Mechanical dyssynchrony and functional mitral regurgitation: pathophysiology and clinical implications

Functional mitral regurgitation (FMR) is a common finding in patients with ischemic or nonischemic dilated cardiomyopathy as a complication of left ventricular (LV) dysfunction and remodeling associated with a fibrotic remodeling response of mitral leaflets to abnormal valvular loading. Although mitral valve tenting is the main determinant of FMR, clinical and experimental observations suggest that intraventricular delay could be a potential co-determinant of FMR. LV dyssynchrony can potentially contribute to FMR by several mechanisms, such as creating an uncoordinated regional LV mechanical activation in segments supporting the papillary muscles, determining diastolic mitral regurgitation, reducing the sphincteric function of the mitral annulus, and decreasing the efficiency of LV contraction and closing forces. Cardiac resynchronization therapy has been demonstrated to reduce FMR with correction of some of the underlying pathophysiological mechanisms. The present review article Introduction Functional mitral regurgitation (FMR) is a common finding in patients with ischemic or nonischemic dilated cardiomyopathy as a complication of left ventricular (LV) dysfunction and remodeling associated with a fibrotic remodeling response of mitral leaflets to abnormal valv- ular loading [1,2]. It is well known that systolic valvular tenting is the main determinant of FMR, due to apical and posterior papillary muscle displacements, whereas mitral annular dilatation and reduced LV contraction play an additional role [3 – 5]. Several clinical and experimen- tal observations, however, have hypothesized that intra- ventricular delay could be a potential co-determinant of FMR. The presence of isolated left bundle branch block in asymptomatic patients is related to mechanical dyssyn- chrony and deformation of the mitral valve (MV) appar- atus [6]. In patients with dilated left ventricles, both the degree and duration of FMR are highly correlated with prolonged QRS duration [7,8]. Moreover, left bundle branch block, but not right bundle branch block, is strongly associated with FMR. Right ventricular pacing, which causes conduction abnormalities with a similar focuses on the role of mechanical dyssynchrony as a pathophysiological determinant of FMR, and on the potential role of cardiac resynchronization therapy as a therapeutic option for treatment of FMR in patients with severe heart failure and advanced LV dysfunction.