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Background-MitraClip has been shown to reduce mitral regurgitation (MR) severity safely but to a lesser degree than surgery. No data exist on the magnitude of MR reduction necessary to reverse left ventricular (LV) and left atrial (LA) dilation in patients with severe MR. Therefore, an analysis was performed to evaluate the relationship between MR reduction and LV and LA volumes after MitraClip therapy. Methods and Results-A total of 801 patients treated with MitraClip and 80 patients treated surgically were included. All patients had severe (3-4+) MR. MR severity, LV volumes at end-diastole and end-systole, and LA volumes were measured at baseline, discharge, 30 days, 6 months, and 1 year by an independent echocardiographic core laboratory. A linear repeated measures model was developed to determine the relationship between MR severity and time of measurement postindex procedure on longitudinal LV and LA volumes. Separate models were fit for functional MR and degenerative MR. In both degenerative and functional MR, reduction in LV volumes at end-diastole was associated with degree of residual MR at 12 months (P<0.0001). LV volumes at end-systole was significantly reduced in functional MR but not degenerative MR. LA volumes were significantly related to reduction of MR severity in both groups. Conclusions-Reduction of LV volumes at end-diastole and LA volumes, but not LV volumes at end-systole in degenerative MR, is consistent with correction of volume overload from primary MR. Reduction of all 3 measurements in functional MR demonstrates reverse remodeling when MR severity is reduced to either 1+ or 2+ by MitraClip therapy. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00209274.