The clinical value of quantitative echocardiography for functional mitral regurgitation in contemporary heart failure

Functional mitral regurgitation (FMR) in heart failure (HF) has evolved substantially with contemporary guideline-directed medical therapy (GDMT); given its prognostic impact, accurate quantification of FMR is critical for risk stratification. This study aims to compare pathophysiological correlates and prognostic role of different echocardiographic approaches to effective regurgitant orifice area (EROA) assessment. We prospectively enrolled consecutive chronic HF outpatients with left ventricular ejection fraction (LVEF) < 50% receiving optimized medical therapy. FMR was quantified using three echocardiographic methods: PISA-derived EROA (EROA-PISA), an indirect two-dimensional volumetric method (EROA-2DVol), and a novel indirect three-dimensional volumetric method based on an automated digital heart model (EROA-3DVol). The primary endpoint was a composite of HF-hospitalization or all-cause death. Among 157 patients, EROA-PISA correlated strongly with EROA-3DVol (R = 0.83, p < 0.0001) and moderately with EROA-2DVol (R = 0.53; p < 0.0001), showing robust associations with the clinical consequences of FMR and markers of cardiac remodeling. Over a median follow-up of 1,042 days, 42 patients reached the primary endpoint. When modeled as a continuous variable, only EROA-PISA (HR 1.08 per 0.1 cm² increase; 95% CI 1.04-1.12; p < 0.0001) and EROA-3DVol (HR 1.03 per 0.1-unit increase; 95% CI 1.01-1.06; p = 0.03) were significantly associated with outcomes. Regardless of the quantification method, the prevalence of FMR has declined compared to the past, driven by the contemporary GDMT. Accurate FMR quantification is crucial for prognostic stratification in a well-treated HF population. EROA-PISA remains the reference standard, while automated 3D volumetric assessment serves as a physiologically consistent complementary approach.