Michael J. Mack M.D.

Hara, H., Ono, M., Kawashima, H., Kogame, N., Mack, M.J., Holmes, D.R., Morice, M.C., Davierwala, P.M., Mohr, F.W., Thuijs, D., Head, S.J., Kappetein, A.P., Onuma, Y. and Serruys, P.W. (2021). “Impact of stent length and diameter on 10-year mortality in the SYNTAXES trial.” Catheter Cardiovasc Interv.

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OBJECTIVES: We investigated the impact of total stent length (TSL) and average nominal stent diameter (ASD) on 10-year mortality after percutaneous coronary intervention (PCI) in the SYNTAXES trial. BACKGROUND: TSL and ASD in patients treated with PCI are associated with major adverse cardiovascular events. However, the treatment effect of PCI with extensive and/or small stenting as compared with coronary artery bypass grafting (CABG) for complex coronary artery disease has not been fully evaluated. METHODS: Impacts on mortality of extensive stenting defined as TSL >100 mm and small stenting as ASD <3 mm were analyzed in 893 PCI patients and were compared to 865 CABG patients. RESULTS: TSL as a continuous variable was significantly associated with 10-year mortality (adjusted hazard ratio [HR], 1.05 [1.01-1.09] per 10 mm increase). PCI patients with extensive stenting had a higher 10 year mortality than CABG patients (adjusted HR, 1.97 [1.41-2.74]) or not- extensive stenting PCI (adjusted HR, 1.94 [1.36-2.77]). Although ASD did not have a significant association with 10 year mortality (adjusted HR, 0.97 [0.85-1.11] per 0.25 mm increase), PCI with small stents was associated with a higher 10 year mortality, compared to CABG (adjusted HR, 1.66 [1.23-2.26]) and PCI performed with large stents (adjusted HR, 1.74 [1.19-2.53]). Patients treated with not-extensive and large stents had similar mortality rates (24.0 versus 23.8%) as those treated with CABG. CONCLUSIONS: Extensive and small stenting were associated with higher 10 year mortality, compared with CABG. When patients have to be treated with extensive or small stenting, revascularization with CABG should be preferred.

Généreux, P., Piazza, N., Alu, M.C., Nazif, T., Hahn, R.T., Pibarot, P., Bax, J.J., Leipsic, J.A., Blanke, P., Blackstone, E.H., Finn, M.T., Kapadia, S., Linke, A., Mack, M.J., Makkar, R., Mehran, R., Popma, J.J., Reardon, M., Rodes-Cabau, J., Van Mieghem, N.M., Webb, J.G., Cohen, D.J. and Leon, M.B. (2021). “Valve Academic Research Consortium 3: Updated Endpoint Definitions for Aortic Valve Clinical Research.” J Am Coll Cardiol.

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AIMS: The Valve Academic Research Consortium (VARC), founded in 2010, was intended to (i) identify appropriate clinical endpoints and (ii) standardize definitions of these endpoints for transcatheter and surgical aortic valve clinical trials. Rapid evolution of the field, including the emergence of new complications, expanding clinical indications, and novel therapy strategies have mandated further refinement and expansion of these definitions to ensure clinical relevance. This document provides an update of the most appropriate clinical endpoint definitions to be used in the conduct of transcatheter and surgical aortic valve clinical research. METHODS AND RESULTS: Several years after the publication of the VARC-2 manuscript, an in-person meeting was held involving over 50 independent clinical experts representing several professional societies, academic research organizations, the US Food and Drug Administration (FDA), and industry representatives to (i) evaluate utilization of VARC endpoint definitions in clinical research, (ii) discuss the scope of this focused update, and (iii) review and revise specific clinical endpoint definitions. A writing committee of independent experts was convened and subsequently met to further address outstanding issues. There were ongoing discussions with FDA and many experts to develop a new classification schema for bioprosthetic valve dysfunction and failure. Overall, this multi-disciplinary process has resulted in important recommendations for data reporting, clinical research methods, and updated endpoint definitions. New definitions or modifications of existing definitions are being proposed for repeat hospitalizations, access site-related complications, bleeding events, conduction disturbances, cardiac structural complications, and bioprosthetic valve dysfunction and failure (including valve leaflet thickening and thrombosis). A more granular 5-class grading scheme for paravalvular regurgitation (PVR) is being proposed to help refine the assessment of PVR. Finally, more specific recommendations on quality-of-life assessments have been included, which have been targeted to specific clinical study designs. CONCLUSIONS: Acknowledging the dynamic and evolving nature of less-invasive aortic valve therapies, further refinements of clinical research processes are required. The adoption of these updated and newly proposed VARC-3 endpoints and definitions will ensure homogenous event reporting, accurate adjudication, and appropriate comparisons of clinical research studies involving devices and new therapeutic strategies.

Chikwe, J., O’Gara, P., Fremes, S., Sundt, T., Habib, R.H., Gammie, J., Gaudino, M., Badhwar, V., Gillinov, M., Acker, M., Rowe, G., Gill, G., Goldstone, A.B., Schwann, T., Gelijns, A., Trento, A., Mack, M. and Adams, D.H. (2021). “Mitral Surgery after Transcatheter Edge-to-Edge Repair: Society of Thoracic Surgeons Database Analysis.” J Am Coll Cardiol.

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BACKGROUND: Transcatheter edge-to-edge (TEER) mitral repair may be complicated by residual or recurrent mitral regurgitation. Increasing need for surgical reintervention has been reported but operative outcomes are ill-defined. OBJECTIVES: This study evaluated national outcomes of mitral surgery after TEER. METHODS: The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database was used to identify 524 adults who underwent mitral surgery after TEER between July 2014 and June 2020. Emergencies (5.0%, n=26), previous mitral surgery (5.3%, n=28) or open implantation of transcatheter prostheses (1.5%, n=8) were excluded. The primary outcome was 30-day or in-hospital mortality. RESULTS: In the study cohort of 463 patients median age was 76 years (interquartile range (IQR) 67-81 years), median left ventricular ejection fraction 57% (IQR 48-62%), and 177 (38.2%) patients had degenerative disease. Major concomitant cardiac surgery was performed in 137 (29.4%) patients: in patients undergoing isolated mitral surgery median STS predicted mortality was 6.5% (IQR 3.9-10.5%), observed mortality was 10.2% (n=23/225) and the ratio of observed to expected mortality was 1.2 (95% CI 0.8-1.9). Predictors of mortality included urgent surgery (odds ratio (OR) 2.4, 95% confidence interval (CI) 1.3-4.6), non-degenerative / unknown etiology (OR 2.2, 95% CI 1.1-4.5), creatinine >2.0mg/dl (OR 3.8, 95% CI 1.9-7.9) and age >80 (OR 2.1, 95% CI 1.1-4.4). In a volume outcomes analysis in an expanded cohort of 591 patients at 227 hospitals, operative mortality was 2.6% (n=2/76) in 4 centers that performed >10 cases versus 12.4% (n= 64/515) in centers performing fewer (p=0.01). The surgical repair rate after failed TEER was 4.8% (n=22), and 6.8% (n=12) in degenerative disease. CONCLUSION: This study indicates mitral repair is infrequently achieved after failed TEER, which may have implications for treatment choice in lower-risk and younger patients with degenerative disease. These findings should inform patient consent for TEER, clinical trial design and clinical performance measures.

Wang, R., Tomaniak, M., Takahashi, K., Gao, C., Kawashima, H., Hara, H., Ono, M., van Klaveren, D., van Geuns, R.J., Morice, M.C., Davierwala, P.M., Mack, M.J., Witkowski, A., Curzen, N., Berti, S., Burzotta, F., James, S., Kappetein, A.P., Head, S.J., Thuijs, D., Mohr, F.W., Holmes, D.R., Tao, L., Onuma, Y. and Serruys, P.W. (2021). “Impact of chronic obstructive pulmonary disease on 10-year mortality after percutaneous coronary intervention and bypass surgery for complex coronary artery disease: insights from the SYNTAX Extended Survival study.” Clin Res Cardiol Mar 12. {Epub ahead of print].

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AIMS: To evaluate the impact of chronic obstructive pulmonary disease (COPD) on 10-year all-cause death and the treatment effect of CABG versus PCI on 10-year all-cause death in patients with three-vessel disease (3VD) and/or left main coronary artery disease (LMCAD) and COPD. METHODS: Patients were stratified according to COPD status and compared with regard to clinical outcomes. Ten-year all-cause death was examined according to the presence of COPD and the revascularization strategy. RESULTS: COPD status was available for all randomized 1800 patients, of whom, 154 had COPD (8.6%) at the time of randomization. Regardless of the revascularization strategy, patients with COPD had a higher risk of 10-year all-cause death, compared with those without COPD (43.1% vs. 24.9%; hazard ratio [HR]: 2.03; 95% confidence interval [CI]: 1.56-2.64; p < 0.001). Among patients with COPD, CABG appeared to have a slightly lower risk of 10-year all-cause death compared with PCI (42.3% vs. 43.9%; HR: 0.96; 95% CI: 0.59-1.56, p = 0.858), whereas among those without COPD, CABG had a significantly lower risk of 10-year all-cause death (22.7% vs. 27.1%; HR: 0.81; 95% CI: 0.67-0.99, p = 0.041). There was no significant differential treatment effect of CABG versus PCI on 10-year all-cause death between patients with and without COPD (p (interaction) = 0.544). CONCLUSIONS: COPD was associated with a higher risk of 10-year all-cause death after revascularization for complex coronary artery disease. The presence of COPD did not significantly modify the beneficial effect of CABG versus PCI on 10-year all-cause death. TRIAL REGISTRATION: SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050.

Shahim, B., Malaisrie, S.C., George, I., Thourani, V.H., Biviano, A.B., Russo, M.J., Brown, D.L., Babaliaros, V., Guyton, R.A., Kodali, S.K., Nazif, T.M., McCabe, J.M., Williams, M.R., Généreux, P., Lu, M., Yu, X., Alu, M.C., Webb, J.G., Mack, M.J., Leon, M.B. and Kosmidou, I. (2021). “Atrial Fibrillation and Outcomes After Transcatheter or Surgical Aortic Valve Replacement (from the PARTNER 3 Trial).” Am J Cardiol Mar 7;S0002-9149(21)00215-0. [Epub ahead of print].

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The prognostic impact of preexisting atrial fibrillation or flutter (AF) in low-risk patients with severe aortic stenosis treated with transcatheter (TAVR) or surgical aortic valve replacement (SAVR) remains unknown. In this sub-analysis of the PARTNER 3 trial of patients with severe aortic stenosis at low surgical risk randomized 1:1 to TAVR versus SAVR, clinical outcomes were analyzed at 2 years according to AF status. Among 948 patients included in the analysis (452 [47.7%] in the SAVR vs 496 [52.3%] in the TAVR arm), 168 (17.6%) patients had AF [88/452 (19.5%) and 80/496 (16.1%) treated with SAVR and TAVR, respectively]. At 2 years, patients with AF had higher unadjusted rates of the composite outcome of death, stroke or rehospitalization (21.2% vs 12.9%, p = 0.007) and rehospitalization alone (15.3% vs 9.4%, p = 0.03) but not all cause death (3.8% vs 2.6%, p = 0.45) or stroke (4.8% vs 2.6%, p = 0.12). In adjusted analyses, patients with AF had a higher risk for the composite outcome of death, stroke or rehospitalization (hazard ratio [HR] 1.80, 95% confidence interval [CI] 1.20-2.71, p = 0.0046) and rehospitalization alone (HR 1.8, 95% CI 0.12-2.9, p = 0.015), but not death or stroke. There was no interaction between treatment modality and AF on the composite outcome (Pinter = 0.83). In conclusion, preexisting AF in patients with severe AS at low surgical risk was associated with increased risk of the composite outcome of death, stroke or rehospitalization at 2 years, irrespective of treatment modality.