Adapting the concepts of proportionate and disproportionate functional mitral regurgitation to clinical practice

Funding Acknowledgements Type of funding sources: None. Background Despite its theoretical appeal, the concept of Proportionate and Disproportionate FMR has been limited by the lack of a simple way to assess it and by the paucity of data showing its prognostic superiority over currently established ways of grading FMR. Objectives This study sought to evaluate the prognostic value of a new and individualized method of assessing Functional Mitral Regurgitation (FMR) Proportionality. Methods Patients with at least mild FMR and reduced left ventricular ejection fraction (< 50%) under optimal guideline-directed medical therapy were retrospectively identified at a single-center. To determine FMR proportionality status, we used a novel approach where two simple equations establish an individual cut-off of regurgitant volume/effective regurgitant orifice area, categorizing the study population into non-severe, proportionate and disproportionate FMR (Figure 1). The primary endpoint was all-cause mortality. Results A total of 572 patients (median age 70 years; 76% male) were included. Median LVEF was 35% (IQR 28-40) and LVEDV was 169 ml (IQR 132-215). Disproportionate FMR was present in 109 patients (19%) with a median EROA of 26 mm2 (IQR 22-31) and a median RegVol of 40 ml (IQR 34-48), proportionate FMR in 148 patients (26%) with a median EROA of 16mm2 (IQR 12-21) and a median RegVol of 26 ml (IQR 19-32). During a median follow-up of 3.8 years (interquartile range: 1.8 to 6.2 years) there were 254 deaths (44%). The unadjusted mortality incidence per 100 persons-year rose as the degree of FMR disproportionality worsened. On multivariable analysis, disproportionate FMR remained independently associated with all-cause mortality (adjusted hazard ratio: 1.785; 95% confidence interval [CI]: 1.249 to 2.550; P = 0.001). The FMR proportionality concept showed greater discriminative power (C-statistic 0.639; 95% CI: 0.597 to 0.680) than the American (C-statistic 0.588; 95% CI: 0.550 to 0.626; P for comparison = .001) and European guidelines (C-statistic 0.563; 95% CI: 0.534 to 0.591; P for comparison < .001). It was also able to increase the net reclassification index (0.167 [P < 0.001] and 0.084 [P = 0.001], respectively). Conclusions A new, simplified and individualized method of assessing FMR Proportionality showed that disproportionate FMR is independently associated with all-cause mortality. This approach seems to outperform the risk stratification of current guidelines. Abstract Figure 1