P5573Disproportionate functional mitral regurgitation: advancing a conceptual framework from bench to bedside

Introduction A recently proposed conceptual framework seeks to rearrange the effective regurgitant orifice area (EROA) and regurgitant volume (RegVol) cut-offs according to left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) in functional mitral regurgitation introducing “disproportionate FMR” to describe clinically meaningful FMR. The conceptual framework, however, remains hypothetical. Purpose To test the significance of disproportionate FMR. Methods Data of 291 heart failure patients with reduced ejection fraction (HFrEF) under guideline directed therapy were embedded into this conceptual framework (Figure 1A). The black line represents the relationship when the degree of FMR is proportionate to LVEDV with a regurgitant fraction of (RegFrac) of 50%. The dashed lines represent the degree of uncertainty determined by the imprecision inherent to the measurement of RegFrac defined as 2SD for inter- and intraobserver variability by Bland-Altmann analysis (equals ±6.6%). Cox-regression and Kaplan-Meier analysis were applied to assess the association between FMR proportionality and mortality. Results Median age was 68 years (IQR 61–75), 77% were male. Median LVEF was 25% (IQR 18–33) and LVEDV was 214ml (IQR 165–267). Disproportionate FMR was present in 71 patients (24%) (red dots Figure 1A) with a median EROA of 0.26cm2 (IQR 0.18–0.34) and a median RegVol of 42ml (IQR 28–52), proportionate FMR (yellow dots Figure 1 A) in 81 patients (28%) with a median EROA of 0.12cm2 (IQR 0.09–0.17) and a median RegVol of 18ml (IQR 14–27). During 7-years follow-up, 166 patients died. Disproportionate FMR was associated with excess mortality compared to patients with non-severe FMR (HR 1.97, 95% CI 1.04–0.71, P<0.001), whereas proportionate FMR was not associated with increased long-term mortality (HR 1.04, 95% CI −1.53–0.71, P=0.83, Figure 1B). Figure 1. Panel A and B Conclusion Every fifth patient suffers from disproportionate FMR which conveys a two-fold increased risk of mortality. Disproprtionate FMR corresponds to an EROA of roughly 0.3cm2 and a RegVol of 45ml – the unifying intersection between ESC and ACC/AHA guidelines to define severe FMR. The RegFrac provides a measure proportionated to left ventricular size and function supporting its use to define clinically relevant FMR. However, RegFrac is subject to compound error due to imputation of multiple measurements limiting its use as the leading contender for FMR grading. Regardless of the term used to describe clinically significant FMR, the conceptual framework emphasizes the unmet clinical need for recalibrated cut-offs for FMR severity condensed to an algorithm that combines the strengths of several measurements of FMR severity in an integrated manner.