Atrial Functional Mitral Regurgitation: Effect of Phenotype Definition on Classification, Valve Features, and...

Atrial functional mitral regurgitation (AfMR) is a distinct entity of functional mitral regurgitation (fMR) with substantial clinical implications. Variation among published definitions introduces uncertainty regarding prevalence, morphology, and mortality, precluding consistent clinical decision making. A JACC Expert Consensus proposed a definition that was recently challenged by the European Society of Cardiology (ESC) valve guidelines. A unified, broadly applicable definition requires systematic evaluation of existing criteria.

The authors undertook sensitivity analyses of previously published AfMR definitions regarding classification, valve features, population characteristics, and prognosis, with a particular focus on the JACC Expert Consensus and the ESC guidelines definitions.

PubMed, Embase, and Web of Science were systematically searched for publications on AfMR. All identified definitions were applied to an independent single-center database of severe fMR patients (n = 581). Moderate fMR (n = 6,755) served as comparator group. Sensitivity analyses evaluated the robustness of results across definition specifications.

Seventy-two unique AfMR definitions were identified. There was considerable variability in prevalence (2%-62%), valve features (annular diameter: 31.5-37.1 mm; tenting area: 146-229 mm²; Carpentier classification IIIb: 0%-49%), and outcome (HR: 1.17-2.42). Clustering by ejection fraction, left atrial dilation, and atrial fibrillation demonstrated that conceptually similar definitions frequently classified distinct populations. The JACC and ESC definitions showed similar overall prevalence but defined heterogeneous populations with differences in left atrial thresholds (40 mL/m² in JACC vs 34 mL/m² in ESC) and inclusion of 25% Carpentier IIIb cases with JACC (ESC: Carpentier type I only). Both were associated with higher mortality vs moderate fMR (JACC HR: 2.08 [95% CI: 1.42-3.04; P < 0.001]; ESC HR: 1.88 [95% CI: 1.26-2.82; P = 0.002]). After multivariate adjustment and correction for multiple testing, the JACC Expert Consensus definition remained significant, whereas the ESC guidelines definition did not.

AfMR definitions show considerable variability in prevalence, valve features, and prognostic performance. Although the ESC guidelines and JACC Expert Consensus definitions yield similar prevalence, the JACC definition demonstrated robust prognostic validity and adaptability to a wider morphologic spectrum, including restrictive posterior leaflet (Carpentier IIIb) configurations. The robustness and flexibility indicate that the JACC definition provides a solid foundation for a unified, clinically applicable AfMR definition.