Mitral Regurgitation " Proportionality " in Functional Mitral Regurgitation and Outcomes After Mitral Valve Transcatheter Edge-to-Edge Repair: A Systematic Review and Meta-Analysis

Background: Certain patients with functional mitral regurgitation survive longer with fewer heart failure hospitalizations after undergoing transcatheter edge-to-edge repair (TEER); however, clinical markers identifying who will benefit have not been established. The 'proportionality ' of mitral regurgitation (MR) severity compared to left ventricular size has been hypothesized to predict clinical outcome. Methods: We sought to combine existing studies to compare outcomes between 'proportionate ' MR and 'disproportionate ' MR in patients undergoing TEER. PubMed and Medline were searched from January 2018 until May 2023. Data was extracted and synthesized by 2 independent authors using random effects models with risk ratios (RRs) for binary outcomes. The primary outcome was a combined endpoint of all-cause mortality or heart failure hospitalization (ACM/HFH). Other outcomes of interest included ACM and residual >2+ MR after TEER. Results: Six trials with a total of 1594 patients (mean age 71 years, 66% male) were included, which assessed MR proportionality using either a ratio of estimated regurgitant orifice area to left ventricular enddi astolic volume (EROA:LVEDV) or regurgitant fraction. Seven hundred and five (mean age 70 years, 75% male) were classified as proportionate MR, and 889 (mean age 72 years, 60% male) had disproportionate MR. There was no significant association between MR proportionality (by EROA:LVEDV) and ACM (RR 0.79, 95% confidence interval [CI] 0.44-1.42). Proportionality did not significantly associate with ACM/ HFH, though there were divergent effect signals when proportionality was measured by EROA:LVEDV (RR 0.80, 95% CI 0.45-1.44 ) or regurgitant fraction (RR 1.48, 95% CI 0.53-4.11). Disproportionate MR showed a greater association with residual MR > 2+ post -TEER that did not meet statistical significance (RR 1.86, 95% CI 0.77-4.49 ). Conclusions: In patients undergoing TEER for functional mitral regurgitation, MR proportionality was not significantly associated with ACM/HFH, all-cause mortality, or residual MR.