Functional mitral regurgitation (FMR) occurs with a structurally normal valve as a complication of systolic left ventricular dysfunction (LVD). Determinants of degree of FMR are poorly defined; thus, mechanistic therapeutic approaches to FMR are hindered. In a prospective study of 21 control subjects and 128 patients with LVD (defined as ejection fraction <50%, mean 31+/-9%) in sinus rhythm, we quantified simultaneously by echocardiography the effective regurgitant orifice (ERO) of FMR by using 2 methods: mitral deformation (valve and annulus) and left ventricular (LV) global (volumes, stress, function, and sphericity) and local (papillary muscle displacements and regional wall motion index) remodeling. A wide range of ERO (15+/-14 mm(2), 0 to 87 mm(2)) was observed, unrelated to ejection fraction (P:=0.32). The major determinant of ERO was mitral deformation, ie, systolic valvular tenting and annular contraction in univariate (r=0.74 and r=-0.61, respectively; both P:<0.0001) and multivariate (both P:<0. 0001) analyses, independent of global LV remodeling. Systolic valvular tenting was strongly determined by local LV alterations, particularly apical (r=0.75) and posterior (r=0.70) displacement of papillary muscle, with confirmation in multivariate analysis (both P:<0.0001), independent of LV volumes, function, and sphericity. The presence and degree of FMR complicating LVD are unrelated to the severity of LVD. Local LV remodeling (apical and posterior displacement of papillary muscles) leads to excess valvular tenting independent of global LV remodeling. In turn, excess tenting and loss of systolic annular contraction are associated with larger EROs. These determinants of FMR warrant consideration for specific approaches to the treatment of FMR complicating LVD.