Profiles of Comprehensive Morphological Phenotypes and Outcomes in Functional Mitral Regurgitation

Current guidelines do not include phenotypical classifications in functional mitral regurgitation (FMR).

The study sought to classify FMR into 3 morphological phenotypes and assess determinants of mortality.

We included patients with ≥moderately severe FMR from 2 tertiary centers. FMR was classified as ventricular functional mitral regurgitation with symmetrical tethering (VFMRst), ventricular functional mitral regurgitation with asymmetrical tethering (VFMRat), or atrial functional mitral regurgitation (AFMR). The primary composite endpoint was cardiovascular death and death equivalent (ie, left ventricular assist device implantation or heart transplantation).

Of 699 patients (70 years [Q1-Q3: 60-79 years], 46% female), VFMRst was the most prevalent (54%). VFMRat exhibited larger mitral regurgitation vena contracta (7.7 mm [Q1-Q3: 7-8.7 mm] vs 7.3 mm [Q1-Q3: 6.7-8.2 mm]) but smaller left ventricular end-diastolic volume index (100 mL/m² [Q1-Q3: 83-128 mL/m²] vs 106 mL/m² [Q1-Q3: 88-132 mL/m²]) than VFMRst (both P ≤ 0.037). AFMR with hamstrung posterior mitral valve (MV) exhibited larger left atrial volume index (96 mL/m² [Q1-Q3: 77-145 mL/m²] vs 78 mL/m² [Q1-Q3: 63-97 mL/m²]) and mitral regurgitation vena contracta (7.5 mm [Q1-Q3: 6.8-8.6 mm] vs 7.0 mm [Q1-Q3: 6.4-8.2] mm) than AFMR with central MV malcoaptation (both P ≤ 0.010). At a median follow-up of 2.6 years (Q1-Q3: 0.9-5 years), 193 primary endpoints occurred. Five-year event-free survival was higher in AFMR (71% ± 4%) than VFMRst (64 ± 3%) and VFMRat (63 ± 4%) (P ≤ 0.030), but adjusted outcomes were similar across groups (all P ≥ 0.139). Besides conventional markers, multivariable models demonstrated that low diastolic blood pressure (DBP), left atrial reservoir strain (LASr), and left ventricular longitudinal strain from the apical 4-chamber view (A4C-LVLS) independently linked to primary endpoints (all P ≤ 0.043). Adjusted spline curves showed increased primary endpoint risk with DBP ≤73.7 mm Hg, LASr ≤14.8%, and A4C-LVLS ≤9.3%.

VFMRat exhibited more disproportionate features than VFMRst. AFMR with hamstrung posterior MV may indicate a more advanced disease stage. Morphological phenotypes alone were not associated with adjusted outcomes. LASr, A4C-LVLS, and DBP may assist in risk stratification in FMR.