Papillary Muscle Dyssynchrony-Mediated Functional Mitral Regurgitation: Mechanistic Insights and Modulation by Cardiac Resynchronization

Abstract

Objectives: This study sought to define interpapillary muscle dyssynchrony as a major contributing factor in functional mitral regurgitation (FMR) and prove the reversibility of FMR by interpapillary muscle resynchronization.

Background: Mechanistic features of FMR include papillary muscle displacement due to left ventricular remodeling. Intraventricular conduction delay might further augment this condition by introducing interpapillary muscle dyssynchrony.

Methods: We enrolled 269 chronic heart failure with reduced ejection fraction patients with conduction delay and comprehensively assessed dyssynchrony by complementary echocardiographic techniques covering the entire spectrum of dyssynchrony.

Results: Patients with severe FMR had markedly increased interpapillary longitudinal dyssynchrony (160 ms [interquartile range (IQR): 120 to 200 ms]) compared with those with moderate (70 ms [IQR: 40 to 110 ms]), no, or mild FMR (60 ms [IQR: 30 to 100 ms]; p < 0.001). Increased interpapillary muscle dyssynchrony was correlated with regurgitant volume (r = 0.50; p < 0.001) and vena contracta width (r = 0.49; p < 0.001). Restoration of longitudinal papillary muscle synchronicity by cardiac resynchronization therapy was correlated with FMR regression, as reflected by the reduction in regurgitant volume (r = 0.46; p < 0.001) and vena contracta width (r = 0.58; p < 0.001). Conversely, the improvement of FMR was associated with improved interpapillary radial (p = 0.006) and longitudinal (p < 0.001) dyssynchrony. The improvement of dyssynchrony-mediated FMR signified a better prognosis compared with no improvement in FMR during the 8-year follow-up period even after comprehensive adjustment by a bootstrap-selected confounder model (adjusted hazard ratio: 0.41; 95% confidence interval: 0.18 to 0.91; p = 0.028). The results remained virtually unchanged after adjustment for left bundle branch block.

Conclusions: Intraventricular dyssynchrony introduces unequal contraction by papillary muscle bearing walls, which has an adverse effect on FMR. Cardiac resynchronization therapy can effectively restore interpapillary balance and thus create a less tented leaflet configuration, resulting in a clinically meaningful reduction of FMR. The restoration of papillary muscle synchronicity in dyssynchrony-mediated FMR translates into a significantly better prognosis.

Keywords: dyssynchrony; functional mitral regurgitation; mitral regurgitation; papillary muscle; secondary mitral regurgitation.