Mortality Associated with Proportionality of Secondary Mitral Regurgitation After Transcatheter Mitral Valve Repair: MFIRE Registry

BACKGROUND The association, if any, between the effective regurgitant orifice (EROA) to left ventricular end-diastolic volume (LVEDV) ratio and 1-year mortality is controversial in patients undergoing mitral transcatheter edge-to-edge repair (m-TEER) with the MitraClip™ system. The objective is to determine the association between EROA/LVEDV and 1-year mortality among patients undergoing m-TEER with MitraClip™. METHODS In patients with severe secondary (functional) mitral regurgitation (MR), we analyzed registry data from 11 centers using generalized linear models with the generalized estimating equations approach. RESULTS We studied 525 patients with secondary MR who underwent m-TEER in 11 centers. Most patients were male (63%) and were NYHA class III (61%) or IV (21%). MR was caused by ischemic cardiomyopathy in 51% of patients. EROA/LVEDV values varied widely with median=0.19 mm2/mL, interquartile range [0.12,0.28] mm2/mL, and 187 (36%) patients had values <0.15 mm2/mL. Post-procedural MR severity improved substantially, being 1+ or less in 74%, 2+ in 20%, 3+ in 4%, and 4+ in 2%. 1-year mortality was 22%. After adjustment for confounders, the logarithmic transformation of EROA/LVEDV was associated with 1-year mortality (odds ratio=0.600, 95% confidence interval [0.386,0.933], p=0.023). A higher Society of Thoracic Surgeons risk score was also associated with increased mortality. CONCLUSIONS Lower values of Ln(EROA/LVEDV) were associated with increased 1-year mortality in a multi-center registry. The slope of the association is steep at low values, but gradually becomes flatter as Ln(EROA/LVEDV) increases. What is Known In recent years, mitral transcatheter edge-to-edge repair (m-TEER) approval has expanded to select patients with functional mitral regurgitation. The paradigm of proportionate and disproportionate MR as measured by EROA/LVEDV has been proposed as a potential rationale to reconcile conflicting trial results. What the Study Adds Before adjustment, EROA/LVEDV was not associated with mortality (0.22 ± 0.13 vs 0.21 ± 0.14, p=0.425, standardized difference = -0.08). However, after adjustment we found that the logarithmic transformation of the pre-procedural EROA/LVEDV, Ln(EROA/LVEDV) was associated with 1-year mortality (OR = 0.600, 95% CI [0.386, 0.933], p=0.023). Progressively higher values of pre-procedural EROA/LVEDV were always associated with a progressively lower odds ratio of death post-procedurally, without a plateau or cutoff but with an “elbow” around 0.15mm2/mL. Graphic Abstract The Association of EROA/LVEDV with Mortality. Plot of the adjusted odds ratios associated (solid line) with 95% confidence intervals (dashed lines) with EROA/LVEDV=0.15 as the reference showing the risk of death increases as EROA/LVEDV decreases. The plot is back transformed from Ln(EROA/LVEDV). ![Figure][1] ### Competing Interest Statement Christopher P Kovach MD - No disclosures to report. D Scott Lim MD - Dr Lim receives institutional grants from Abbott, Boston Scientific, Corvia, Edwards, Medtronic, and Trisol. He is a consultant for Philips, Valgen, and Venus. Deepa Raghunathan MD - No disclosures to report. Edward A Gill MD - No disclosures to report. Enrique Garcia-Sayan MD - No disclosures to report. Evelio Rodriguez MD - Dr. Rodriguez is a consultant and speaker for Abbott. He receives research funding from Abbott. Firas E Zahr MD - Dr. Zahr is a consultant and on the advisory board for Medtronic. He receives educational and research grants from Medtronic and Edwards. He receives educational grants from Siemens. Flora M Li MD - No disclosures to report. Gorav Ailawadi MD - Dr. Ailawadi is a consultant for Medtronic, Abbott, Edwards, Gore, Anteris, Atricure, CryoLife, Philips, Johnson & Johnson Graciela B Mentz PhD - No disclosures to report. Jason H Rogers MD - Dr. Rogers receives research/institutional grants from Abbott and Boston Scientific. He is a consultant for Abbott, Baylis, and Boston Scientific. Lily Chen MD - Dr. Chen is a consultant for Philips, Abbott, and Akura Medical. M Andrew Morse MD - Dr Morse previously served as a consultant for Abbott. Mani A Vannan MD - Dr Vannan receives research support and speakers bureau from Abbott - all payments to the Piedmont Heart Institute, not to self. Marcella A Calfon Press MD, PhD - No disclosures to report. Mark Reisman MD - No disclosures to report. Michael Morcos MD - No disclosures to report. Milo C Engoren MD - No disclosures to report. Neal M Duggal MD - No disclosures to report Nishtha Sodhi MD - Dr. Sodhi is a consultant for Medtronic and Boston Scientific. Paul Sorajja MD - Dr. Sorajja is a consultant for 4C Medical, Anteris, Abbott Structural, Boston Scientific, Edwards Lifesciences, Evolution Medical, Foldax, GLG, Medtronic, Phillips, Siemens, Shifamed, WL Gore, vDyne, xDot. Pradeep K Yadav MD - Dr. Yadav is consultant and speaker for Edwards Lifesciences, Abbott Vascular, Boston Scientific. He sits on the advisory board for Dasi Simulations. Scott M Chadderdon MD - Dr Chadderdon is a consultant for Medtronic and Edwards. He receives a research grant from GE Healthcare. Stanley J Chetcuti MD - Dr. Chetcuti is a consultant for Medtronic and Boston Scientific. He receives research grants from Jena, Abbott, Edwards, Gore , Medtronic and Boston Scientific. Yuan Yuan MS - No disclosures to report. ### Funding Statement No funding was received for this work. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study received a certificate of exemption from the University of Michigan Institutional Review Board (HUM00191906, Ann Arbor, MI). As no patient care interventions were involved, signed patient consent was waived. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Study data was collected via combined queries from each participating institution's electronic medical record and the Society of Thoracic Surgeons (STS) & American College of Cardiology (ACC) Transcatheter Valve Therapy (TVT) Registry. Echocardiographic data were reviewed by each of the participating sites. * CI : confidence interval COAPT : Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation EROA : effective regurgitant orifice area FMR : functional mitral regurgitation LVEDV : left ventricular end diastolic volume LVEF : left ventricle ejection fraction M-FIRE : North American Mitraclip for Functional Mitral Regurgitation MR : mitral regurgitation m-TEER : mitral transcatheter edge to edge repair OR : odds ratio TVT : Transcatheter Valve Therapy registry [1]: pending:yes