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

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.

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.

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.

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.

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.