Societal definitions of VfMR and their impact on prevalence, valve morphology and prognosis

Background/Introduction

Functional mitral regurgitation (fMR) in the setting of heart failure (HF) is a heterogeneous condition. The 2025 ESC Guidelines on Valvular Heart Disease and the 2022 JACC Expert Consensus introduced distinct criteria for ventricular fMR (VfMR). The implications of these definitional differences in patient selection and prognosis remain unclear.

Purpose

To compare prevalence, baseline characteristics, and long-term prognostic impact of both VfMR definitions in patients with severe fMR.

Methods

Both societal VfMR definitions were applied to a comprehensive database of 1163 patients with severe fMR; moderate fMR (n=7890) served as reference group. Survival was assessed using Kaplan-Meier estimates and Cox proportional hazard regression. Multivariable models were adjusted for common clinical risk-factors. The primary endpoint was all-cause mortality.

Results

ESC criteria classified 42.1% of severe cases as VfMR versus 66.2% by JACC (Figure 1). JACC-defined VfMR patients were slightly older (70 vs. 67 years) and more frequently female (32% vs. 23%), with comparable comorbidities and NT-proBNP levels. ESC-defined VfMR more often comprised patients with HF with reduced ejection fraction (84% vs. 66%), whereas the JACC definition also included a small proportion with HF with preserved ejection fraction (3% vs. 0%).

Cardiac remodeling was more advanced in the ESC cohort with larger indexed LA volumes (52 vs. 42 ml/m²) and LV end-diastolic volumes (109 vs. 86 ml/m²). Furthermore, mitral annular diameters were greater (4-CV: 41.4 vs. 38.2 mm; 3-CV: 36.5 vs. 33.8 mm), as were tenting height (4-CV: 9.3 vs. 8.3 mm; 3-CV: 12.4 vs. 11.2 mm) and tenting area (4-CV: 229 vs. 182 mm²; 3-CV: 261 vs. 222 mm²). Leaflet tethering angles were comparable.

Both ESC- and JACC-defined VfMR were associated with increased mortality (Figure 2) compared with moderate fMR (ESC: HR 1.58, 95% CI 1.33-1.89; JACC: HR 1.52, 95% CI 1.35-1.71; both p<0.001). After adjustment, associations remained significant and were more pronounced for ESC-defined VfMR (ESC: adjusted HR 1.81, 95% CI 1.44-2.29; JACC: adjusted HR 1.46, 95% CI 1.23-1.74; both p<0.001).

Conclusions

JACC criteria identify a broader VfMR population, whereas ESC criteria define a smaller but higher-risk subgroup with more advanced remodeling and stronger mortality association. These findings suggest greater prognostic specificity of the ESC definition with potential implications for risk stratification and timing of intervention. Nevertheless, both definitions consistently identify a subgroup of fMR with significantly impaired long-term survival compared with moderate fMR. These findings highlight the prognostic relevance of contemporary VfMR definitions and underscore the need for harmonisation of classification criteria.Figure 1:Pie ChartsFigure 2:Kaplan-Meier Curves