Michael J. Mack M.D.

Saxon, J.T., Cohen, D.J., Chhatriwalla, A.K., Kotinkaduwa, L.N., Kar, S., Lim, D.S., Abraham, W.T., Lindenfeld, J., Mack, M.J., Arnold, S.V. and Stone, G.W. (2020). “Impact of COPD on Outcomes After MitraClip for Secondary Mitral Regurgitation: The COAPT Trial.” JACC Cardiovasc Interv 13(23): 2795-2803.

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OBJECTIVES: The aim of this study was to examine the relationship between chronic obstructive pulmonary disease (COPD) and outcomes after transcatheter mitral valve repair (TMVr) for severe secondary mitral regurgitation. BACKGROUND: TMVr with the MitraClip improves clinical and health-status outcomes in patients with heart failure and severe (3+ to 4+) secondary mitral regurgitation. Whether these benefits are modified by COPD is unknown. METHODS: COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) was an open-label, multicenter, randomized trial of TMVr plus guideline-directed medical therapy (GDMT) versus GDMT alone. Patients on corticosteroids or continuous oxygen were excluded. Multivariable models were used to examine the associations of COPD with mortality, heart failure hospitalization (HFH), and health status and to test whether COPD modified the benefit of TMVr compared with GDMT. RESULTS: Among 614 patients, 143 (23.2%) had COPD. Among patients treated with TMVr, unadjusted analyses demonstrated increased 2-year mortality in those with COPD (hazard ratio [HR]: 2.08; 95% confidence interval [CI]: 1.33 to 3.26), but this association was attenuated after risk adjustment (adjusted HR: 1.48; 95% CI: 0.87 to 2.52). Although TMVr led to reduced 2-year mortality among patients without COPD (adjusted HR: 0.47; 95% CI: 0.33 to 0.67), for patients with COPD, 2-year all-cause mortality was similar after TMVr versus GDMT alone (adjusted HR: 0.94; 95% CI: 0.54 to 1.65; p(int) = 0.04), findings that reflect offsetting effects on cardiovascular and noncardiovascular mortality. In contrast, TMVr reduced HFH (adjusted HR: 0.48 [95% CI: 0.28 to 0.83] vs. 0.46 [95% CI: 0.34 to 0.63]; p(int) = 0.89) and improved both generic and disease-specific health status to a similar extent compared with GDMT alone in patients with and without COPD (p(int) >0.30 for all scales). CONCLUSIONS: In the COAPT trial, COPD was associated with attenuation of the survival benefit of TMVr versus GDMT compared with patients without COPD. However, the benefits of TMVr on both HFH and health status were similar regardless of COPD. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] [COAPT]; NCT01626079).

Holmes, D.R., Jr., Farb, A.A., Chip Hance, R., Leon, M.B., Goldberg, P., Zuckerman, B.D., Kaplan, A.V., Rincon-Gonzalez, L., Hunt, J., Walkowiak, J. and Mack, M.J. (2020). “Early Feasibility Studies for Cardiovascular Devices in the United States: JACC State-of-the-Art Review.” J Am Coll Cardiol 76(23): 2786-2794.

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The development of technology to treat unmet clinical patient needs in the United States has been an important focus for the U.S. Food and Drug Administration and the 2016 Congressional 21st Century Cures Act. In response, a program of early feasibility studies (EFS) has been developed. One of the important issues has been the outmigration of the development and testing of medical devices from the United States. The EFS committee has developed and implemented processes to address issues to develop strategies for early treatment of these patient groups. Initial implementation of the U.S. Food and Drug Administration EFS program has been successful, but residual significant problems have hindered the opportunity to take full advantage of the program. These include delays in gaining Institutional Review Board approval, timeliness of budget and contractual negotiations, and lack of access to and enrollment of study subjects. This paper reviews improvements that have been made to the U.S. EFS ecosystem and outlines potential approaches to address remaining impediments to program success.

Holmes, D.R., Jr., Farb, A.A., Chip Hance, R., Leon, M.B., Goldberg, P., Zuckerman, B.D., Kaplan, A.V., Rincon-Gonzalez, L., Hunt, J., Walkowiak, J. and Mack, M.J. (2020). “Early Feasibility Studies for Cardiovascular Devices in the United States: JACC State-of-the-Art Review.” J Am Coll Cardiol 76(23): 2786-2794.

Full text of this article.

The development of technology to treat unmet clinical patient needs in the United States has been an important focus for the U.S. Food and Drug Administration and the 2016 Congressional 21st Century Cures Act. In response, a program of early feasibility studies (EFS) has been developed. One of the important issues has been the outmigration of the development and testing of medical devices from the United States. The EFS committee has developed and implemented processes to address issues to develop strategies for early treatment of these patient groups. Initial implementation of the U.S. Food and Drug Administration EFS program has been successful, but residual significant problems have hindered the opportunity to take full advantage of the program. These include delays in gaining Institutional Review Board approval, timeliness of budget and contractual negotiations, and lack of access to and enrollment of study subjects. This paper reviews improvements that have been made to the U.S. EFS ecosystem and outlines potential approaches to address remaining impediments to program success.

Kosmidou, I., Lindenfeld, J., Abraham, W.T., Kar, S., Lim, D.S., Mishell, J.M., Whisenant, B.K., Kipperman, R.M., Boudoulas, K.D., Redfors, B., Shahim, B., Zhang, Z., Mack, M.J. and Stone, G.W. (2020). “Transcatheter Mitral Valve Repair in Patients With and Without Cardiac Resynchronization Therapy: The COAPT Trial.” Circ Heart Fail 13(11): e007293.

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BACKGROUND: In the COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation), treatment of heart failure (HF) patients with moderate-severe or severe secondary mitral regurgitation with transcatheter mitral valve repair (TMVr) using the MitraClip plus guideline-directed medical therapy (GDMT) reduced 2-year rates of HF hospitalization and all-cause mortality compared with GDMT alone. Whether the benefits of the MitraClip extend to patients with previously implanted cardiac resynchronization therapy (CRT) is unknown. We sought to examine the effect of prior CRT in patients enrolled in COAPT. METHODS: Patients (N=614) with moderate-severe or severe secondary mitral regurgitation who remained symptomatic despite maximally tolerated doses of GDMT were randomized 1:1 to the MitraClip (TMVr arm) versus GDMT only (control arm). Outcomes were assessed according to prior CRT use. RESULTS: Among 614 patients, 224 (36.5%) had prior CRT (115 and 109 randomized to TMVr and control, respectively) and 390 (63.5%) had no CRT (187 and 203 randomized to TMVr and control, respectively). Patients with CRT had similar 2-year rates of the composite of death or HF hospitalization compared with those without CRT (57.6% versus 55%, P=0.32). Death or HF hospitalization at 2 years was lower with TMVr versus control treatment in patients with prior CRT (48.6% versus 67.2%, hazard ratio, 0.60 [95% CI, 0.42-0.86]) and without CRT (42.5% versus 66.9%, hazard ratio, 0.52 [95% CI, 0.39-0.69]; adjusted P(interaction)=0.23). The effects of TMVr with the MitraClip on reducing the 2-year rates of all-cause death (adjusted P(interaction)=0.14) and HF hospitalization (adjusted P(interaction)=0.82) were also consistent in patients with and without CRT as were improvements in quality-of-life and exercise capacity. CONCLUSIONS: In the COAPT trial, TMVr with the MitraClip improved the 2-year prognosis of patients with HF and moderate-severe or severe secondary mitral regurgitation who remained symptomatic despite maximally tolerated GDMT, regardless of prior CRT implantation. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01626079.

Carroll, J.D., Mack, M.J., Vemulapalli, S., Herrmann, H.C., Gleason, T.G., Hanzel, G., Deeb, G.M., Thourani, V.H., Cohen, D.J., Desai, N., Kirtane, A.J., Fitzgerald, S., Michaels, J., Krohn, C., Masoudi, F.A., Brindis, R.G. and Bavaria, J.E. (2020). “STS-ACC TVT Registry of Transcatheter Aortic Valve Replacement.” Ann Thorac Surg Nov 16;S0003-4975(20)31514-9. [Epub ahead of print.].

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The STS-ACC TVT Registry (Society of Thoracic Surgeons-American College of Cardiology Transcatheter Valve Therapy Registry) from 2011 to 2019 has collected data on 276,316 patients undergoing transcatheter aortic valve replacement (TAVR) at sites in all U.S. states. Volumes have increased every year, exceeding surgical aortic valve replacement in 2019 (72,991 vs. 57,626), and it is now performed in all U.S. states. TAVR now extends from extreme- to low-risk patients. This is the first presentation on 8,395 low-risk patients treated in 2019. In 2019, for the entire cohort, femoral access increased to 95.3%, hospital stay was 2 days, and 90.3% were discharged home. Since 2011, the 30-day mortality rate has decreased (7.2% to 2.5%), stroke has started to decrease (2.75% to 2.3%), but pacemaker need is unchanged (10.9% to 10.8%). Alive with acceptable patient-reported outcomes is achieved in 8 of 10 patients at 1 year. The Registry is a national resource to improve care and analyze TAVR’s evolution. Real-world outcomes, site performance, and the impact of coronavirus disease 2019 will be subsequently studied. (STS/ACC Transcatheter Valve Therapy Registry [TVT Registry]; NCT01737528).