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Various dyssynchrony indexes derived from tissue velocity and strain imaging have been proposed to predict the effectiveness of cardiac resynchronization therapy (CRT). We sought to compare the effect of CRT on dyssynchrony indexes derived by tissue velocity and strain and to determine which baseline intraventricular dyssynchrony parameters correlate with improvement in left ventricular volume after CRT.Echocardiography with tissue Doppler imaging was performed in 45 patients with systolic heart failure at baseline, 1 day after CRT, and a median of 6 months after CRT. We calculated septal–lateral delay and anteroseptal–posterior delay and standard deviation of time to peak systolic velocity in the 12 basal and mid-left ventricular segments (Tv-SD). The standard deviation for time to peak strain in the 12 basal and mid-left ventricular segments (Tε-SD) was calculated as a strain-derived dyssynchrony index. None of the tissue velocity–derived dyssynchrony indexes improved after CRT (septal–lateral delay, P=0.39; anteroseptal–posterior delay, P=0.46; Tv-SD, P=0.30), whereas Tε-SD decreased significantly after CRT (P<0.001). Improvement in Tε-SD 1 day after CRT correlated with the reduction in end-systolic volume at follow-up (r=0.66; P<0.001). Baseline Tε-SD demonstrated significant correlation with the reduction of end-systolic volume at follow-up (r=0.57; P<0.001); however, baseline tissue velocity–derived dyssynchrony indexes failed to predict the effect of CRT.The strain-derived dyssynchrony index is a better measurement than the tissue velocity dyssynchrony index for monitoring changes in mechanical dyssynchrony after CRT and for predicting reduction in left ventricular volume after CRT.