BACKGROUND: Recent advances in three-dimensional (3D) echocardiography allow us to address uniquely 3D scientific questions, such as the mechanism of functional mitral regurgitation (MR) in patients with left ventricular (LV) dysfunction and its relation to the 3D geometry of mitral leaflet attachments. Competing hypotheses include global LV dysfunction with inadequate leaflet closing force versus geometric distortion of the mitral apparatus by LV dilatation, which increases leaflet tethering and restricts closure. Because geometric changes generally accompany dysfunction, these possibilities have been difficult to separate. METHODS AND RESULTS: We created a model of global LV dysfunction by esmolol and phenylephrine infusion in six dogs. initially with LV expansion limited by increasing pericardial restraint and then with the pericardium opened. The mid-systolic 3D relations of the papillary muscle (PM) tips and mitral valve were reconstructed. Despite severe LV dysfunction (ejection fraction, 18+/-6%), only trace MR developed when pericardial restraint limited LV dilatation; with the pericardium opened, moderate MR accompanied LV dilatation (end-systolic volume, 44+/-5 mL versus 12+/-5 mL control, P<.001). Mitral regurgitant volume and orifice area did not correlate with LV ejection fraction and dP/dt (global function) but did correlate with changes in the tethering distance from the PMs to the anterior annulus derived from the 3D reconstructions, especially PM shifts in the posterior and mediolateral directions, as well as with annular area (P<.0005). By multiple regression, only changes in the PM-to-annulus distance independently predicted MR volume and orifice area (R2=.82 to .85, P=2x10(-7) to 6x10(-8)). CONCLUSIONS: LV dysfunction without dilatation fails to produce important MR. Functional MR relates strongly to changes in the 3D geometry of the mitral valve attachments at the PM and annular levels, with practical implications for approaches that would restore a more favorable configuration.