Michael J. Mack M.D.

Mack, M.J., Fullerton, D.A. and Fann, J.I. (2021). “The Answers You Get Depend On the Questions You Ask: Insights from the Recent EXCEL Trial Controversy.” Ann Thorac Surg Mar 6;S0003-4975(21)00447-1. [Epub ahead of print].

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The SYYNTAX authors found that the impact of these “enzyme-driven events” on time-to-event curves and the composite endpoints was greater in the surgical cohort. PMIs after PCI were associated with 10-year mortality regardless of definition, whereas their impact on mortality after CABG was limited to 1 year, leading to the conclusion that “the rates of PMI are highly dependent on their definition, which affects time-to-event curves, composite endpoints, and their lethal prognostic relevance”. This serves to stress the importance of engagement of all investigators during the design phase of a trial because of the importance of the decisions at that time in determining trial outcomes. [No abstract; excerpt from article].

Leon, M.B., Mack, M.J., Hahn, R.T., Thourani, V.H., Makkar, R., Kodali, S.K., Alu, M.C., Madhavan, M.V., Chau, K.H., Russo, M., Kapadia, S.R., Malaisrie, S.C., Cohen, D.J., Blanke, P., Leipsic, J.A., Williams, M.R., McCabe, J.M., Brown, D.L., Babaliaros, V., Goldman, S., Herrmann, H.C., Szeto, W.Y., Genereux, P., Pershad, A., Lu, M., Webb, J.G., Smith, C.R. and Pibarot, P. (2021). “Outcomes 2 Years After Transcatheter Aortic Valve Replacement in Patients at Low Surgical Risk.” J Am Coll Cardiol 77(9): 1149-1161.

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BACKGROUND: In low surgical risk patients with symptomatic severe aortic stenosis, the PARTNER 3 (Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low Risk Patients With Aortic Stenosis) trial demonstrated superiority of transcatheter aortic valve replacement (TAVR) versus surgery for the primary endpoint of death, stroke, or re-hospitalization at 1 year. OBJECTIVES: This study determined both clinical and echocardiographic outcomes between 1 and 2 years in the PARTNER 3 trial. METHODS: This study randomly assigned 1,000 patients (1:1) to transfemoral TAVR with the SAPIEN 3 valve versus surgery (mean Society of Thoracic Surgeons score: 1.9%; mean age: 73 years) with clinical and echocardiography follow-up at 30 days and at 1 and 2 years. This study assessed 2-year rates of the primary endpoint and several secondary endpoints (clinical, echocardiography, and quality-of-life measures) in this as-treated analysis. RESULTS: Primary endpoint follow-up at 2 years was available in 96.5% of patients. The 2-year primary endpoint was significantly reduced after TAVR versus surgery (11.5% vs. 17.4%; hazard ratio: 0.63; 95% confidence interval: 0.45 to 0.88; p = 0.007). Differences in death and stroke favoring TAVR at 1 year were not statistically significant at 2 years (death: TAVR 2.4% vs. surgery 3.2%; p = 0.47; stroke: TAVR 2.4% vs. surgery 3.6%; p = 0.28). Valve thrombosis at 2 years was increased after TAVR (2.6%; 13 events) compared with surgery (0.7%; 3 events; p = 0.02). Disease-specific health status continued to be better after TAVR versus surgery through 2 years. Echocardiographic findings, including hemodynamic valve deterioration and bioprosthetic valve failure, were similar for TAVR and surgery at 2 years. CONCLUSIONS: At 2 years, the primary endpoint remained significantly lower with TAVR versus surgery, but initial differences in death and stroke favoring TAVR were diminished and patients who underwent TAVR had increased valve thrombosis. (Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low Risk Patients With Aortic Stenosis [PARTNER 3]; NCT02675114).

Gertz, Z.M., Herrmann, H.C., Lim, D.S., Kar, S., Kapadia, S.R., Reed, G.W., Puri, R., Krishnaswamy, A., Gersh, B.J., Weissman, N.J., Asch, F.M., Grayburn, P.A., Kosmidou, I., Redfors, B., Zhang, Z., Abraham, W.T., Lindenfeld, J., Stone, G.W. and Mack, M.J. (2021). “Implications of Atrial Fibrillation on the Mechanisms of Mitral Regurgitation and Response to MitraClip in the COAPT Trial.” Circ Cardiovasc Interv Mar 15;CIRCINTERVENTIONS120010300. [Epub ahead of print]. Circinterventions120010300.

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BACKGROUND: Atrial fibrillation (AF), mitral regurgitation (MR), and left ventricular (LV) ejection fraction have a complex interplay. We evaluated the role of AF in patients with heart failure and moderate-to-severe or severe secondary MR enrolled in the randomized COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) and its impact on mechanisms and outcomes with the MitraClip. METHODS: Patients in the COAPT trial were stratified by the presence (n=327) or absence (n=287) of a history of AF and by assignment to treatment group. Clinical, echocardiographic, and outcome measures were assessed. The primary outcome was the composite rate of death or heart failure hospitalization at 24 months. RESULTS: Patients with history of AF were older and more often male. They had a higher LV ejection fraction, larger left atrial volumes and mitral valve orifice areas, smaller LV volumes, and similar MR severity. Patients with AF compared with those without a history of AF had a higher unadjusted (hazard ratio [HR], 1.32 [95% CI, 1.06-1.64], P=0.01) and adjusted (HR, 1.30 [1.03-1.64], P=0.03) 2-year rate of the primary outcome. Treatment with the MitraClip compared with guideline-directed medical therapy alone reduced death or heart failure hospitalization in both those with (HR, 0.61 [0.46-0.82]) and without (HR, 0.46 [0.33-0.66]) a history of AF (P(int)=0.18). Treatment with the MitraClip was associated with a lower risk of stroke in patients with a history of AF (HR, 0.18 [0.04-0.86]) but not in those without a history of AF (HR, 1.64 [0.58-4.62]; P(int)=0.02). CONCLUSIONS: In the COAPT trial, patients with a history of AF had larger left atrial and mitral valve orifice areas with higher LV ejection fraction and smaller LV volumes, suggesting an atrial mechanism contribution to functional MR. Despite the worse prognosis of heart failure patients with a history of AF, MR reduction with the MitraClip still afforded substantial clinical benefits. Treatment with MitraClip was associated with a lower risk of stroke in patients with a history of AF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01626079.

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. and Biviano, A.B. (2021). “Atrial Fibrillation Is Associated With Mortality in Intermediate Surgical Risk Patients With Severe Aortic Stenosis: Analyses From the PARTNER 2A and PARTNER S3i Trials.” J Am Heart Assoc 10(7): e019584.

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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.

Arnold, S.V., Manandhar, P., Vemulapalli, S., Kosinski, A., Desai, N.D., Bavaria, J.E., Carroll, J.D., Mack, M.J., Thourani, V.H. and Cohen, D.J. (2021). “Impact of short-term complications of transcatheter aortic valve replacement on longer-term outcomes: results from the STS/ACC Transcatheter Valve Therapy Registry.” Eur Heart J Qual Care Clin Outcomes 7(2): 208-213.

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AIMS: While complications of transcatheter aortic valve replacement (TAVR) have decreased, they still occur commonly and may negatively impact both short- and long-term outcomes. We sought to examine the association of complications after TAVR with survival and health status in a real-world cohort. METHODS AND RESULTS: Among 45 884 TAVR patients from 513 US sites who survived 30 days, 21.4% had at least one major complication [stroke, bleed, vascular complication, new pacemaker, acute kidney injury (AKI), and moderate/severe paravalvular leak (PVL)]. In multivariable models, Stage 3 AKI [hazard ratio (HR) 3.43, 95% confidence interval (CI) 2.64-4.45], stroke (HR 2.62, 95% CI 2.06-3.32), and bleeding (HR 1.83, 95% CI 1.55-2.16) were independently associated with significantly increased risk of early death (<3 months) with slight attenuation in these hazards between 3 and 12 months. Moderate/severe PVL (HR 1.37, 95% CI 1.21-1.55) and new pacemaker (HR 1.15, 95% CI 1.05-1.25) were associated with more modest risk of excess mortality that was consistent through 12 months. Among surviving patients, stroke (-6.1 points, 95% CI -8.4 to -3.7), moderate/severe PVL (-3.2 points, 95% CI -4.9 to -1.6), and new pacemaker (-2.3 points, 95% CI -3.2 to -1.5) were associated with less improvement in 1-year health status, as assessed by the Kansas City Cardiomyopathy Questionnaire. CONCLUSION: In this study of contemporary TAVR, we found that complications remain common within the first 30 days after TAVR and are associated with worse 1-year survival and health status among survivors. These findings support continued efforts to reduce major complications of TAVR and may also help define quality of care.