed in 16 patients (76%), and restenosis was observed in 4 (19%). No stent thrombosis of the ULMCA was observed. One patient (5%) underwent coronary artery bypass grafting, and 5 patients (24%) underwent repeat OHT. In conclusion, the results of our study have shown ULMCA PCI to be safe and reasonably effective in patients with OHT and represents a viable treatment strategy for CAV in these patients.

  View details for DOI 10.1016/j.amjcard.2010.06.019

  View details for Web of Science ID 000283568700005

  View details for PubMedID 20920643

• Alcohol-Related Cirrhosis is Associated with Significantly Less Angiographically Severe Disease than Non-Alcoholic Related Cirrhosis Patel, S., Kiefer, T. L., Lin, T., Ali, Z. A., Tremmel, J. A., Lee, D. P., Yeung, A. C., Fearon, W. F. ELSEVIER SCIENCE INC. 2010: B42

  View details for Web of Science ID 000209824200180

• CCR2 Antagonist Inhibits Neointimal Proliferation Post Coronary Stent Deployment Teramoto, T., Ikeno, F., Nakatani, D., Otake, H., Lyons, J. K., Sullivan, T., Jaen, J., Schall, T., Tio, F., Fearon, W. F., Yeung, A. C. ELSEVIER SCIENCE INC. 2010: B91

  View details for Web of Science ID 000209824200391

• CCR2 antagonist inhibits neointimal proliferation post coronary stent deployment Congress of the European-Society-of-Cardiology Teramoto, T., Ikeno, F., Nakatani, D., Otake, H., Lyons, J. K., Sullivan, T., Jaen, J., Schall, T., Yeung, A. C., Fearon, W. F. OXFORD UNIV PRESS. 2010: 368–368

  View details for Web of Science ID 000281531902268

• 3 ',4-Dihydroxyflavonol reduces infarct size in a porcine acute myocardial ischaemia-reperfusion model Congress of the European-Society-of-Cardiology Teramoto, T., Ikeno, F., Lyons, J., Thomas, C. J., May, C. N., Woodman, O. L., Jarrott, B., Yeung, A. C., Fearon, W. F. OXFORD UNIV PRESS. 2010: 493–494

  View details for Web of Science ID 000281531903177

• Outcomes of Percutaneous Coronary Intervention in Intermediate Coronary Artery Disease Fractional Flow Reserve-Guided Versus Intravascular Ultrasound Guided JACC-CARDIOVASCULAR INTERVENTIONS Nam, C., Yoon, H., Cho, Y., Park, H., Kim, H., Hur, S., Kim, Y., Chung, I., Koo, B., Tahk, S., Fearon, W. F., Kim, K. 2010; 3 (8): 812-817

  Abstract

  This study sought to evaluate the long-term clinical outcomes of a fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) strategy compared with intravascular ultrasound (IVUS)-guided PCI for intermediate coronary lesions.Both FFR- and IVUS-guided PCI strategies have been reported to be safe and effective in intermediate coronary lesions.The study included 167 consecutive patients, with intermediate coronary lesions evaluated by FFR or IVUS (FFR-guided, 83 lesions vs. IVUS-guided, 94 lesions). Cutoff value of FFR in FFR-guided PCI was 0.80, whereas that for minimal lumen cross sectional area in IVUS-guided PCI was 4.0 mm(2). The primary outcome was defined as a composite of major adverse cardiac events including death, myocardial infarction, and ischemia-driven target vessel revascularization at 1 year after the index procedure.Baseline percent diameter stenosis and lesion length were similar in both groups (51 +/- 8% and 24 +/- 12 mm in the FFR group vs. 52 +/- 8% and 24 +/- 13 mm in the IVUS group, respectively). However, the IVUS-guided group underwent revascularization therapy significantly more often (91.5% vs. 33.7%, p < 0.001). No significant difference was found in major adverse cardiac event rates between the 2 groups (3.6% in FFR-guided PCI vs. 3.2% in IVUS-guided PCI). Independent predictors for performing intervention were guiding device: FFR versus IVUS (relative risk [RR]: 0.02); left anterior descending coronary artery versus non-left anterior descending coronary artery disease (RR: 5.60); and multi- versus single-vessel disease (RR: 3.28).Both FFR- and IVUS-guided PCI strategy for intermediate coronary artery disease were associated with favorable outcomes. The FFR-guided PCI reduces the need for revascularization of many of these lesions.

  View details for DOI 10.1016/j.jcin.2010.04.016

  View details for Web of Science ID 000281458700005

  View details for PubMedID 20723852

• Fractional Flow Reserve: A Practical Update CURRENT CARDIOVASCULAR IMAGING REPORTS Daniels, D. V., Fearon, W. F. 2010; 3 (4): 215–21

  View details for DOI 10.1007/s12410-010-9030-z

  View details for Web of Science ID 000219769300005

• Fractional Flow Reserve Versus Angiography for Guiding Percutaneous Coronary Intervention in Patients With Multivessel Coronary Artery Disease 2-Year Follow-Up of the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) Study JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Pijls, N. H., Fearon, W. F., Tonino, P. A., Siebert, U., Ikeno, F., Bornschein, B., van't Veer, M., Klauss, V., Manoharan, G., Engstrom, T., Oldroyd, K. G., Lee, P. N., MacCarthy, P. A., De Bruyne, B. 2010; 56 (3): 177-184

  Abstract

  The purpose of this study was to investigate the 2-year outcome of percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) in patients with multivessel coronary artery disease (CAD).In patients with multivessel CAD undergoing PCI, coronary angiography is the standard method for guiding stent placement. The FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study showed that routine FFR in addition to angiography improves outcomes of PCI at 1 year. It is unknown if these favorable results are maintained at 2 years of follow-up.At 20 U.S. and European medical centers, 1,005 patients with multivessel CAD were randomly assigned to PCI with drug-eluting stents guided by angiography alone or guided by FFR measurements. Before randomization, lesions requiring PCI were identified based on their angiographic appearance. Patients randomized to angiography-guided PCI underwent stenting of all indicated lesions, whereas those randomized to FFR-guided PCI underwent stenting of indicated lesions only if the FFR was 0.80, the rate of myocardial infarction was 0.2% and the rate of revascularization was 3.2 % after 2 years.Routine measurement of FFR in patients with multivessel CAD undergoing PCI with drug-eluting stents significantly reduces mortality and myocardial infarction at 2 years when compared with standard angiography-guided PCI. (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation [FAME]; NCT00267774).

  View details for DOI 10.1016/j.jacc.2010.04.012

  View details for Web of Science ID 000279520200002

  View details for PubMedID 20537493

• Balloon aortic valvuloplasty: modern indications and techniques for a niche therapy. Expert review of cardiovascular therapy Yamen, E., Fearon, W. F. 2010; 8 (7): 885-887

  View details for DOI 10.1586/erc.10.68

  View details for PubMedID 20602546

• Angiographic Versus Functional Severity of Coronary Artery Stenoses in the FAME Study Fractional Flow Reserve Versus Angiography in Multivessel Evaluation JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Tonino, P. A., Fearon, W. F., De Bruyne, B., Oldroyd, K. G., Leesar, M. A., Lee, P. N., MacCarthy, P. A., van't Veer, M., Pijls, N. H. 2010; 55 (25): 2816-2821

  Abstract

  The purpose of this study was to investigate the relationship between angiographic and functional severity of coronary artery stenoses in the FAME (Fractional Flow Reserve Versus Angiography in Multivessel Evaluation) study.It can be difficult to determine on the coronary angiogram which lesions cause ischemia. Revascularization of coronary stenoses that induce ischemia improves a patient's functional status and outcome. For stenoses that do not induce ischemia, however, the benefit of revascularization is less clear.In the FAME study, routine measurement of the fractional flow reserve (FFR) was compared with angiography for guiding percutaneous coronary intervention in patients with multivessel coronary artery disease. The use of the FFR in addition to angiography significantly reduced the rate of all major adverse cardiac events at 1 year. Of the 1,414 lesions (509 patients) in the FFR-guided arm of the FAME study, 1,329 were successfully assessed by the FFR and are included in this analysis.Before FFR measurement, these lesions were categorized into 50% to 70% (47% of all lesions), 71% to 90% (39% of all lesions), and 91% to 99% (15% of all lesions) diameter stenosis by visual assessment. In the category 50% to 70% stenosis, 35% were functionally significant (FFR 0.80). In the category 71% to 90% stenosis, 80% were functionally significant and 20% were not. In the category of subtotal stenoses, 96% were functionally significant. Of all 509 patients with angiographically defined multivessel disease, only 235 (46%) had functional multivessel disease (>or=2 coronary arteries with an FFR

  View details for DOI 10.1016/j.jacc.2009.11.096

  View details for Web of Science ID 000278779300005

  View details for PubMedID 20579537

• Intriguing Pen-Strut Low-Intensity Area Detected by Optical Coherence Tomography After Coronary Stent Deployment CIRCULATION JOURNAL Teramoto, T., Ikeno, F., Otake, H., Lyons, J. K., van Beusekom, H. M., Fearon, W. F., Yeung, A. C. 2010; 74 (6): 1257-1259

  Abstract

  Although peri-strut low-intensity area (PLIA) is frequently observed on post-stenting optical coherence tomography (OCT) images, the histology associated with PLIA is undocumented.The 36 porcine coronary lesions treated with bare-metal (BMS: n=16) or drug-eluting (DES: n=20) stents were assessed by OCT and histology at 28 days. DES showed a significantly higher incidence of PLIA than BMS. Also, +PLIA stents had greater neointima than PLIA stents. Histological analysis revealed the existence of fibrinoid and proteoglycans at the site of PLIA.PLIA might be represented by the presence of fibrinoid and proteoglycans, and associated with neointimal proliferation after stenting.

  View details for DOI 10.1253/circj.CJ-10-0189

  View details for PubMedID 20453394

• Quantitative assessment of coronary microvascular function in patients with and without epicardial atherosclerosis EUROINTERVENTION Melikian, N., Vercauteren, S., Fearon, W. F., Cuisset, T., MacCarthy, P. A., Davidavicius, G., Aarnoudse, W., Bartunek, J., Vanderheyden, M., Wyffels, E., Wijns, W., Heyndrickx, G. R., Pijls, N. H., De Bruyne, B. 2010; 5 (8): 939-945

  Abstract

  The influence of atherosclerosis and its risk factors on coronary microvascular function remain unclear as current methods of assessing microvascular function do not specifically test the microcirculation in isolation. We examined the influence of epicardial vessel atherosclerosis on coronary microvascular function using the index of myocardial resistance (IMR).IMR (a measure of microvascular function) and fractional flow reserve (FFR, a measure of the epicardial compartment) were measured in 143 coronary arteries (116 patients). Fifteen patients (22 arteries, mean age 48+/-16 years) had no clinical evidence of atherosclerosis (control group). One hundred and one patients (121 arteries, mean age 63+/-11 years) had established atherosclerosis and multiple cardiovascular risk factors (atheroma group). Mean IMR in the control group (19+/-5, range 8-28) was significantly lower than in the atheroma group (25+/-13, range 6-75) (P<0.01). However, there was large overlap between IMR in both groups, with 69% of IMR values in patients with atheroma being within the control range. Mean FFR was also higher in the control group (0.96+/-0.02, range 0.93-1.00) than in the atheroma group (0.85+/-0.14, range 0.19-1.00) (P<0.01). There was no correlation between IMR and FFR (r=0.09; P=0.24), even when results in the control (r=0.02; P=0.92) and atheroma (r=0.15; P=0.10) groups were analysed in isolation. Using stepwise multiple regression analysis presence/absence of atheroma (ss=0.42; P=0.02) was the only independent determinant of IMR.Mean IMR is higher in patients with epicardial atherosclerosis. However, there is a large overlap between IMR in patients with and without epicardial atherosclerosis.

  View details for Web of Science ID 000294134000011

  View details for PubMedID 20542779

• Anatomic and Functional Evaluation of Bifurcation Lesions Undergoing Percutaneous Coronary Intervention CIRCULATION-CARDIOVASCULAR INTERVENTIONS Koo, B., Waseda, K., Kang, H., Kim, H., Nam, C., Hur, S., Kim, J., Choi, D., Jang, Y., Hahn, J., Gwon, H., Yoon, M., Tahk, S., Chung, W., Cho, Y., Choi, D., Hasegawa, T., Kataoka, T., Oh, S. J., Honda, Y., Fitzgerald, P. J., Fearon, W. F. 2010; 3 (2): 113-119

  Abstract

  We sought to investigate the mechanism of geometric changes after main branch (MB) stent implantation and to identify the predictors of functionally significant "jailed" side branch (SB) lesions.Seventy-seven patients with bifurcation lesions were prospectively enrolled from 8 centers. MB intravascular ultrasound was performed before and after MB stent implantation, and fractional flow reserve was measured in the jailed SB. The vessel volume index of both the proximal and distal MB was increased after stent implantation. The plaque volume index decreased in the proximal MB (9.1+/-3.0 to 8.4+/-2.4 mm(3)/mm, P=0.001), implicating plaque shift, but not in the distal MB (5.4+/-1.8 to 5.3+/-1.7 mm(3)/mm, P=0.227), implicating carina shifting to account for the change in vessel size (N=56). The mean SB fractional flow reserve was 0.71+/-0.20 (N=68) and 43% of the lesions were functionally significant. Binary logistic-regression analysis revealed that preintervention % diameter stenosis of the SB (odds ratio=1.05; 95% CI, 1.01 to 1.09) and the MB minimum lumen diameter located distal to the SB ostium (odds ratio=3.86; 95% CI, 1.03 to 14.43) were independent predictors of functionally significant SB jailing. In patients with > or =75% stenosis and Thrombolysis In Myocardial Infarction grade 3 flow in the SB, no difference in post-stent angiographic and intravascular ultrasound parameters was found between SB lesions with and without functional significance.Both plaque shift from the MB and carina shift contribute to the creation/aggravation of an SB ostial lesion after MB stent implantation. Anatomic evaluation does not reliably predict the functional significance of a jailed SB stenosis.

  View details for DOI 10.1161/CIRCINTERVENTIONS.109.887406

  View details for PubMedID 20407111

• Use of a Low-Profile, Compliant Balloon for Percutaneous Aortic Valvuloplasty CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Yamen, E., Daniels, D. V., Van, H., Yeung, A. C., Fearon, W. F. 2010; 75 (5): 794-798

  Abstract

  To determine the safety and immediate efficacy after balloon aortic valvuloplasty (BAV) with a new, low-profile balloon.BAV has a continuing role in the management of high-risk patients with severe aortic stenosis (AS). BAV with traditional noncompliant balloons requires a large femoral arteriotomy and is associated with high rates of access site complications.We retrospectively reviewed medical records of 20 consecutive patients undergoing BAV for severe AS. Retrograde transfemoral BAV was performed with a low-profile, compliant valvuloplasty balloon. Before and after BAV, transaortic gradients were measured invasively and by echocardiography, and aortic valve area (AVA) calculated. Access site complications, functional class and survival were recorded.Patients were 79 +/- 12 years old and had an estimated mortality from open aortic valve replacement of (12.5 +/- 9.6)%. By catheterization, mean aortic gradient fell from 44 +/- 15 to 29 +/- 10 mm Hg (P < 0.001) and AVA increased from 0.63 +/- 0.22 to 0.89 +/- 0.33 cm(2) (P < 0.001). New York Heart Association functional class improved from 3.5 +/- 0.7 to 2.7 +/- 0.8. Procedural mortality was 0%. There were no vascular complications or significant worsening of aortic regurgitation.Transfemoral BAV using a low-profile compliant balloon is feasible with acceptable immediate results and safety.

  View details for DOI 10.1002/ccd.22355

  View details for PubMedID 20146311

• TWO YEARS CLINICAL OUTCOMES AFTER LARGE CORONARY STENT (4.0MM) PLACEMENT: COMPARISION OF BARE-METAL STENT VERSUS DRUG-ELUTING STENT Nam, C., Cho, Y., Hur, S., Kim, K., Kim, H., Kim, Y., Park, J., Lee, S., Hong, G., Kim, U., Seol, S., Yang, T., Kim, D., Fearon, W. F. ELSEVIER SCIENCE INC. 2010

  View details for Web of Science ID 001045644802019

• MECHANISM OF SIDE BRANCH JAILING IN BIFURCATION LESION: PLAQUE OR CARINA SHIFT? Kim, J., Koo, B., Seo, M., Park, S., Park, K., Lee, H., Kang, H., Kim, H., Oh, B., Park, Y., Nam, C., Hur, S., Choi, D., Jang, Y., Hahn, J., Gwon, H., Yoon, M., Tahk, S., Chung, W., Cho, Y., Choi, D., Oh, S., Honda, Y., Fitzgerald, P. J., Fearon, W. F. ELSEVIER SCIENCE INC. 2010

  View details for Web of Science ID 001045644801238

• Fractional Flow Reserve and Myocardial Perfusion Imaging in Patients With Angiographic Multivessel Coronary Artery Disease JACC-CARDIOVASCULAR INTERVENTIONS Melikian, N., De Bondt, P., Tonino, P., De Winter, O., Wyffels, E., Bartunek, J., Heyndrickx, G. R., Fearon, W. F., Pijls, N. H., Wijns, W., De Bruyne, B. 2010; 3 (3): 307-314

  Abstract

  The aim of this study was to investigate the correlation between myocardial ischemia detected by myocardial perfusion imaging (MPI) with single-photon emission computed tomography with intracoronary pressure-derived fractional flow reserve (FFR) in patients with multivessel coronary disease at angiography.Myocardial perfusion imaging can underestimate the number of ischemic territories in patients with multivessel disease. However, there are limited data comparing MPI and FFR, a highly accurate functional index of myocardial ischemia, in multivessel coronary disease.Sixty-seven patients (201 vascular territories) with angiographic 2- or 3-vessel coronary disease were prospectively scheduled to undergo within 2 weeks MPI (rest/stress adenosine) and FFR in each vessel.In 42% of patients, MPI and FFR detected identical ischemic territories (mean number of territories 0.9 +/- 0.8 for both; p = 1.00). In the remaining 36% MPI underestimated (mean number of territories; MPI: 0.46 +/- 0.6, FFR: 2.0 +/- 0.6; p < 0.001) and in 22% overestimated (mean number of territories; MPI: 1.9 +/- 0.8, FFR: 0.5 +/- 0.8; p < 0.001) the number of ischemic territories in comparison with FFR. There was poor concordance between the ability of the 2 methods to detect myocardial ischemia on both a per-patient (kappa = 0.14 [95% confidence interval: -0.10 to 0.39]) and per-vessel (kappa = 0.28 [95% confidence interval: 0.15 to 0.42]) basis.Myocardial perfusion imaging with single-photon emission computed tomography has poor concordance with FFR and tends to underestimate or overestimate the functional importance of coronary stenosis seen at angiography in comparison with FFR in patients with multivessel disease. These findings might have important consequences in using MPI to determine the optimal revascularization strategy in patients with multivessel coronary disease.

  View details for DOI 10.1016/j.jcin.2009.12.010

  View details for Web of Science ID 000278972100008

  View details for PubMedID 20298990

• Impact of Drug-Eluting Stent Length on Outcomes Less Is More ... More or Less JACC-CARDIOVASCULAR INTERVENTIONS Fearon, W. F. 2010; 3 (2): 189-190

  View details for DOI 10.1016/j.jcin.2009.12.006

  View details for Web of Science ID 000278972000008

  View details for PubMedID 20170876

• 3 ', 4-Dihydroxyflavonol Reduces Infarct Size in a Porcine Acute Myocardial Infarction-Reperfusion Model 82nd National Conference and Exhibitions and Scientific Sessions of the American-Heart-Association Tomohiko, T., Ikeno, F., Lyons, J. K., Jarrott, B., Woodman, O. L., May, C. N., Thomas, C. J., Yeung, A. C., Fearon, W. LIPPINCOTT WILLIAMS & WILKINS. 2009: S1174–S1174

  View details for Web of Science ID 000271831504351

• Economic Evaluation of the Fractional Flow Reserve vs. Angiography for Multivessel Evaluation (FAME) Study Fearon, W., Bornschein, B., Gothe, R., Tonino, P., de Bruyne, B., Pijls, N., Siebert, U. LIPPINCOTT WILLIAMS & WILKINS. 2009: S437

  View details for Web of Science ID 000271831500548

• Safety and Efficacy of Drug Eluting Stents for Treatment of Cardiac Allograft Vasculopathy: A Prospective Clinical and Angiographic Study 21st Annual Transcatheter Cardiovascular Therapeutics Conference Ng, M. K., Tremmel, J., Ikeno, F., Lee, D. P., Yeung, A. C., Fearon, W. F. EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2009: 138D–138D

  View details for Web of Science ID 000269981600385

• Expanding role of fractional flow reserve in the cardiac catheterization laboratory. Expert review of cardiovascular therapy Fearon, W. F. 2009; 7 (5): 447-449

  View details for DOI 10.1586/erc.09.27

  View details for PubMedID 19419250

• Baseline Fractional Flow Reserve and Stent Diameter Predict Optimal Post-Stent Fractional Flow Reserve and Major Adverse Cardiac Events After Bare-Metal Stent Deployment JACC-CARDIOVASCULAR INTERVENTIONS Samady, H., McDaniel, M., Veledar, E., De Bruyne, B., Pijls, N. H., Fearon, W. F., Vaccarino, V. 2009; 2 (4): 357-363

  Abstract

  We sought to identify baseline clinical, angiographic, and hemodynamic variables associated with optimal bare-metal stent (BMS) deployment, allowing selection of patients for treatment with BMS.Patients with fractional flow reserve (FFR) >0.90 after BMS have low (<6%) major adverse cardiac event rates (MACE). We hypothesized that baseline variables can predict post-stent FFR >0.90 and MACE after BMS.In 586 patients from the multicenter post-BMS FFR registry, we developed multivariable logistic regression models to identify clinical, angiographic, and hemodynamic variables associated with post-stent FFR >or=0.90 and 6-month MACE.After adjusting for potential confounders, baseline FFR (odds ratio [OR]: 5.0) and stent diameter (OR: 2.5 per millimeter) were predictive of post-stent FFR >0.90. Lower FFR (OR: 7.8); smaller stent diameter (OR: 3.7 per millimeter); longer stent length (OR: 1.0 per millimeter); and larger minimal luminal diameter (OR: 2.2 per millimeter) were predictors of MACE. In patients receiving 3-mm diameter stents, baseline FFR >0.70 yielded significantly higher likelihood of achieving post-stent FFR >0.90 than baseline FFR 0.70 (40% vs. 15% vs. 13%, p < 0.05).In patients receiving BMS, baseline FFR and stent diameter are predictors of post-stent FFR >0.90; and baseline FFR, stent diameter, stent length, and minimal luminal diameter are predictors of MACE. These variables may allow selection of patients who will have excellent results with BMS.

  View details for DOI 10.1016/j.jcin.2009.01.008

  View details for Web of Science ID 000278970900015

  View details for PubMedID 19463450

• Microvascular Dysfunction and Suboptimal Glycemic Control Predicts Poor Outcome Following Heart Transplantation 58th Annual Scientific Session of the American-College-of-Cardiology Khazanie, P., Haddad, F., Simos, A. M., Pham, M., Weisshaar, D. M., Desai, S. V., Shah, M. G., McLaughlin, T. L., Hunt, S. A., Valantine, H. A., Fearon, W. ELSEVIER SCIENCE INC. 2009: A182–A182

  View details for Web of Science ID 000263864200760

• Fractional Flow Reserve versus Angiography in Multivessel Evaluation Tonino, P. L., De Bruyne, B., Pijls, N. J., Siebert, U., Ikeno, F., van 't Veer, M., Klauss, V., Manoharan, G., Engstrom, T., Oldroyd, K. G., Verlee, P. N., MacCarthy, P. A., Fearon, W. F., Fame Study Investigators ELSEVIER SCIENCE INC. 2009: A6

  View details for Web of Science ID 000263864200024

• Safety and Performance of Targeted Renal Therapy: The Be-RITe! Registry JOURNAL OF ENDOVASCULAR THERAPY Weisz, G., Filby, S. J., Cohen, M. G., Allie, D. E., Weinstock, B. S., Kyriazis, D., Walker, C. M., Moses, J. W., Danna, P., Fearon, W. F., Sachdev, N., Wiechmann, B. N., Vora, K., Findeiss, L., Price, M. J., Mehran, R., Leon, M. B., Teirstein, P. S. 2009; 16 (1): 1-12

  Abstract

  To evaluate the safety and patterns of use of targeted renal therapy (TRT) with the Benephit system. TRT, the delivery of therapeutic agents directly to the kidneys by renal arterial infusion, has the advantage of providing a higher local effective dose with potentially greater renal effects, while limiting systemic adverse effects due to renal first-pass elimination.The Benephit System Renal Infusion Therapy (Be-RITe!) Multicenter Registry was a post-market registry following patients treated using the Benephit systems for TRT. The registry enrolled 501 patients (332 men; mean age 72.2+/-9.5 years) at high risk for contrast-induced nephropathy (CIN) during coronary or peripheral angiography/intervention or cardiovascular surgery. The Mehran score was used to compare the actual to predicted incidence of CIN within 48 hours post procedure.Bilateral renal artery cannulation was successful in 94.2%, with a mean cannulation time of 2.0 minutes. Either fenoldopam mesylate, sodium bicarbonate, alprostadil, or B-type natriuretic peptide (BNP) was infused for 184+/-212 minutes. Mean creatinine levels did not change significantly (baseline, 24, and 48 hours post procedure: 1.95, 1.99, and 1.98 mg/dL, respectively; p = NS). In 285 patients who received TRT with fenoldopam and were followed for at least 48 hours, the incidence of CIN was 71% lower than predicted (8.1% actual CIN versus 28.0% predicted; p<0.0001). Only 4 (1.4%) patients required dialysis (versus the 2.6% predicted rate, p = NS).The Benephit system and TRT during coronary and endovascular procedures in patients at high risk for renal failure is simple to use and safe. With the infusion of intrarenal fenoldopam, the incidence of CIN was significantly lower than predicted by risk score calculations.

  View details for Web of Science ID 000263307900001

  View details for PubMedID 19281283

• Microvascular Drysfunction and Suboptimal Glycemic Control Predicts Poor Outcome Following Heart Transplantation 29th Annual Meeting and Scientific Session of the International-Society-for-Heart-and-Lung-Transplantation Khazanie, P., Haddad, F., Simos, A. M., Weissbaar, D. M., Desai, S. V., Pham, M., McLaugblin, T. L., Shah, M. G., Hunt, S. A., Valantine, H. A., Fearon, W. ELSEVIER SCIENCE INC. 2009: S228–S228

  View details for Web of Science ID 000263539800464

• The Importance of Right Ventricular Dysfunction In patients with Hemodynamically Compromising Rejection Haddad, F., Fisher, P., Pham, M., Kuppahally, S., Berry, G., Fearon, W., Vrtovec, B., Welsshaar, D., Valentine, H., Hunt, S. LIPPINCOTT WILLIAMS & WILKINS. 2008: S721

  View details for Web of Science ID 000262104502354

• QT Interval Prolongation during Severe Acute Rejection is Predictive of Sudden Cardiac Death in Heart Transplant Recipients Vrtovec, B., Haddad, F., Tsai, V., Al-Ahmad, A., Cause, T., Pham, M., Fisher, P., Fearon, W., Valentine, H., Hunt, S. LIPPINCOTT WILLIAMS & WILKINS. 2008: S801

  View details for Web of Science ID 000262104502679

• Granulocyte-Colony Stimulating Factor Therapy is Associated with Reduced Incidence of Acute Rejections and Allograft Vasculopathy in Heart Transplant Recipients Haddad, F., Vrtovec, B., Pham, M., Deuse, T., Fearon, W., Valantine, H., Hunt, S. LIPPINCOTT WILLIAMS & WILKINS. 2008: S800

  View details for Web of Science ID 000262104502673

• Inflammation and cardiovascular disease - Role of the interleukin-1 receptor antagonist CIRCULATION Fearon, W. F., Fearon, D. T. 2008; 117 (20): 2577-2579

  View details for DOI 10.1161/CIRCULATIONAHA.108.772491

  View details for Web of Science ID 000256053200003

  View details for PubMedID 18490534

• Effect of rapamycin therapy on coronary artery physiology early after cardiac transplantation AMERICAN HEART JOURNAL Sinha, S. S., Pham, M. X., Vagelos, R. H., Perlroth, M. G., Hunt, S. A., Lee, D. P., Valantine, H. A., Yeung, A. C., Fearon, W. F. 2008; 155 (5)

  Abstract

  Rapamycin has been shown to reduce anatomical evidence of cardiac allograft vasculopathy, but its effect on coronary artery physiology is unknown.Twenty-seven patients without angiographic evidence of coronary artery disease underwent measurement of fractional flow reserve (FFR), coronary flow reserve (CFR), and the index of microcirculatory resistance (IMR) within 8 weeks and then 1 year after transplantation using a pressure sensor/thermistor-tipped guidewire. Measurements were compared between consecutive patients who were on rapamycin for at least 3 months during the first year after transplantation (rapamycin group, n = 9) and a comparable group on mycophenolate mofetil (MMF) instead (MMF group, n = 18).At baseline, there was no significant difference in FFR, CFR, or IMR between the 2 groups. At 1 year, FFR declined significantly in the MMF group (0.87 +/- 0.06 to 0.82 +/- 0.06, P = .009) but did not change in the rapamycin group (0.91 +/- 0.05 to 0.89 +/- 0.04, P = .33). Coronary flow reserve and IMR did not change significantly in the MMF group (3.1 +/- 1.7 to 3.2 +/- 1.0, P = .76; and 27.5 +/- 18.1 to 19.1 +/- 7.6, P = .10, respectively) but improved significantly in the rapamycin group (2.3 +/- 0.8 to 3.8 +/- 1.4, P < .03; and 27.0 +/- 11.5 to 17.6 +/- 7.5, P < .03, respectively). Multivariate regression analysis revealed that rapamycin therapy was an independent predictor of CFR and FFR at 1 year after transplantation.Early after cardiac transplantation, rapamycin therapy is associated with improved coronary artery physiology involving both the epicardial vessel and the microvasculature.

  View details for DOI 10.1016/j.ahj.2008.02.004

  View details for PubMedID 18440337

• Effect of rapamycin therapy on coronary artery physiology early after cardiac transplantation AMERICAN HEART JOURNAL Sinha, S. S., Pham, M. X., Vagelos, R. H., Perlroth, M. G., Hunt, S. A., Lee, D. P., Valantine, H. A., Yeung, A. C., Fearon, W. F. 2008; 155 (5)

  View details for DOI 10.1016/j.ahj.2008.02.004

  View details for Web of Science ID 000256001500014

• In Vivo Comparison Between Optical Coherence Tomography and Intravascular Ultrasound for Detecting Small Degrees of In-Stent Neointima After Stent Implantation JACC-CARDIOVASCULAR INTERVENTIONS Suzuki, Y., Ikeno, F., Koizumi, T., Tio, F., Yeung, A. C., Yock, P. G., Fitzgerald, P. J., Fearon, W. F. 2008; 1 (2): 168-173

  Abstract

  The purpose of this study was to evaluate optical coherence tomography (OCT) for detecting small degrees of in-stent neointima (ISN) after stent implantation compared with intravascular ultrasound (IVUS).The importance of detecting neointimal coverage of stent struts has grown with the appreciation of the increased risk for late stent thrombosis after drug-eluting stent (DES) implantation. Intravascular ultrasound, the current standard for evaluating the status of DES, lacks the resolution to detect the initial neointimal coverage. Optical coherence tomography has greater resolution but has not yet been compared with IVUS in vivo with histological correlation for validation.Intravascular ultrasound and OCT were performed with motorized pullback imaging in 6 pigs across 33 stents, 1 month after implantation. Each pig was euthanized, and histological measurements of vessel, stent, and lumen dimensions were performed in 3 sections of each stent. A small degree of ISN was defined as occupying <30% of the stent area measured with histology. The IVUS, OCT, and histological assessment of ISN were compared in matched cross-sections of the stents with a small degree of ISN.Eleven stents had a small degree of ISN (average ISN area: 1.26 +/- 0.46 mm(2), and percent area obstruction: 21.4 +/- 5.2%). Compared with histology, the diagnostic accuracy of OCT (area under the receiver operating characteristic curve [AUC] = 0.967, 95% confidence interval [CI] 0.914 to 1.019) was higher than that of IVUS (AUC = 0.781, 95% CI 0.621 to 0.838).Optical coherence tomography detects smaller degrees of ISN more accurately than IVUS and might be a useful method for identifying neointimal coverage of stent struts after DES implantation.

  View details for DOI 10.1016/j.jcin.2007.12.007

  View details for PubMedID 19463295

• Asymmetric dimethylarginine and cardiac allograft vasculopathy progression: Modulation by sirolimus TRANSPLANTATION Potena, L., Fearon, W. F., Sydow, K., Holweg, C., Luikart, H., Chin, C., Weisshaar, D., Mocarski, E. S., Lewis, D. B., Valantine, H. A., Cooke, J. P. 2008; 85 (6): 827-833

  Abstract

  Cardiac allograft vasculopathy (CAV) is a major cause of death after heart transplantation (HT). The reduced bioavailability of endothelium-derived nitric oxide may play a role in endothelial vasodilator dysfunction and thus in the structural changes characterizing CAV. A potential contributor to endothelial pathobiology is asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor. It was hypothesized that ADMA concentrations may influence CAV progression during the first postoperative year.Thirty-two consecutive HT recipients underwent intravascular ultrasound evaluation at month 1 and year 1 after HT. Immunosuppression included mycophenolate mofetil (MMF, n=16) and sirolimus (n=16). Change in intimal volume greater than the median and vascular remodeling were major outcome measures.Plasma ADMA levels were associated with subsequent development of intimal hyperplasia (risk ratio [95% confidence interval] =2.72 [1.06-6.94]; P=0.038), and plasma ADMA levels greater than 0.70 micromol/L most accurately identified patients who would have developed intimal hyperplasia. However, ADMA levels did not correlate with negative coronary remodeling. Treatment with sirolimus, as compared with MMF, was associated with significantly lower ADMA levels (0.65+/-0.12 vs. 0.77+/-0.10 micromol/L; P<0.01) and less intimal hyperplasia (risk ratio [95% confidence interval] = 0.08 [0.01-0.56]; P=0.01).Elevated plasma ADMA is associated with coronary intimal hyperplasia, supporting the importance of nitric oxide synthase inhibition in CAV pathogenesis. Treatment with sirolimus (rather than MMF) is associated with lower ADMA levels and reduced risk of accelerated CAV.

  View details for DOI 10.1097/TP.0b013e318166a3a4

  View details for PubMedID 18360263

• The pathophysiology and clinical course of the normal coronary angina syndrome (cardiac syndrome x) PROGRESS IN CARDIOVASCULAR DISEASES Melikian, N., De Bruyne, B., Fearon, W. F., MacCarthy, P. A. 2008; 50 (4): 294-310

  View details for DOI 10.1016/j.pcad.2007.01.003

  View details for Web of Science ID 000252208300006

  View details for PubMedID 18156008

• Determinants of lumen loss between years 1 and 2 after cardiac transplantation TRANSPLANTATION Sakurai, R., Yamasaki, M., Nakamura, M., Hirohata, A., Honda, Y., Bonneau, H. N., Luikart, H., Yock, P. G., Fitzgerald, P. J., Yeung, A. C., Valantine, H. A., Fearon, W. F. 2007; 84 (9): 1097-1102

  Abstract

  We previously reported that negative remodeling, not plaque progression, correlated with lumen loss during the first year after cardiac transplantation and that cytomegalovirus antibody seropositivity correlated with increased negative remodeling and greater lumen loss. Whether these findings persist between years 1 and 2 after transplantation is unknown.Serial 3-dimensional intravascular ultrasound analysis in the left anterior descending coronary artery was performed in 30 cardiac transplant recipients at year 1 and 2 after transplantation. Vessel, lumen, and plaque area were determined at 0.5-mm axial intervals in the first 50 mm of the left anterior descending coronary artery, and volumes were computed using Simpson's method. Univariate and multivariate regression analyses were performed to identify clinical predictors of change in coronary dimensions.Although mean vessel area did not change (13.6+/-3.4 to 13.4+/-3.3 mm/mm(3), P=0.45), mean plaque area increased (3.4+/-2.3 to 3.8+/-2.2 mm/mm(3), P=0.012), resulting in significant mean lumen area loss (10.3+/-2.5 to 9.6+/-2.3 mm/mm(3), P=0.016). However, the degree of luminal change strongly correlated with the degree of change in vessel size (R=0.81, P<0.0001), but not with change in plaque amount (R=-0.19, P=0.32). In fact, in 57% of the patients who demonstrated lumen loss, negative remodeling contributed more to lumen loss than did plaque progression. Diabetes at 2 years was the only significant independent clinical predictor of plaque progression and lumen loss.Despite significant plaque progression, negative remodeling correlated with coronary lumen loss between years 1 and 2 after cardiac transplantation.

  View details for DOI 10.1097/01.tp.0000285987.27033.65

  View details for PubMedID 17998863

• Optical coherence tomography compared to intravascular ultrasound for detecting small degrees of neointimal hyperplasia 19th Annual Transcatheter Cardiovascular Therapeutics Symposium Ikeno, F., Suzuki, Y., Koizumi, T., Yeung, A. C., Fitzgerald, P. J., Fearon, W. F. EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2007: 143L–143L

  View details for Web of Science ID 000250393900359

• Invasive assessment of the coronary microcirculation: Novel thermodilution based measure of absolute microvascular resistance 80th Annual Scientific Session of the American-Heart-Association (AHA) Ho, Y., Nguyen, T. C., Itoh, A., Yeung, A. C., Fearon, W. F. LIPPINCOTT WILLIAMS & WILKINS. 2007: 354–54

  View details for Web of Science ID 000250394301607

• Invasive assessment of coronary physiology using a pressure wire correlates with cardiac positron emission tomography in patients with coronary disease. Brinton, T. J., Quon, A., Schindler, T. H., Luero, J. L., Hansen, H., Segall, G., Giacormni, J. C., Schellbert, H. R., Gambhir, S. S., Fearon, W. F. LIPPINCOTT WILLIAMS & WILKINS. 2007: 751

  View details for Web of Science ID 000250394303430

• Altered metabolism of asymetric dimethylarginine (ADMA) is associated with endothelial dysfunction and negative arterial remodelling after heart transplantation Wilson, A., Virani, S., Holweg, C., Kielstein, J., Bode-Boger, S., Valantine, H., Cooke, J. P., Fearon, W. F. LIPPINCOTT WILLIAMS & WILKINS. 2007: 506

  View details for Web of Science ID 000250394302317

• The pre-operative utility of dobutamine stress echocardiography in patients undergoing liver transplantation 72nd Annual Meeting of the American-College-of-Gastroenterology Shapiro, L., Lee, M., Lee, J., Lapasaran, A. S., Fearon, W., Kamal, A., Ahmed, A. NATURE PUBLISHING GROUP. 2007: S437–S437

  View details for Web of Science ID 000249397800865

• Changes in coronary anatomy and physiology after heart transplantation AMERICAN JOURNAL OF CARDIOLOGY Hirohata, A., Nakamura, M., Waseda, K., Honda, Y., Lee, D. P., Vagelos, R. H., Hunt, S. A., Valantine, H. A., Yock, P. G., Fitzgerald, P. J., Yeung, A. C., Fearon, W. F. 2007; 99 (11): 1603-1607

  Abstract

  Cardiac allograft vasculopathy (CAV) is a progressive process involving the epicardial and microvascular coronary systems. The timing of the development of abnormalities in these 2 compartments and the correlation between changes in physiology and anatomy are undefined. The invasive evaluation of coronary artery anatomy and physiology with intravascular ultrasound, fractional flow reserve, coronary flow reserve, and the index of microcirculatory resistance (IMR) was performed in the left anterior descending coronary artery during 151 angiographic evaluations of asymptomatic heart transplant recipients from 0 to >5 years after heart transplantation (HT). There was no angiographic evidence of significant CAV, but during the first year after HT, fractional flow reserve decreased significantly (0.89 +/- 0.06 vs 0.85 +/- 0.07, p = 0.001), and percentage plaque volume derived by intravascular ultrasound increased significantly (15.6 +/- 7.7% to 22.5 +/- 12.3%, p = 0.0002), resulting in a significant inverse correlation between epicardial physiology and anatomy (r = -0.58, p <0.0001). The IMR was lower in these patients compared with those > or =2 years after HT (24.1 +/- 14.3 vs 29.4 +/- 18.8 units, p = 0.05), suggesting later spread of CAV to the microvasculature. As the IMR increased, fractional flow reserve increased (0.86 +/- 0.06 to 0.90 +/- 0.06, p = 0.0035 comparing recipients with IMRs < or =20 to those with IMRs > or =40), despite no difference in percentage plaque volume (21.0 +/- 11.2% vs 20.5 +/- 10.5%, p = NS). In conclusion, early after HT, anatomic and physiologic evidence of epicardial CAV was found. Later after HT, the physiologic effect of epicardial CAV may be less, because of increased microvascular dysfunction.

  View details for DOI 10.1016/j.amjcard.2007.01.039

  View details for PubMedID 17531589

• Prognostic significance of PVCs and resting heart rate ANNALS OF NONINVASIVE ELECTROCARDIOLOGY Engel, G., Cho, S., Ghayoumi, A., Yamazaki, T., Chun, S., Fearon, W. F., Froelicher, V. F. 2007; 12 (2): 121-129

  Abstract

  We sought to evaluate the prognostic significance of premature ventricular contractions (PVCs) on a routine electrocardiogram (ECG) and to evaluate the relationship between heart rate and PVCs.Computerized 12-lead ECGs of 45,402 veterans were analyzed. Vital status was available through the California Health Department Service.There were 1731 patients with PVCs (3.8%). Compared to patients without PVCs, those with PVCs had significantly higher all-cause (39% vs 22%, P < 0.001) and cardiovascular mortality (20% vs 8%, P < 0.001). PVCs remain a significant predictor even after adjustment for age and other ECG abnormalities. The presence of multiple PVCs or complex morphologies did not add significant additional prognostic information. Those patients with PVCs had a significantly higher heart rate than those without PVCs (mean +/- SD: 78.6 +/- 15 vs 73.5 +/- 16 bpm, P < 0.001). When patients were divided into groups by heart rate (<60, 60-79, 80-99 and >100 bpm) and by the presence or absence of PVCs, mortality increased progressively with heart rate and doubled with the presence of PVCs. Using regression analysis, heart rate was demonstrated to be an independent and significant predictor of PVCs.PVCs on a resting ECG are a significant and independent predictor of all-cause and cardiovascular mortality. Increased heart rate predicts mortality in patients with and without PVCs and the combination dramatically increases mortality. These findings together with the demonstrated independent association of heart rate with PVCs suggest that a hyperadrenergic state is present in patients with PVCs and that it likely contributes to their adverse prognosis.

  View details for PubMedID 17593180

• Interplay between systemic inflammation and markers of insulin resistance in cardiovascular prognosis after heart transplantation JOURNAL OF HEART AND LUNG TRANSPLANTATION Biadi, O., Potena, L., Fearon, W. F., Luikart, H. I., Yeung, A., Ferrara, R., Hunt, S. A., Mocarski, E. S., Valantine, H. A. 2007; 26 (4): 324-330

  Abstract

  Metabolic and immuno-inflammatory risk factors contribute to cardiac allograft vasculopathy (CAV) pathogenesis. Although systemic inflammation, as detected by C-reactive protein (CRP), predicts CAV development, the relationship between CRP and markers of metabolic abnormalities remains unexplored.CRP and the entire metabolic panel were evaluated in 98 consecutive heart transplant recipients at the time of annual coronary angiography, 5.8 years after transplant (range, 1-12 years). A ratio of triglycerides (TG) to high-density lipoproteins (HDL) of 3.0 or more was considered a marker of insulin resistance. CAV prevalence was defined by angiography, and subsequent prognosis was evaluated as incidence of major cardiac adverse events.CRP was higher in the 34 patients with angiographic CAV than in those without CAV (1.10 +/- 0.20 vs 0.50 +/- 0.05 mg/dl, p < 0.001). Patients with insulin resistance had higher CRP concentrations (p = 0.023) and higher CAV prevalence (p = 0.005). High CRP and a TG/HDL of 3.0 or more were independently associated with an increased likelihood of CAV (odds ratio, > or = 3.9; p = 0.02) and predicted an increased risk of major cardiac adverse events. The combination of high CRP and a TG/HDL of 3.0 or more identified a subgroup of patients having a 4-fold increased risk for CAV and a 3-fold increased risk for major cardiac adverse events compared with patients with low CRP and normal values for metabolic indicators.Both CRP and insulin resistance, as estimated by TG/HDL, appear to be strong, synergic risk factors for CAV and for major cardiac adverse events. These findings support the hypothesis that in heart transplant recipients, systemic inflammation may be an important mediator of graft vascular injury associated with metabolic syndrome.

  View details for DOI 10.1016/j.healun.2007.01.020

  View details for PubMedID 17403472

• Changes in coronary arterial dimensions early after cardiac transplantation TRANSPLANTATION Fearon, W. F., Potena, L., Hirohata, A., Sakurai, R., Yamasaki, M., Luikart, H., Lee, J., Vana, M. L., Cooke, J. P., Mocarski, E. S., Yeung, A. C., Valantine, H. A. 2007; 83 (6): 700-705

  Abstract

  Significant changes in coronary artery structure, including intimal thickening and vessel remodeling, occur early after cardiac transplantation. The degree to which these changes compromise coronary lumen dimensions, and the clinical factors that affect these changes, remain controversial.Thirty-eight adult cardiac transplant recipients underwent coronary angiography and volumetric intravascular ultrasound (IVUS) evaluation of the left anterior descending artery within 8 weeks of transplantation and at 1 year. Clinical parameters including donor and recipient characteristics, rejection episodes, and serology were prospectively recorded. Two-dimensional IVUS measurements and vessel, lumen and plaque volume were calculated at both time points and compared. Multivariate regression analysis was performed to reveal clinical predictors of change in coronary dimensions.During the first year after transplantation, significant decreases in vessel size (negative remodeling) and lumen size were observed with significant increases in plaque burden based on IVUS analyses. Loss of lumen volume correlated significantly with the degree of negative remodeling (R=0.82, P<0.0001), but not with changes in plaque burden (R=0.08, P=0.64). Patients with the greatest increase in plaque volume had significantly less negative remodeling (R=0.53, P=0.0006). Transplant recipient cytomegalovirus (CMV) antibody seropositivity and lack of aggressive prophylaxis against CMV infection/reactivation were significant independent predictors of greater negative remodeling (P<0.01 and P=0.03, respectively) and greater lumen loss (P=0.02 and P=0.03, respectively).Negative remodeling is primarily responsible for coronary artery lumen loss during the first year after cardiac transplantation. CMV seropositivity and lack of aggressive CMV prophylaxis correlate with increased negative remodeling, resulting in greater lumen loss.

  View details for DOI 10.1097/01.tp.0000256335.84363.9b

  View details for PubMedID 17414701

• Aggressive prophylaxis against cytomegalovirus plays a key role in preseving epicardial artery flow early after cardiac transplantation 56th Annual Scientific Session of the American-College-of-Cardiology Sakurai, R., Yamasaki, M., Potena, L., Hirohata, A., Honda, Y., Yock, P. G., Fitzgerald, P. J., Yeung, A. C., Valantine, H. A., Fearon, W. F. ELSEVIER SCIENCE INC. 2007: 78A–78A

  View details for Web of Science ID 000244651800322

• Relationship between insulin resistance features and progression of cardiac allograft vasculopathy Virani, S. A., Wilson, A. M., Pham, M. X., Valentine, H. A., Cooke, J. P., Fearon, W. F. ELSEVIER SCIENCE INC. 2007: 57A–58A

  View details for Web of Science ID 000244651800236

• Physiologic assessment of renal artery stenosis - Will history repeat itself? Editorial comment JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Fearon, W. F. 2006; 48 (9): 1856-1858

  View details for DOI 10.1016/j.jacc.2006.08.005

  View details for Web of Science ID 000241804400021

  View details for PubMedID 17084262

• Impact of donor-transmitted atherosclerosis on early cardiac allograft vasculopathy; New findings by 3-D IVUS 79th Annual Scientific Session of the American-Heart-Association Yamasaki, M., Sakurai, R., Hirohata, A., Honda, Y., Yock, P. G., Fitzgerald, P. J., Yeung, A. C., Valantine, H. A., Fearon, W. F. LIPPINCOTT WILLIAMS & WILKINS. 2006: 533–33

  View details for Web of Science ID 000241792803414

• Negative remodeling is primarily responsible for coronary artery lumen loss early after cardiac transplantation: Role of cytomegalovirus Sakurai, R., Yamasaki, M., Potena, L., Hirohata, A., Honda, Y., Yock, P. G., Fitzgerald, P. J., Yeung, A. C., Valantine, H. A., Fearon, W. F. LIPPINCOTT WILLIAMS & WILKINS. 2006: 533

  View details for Web of Science ID 000241792803413

• Index of microcirculatory resistance: A novel measure for predicting myocardial damage in patients with acute myocardial infarction 79th Annual Scientific Session of the American-Heart-Association Shah, M., Tremmel, J., Brinton, T., Wilson, A., Schnittger, I., Lee, D. P., Yeung, A. C., Fearon, W. F. LIPPINCOTT WILLIAMS & WILKINS. 2006: 586–87

  View details for Web of Science ID 000241792803637

• Optical coherence tomography: In-vivo correlation withhistology 18th Annual Transcatheter Cardiovascular Therapeutics Symposium Ikeno, F., Koizumi, T., Yeung, A. C., Yock, P. G., Fitzgerald, P. J., Fearon, W. F. EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2006: 93M–93M

  View details for Web of Science ID 000241442800218

• T-cell immunity to subclinical cytomegalovirus infection reduces cardiac allograft disease CIRCULATION Tu, W., Potena, L., Stepick-Biek, P., Liu, L., Dionis, K. Y., Luikart, H., Fearon, W. F., Holmes, T. H., Chin, C., Cooke, J. P., Valantine, H. A., Mocarski, E. S., Lewis, D. B. 2006; 114 (15): 1608-1615

  Abstract

  Asymptomatic cytomegalovirus (CMV) replication is frequent after cardiac transplantation in recipients with pretransplantation CMV infection. How subclinical viral replication influences cardiac allograft disease remains poorly understood, as does the importance of T-cell immunity in controlling such replication.Thirty-nine cardiac recipients who were pretransplantation CMV antibody positive were longitudinally studied for circulating CMV-specific CD4 and CD8 T-cell responses, CMV viral load in blood neutrophils, and allograft rejection during the first posttransplantation year. Nineteen of these recipients were also analyzed for changes of coronary artery intimal, lumen, and whole-vessel area. All recipients received early prophylactic therapy with ganciclovir. No recipients developed overt CMV disease. Those with detectable levels of CMV-specific CD4 T cells in the first month after transplantation were significantly protected from high mean and peak posttransplantation viral load (P<0.05), acute rejection (P<0.005), and loss of allograft coronary artery lumen (P<0.05) and of whole-vessel area (P<0.05) compared with those who lacked this immune response. The losses of lumen and vessel area were both significantly correlated with the time after transplantation at which a CD4 T-cell response was first detected (P<0.05) and with the cumulative graft rejection score (P<0.05).The early control of subclinical CMV replication after transplantation by T-cell immunity may limit cardiac allograft rejection and vascular disease. Interventions to increase T-cell immunity might be clinically useful in limiting these adverse viral effects.

  View details for DOI 10.1161/CIRCULATIONAHA.105.607549

  View details for PubMedID 17015794

• Physiological assessment of coronary artery disease in the cardiac catheterization laboratory - A scientific statement from the American Heart Association Committee on Diagnostic and Interventional Cardiac Catheterization, Council on Clinical Cardiology CIRCULATION Kern, M. J., Lerman, A., Bech, J., De Bruyne, B., Eeckhout, E., Fearon, W. F., Higano, S. T., Lim, M. J., Meuwissen, M., Piek, J. J., Pijls, N. H., Siebes, M., Spaan, J. A. 2006; 114 (12): 1321-1341

  Abstract

  With advances in technology, the physiological assessment of coronary artery disease in patients in the catheterization laboratory has become increasingly important in both clinical and research applications, but this assessment has evolved without standard nomenclature or techniques of data acquisition and measurement. Some questions regarding the interpretation, application, and outcome related to the results also remain unanswered. Accordingly, this consensus statement was designed to provide the background and evidence about physiological measurements and to describe standard methods for data acquisition and interpretation. The most common uses and support data from numerous clinical studies for the physiological assessment of coronary artery disease in the cardiac catheterization laboratory are reviewed. The goal of this statement is to provide a logical approach to the use of coronary physiological measurements in the catheterization lab to assist both clinicians and investigators in improving patient care.

  View details for DOI 10.1161/CIRCULATIONAHA.106.177276

  View details for Web of Science ID 000240556700017

  View details for PubMedID 16940193

• Acute rejection and cardiac allograft vascular disease is reduced by suppression of subclinical cytomegalovirus infection TRANSPLANTATION Potena, L., Holweg, C. T., Chin, C., Luikart, H., Weisshaar, D., Narasimhan, B., Fearon, W. F., Lewis, D. B., Cooke, J. P., Mocarski, E. S., Valantine, H. A. 2006; 82 (3): 398-405

  Abstract

  Anticytomegalovirus (CMV) prophylaxis prevents the acute disease but its impact on subclinical infection and allograft outcome is unknown. We sought to determine whether CMV prophylaxis administered for three months after heart transplant would improve patient outcomes.This prospective cohort study of 66 heart transplant recipients compared aggressive CMV prophylaxis (n = 21, CMV hyperimmune globulin [CMVIG] plus four weeks of intravenous ganciclovir followed by two months of valganciclovir); with standard prophylaxis (n = 45, intravenous ganciclovir for four weeks). Prophylaxis was based on pretransplant donor (D) and recipient (R) CMV serology: R-/D+ received aggressive prophylaxis; R+ received standard prophylaxis. Outcome measures were: CMV infection assessed by DNA-polymerase chain reaction on peripheral blood polymorphonuclear leukocytes, acute rejection, and cardiac allograft vascular disease (CAV) assessed by intravascular ultrasound. All patients completed one year of follow-up. RESULTS.: CMV infection was subclinical in all but four patients (two in each group). Aggressively treated patients had a lower incidence of CMV infection (73 +/- 10% vs. 94 +/- 4%; P = 0.038), and an independent reduced relative risk for acute rejection graded > or =3A (relative risk [95% CI] = 0.55 [0.26-0.96]; P = 0.03), as compared with the standard prophylaxis group. Aggressively prophylaxed patients also showed a slower progression of CAV, in terms of coronary artery lumen loss (lumen volume change=-21 +/- 13% vs. -10+/-14%; P = 0.05); and vessel shrinkage (vessel volume change = -15 +/- 11% vs. -3 +/- 18%; P = 0.03).Prolonged (val)ganciclovir plus CMVIG reduces viral levels, acute rejection, and allograft vascular disease, suggesting a role for chronic subclinical infection in the pathophysiology of the most common diseases affecting heart transplant recipients.

  View details for DOI 10.1097/01.tp.0000229039.87735.76

  View details for PubMedID 16906040

• Discordant changes in epicardial and microvascular coronary physiology after cardiac transplantation: Physiologic investigation for transplant arteriopathy II (PITA II) study JOURNAL OF HEART AND LUNG TRANSPLANTATION Fearon, W. F., Hirohata, A., Nakamura, M., Luikart, H., Lee, D. P., Vagelos, R. H., Hunt, S. A., Valantine, H. A., Fitzgerald, P. J., Yock, P. G., Yeung, A. C. 2006; 25 (7): 765-771

  Abstract

  Investigating changes in coronary physiology that occur after cardiac transplantation has been challenging. Simultaneous and independent assessment of the epicardial artery by measuring fractional flow reserve (FFR) and of the microvasculature by calculating the index of microvascular resistance (IMR) with a single coronary pressure wire may be useful.Twenty-five asymptomatic patients with normal coronary angiograms underwent FFR, thermodilution-derived IMR and coronary flow reserve (CFR) and intravascular ultrasound (IVUS) evaluation soon after cardiac transplantation and 1 year later.FFR significantly worsened (0.90 +/- 0.05 at baseline to 0.85 +/- 0.06 at 1 year, p = 0.004). FFR correlated strongly with percent plaque volume as measured by IVUS (r = -0.58, p < 0.0001). IMR improved significantly (29.2 +/- 15.9 at baseline to 19.3 +/- 7.6 units at 1 year, p = 0.007). CFR increased, but not significantly (2.6 +/- 1.4 at baseline to 3.2 +/- 1.2 at 1 year, p = not significant). Diabetes and donor heart ischemic time independently predicted baseline IMR. Treatment with rapamycin independently predicted FFR at 1 year.New coronary physiologic measures, FFR and IMR, show that epicardial artery physiology worsens and correlates with anatomic changes, whereas microvascular physiology improves during the first year after cardiac transplantation. CFR, the traditional method for evaluating coronary circulatory physiology, did not identify these changes.

  View details for DOI 10.1016/j.healun.2006.03.003

  View details for PubMedID 16818118

• Rapamycin therapy improves coronary physiology after cardiac transplantation 55th Annual Scientific Session of the American-College-of-Cardiology Sinha, S. S., Lee, D. P., Pham, M. X., Vagelos, R. H., Hunt, S. A., Valentine, H. A., Yeung, A. C., Fearon, W. F. ELSEVIER SCIENCE INC. 2006: 51A–51A

  View details for Web of Science ID 000235530400222

• Index of microcirculatory resistance: A novel measure for predicting myocardial damage in patients with acute myocardial infarction 55th Annual Scientific Session of the American-College-of-Cardiology Shah, M. G., Tremmel, J., Brinton, T., Wilson, A., Schnittger, I., Lee, D. P., Yeung, A. C., Fearon, W. F. ELSEVIER SCIENCE INC. 2006: 182A–182A

  View details for Web of Science ID 000235530401102

• Prevention of subclinical CMV infection reduces cardiac allograft disease progression by positively affecting coronary remodeling Potena, L., Fearon, W., Holweg, C., Luikart, H., Chin, C., Cooke, J., Lewis, D., Mocarski, E., Valantine, H. ELSEVIER SCIENCE INC. 2006: S138–S139

  View details for Web of Science ID 000203407400273

• Inhibition of cardiac allograft vasculopathy by sirolimus and mycofenolate: Asymmetric dimethyl arginine as a potential therapeutic target Potena, L., Fearon, W., Sydow, K., Holweg, C., Luikart, H., Mocarski, E., Valantine, H., Cooke, J. ELSEVIER SCIENCE INC. 2006: S100–S100

  View details for Web of Science ID 000203407400162

• Selective renal arterial infusion of fenoldopam for the prevention of contrast-induced nephropathy. Journal of interventional cardiology Ng, M. K., Tremmel, J., Fitzgerald, P. J., Fearon, W. F. 2006; 19 (1): 75-79

  Abstract

  Contrast-induced nephropathy (CIN) remains an important complication of angiographic procedures, particularly among patients with significant renal impairment. To date, vasodilator therapies such as fenoldopam have failed to prevent CIN, possibly because significant hypotension as a result of systemic infusion has limited the ability to deliver adequate drug levels to the renal vasculature. We present a case of averted CIN after multivessel coronary intervention in a diabetic patient with severe renal insufficiency, potentially due to bilateral renal arterial infusion of fenoldopam. Our subsequent experience with intrarenal fenoldopam in nine additional procedures in eight other high risk patients resulted in one case of asymptomatic transient CIN. Further studies are warranted to evaluate the efficacy of intrarenal administration of vasodilator therapies such as fenoldopam for the prevention of CIN.

  View details for PubMedID 16483344

• Changes in the anatomy and physiology of the coronary circulation after cardiac transplantation: Novel structural and physiologic evidence of cardiac transplant arteriopathy 78th Annual Scientific Session of the American-Heart-Association Hirohata, A., Nakamura, M., Waseda, K., Valantine, H. A., Hunt, S. A., Honda, Y., Yock, P. G., Fitzgerald, P. J., Yeung, A. C., Fearon, W. F. LIPPINCOTT WILLIAMS & WILKINS. 2005: U517–U517

  View details for Web of Science ID 000232956403127

• Inhibition of vein graft intimal hyperplasia with L-arginine polymers Hendry, S. L., Ikeno, F., Ako, J., Sheikh, A. Y., Kutschka, Hoyt, G., Fearon, W., Pelletier, M., Robbins, R. C. LIPPINCOTT WILLIAMS & WILKINS. 2005: U501

  View details for Web of Science ID 000232956403053

• Invasive assessment of the coronary microcirculation: Superior reproducibility and less hemodynamic dependence of index of microcirculatory resistance as compared to coronary flow reserve 78th Annual Scientific Session of the American-Heart-Association Ng, M. K., Yeung, A. C., Fearon, W. F. LIPPINCOTT WILLIAMS & WILKINS. 2005: U830–U830

  View details for Web of Science ID 000232956405237

• Design and rationale for the targeted intra-renal fenoldopam for avoidance of nephropathy (TIFFANY) trial 17th Annual Transcatheter Cardiovascular Therapeutics Symposium/4th Annual Transcatheter Cardiovascular Therapeutics Inflammation Summit Price, M. J., Garcia, L., Davidson, C., McNeil, J., Cohen, M. G., Mathur, V., Fearon, W. F., Weisz, G., Rogers, C., Madyoon, H., Feit, F., Low, R., Reisman, M., Teirstein, P. S. EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2005: 117H–117H

  View details for Web of Science ID 000232725200287

• Risk factors for the development of retroperitoneal hematoma after percutaneous coronary intervention in the era of glycoprotein IIb/IIIa inhibitors and vascular closure devices JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Farouque, H. M., Tremmel, J. A., Shabari, F. R., Aggarwal, M., Fearon, W. F., Ng, M. K., Rezaee, M., Yeung, A. C., Lee, D. P. 2005; 45 (3): 363-368

  Abstract

  We sought to determine the incidence, clinical features, and risk factors for retroperitoneal hematoma (RPH) after percutaneous coronary intervention (PCI).Little is known about the clinical features, outcomes, and determinants of this serious complication in the contemporary era of PCI.A retrospective analysis yielded 26 cases of RPH out of 3,508 consecutive patients undergoing PCI between January 2000 and January 2004. Cases were compared with a randomly selected sample of 50 control subjects without RPH.The incidence of RPH was 0.74%. Features of RPH included abdominal pain (42%), groin pain (46%), back pain (23%), diaphoresis (58%), bradycardia (31%), and hypotension (92%). The mean systolic blood pressure nadir was 75 mm Hg. The hematocrit dropped by 11.5 +/- 5.1 points from baseline in RPH patients, as compared with 2.3 +/- 3.3 points in controls (p < 0.0001). The mean hospital stay was longer in RPH patients (2.9 +/- 3.8 days vs. 1.7 +/- 1.5 days, p = 0.06). The following variables were found to be independent predictors of RPH: female gender (odds ratio [OR] 5.4, p = 0.005), low body surface area (BSA <1.73 m(2); OR 7.1, p = 0.008), and higher femoral artery puncture (OR 5.3, p = 0.013). There was no association between RPH and arterial sheath size, use of glycoprotein IIb/IIIa inhibitors, or deployment of a vascular closure device.Female gender, low BSA, and higher femoral artery puncture are significant risk factors for RPH. Awareness of the determinants and clinical features of RPH may aid in prevention, early recognition, and prompt treatment.

  View details for DOI 10.1016/j.jacc.2004.10.042

  View details for PubMedID 15680713

• Coronary endothelial dysfunction in cardiac transplant recipients is related to elevated levels of ADMA 54th Annual Scientific Session of the American-College-of-Cardiology Fearon, W. F., Wang, B. Y., Hirohata, A., Nakamura, M., Potena, L., Valentine, H. A., Yeung, A. C., Cooke, J. P. ELSEVIER SCIENCE INC. 2005: 150A–150A

  View details for Web of Science ID 000226808200658

• Impact of direct coronary stenting on neointimal distribution within sirolimus-eluting stents - IVUS subanalysis from the DIRECT trial 54th Annual Scientific Session of the American-College-of-Cardiology Hirohata, A., Ako, J., Sakurai, R., Fearon, W. F., Caputo, R., Mishkel, G., Mooney, M., O'Shaughnessy, C., Raizner, A., Wilensky, R., Williams, D., Wong, S. C., Karas, S., Yock, P. G., Honda, Y., Moses, J., Fitzgerald, P. J. ELSEVIER SCIENCE INC. 2005: 70A–70A

  View details for Web of Science ID 000226808200300

• Pioglitazone-induced heart failure despite normal left ventricular function AMERICAN JOURNAL OF MEDICINE Shah, M., Kolandaivelu, A., Fearon, W. E. 2004; 117 (12): 973-974

  View details for Web of Science ID 000226106300019

  View details for PubMedID 15629744

• "Tako-tsubo-like left ventricular dysfunction": a clinical entity mimicking acute myocardial infarction with a favorable prognosis. American journal of geriatric cardiology Farouque, H. M., Kaltenbach, T., Ako, J., Tremmel, J. A., Fearon, W. F., Yeung, A. C., Vagelos, R. H. 2004; 13 (6): 323-326

  Abstract

  An emotionally-distressed, elderly Caucasian woman presented with chest pain and hypertension. Electrocardiogram showed inferior ST-segment elevation, and an urgent cardiac catheterization was performed. Coronary angiography revealed normal appearing coronary arteries; however, left ventriculography showed extensive left ventricular apical akinesis. The patient had a mild rise in cardiac enzyme levels indicative of myocardial injury. She was discharged after an uncomplicated in-hospital course. One month later, the left ventricular wall motion abnormality had improved. In this report, the authors discuss this compilation of findings known as tako-tsubo-like left ventricular dysfunction.

  View details for PubMedID 15538070

• Systemic inflammation links impaired glucose metabolism to cardiac allograft vasculopathy development 77th Scientific Meeting of the American-Heart-Association Potena, L., Biadi, O., Fearon, W. B., Holweg, C. T., Luikart, H. I., Mocarski, E. S., Lewis, D. B., Valantine, H. A. LIPPINCOTT WILLIAMS & WILKINS. 2004: 753–53

  View details for Web of Science ID 000224783504063

• Coronary endothelial dysfunction in cardiac transplant recipients is related to elevated levels of ADMA 77th Scientific Meeting of the American-Heart-Association Fearon, W. F., Wang, B. Y., Nakamura, M., Potena, L., Valantine, H. A., Yeung, A. C., Cooke, J. P. LIPPINCOTT WILLIAMS & WILKINS. 2004: 73–73

  View details for Web of Science ID 000224783500340

• Epicardial stenosis severity does not affect minimal microcirculatory resistance CIRCULATION Aarnoudse, W., Fearon, W. F., Manoharan, G., Geven, M., Van De Vosse, F., Rutten, M., De Bruyne, B., Pijls, N. H. 2004; 110 (15): 2137-2142

  Abstract

  Whether minimal microvascular resistance of the myocardium is affected by the presence of an epicardial stenosis is controversial. Recently, an index of microcirculatory resistance (IMR) was developed that is based on combined measurements of distal coronary pressure and thermodilution-derived mean transit time. In normal coronary arteries, IMR correlates well with true microvascular resistance. However, to be applicable in the case of an epicardial stenosis, IMR should account for collateral flow. We investigated the feasibility of determining IMR in humans and tested the hypothesis that microvascular resistance is independent of epicardial stenosis.Thirty patients scheduled for percutaneous coronary intervention were studied. The stenosis was stented with a pressure guidewire, and coronary wedge pressure (P(w)) was measured during balloon occlusion. After successful stenting, a short compliant balloon with a diameter 1.0 mm smaller than the stent was placed in the stented segment and inflated with increasing pressures, creating a 10%, 50%, and 75% area stenosis. At each of the 3 degrees of stenosis, fractional flow reserve (FFR) and IMR were measured at steady-state maximum hyperemia induced by intravenous adenosine. A total of 90 measurements were performed in 30 patients. When uncorrected for P(w), an apparent increase in microvascular resistance was observed with increasing stenosis severity (IMR=24, 27, and 37 U for the 3 different degrees of stenosis; P<0.001). In contrast, when P(w) is appropriately accounted for, microvascular resistance did not change with stenosis severity (IMR=22, 23, and 23 U, respectively; P=0.28).Minimal microvascular resistance does not change with epicardial stenosis severity, and IMR is a specific index of microvascular resistance when collateral flow is properly taken into account.

  View details for DOI 10.1161/01.CIR.0000143893.18451.0E

  View details for Web of Science ID 000224407000011

  View details for PubMedID 15466646

• The current and future role of percutaneous coronary intervention in patients with coronary artery disease. Journal of interventional cardiology Lipinski, M. J., Fearon, W. F., Froelicher, V. F., Vetrovec, G. W. 2004; 17 (5): 283-294

  Abstract

  With increasing research on vulnerable plaques and uncertainty regarding which lesions require revascularization, the goal of this review is to clarify the indications for percutaneous coronary intervention and discuss which lesions do not warrant treatment by intervention. This paper also briefly reviews the potential advantages and limitations of technology that may enable detection of atherosclerotic plaques that are prone to rupture and discusses the future utility of these technologies in prevention of acute coronary syndromes. Providing an evidence-based understanding of lesion morphology and clinical variables that influence outcome enables the interventional cardiologist to determine which atherosclerotic plaques require PCI.

  View details for PubMedID 15491331

• Minimal microvascular resistance is not influenced by epicardial stenosis severity: animal validation ESC Congress 2004 Fearon, W. F., Aarnoudse, W., De Bruyne, B., Cooke, D. T., Balsam, L. B., Yeung, A. C., Yock, P. G., Pijls, N. H. OXFORD UNIV PRESS. 2004: 431–431

  View details for Web of Science ID 000224056501731

• Cytomegalovirus infectious burden is proportional to cardiac allograft vasculopathy in heart transplant recipients 53rd Annual Scientific Session of the American-College-of-Cardiology Potena, L., Magelli, C., Ortolani, P., Fearon, W. F., Grigioni, F., Magnani, G., Coccolo, F., Yeung, A. C., Luikart, H. I., Hunt, S. A., Mocarski, E. S., Cooke, J. P., Lewis, D. B., Branzi, A., Valantine, H. A. ELSEVIER SCIENCE INC. 2004: 185A–185A

  View details for Web of Science ID 000189388500790

• Impact of periprocedural plaque/thrombus reduction on myocardial injury after stent deployment Nakamura, M., Tamai, H., Aizawa, T., Hirohata, A., Honda, Y., Bonneau, H. N., Fearon, W. F., Yeung, A. C., Yock, P. G., Fitzgerald, P. J. ELSEVIER SCIENCE INC. 2004: 55A

  View details for DOI 10.1016/S0735-1097(04)90231-8

  View details for Web of Science ID 000189388500233

• Women remain at higher risk for retroperitoneal hematoma after percutaneous coronary intervention in the era of glycoprotein IIb/IIIa inhibitors and vascular closure devices 53rd Annual Scientific Session of the American-College-of-Cardiology Farouque, H. M., Tremmel, J. A., Aggarwal, M., Shabari, F. R., Fearon, W. F., Rezaee, M., Yeung, A. C., Lee, D. P. ELSEVIER SCIENCE INC. 2004: 63A–63A

  View details for Web of Science ID 000189388500266

• Exaggeration of neointimal hyperplasia following stent deployment in type B bifurcation lesions 53rd Annual Scientific Session of the American-College-of-Cardiology Hirohata, A., Nakamura, M., Fearon, W. F., Honda, Y., Yock, P. G., Fitzgerald, P. J. ELSEVIER SCIENCE INC. 2004: 55A–55A

  View details for Web of Science ID 000189388500234

• Evaluation of high-pressure retrograde coronary venous delivery of FGF-2 protein CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS Fearon, W. F., Ikeno, F., Bailey, L. R., Hiatt, B. L., Herity, N. A., Carter, A. J., Fitzgerald, P. J., Rezaee, M., Yeung, A. C., Yock, P. G. 2004; 61 (3): 422-428

  Abstract

  Delivery of angiogenic factors to ischemic myocardium remains a practical challenge. We evaluated the efficiency and efficacy of delivery of fibroblast growth factor-2 (FGF-2) protein via high-pressure retrograde injection into the anterior interventricular vein (AIV) in a porcine model of chronic myocardial ischemia. Labeled FGF-2 protein was delivered to the myocardium of three pigs via the AIV and the left anterior descending (LAD) coronary artery in three others. At 1 hr, the amount of protein in the left ventricle and the LAD region was quantified. Copper stents were implanted in the LAD of 25 pigs, resulting in chronic myocardial ischemia. At 4 weeks, microsphere-derived myocardial blood flow was assessed at rest and during pacing. In eight pigs (AIV FGF), FGF-2 protein (6 microg/kg) was delivered via high-pressure retrograde injection into the AIV. Six pigs (intracoronary FGF) received the same amount of FGF-2 by intracoronary delivery. Five pigs (AIV saline) received a placebo injection into the AIV and six pigs (control) served as controls. Four weeks later, myocardial blood flow was reassessed. At 1 hr, significantly more FGF remained in the left ventricle (1.3 vs. 0.82 microg; P < 0.04) and in the LAD region (1.2 vs. 0.64 microg; P = 0.03) after AIV compared to intracoronary delivery. Four weeks after treatment, resting LAD blood flow (normalized to right ventricular flow) improved slightly in the AIV FGF and intracoronary FGF arms (1.32-1.37 for both; P = 0.11), while it decreased significantly in the AIV saline (1.32-1.23; P = 0.02) and the control arms (1.32-1.19; P = 0.0004). Pacing LAD blood flow decreased significantly in the control arm (1.30-1.23; P < 0.05), but did not change significantly in the other three arms. High-pressure retrograde injection into the AIV may represent an efficient and effective means for delivering angiogenic factors to ischemic myocardium.

  View details for DOI 10.1002/ccd.10790

  View details for PubMedID 14988909

• Comparison of coronary thermodilution and Doppler velocity for assessing coronary flow reserve CIRCULATION Fearon, W. F., Farouque, H. M., Balsam, L. B., Cooke, D. T., Robbins, R. C., Fitzgerald, P. J., Yeung, A. C., Yock, P. G. 2003; 108 (18): 2198-2200

  Abstract

  Thermodilution coronary flow reserve (CFRthermo) is a new technique for invasively measuring coronary flow reserve (CFR) with a coronary pressure wire and is based on the ability of the pressure transducer to also measure temperature changes. Whether CFRthermo correlates well enough with absolute flow-derived CFR (CFRflow) to replace Doppler wire-derived CFR (CFRDoppler) remains unclear.In an open-chest pig model, CFRthermo was measured in the left anterior descending (LAD) artery and compared with CFRDoppler and CFRflow, measured with an external flow probe placed around the LAD. In 9 pigs, CFR was measured simultaneously by all 3 means in the normal LAD and after creation of an epicardial LAD stenosis. To determine the added effect of microvascular disease, measurements of flow reserve were also performed after disruption of the coronary microcirculation with embolized microspheres. Intracoronary papaverine (20 mg) was used to induce hyperemia. In a total of 61 paired measurements, CFRthermo correlated strongly with the reference standard CFRflow (r=0.85, P<0.001). CFRDoppler correlated less well with CFRflow (r=0.72, P<0.001). Bland-Altman analysis showed a closer agreement between CFRthermo and CFRflow.CFRthermo correlates better with CFRflow than does CFRDoppler.

  View details for DOI 10.1161/01.CIR.0000099521.31396.9D

  View details for PubMedID 14568891

• Endothelial nitric oxide synthesis is severely impaired after cardiac transplantation: Role of ADMA 76th Annual Scientific Session of the American-Heart-Association Fearon, W. F., Wang, B. Y., Valantine, H. A., Mocarsky, E. S., Yeung, A. C., Cooke, J. P. LIPPINCOTT WILLIAMS & WILKINS. 2003: 303–

  View details for Web of Science ID 000186360601501

• Simultaneous assessment of fractional and coronary flow reserves in cardiac transplant recipients - Physiologic investigation for transplant arteriopathy (PITA study) CIRCULATION Fearon, W. F., Nakamura, M., Lee, D. P., Rezaee, M., Vagelos, R. H., Hunt, S. A., Fitzgerald, P. J., Yock, P. G., Yeung, A. C. 2003; 108 (13): 1605-1610

  Abstract

  The utility of measuring fractional flow reserve (FFR) to assess cardiac transplant arteriopathy has not been evaluated. Measuring coronary flow reserve (CFR) as well as FFR could add information about the microcirculation, but until recently, this has required two coronary wires. We evaluated a new method for simultaneously measuring FFR and CFR with a single wire to investigate transplant arteriopathy.In 53 cases of asymptomatic cardiac transplant recipients without angiographically significant coronary disease, FFR and thermodilution-derived CFR (CFRthermo) were measured simultaneously with the same coronary pressure wire in the left anterior descending artery and compared with volumetric intravascular ultrasound (IVUS) imaging. The average FFR was 0.88+/-0.07; in 75% of cases, the FFR was less than the normal threshold of 0.94; and in 15% of cases, the FFR was < or =0.80, the upper boundary of the gray zone of the ischemic threshold. There was a significant inverse correlation between FFR and IVUS-derived measures of plaque burden, including percent plaque volume (r=0.55, P<0.0001). The average CFRthermo was 2.5+/-1.2; in 47% of cases, CFRthermo was < or =2.0. In 14%, the FFR was normal (> or =0.94) and the CFR was abnormal (<2.0), suggesting predominant microcirculatory dysfunction.FFR correlates with IVUS findings and is abnormal in a significant proportion of asymptomatic cardiac transplant patients with normal angiograms. Simultaneous measurement of CFR with the same pressure wire, with the use of a novel coronary thermodilution technique, is feasible and adds information to the physiological evaluation of these patients.

  View details for DOI 10.1161/01.CIR.0000091116.84926.6F

  View details for PubMedID 12963639

• Cost-effectiveness of measuring fractional flow reserve to guide coronary interventions AMERICAN HEART JOURNAL Fearon, W. F., Yeung, A. C., Lee, D. P., Yock, P. G., Heidenreich, P. A. 2003; 145 (5): 882-887

  Abstract

  Most patients come to the catheterization laboratory without prior functional tests, which makes the cost-effective treatment of patients with intermediate coronary lesions a practical challenge.We developed a decision model to compare the long-term costs and benefits of 3 strategies for treating patients with an intermediate coronary lesion and no prior functional study: 1) deferring the decision for percutaneous coronary intervention (PCI) to obtain a nuclear stress imaging study (NUC strategy); 2) measuring fractional flow reserve (FFR) at the time of angiography to help guide the decision for PCI (FFR strategy); and 3) stenting all intermediate lesions (STENT strategy). On the basis of the literature, we estimated that 40% of intermediate lesions would produce ischemia, 70% of patients treated with PCI and 30% of patients treated medically would be free of angina after 4 years, and the quality-of-life adjustment for living with angina was 0.9 (1.0 = perfect health). We estimated the cost of FFR to be 761 dollars, the cost of nuclear stress imaging to be 1093 dollars, and the cost of medical treatment for angina to be 1775 dollars per year. The extra cost of splitting the angiogram and PCI as dictated by the NUC strategy was 3886 dollars by use of hospital cost-accounting data. Sensitivity and threshold analyses were performed to determine which variables affected our results.The FFR strategy saved 1795 dollars per patient compared with the NUC strategy and 3830 dollars compared with the STENT strategy. Quality-adjusted life expectancy was similar among the 3 strategies (NUC-FFR = 0.8 quality-adjusted days, FFR-STENT = 6 quality-adjusted life days). Compared with the FFR strategy, the NUC strategy was expensive (>800,000 dollars per quality-adjusted life year gained). Both screening strategies were superior to (less cost, better outcomes) the STENT strategy. Sensitivity analysis indicated that the NUC strategy would only become attractive (<50,000 dollars/quality-adjusted life years compared with FFR) if the specificity of nuclear stress imaging was >25% better than FFR. Our results were not altered significantly by changing the other assumptions.In patients with an intermediate coronary lesion and no prior functional study, measuring FFR to guide the decision to perform PCI may lead to significant cost savings compared with performing nuclear stress imaging or with simply stenting lesions in all patients.

  View details for DOI 10.1016/S0002-8703(03)00072-3

  View details for PubMedID 12766748

• Adjunctive platelet glycoprotein IIb/IIIa receptor inhibition with tirofiban before primary Angioplasty improves angiographic outcomes - Results of the TIrofiban given in the emergency room before primary angioplasty (TIGER-PA) pilot trial CIRCULATION Lee, D. P., Herity, N. A., Hiatt, B. L., Fearon, W. F., Rezaee, M., Carter, A. J., Huston, M., Schreiber, D., DiBattiste, P. M., Yeung, A. C. 2003; 107 (11): 1497-1501

  Abstract

  Previous work has suggested that platelet glycoprotein IIb/IIIa receptor blockade may confer benefit in the treatment of acute myocardial infarction. The TIGER-PA pilot trial was a single-center randomized study to evaluate the safety, feasibility, and utility of early tirofiban administration before planned primary angioplasty in patients presenting with acute myocardial infarction.A total of 100 patients presenting with acute myocardial infarction were randomized to either early administration of tirofiban in the emergency room or later administration in the catheterization laboratory. The primary outcome measures were initial TIMI grade flow, corrected TIMI frame counts, and TIMI grade myocardial perfusion ("blush"). Thirty-day major adverse cardiac events were also assessed. Angiographic outcomes demonstrate a significant improvement in initial TIMI grade flow, corrected TIMI frame counts, and TIMI grade myocardial perfusion when patients are given tirofiban in the emergency room before primary angioplasty. The rate of 30-day major adverse cardiac events suggests that early administration may be beneficial.This pilot study suggests that early administration of tirofiban improves angiographic outcomes and is safe and feasible in patients undergoing primary angioplasty for acute myocardial infarction.

  View details for DOI 10.1161/01.CIR.0000056120.00513.7A

  View details for PubMedID 12654606

• Is coronary thermodilution as accurate as Doppler velocity for measuring coronary flow reserve? 52nd Annual Scientific Session of the American-College-of-Cardiology Fearon, W. F., Balsam, L. B., Farouque, H. M., Caffarelli, A. D., Robbins, R. C., Fitzgerald, P. J., Yeung, A. C., Yock, P. G. ELSEVIER SCIENCE INC. 2003: 59A–59A

  View details for Web of Science ID 000181669500253

• Physiologic interrogation of transplant arterioparthy: Final results 52nd Annual Scientific Session of the American-College-of-Cardiology Fearon, W. F., Nakamura, M., Lee, D. P., Rezaee, M., Vagelos, R. H., Hunt, S. A., Fitzgerald, P. J., Yock, P. G., Yeung, A. C. ELSEVIER SCIENCE INC. 2003: 29A–29A

  View details for Web of Science ID 000181669500129

• A novel invasive assessment of the coronary microcirculation 52nd Annual Scientific Session of the American-College-of-Cardiology Fearon, W. F., Balsam, L. B., Farouque, H. M., Caffarelli, A. D., Robbins, R. C., Fitzgerald, P. J., Yock, P. G., Yeung, A. C. ELSEVIER SCIENCE INC. 2003: 10A–10A

  View details for Web of Science ID 000181669500042

• Evaluating intermediate coronary lesions in the cardiac catheterization laboratory. Reviews in cardiovascular medicine Fearon, W. F., Yeung, A. C. 2003; 4 (1): 1-7

  Abstract

  Angiography is notoriously poor at distinguishing ischemia-producing from non-ischemia-producing intermediate coronary lesions. Here, three invasive modalities for evaluating the physiologic significance of moderate coronary stenoses are reviewed: Doppler wire-derived measurement of coronary flow reserve (CFR), coronary pressure wire-derived fractional flow reserve (FFR), and intravascular ultrasound (IVUS) imaging. Studies investigating the correlation between each of these modalities and various noninvasive tests (eg, nuclear perfusion imaging or stress echocardiography) are discussed. Each of these invasive modalities has its limitations: CFR is limited by its dependence on heart rate and blood pressure, calling into question its reproducibility; both FFR and CFR are limited by their reliance upon achieving maximal hyperemia; and IVUS is limited by the fact that it provides anatomic information only. Ultimately, FFR appears to be the ideal method for interrogating intermediate coronary lesions.

  View details for PubMedID 12684598

• Physiologic interrogation of transplant arteriopathy American-Heart-Association Abstracts From Scientific Sessions Fearon, W. F., Nakamura, M., Lee, D. P., Rezaee, M., Vagelos, R. H., Hunt, S. A., Yock, P. G., Yeung, A. C. LIPPINCOTT WILLIAMS & WILKINS. 2002: 591–91

  View details for Web of Science ID 000179142702958

• Myocardial delivery of labeled fibroblast growth factor-2 protein by high pressure, retrograde coronary venous injection is more efficient than intracoronary administration American-Heart-Association Abstracts From Scientific Sessions Fearon, W. F., Ikeno, F., Price, E., Bailey, L. R., Herity, N. A., Fitzgerald, P. J., Rezaee, M., Yeung, A. C., Yock, P. G. LIPPINCOTT WILLIAMS & WILKINS. 2002: 656–56

  View details for Web of Science ID 000179142703274

• Coronary pressure measurement after stenting predicts adverse events at follow-up - A multicenter registry CIRCULATION Pijls, N. H., Klauss, V., Siebert, U., Powers, E., Takazawa, K., Fearon, W. F., Escaned, J., Tsurumi, Y., Akasaka, T., Samady, H., De Bruyne, B. 2002; 105 (25): 2950-2954

  Abstract

  Coronary stenting is associated with a restenosis rate of 15% to 20% at 6-month follow-up, despite optimum angiographic stent implantation. In this multicenter registry, we investigated the relation between optimum physiological stent implantation as assessed by poststent fractional flow reserve (FFR) and outcome at 6 months.In 750 patients, coronary pressure measurement at maximum hyperemia was performed after angiographically apparently satisfactory stent implantation. Poststenting FFR was calculated and related to major adverse events (including need for repeat target vessel revascularization) at 6 months. In 76 patients (10.2%), at least 1 adverse event occurred. Five patients died, 19 experienced myocardial infarction, and 52 underwent at least 1 repeat target vessel revascularization. By multivariate analysis, FFR immediately after stenting was the most significant independent variable related to all types of events. In 36% of the patients, FFR normalized (>0.95), and event rate was 4.9% in that group. In 32% of the patients, poststent FFR was between 0.90 and 0.95, and event rate was 6.2%. In 32% of patients, poststent FFR was <0.90, and event rate was 20.3%. In 6% of the patients, FFR was <0.80, and event rate was 29.5% (P<0.001).FFR after stenting is a strong independent predictor of outcome at 6 months.

  View details for DOI 10.1161/01.CIR.0000020547.92091.76

  View details for Web of Science ID 000176818800016

  View details for PubMedID 12081986

• High pressure, retrograde, coronary venous delivery of FGF-2 protein improves coronary blood flow in a porcine model of myocardial ischemia Fearon, W. F., Rezaee, M., Hiatt, B. L., Ikeno, F., Bailey, L., Suzuki, T., Herity, N., Fitzgerald, P. J., Carter, A. J., Yeung, A. C., Yock, P. G. ELSEVIER SCIENCE INC. 2002: 10A–10A

  View details for Web of Science ID 000174106700042

• Acute and long-term safety of pressurized myocardial transvenous delivery: Confirmation by biochemical, echocardiographic, and histologic parameters Herity, N. A., Hiatt, B. L., Fearon, W. F., Suzuki, T., McEneaney, D. J., Berry, G., Yeung, A. C., Carter, A. J., Fitzgerald, P. J., Yock, P. G. ELSEVIER SCIENCE INC. 2002: 10A

  View details for Web of Science ID 000174106700043

• A comparison of treadmill scores to diagnose coronary artery disease CLINICAL CARDIOLOGY Fearon, W. F., Gauri, A. J., Myers, J., Raxwal, V. K., Atwood, J. E., Froelicher, V. F. 2002; 25 (3): 117-122

  Abstract

  Recently, several treadmill scores have been proposed as means for improving the diagnostic accuracy of the exercise treadmill test (ETT). Questions remain regarding the diagnostic accuracy of treadmill scores when applied to a different patient population than that from which they were derived; furthermore, many treadmill scores have not been compared with one another in the same population.The diagnostic accuracy of treadmill scores may not be the same.A retrospective analysis of data collected prospectively was performed on consecutive patients referred for evaluation of chest pain. All patients underwent a standard ETT followed by coronary angiography. Using angiographic evidence of coronary artery disease (CAD) as a reference, the area under the curve (AUC) of receiver operator characteristic (ROC) plots of the ST response alone, the Duke Treadmill Score (DTS), the Morise score, the Detrano score, the VA score, and a Consensus score consisting of the Morise, Detrano, and VA scores together were calculated and compared. The predictive accuracies of the DTS and the Consensus score to stratify patients for the likelihood of CAD were calculated and compared.In all, 1,282 patients without a prior myocardial infarction had an ETT and coronary angiography. The AUC (+/- standard error) was 0.67+/-0.01 for the ST response, 0.73+/-0.01 for DTS, 0.76+/-0.01 for Detrano score, 0.77+/-0.01 for Morise score, 0.78+/-0.01 for VA score, and 0.78+/-0.01 for Consensus score. The AUC for each treadmill score was significantly higher (z-score > 1.96) than for the ST response alone. The AUC of DTS was significantly lower than all other treadmill scores (z-score > 1.96). The predictive accuracy (+/-95% confidence interval) of the DTS to risk stratify patients into high and low likelihood for CAD was 71 (65-77)%, versus 80 (74-86)% for the Consensus score (p < 0.0001).In this population, the DTS remains useful for diagnosing CAD and stratifying for the likelihood of CAD, although it is less accurate than other treadmill scores.

  View details for PubMedID 11890370

• A comparison of angiographic and physiologic correlates to myocardial perfusion Fearon, W., Hiatt, B., Rezaee, M., Herity, N., Suzuki, T., Ikeno, F., Yeung, A. G., Carter, A. J., Yock, P. LIPPINCOTT WILLIAMS & WILKINS. 2001: 580–80

  View details for Web of Science ID 000171895002723

• Fractional flow reserve compared with intravascular ultrasound guidance for optimizing stent deployment CIRCULATION Fearon, W. F., Luna, J., Samady, H., Powers, E. R., Feldman, T., Dib, N., Tuzcu, E. M., Cleman, M. W., Chou, T. M., Cohen, D. J., Ragosta, M., Takagi, A., Jeremias, A., Fitzgerald, P. J., Yeung, A. C., Kern, M. J., Yock, P. G. 2001; 104 (16): 1917-1922

  Abstract

  Determination of fractional flow reserve (FFR) has been proposed as a means to assess stent deployment. In this prospective, multicenter trial, we evaluate the use of FFR to optimize stenting by comparing it with standard intravascular ultrasound (IVUS) criteria.Eighty-four stable patients with isolated coronary lesions underwent coronary stent deployment starting at 10 atm and increased serially by 2 atm until the FFR was >/=0.94 or 16 atm was achieved. IVUS was then performed. FFR was measured with a coronary pressure wire with intracoronary adenosine to induce hyperemia. The diagnostic characteristics of an FFR <0.94 to predict suboptimal stent expansion by IVUS, defined in both absolute and relative terms, were calculated. Over a range of IVUS criteria, the highest sensitivity, specificity, and predictive accuracy of FFR were 80%, 30%, and 42%, respectively. Receiver operator characteristic analysis defined an optimal FFR cut point at >/=0.96; at this threshold, the sensitivity, specificity, and predictive accuracy of FFR were 75%, 58%, and 62%, respectively (P=0.03 for comparison of predictive accuracy, P=0.01 for concordance between FFR and IVUS). The negative predictive value was 88%. Significantly better diagnostic performance was achieved in a subgroup that received higher doses (>30 microgram) of intracoronary adenosine during pressure measurements, suggesting that FFR might be overestimated in the other group.A fractional flow reserve <0.96, measured after stent deployment, predicts a suboptimal result based on validated intravascular ultrasound criteria; however, an FFR >/=0.96 does not reliably predict an optimal stent result. Higher doses of intracoronary adenosine than previously used to measure FFR improve these results.

  View details for PubMedID 11602494

• Effects of chronotropic incompetence and beta-blocker use on the exercise treadmill test in men AMERICAN HEART JOURNAL Gauri, A. J., Raxwal, V. K., Roux, L., Fearon, W. F., Froelicher, V. F. 2001; 142 (1): 136-141

  Abstract

  Our purpose was to assess the diagnostic characteristics of the exercise test in patients who fail to reach conventional target heart rates and in patients on beta-blockers.Exercise test results are often considered "inadequate" or "nondiagnostic" in patients taking beta-blockers and in patients who do not achieve 85% of their age-predicted maximal heart rate.The results of exercise tests and coronary angiography performed to evaluate chest pain in 1282 male patients without a prior history of myocardial infarction, coronary revascularization, diagnostic Q wave on the baseline electrocardiogram, or previous cardiac catheterization were analyzed with respect to beta-blocker exposure and failure to reach 85% age-predicted maximal heart rate. Sensitivity, specificity, and predictive accuracy of exercise testing, as well as area under the curve for the receiver operating characteristic plots were calculated for these subgroups with use of coronary angiography as the reference. The angiographic criterion for significant coronary artery disease was 50% narrowing or greater in one or more major coronary arteries.The population was divided into 4 exclusive groups on the basis of whether they reached their target heart rates and whether they were receiving beta-blockers. Sixty to 40 percent of this clinical population failed to reach target heart rate, of which 24% (n = 303) were receiving beta-blockers and 40% (n = 518) were not. The group of patients who reached target heart rate and were not taking beta-blockers was taken as the reference group (n = 409). The group of patients supposedly beta-blocked but who reached the target heart rate (n = 52) had hemodynamic and test characteristics similar to those of the reference group and most likely were not taking their beta-blockers or were not adequately dosed. The prevalence of angiographic coronary disease was significantly higher in the 2 groups failing to reach target heart rate, both in the presence and absence of beta-blockers, compared with the reference group (68% and 64%, respectively, vs 49%, P <.01). Although the areas under the curve of the receiver operating characteristic curves for ST depression of the groups failing to reach target heart rate were not significantly different from the reference group, the predictive accuracy and sensitivity were significantly lower for 1 mm of ST depression in the beta-blocked group who did not reach target heart rate (predictive accuracy of 56% vs 67%, sensitivity of 44% vs 58%, P <.01). The only way to maintain sensitivity with the standard exercise test in the beta-blocker group who failed to reach target heart rate was to use a treadmill score or 0.5-mm ST depression as the criteria for abnormal.Sensitivity and predictive accuracy of standard ST criteria for exercise-induced ST depression are significantly decreased in male patients who are taking beta-blockers and do not reach target heart rate. In those who fail to reach target heart rate and are not beta-blocked, sensitivity and predictive accuracy are maintained.

  View details for PubMedID 11431669

• Clinical utility of the exercise ECG in patients with diabetes and chest pain CHEST Lee, D. P., Fearon, W. F., Froelicher, V. F. 2001; 119 (5): 1576-1581

  Abstract

  The purpose of this study was to determine the characteristics of exercise treadmill testing in diabetic patients presenting with chest pain.The diagnosis of coronary artery disease (CAD) in diabetic patients is confounded by different manifestations of coronary disease than are seen in the general population. Because of the association of diabetes with accelerated CAD, it is critical to assess the diagnostic utility of the standard exercise test in diabetic patients with chest pain.This study was a retrospective analysis of standard exercise test results in 1,282 male patients without prior myocardial infarction who had undergone coronary angiography and were being evaluated for possible CAD at two Veterans' Administration institutions.In patients with diabetes, 38% had an abnormal exercise test result, and the prevalence of angiographic CAD was 69%; the sensitivity of the exercise test was 47% (95% confidence interval [CI], 41 to 58), and specificity was 81% (95% CI, 68 to 89). In patients without diabetes, 38% had an abnormal exercise test result, and the prevalence of angiographic CAD was 58%; the sensitivity of the exercise test was 52% (95% CI, 48 to 56), and specificity was 80% (95% CI, 76 to 83). The receiver operating characteristic curves were also similar in both diabetic and nondiabetic patients (0.67 and 0.68, respectively).These data demonstrate that the standard exercise test has similar diagnostic characteristics in diabetic as in nondiabetic patients.

  View details for PubMedID 11348969

• Images in cardiology. Giant left ventricular pseudoaneurysm. Clinical cardiology Fearon, W. F., Lo, S., Stertzer, S. 2001; 24 (4): 345-?

  View details for PubMedID 11303706

• Safety and efficacy of high pressure retrograde cardiac venous injection. Implications for regional myocardial delivery Herity, N. A., Fearon, W., Hiatt, B. L., Rezaee, M., Suzuki, T., Lee, D. P., Yeung, A. C., Carter, A. J., Fitzgerald, P. J., Yock, P. G. ELSEVIER SCIENCE INC. 2001: 6A–6A

  View details for Web of Science ID 000166914400029

• Higher doses of intracoronary adenosine are necessary for FFR-based stent optimization Fearon, W. F., Samady, H., Powers, E. R., Feldman, T., Dib, N., Tuzcu, E. M., Cleman, M. W., Chou, T. M., Cohen, D. J., Takagi, A., Luna, J., Jeremias, A., Yeung, A. C., Kern, M. J., Yock, P. G. ELSEVIER SCIENCE INC. 2001: 12A

  View details for Web of Science ID 000166914400054

• Fractional flow reserve compared to intravascular ultrasound guidance for optimal stent deployment: Final results of the FUSION study Fearon, W. F., Takagi, A., Luna, J., Jeremias, A., Samady, H., Powers, E. R., Feldman, T., Dib, N., Tuzcu, E. M., Cleman, M. W., Chou, T. M., Cohen, D. J., Yeung, A. C., Kern, M. J., Yock, P. G. ELSEVIER SCIENCE INC. 2001: 85A–85A

  View details for Web of Science ID 000166914400390

• Is the use of fractional flow reserve to guide coronary interventions cost-effective? Fearon, W. F., Yeung, A. C., Honda, Y., Yock, P. G., Heidenreich, P. A. ELSEVIER SCIENCE INC. 2001: 12A–12A

  View details for Web of Science ID 000166914400053

• Use of fractional myocardial flow reserve to assess the functional significance of intermediate coronary stenoses AMERICAN JOURNAL OF CARDIOLOGY Fearon, W. F., Takagi, A., Jeremias, A., Yeung, A. C., Joye, J. D., Cohen, D. J., Chou, T. M., Kern, M. J., Yock, P. G. 2000; 86 (9): 1013-1014

  Abstract

  The goal of the present study was to compare the use of pressure-derived myocardial fractional flow reserve for detecting ischemia with nuclear stress imaging in patients undergoing stent placement for intermediate coronary lesions. We demonstrated that myocardial fractional flow reserve detects ischemia in intermediate coronary lesions accurately when compared with nuclear stress imaging.

  View details for Web of Science ID 000165096000023

  View details for PubMedID 11053717

• A comparison between the use of fractional flow reserve and intravascular ultrasound for determining optimal stent deployment (FUSION study) Fearon, W. F., Takagi, A., Luna, J., Samady, H., Powers, E. R., Feldman, T., Cleman, M. W., Chou, T. M., Cohen, D. J., Dib, N., Yeung, A. C., Kern, M. J. LIPPINCOTT WILLIAMS & WILKINS. 2000: 635-?

  View details for Web of Science ID 000090072303071

• The effect of resting ST segment depression on the diagnostic characteristics of the exercise treadmill test JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Fearon, W. F., Lee, D. P., Froelicher, V. F. 2000; 35 (5): 1206-1211

  Abstract

  The aim of this study is to demonstrate the effect of resting ST segment depression on the diagnostic characteristics of the exercise treadmill test.Previous studies evaluating the effect of resting ST segment depression on the diagnostic characteristics of exercise treadmill test have been conducted on relatively small patient groups and based only on visual electrocardiogram (ECG) analysis.A retrospective analysis of data collected prospectively was performed on consecutive patients referred for evaluation of chest pain. One thousand two hundred eighty-two patients without a prior myocardial infarction underwent standard exercise treadmill tests followed by coronary angiography, with coronary artery disease defined as a 50% narrowing in at least one major epicardial coronary artery. Sensitivity, specificity, predictive accuracy and area under the curve of the receiver operating characteristic (ROC) plots were calculated for patients with and without resting ST segment depression as determined by visual or computerized analysis of the baseline ECG.Sensitivity of the exercise treadmill test increased in 206 patients with resting ST segment depression determined by visual ECG analysis compared with patients without resting ST segment depression (77 +/- 7% vs. 45 +/- 4%) and specificity decreased (48 +/- 12% vs. 84 +/- 3%). With computerized analysis, sensitivity of the treadmill test increased in 349 patients with resting ST segment depression compared with patients without resting ST segment depression (71 +/- 6% vs. 42 +/- 4%) and specificity decreased (52 +/- 9% vs. 87 +/- 3%) (p < 0.0001 for all comparisons). There was no significant difference in the area under the curve of the ROC plots (0.66-0.69) or the predictive accuracy (62-68%) between the four subgroups.The diagnostic accuracy and high sensitivity of the exercise treadmill test in a large cohort of patients with resting ST segment depression and no prior myocardial infarction support the initial use of the test for diagnosis of coronary artery disease. The classification of resting ST segment depression by method of analysis (visual vs. computerized) did not affect the results.

  View details for PubMedID 10758962

• Pneumocephalus due to invasive fungal sinusitis CLINICAL INFECTIOUS DISEASES Engel, G., Fearon, W. F., Kosek, J. C., Loutit, J. S. 2000; 30 (1): 215-217

  View details for Web of Science ID 000085004800043

  View details for PubMedID 10619764

• Does elevated cardiac troponin I in patients with unstable angina predict ischemia on stress testing? AMERICAN JOURNAL OF CARDIOLOGY Fearon, W. F., Lee, F. H., Froelicher, V. F. 1999; 84 (12): 1440-?

  Abstract

  To help guide physicians in their evaluation of patients with acute coronary syndromes, we investigated whether elevated cardiac troponin I in patients presenting with unstable angina predicts ischemia on stress testing. Elevated cardiac troponin I in patients who present with chest pain and normal creatine kinase levels is associated with ischemia on stress testing, as well as with future cardiac events.

  View details for PubMedID 10606119

• Lessons learned from studies of the standard exercise ECG test CHEST Froelicher, V. F., Fearon, W. F., Ferguson, C. M., Morise, A. P., Heidenreich, P., West, J., Atwood, J. E. 1999; 116 (5): 1442-1451

  View details for PubMedID 10559110

• Should only the squeaky wheel get the grease? The prognostic significance of silent ischemia detected by exercise treadmill testing AMERICAN HEART JOURNAL Fearon, W. F., Voodi, L., Atwood, J. E., Froelicher, V. 1998; 136 (5): 759-761

  View details for Web of Science ID 000076852300003

  View details for PubMedID 9812067

• Iliofemoral venous thrombosis treated by catheter-directed thrombolysis, angioplasty, and endoluminal stenting WESTERN JOURNAL OF MEDICINE Fearon, W. F., Semba, C. P. 1998; 168 (4): 277-279

  View details for Web of Science ID 000073259300017

  View details for PubMedID 9584676

• Acute myocardial infarction in a young woman with systemic lupus erythematosus. Vascular medicine Fearon, W. F., Cooke, J. P. 1996; 1 (1): 19-23

  Abstract

  A young woman was diagnosed with systemic lupus erythematosus at the age of 7 years and incurred an acute myocardial infarction at the age of 17 years. Her risk factors for coronary artery disease include hypertension, hypercholesterolemia, a relatively long disease duration, a fairly active disease as evidenced by the history of nephrotic syndrome and other organ system involvement, and a long history of prednisone use. It is difficult to determine the etiology of this patient's acute myocardial infarction without coronary artery histopathology, but aspects of her presentation (a history of virulent systemic lupus erythematosus, and the angiographic findings of ectasia and aneurysm) suggest that coronary arteritis was the etiology of her accelerated coronary artery disease and subsequent myocardial infarction. Acute myocardial infarction is an uncommon occurrence in premenopausal women less than 30 years old.35 These patients are typically found to have an associated systemic disease such as diabetes mellitus or familial hypercholesterolemia. Systemic lupus erythematosus is a less common systemic disease associated with premature coronary artery disease. Mechanisms of acute coronary syndromes in these patients include accelerated atherosclerosis, active coronary vasculitis, and/or vasospasm with superimposed thrombosis.

  View details for PubMedID 9546909