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Original Investigation
February 3, 2021

Association of Effective Regurgitation Orifice Area to Left Ventricular End-Diastolic Volume Ratio With Transcatheter Mitral Valve Repair Outcomes: A Secondary Analysis of the COAPT Trial

JoAnn Lindenfeld, MD1; William T. Abraham, MD2; Paul A. Grayburn, MD3; et al Saibal Kar, MD4; Federico M. Asch, MD5; D. Scott Lim, MD6; Hong Nie, PhD7; Pooja Singhal, PhD7; Kartik S. Sundareswaran, PhD7; Neil J. Weissman, MD8; Michael J. Mack, MD9; Gregg W. Stone, MD10; for the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (COAPT) Investigators
Author Affiliations
  • 1Advanced Heart Failure, Vanderbilt Heart and Vascular Institute, Nashville, Tennessee
  • 2Division of Cardiovascular Medicine, The Ohio State University, Columbus
  • 3Baylor University Medical Center, Baylor Heart and Vascular Institute, Dallas, Texas
  • 4Center of Advanced Cardiac and Vascular Interventions, Los Angeles, California
  • 5MedStar Health Research Institute, Hyattsville, Maryland
  • 6Division of Cardiology, University of Virginia, Charlottesville
  • 7Abbott, Santa Clara, California
  • 8MedStar Health Research Institute, Hyattsville, Maryland
  • 9Baylor Scott & White Heart Hospital Plano, Plano, Texas
  • 10The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York
JAMA Cardiol. 2021;6(4):427-436. doi:10.1001/jamacardio.2020.7200
Key Points

Question  Does the ratio of effective regurgitant orifice area (EROA) to left ventricular end-diastolic volume (LVEDV) support the proportionate-disproportionate hypothesis for the disparate results of the Multicenter Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation and Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation in patients with secondary mitral regurgitation?

Findings  In this secondary analysis of a randomized clinical trial of EROA and regurgitant volume relative to LVEDV, which involved a total of 548 patients, follow-up at 24 months did not strongly support the proportionate-disproportionate hypothesis in determining patient outcome.

Meaning  The ratio of EROA to LVEDV may not be the best factor associated with the benefits of transcatheter mitral valve repair for all-cause mortality or hospitalization for heart failure.

Abstract

Importance  Transcatheter mitral valve repair (TMVr) plus maximally tolerated guideline-directed medical therapy (GDMT) reduced heart failure (HF) hospitalizations (HFHs) and all-cause mortality (ACM) in symptomatic patients with HF and secondary mitral regurgitation (SMR) compared with GDMT alone in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (COAPT) trial but not in a similar trial, Multicenter Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation (MITRA-FR), possibly because the degree of SMR relative to the left ventricular end-diastolic volume index (LVEDVi) was substantially lower.

Objective  To explore contributions of the degree of SMR using the effective regurgitation orifice area (EROA), regurgitant volume (RV), and LVEDVi to the benefit of TMVr in the COAPT trial.

Design, Setting, and Participants  This post hoc secondary analysis of the COAPT randomized clinical trial performed December 27, 2012, to June 23, 2017, evaluated a subgroup of COAPT patients (group 1) with characteristics consistent with patients enrolled in MITRA-FR (n = 56) (HF with grade 3+ to 4+ SMR, left ventricular ejection fraction of 20%-50%, and New York Heart Association function class II-IV) compared with remaining (group 2) COAPT patients (n = 492) using the end point of ACM or HFH at 24 months, components of the primary end point, and quality of life (QOL) (per the Kansas City Cardiomyopathy Questionnaire overall summary score) and 6-minute walk distance (6MWD). The same end points were evaluated in 6 subgroups of COAPT by combinations of EROA and LVEDVi and of RV relative to LVEDVi.

Interventions  Interventions were TMVr plus GDMT vs GDMT alone.

Results  A total of 548 participants (mean [SD] age, 71.9 [11.2] years; 351 [64%] male) were included. In group 1, no significant difference was found in the composite rate of ACM or HFH between TMVr plus GDMT vs GDMT alone at 24 months (27.8% vs 33.1%, P = .83) compared with a significant difference at 24 months (31.5% vs 50.2%, P < .001) in group 2. However, patients randomized to receive TMVr vs those treated with GDMT alone had significantly greater improvement in QOL at 12 months (mean [SD] Kansas City Cardiomyopathy Questionnaire summary scores: group 1: 18.36 [5.38] vs 0.43 [4.00] points; P = .01; group 2: 16.54 [1.57] vs 5.78 [1.82] points; P < .001). Group 1 TMVr-randomized patients vs those treated with GDMT alone also had significantly greater improvement in 6MWD at 12 months (mean [SD] paired improvement: 39.0 [28.6] vs −48.0 [18.6] m; P = .02). Group 2 TMVr-randomized patients vs those treated with GDMT alone tended to have greater improvement in 6MWD at 12 months, but the difference did not reach statistical significance (mean [SD] paired improvement: 35.0 [7.7] vs 16.0 [9.1] m; P = .11).

Conclusions and Relevance  A small subgroup of COAPT-resembling patients enrolled in MITRA-FR did not achieve improvement in ACM or HFH at 24 months but had a significant benefit on patient-centered outcomes (eg, QOL and 6MWD). Further subgroup analyses with 24-month follow-up suggest that the benefit of TMVr is not fully supported by the proportionate-disproportionate hypothesis.

Trial Registration  ClinicalTrials.gov Identifier: NCT01626079

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