P1763 Impact of disproportionate functional mitral regurgitation

Background Application of the effective regurgitant orifice area (EROA) and regurgitant volume (RegVol) is potentially limited as such lesion-focused metrics inevitably lack flexibility to account for the heterogeneity of left ventricular size and function. A recently proposed conceptual framework seeks to rearrange EROA and RegVol cut-offs according to left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF), introducing the novel term "disproportionate FMR" to describe clinically meaningful FMR. Methods To test the impact of disproportionate FMR, we embedded data of 291 heart failure patients with reduced ejection fraction (HFrEF) under guideline directed therapy (GDT) into this framework. Regurgitant Volume and EROA were plotted against LVEDV using bubble plots that also account for the heterogeneity of EF (Figure 1 A and C). The black lines depict a regurgitant fraction (RegFrac) of 50% at the median EF (25%) or Vmax (4.3m/s) of the study population. Thus, above individual center lines (illustrated by different bubble sizes) FMR severity is disproportionate, within the area of measurement uncertainty it is proportionate to LV dilation and below, it is likely non-severe. The degree of uncertainty of proportionate FMR is determined by the imprecision of the measurements defined as 2SDs of regurgitant fraction (±6.6%) per Bland-Altmann analysis. Results During a median follow-up of 84 months (IQR 84-136), 166 patients died. Disproportionate FMR was associated with excess mortality (RegVol: HR 1.97, 95%CI 1.38-2.81, P < 0.001; EROA: HR 2.22, 95%CI 1.52-3.22), whereas proportionate FMR was not associated with increased long-term mortality (RegVol: HR 1.04, 95%CI 0.71-1.53, P = 0.83; EROA: HR 1.06, 95%CI 0.71-1.58, P = 0.79; Figure 1B&D). Conclusions In this contemporary HFrEF cohort every fifth patient has disproportionate FMR which conveys a two-fold increased risk of mortality which provides evidence for the validity of the conceptual framework. Advancement of the proposed framework to clinical practice has several implications: 1)EROA and RegVol are metrics that do not account for the contextual variability of LVEDV and EF. 2)The RegFrac -not incorporated in ESC guidelines but integrated in AHA/ACC definitions- provides a metric proportionated to left ventricular size and function supporting its use to define relevant FMR. However, technical limits suggest its complementary use on top of more robust metrics such as EROA and RegVol. Future studies need to clarify whether disproportionate FMR reflects the subgroup of patients that benefit from mitral valve repair, and provide a robust algorithm that integrates the metrics of FMR severity in a complementary manner. Abstract P1763 Figure.