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The influence of location and extent of transmural scar and its relation with dyssynchrony in cardiac resynchronization therapy (CRT) was investigated as posterolateral scar tissue has been invoked as a cause of non-response to CRT.Fifty-seven patients eligible for CRT were assessed for transmural scar with gadolinium-enhanced MRI and for left ventricular (LV) dyssynchrony with tissue Doppler. After implant, both atrioventricular and interventricular pacing intervals were optimized. LV reverse remodeling was defined as ≥10% decrease in LV end-systolic volume after 3 months. Sixteen patients had transmural scar in the posterolateral (PL) area (LV lead location), 14 at a remote site (non-PL) and 27 patients had no scar. LV reverse remodeling was observed in respectively 25%, 64% and 89% (P=0.0001). Univariate analyses showed a relation with LV dyssynchrony (P=0.004) and with absence of PL scar (P=0.04) but not with QRS duration and the extent of LV scar tissue. In multivariate analysis, only LV dyssynchrony (OR: 19.62; 95% CI: 2.5–151.9; P=0.004) independently predicted LV reverse remodeling.In this study LV dyssynchrony remains the most important determinant of response to CRT, even in the presence of posterolateral scar provided atrioventricular and interventricular pacing intervals are optimized.