COAPT Echocardiographic Outcomes

Study Questions:

In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial, what was the screening algorithm used by the echocardiographic core laboratory to qualify patients, did transcatheter mitral valve repair (TMVr) affect echo parameters, and did outcomes vary amongst echocardiographic subgroups?

Methods:

COAPT was a multicenter, open-label randomized controlled trial comparing guideline-directed medical therapy (GDMT) to transcatheter mitral valve repair (TMVr) through leaflet approximation with a MitraClip.1 Patient enrollment was complex, with 12 inclusion and 28 exclusion criteria listed in the original publication.1 Eligible patients had ischemic or nonischemic cardiomyopathy with LVEF 20-50%, moderate-severe (3+) or severe (4+) secondary MR, and LV end-diastolic diameter (LVEDD) ≤70 mm. Patients with pulmonary hypertension, as evidenced by right ventricular systolic pressure (RVSP) >70 mm Hg or moderate or worse RV dysfunction, were excluded.

Patients identified at participating sites were further screened for eligibility prior to randomization by an echocardiographic core laboratory, which applied a three-tiered algorithm (based on quantitative Doppler parameters derived from American Society of Echocardiography and American College of Cardiology guidelines):

  • Tier 1: Effective regurgitant orifice area (EROA) ≥0.3 cm2 or pulmonary vein systolic flow reversal
  • Tier 2: EROA between 0.2 cm2 and 0.3 cm2 plus one of the following MR criteria: regurgitant volume ≥45 ml/beat; regurgitant fraction >40%; vena contracta width >0.5 cm
  • Tier 3: EROA <0.2 cm2 plus two of six MR criteria

Echo follow-up was obtained at 1, 6, 12, 18, and 24 months. The primary endpoints were heart failure (HF)-related hospitalizations or death.

Results:

The original COAPT trial reported enrollment of 614 patients, with 302 randomized to TMVr plus GDMT versus 312 to GDMT alone. This article reports several additional details regarding enrollment. First, an additional 51 patients treated with TMVr were “roll-ins”—no further details are given. Second, nearly one third of patients referred by participating sites did not qualify for randomization once reviewed by the core echo laboratory. Of the 665 total patients enrolled, MR was 3+ in 52% and 4+ in 48%, with mean EROA of 0.41 ± 0.15 cm2. The vast majority (86%) met Tier 1 criteria, versus 10% Tier 2 and 4% Tier 3.

At 1 month, only 7.4% of the TMVr patients had ≥3+ MR (vs. 66% control, p < 0.001), and by 12 months, 84% had improved by ≥2 grades (vs. 16% control, p < 0.001). LVEDV and LVESV increased in both groups but to a lesser extent in TMVr patients (p < 0.05). LVEF decreased more initially in the device group, but this pattern reversed by 12-month follow-up (p < 0.05).

The beneficial effects of TMVr (vs. control) on the primary outcomes were consistent across all echocardiographic subgroups.

Conclusions:

In the COAPT trial, TMVr versus GDMT alone had significant effects not only on HF hospitalization and death (as reported in the initial publication), but also on echocardiographic parameters such as MR severity, LVEDV, and LVEF. TMVr improvements were sustained throughout the 24-month follow-up period and consistent regardless of baseline LV size or dysfunction, RVSP, or degree of MR or TR.

Use of a multiparametric screening algorithm and a core echocardiographic laboratory significantly altered enrollment. Based on the positive results and robust effect size of the experimental treatment in the COAPT trial versus the MITRA-FR trial,2 an earlier MitraClip study with negative results, the authors argue that the screening algorithm identified patients with greater potential benefit from TMVr.

Perspective:

COAPT has robust findings—not only primary outcomes but echocardiographic improvement across all baseline subgroups. That said, it is not clear why COAPT was a positive trial when the prior MITRA-FR trial failed to show benefit. This could be (as the authors suggest) differences in the patients enrolled – the prior trial included patients with less severe MR, yet greater LV dilation. Direct comparison of enrollment strategies, however, would be needed to firmly establish the utility of the multiparametric screening algorithm.

One clear limitation of this study is a lack of explanation of the 51 “roll-in” TMVr patients, which were not included in the original COAPT publication. These patients were not randomized and no information is given as to how they were enrolled. Finally, the exclusion of nearly one third of patients by the core echocardiographic laboratory, despite considerable expertise at the enrollment sites, raises the question of broader applicability and may stress the need for specialized training.

References:

  1. Stone GW, Lindenfeld J, Abraham WT, et al., on behalf of the COAPT Investigators. Transcatheter Mitral-Valve Repair in Patients With Heart Failure. N Engl J Med 2018;379:2307-18.
  2. Obadia JF, Messika-Zeitoun D, Leurent G, et al., on behalf of the MITRA-FR Investigators. Percutaneous Repair or Medical Treatment for Secondary Mitral Regurgitation. N Engl J Med 2018;379:2297-306.

Clinical Topics: Heart Failure and Cardiomyopathies, Noninvasive Imaging, Pulmonary Hypertension and Venous Thromboembolism, Valvular Heart Disease, Acute Heart Failure, Pulmonary Hypertension, Echocardiography/Ultrasound, Mitral Regurgitation

Keywords: Blood Pressure, Cardiomyopathies, Diagnostic Imaging, Dilatation, Echocardiography, Heart Failure, Heart Valve Diseases, Hypertension, Pulmonary, Mitral Valve Insufficiency, Outcome Assessment (Health Care), Systole


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