PMID- 33533873 OWN - NLM STAT- MEDLINE DCOM- 20220105 LR - 20220204 IS - 2380-6591 (Electronic) IS - 2380-6583 (Print) VI - 6 IP - 4 DP - 2021 Apr 1 TI - 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. PG - 427-436 LID - 10.1001/jamacardio.2020.7200 [doi] AB - 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. FAU - Lindenfeld, JoAnn AU - Lindenfeld J AD - Advanced Heart Failure, Vanderbilt Heart and Vascular Institute, Nashville, Tennessee. FAU - Abraham, William T AU - Abraham WT AD - Division of Cardiovascular Medicine, The Ohio State University, Columbus. FAU - Grayburn, Paul A AU - Grayburn PA AD - Baylor University Medical Center, Baylor Heart and Vascular Institute, Dallas, Texas. FAU - Kar, Saibal AU - Kar S AD - Center of Advanced Cardiac and Vascular Interventions, Los Angeles, California. FAU - Asch, Federico M AU - Asch FM AD - MedStar Health Research Institute, Hyattsville, Maryland. FAU - Lim, D Scott AU - Lim DS AD - Division of Cardiology, University of Virginia, Charlottesville. FAU - Nie, Hong AU - Nie H AD - Abbott, Santa Clara, California. FAU - Singhal, Pooja AU - Singhal P AD - Abbott, Santa Clara, California. FAU - Sundareswaran, Kartik S AU - Sundareswaran KS AD - Abbott, Santa Clara, California. FAU - Weissman, Neil J AU - Weissman NJ AD - MedStar Health Research Institute, Hyattsville, Maryland. FAU - Mack, Michael J AU - Mack MJ AD - Baylor Scott & White Heart Hospital Plano, Plano, Texas. FAU - Stone, Gregg W AU - Stone GW AD - The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York. CN - Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (COAPT) Investigators LA - eng SI - ClinicalTrials.gov/NCT01626079 GR - UL1 TR001409/TR/NCATS NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA Cardiol JT - JAMA cardiology JID - 101676033 SB - IM CIN - JAMA Cardiol. 2021 Apr 1;6(4):376-378. PMID: 33533877 MH - Aged MH - Female MH - Heart Failure/mortality MH - Heart Valve Prosthesis Implantation/*methods MH - Humans MH - Male MH - Mitral Valve Insufficiency/mortality/pathology/physiopathology/*surgery MH - Treatment Outcome MH - Ventricular Dysfunction, Left/*physiopathology PMC - PMC7859876 COIS- Conflict of Interest Disclosures: Dr Lindenfeld reported receiving personal fees from Abbott, Boehringer Ingelheim, CVRx, Impulse Dynamics, Edwards Lifesciences, and VWave; grants and personal fees from AstraZeneca; and grants from Sensible Medical and Volumetrix during the conduct of the study and personal fees from Abbott, Boehringer Ingelheim, CVRx, Impulse Dynamics, Edwards Lifesciences, and VWave; grants and personal fees from Astra Zeneca; and grants from Sensible Medical and Volumetrix outside the submitted work. Dr Abraham reported receiving personal fees from Abbott during the conduct of the study and personal fees from Edwards Lifesciences outside the submitted work. Dr Grayburn reported receiving grants and personal fees from Abbott Vascular and Edwards Lifesciences, echocardiography core laboratory contracts from Cardiovalve and Neochord, grants from Medtronic, personal fees from 4C Medical, and personal fees for serving as a consultant and an imaging core laboratory from W. L. Gore during the conduct of the study. Dr Kar reported receiving personal fees from Abbott, Boston Scientific, Medtronic, and WL Gore during the conduct of the study; serving as the principal investigator of the REPAIR MR (Percutaneous MitraClip Device or Surgical Mitral Valve Repair in Patients With Primary Mitral Regurgitation Who Are Candidates for Surgery) trial; and serving as a member of the steering committee for the Triluminate Trial. Dr Asch reported receiving grants from Abbott during the conduct of the study and grants from Edwards, Boston Scientific, Medtronic, MVRx, Livanova, Ancora GDS, Neovasc, Innovheart, and Polares Medical outside the submitted work. Dr Lim reported receiving grants from Abbott Vascular during the conduct of the study. Dr Mack reported receiving nonfinancial support from Abbott during the conduct of the study and nonfinancial support from Edwards Lifesciences and Medtronic outside the submitted work. Dr Weissman reported receiving grants from Abbott during the conduct of the study. Dr Stone reported receiving grants from Cardiovascular Research Foundation for trial-related services during the conduct of the study and personal fees from Terumo, Cook, Miracor, Neovasc, V-wave, Abiomed, MAIA Pharmaceuticals, Shockwave, Vectorious, Cardiomech, Applied Therapeutics, MedFocus, Biostar, Spectrawave, Valfix, Ancora, Orchestra Biomed, and Qool Therapeutics and equity/options from Aria, Cagent, Cardiac Success, Spectrawave, Valfix, Ancora, Orchestra Biomed, and Qool Therapeutics outside the submitted work. No other disclosures were reported. EDAT- 2021/02/04 06:00 MHDA- 2022/01/06 06:00 PMCR- 2022/02/03 CRDT- 2021/02/03 12:13 PHST- 2021/02/04 06:00 [pubmed] PHST- 2022/01/06 06:00 [medline] PHST- 2021/02/03 12:13 [entrez] PHST- 2022/02/03 00:00 [pmc-release] AID - 2775801 [pii] AID - hoi200093 [pii] AID - 10.1001/jamacardio.2020.7200 [doi] PST - ppublish SO - JAMA Cardiol. 2021 Apr 1;6(4):427-436. doi: 10.1001/jamacardio.2020.7200.