BackgroundOptimal lead positioning is an important determinant of cardiac resynchronization therapy (CRT) response.ObjectiveThe purpose of this study was to evaluate cardiac computed tomography (CT) selection of the optimal epicardial vein for left ventricular (LV) lead placement by targeting regions of late mechanical activation and avoiding myocardial scar.MethodsEighteen patients undergoing CRT upgrade with existing pacing systems underwent preimplant electrocardiogram-gated cardiac CT to assess wall thickness, hypoperfusion, late mechanical activation, and regions of myocardial scar by the derivation of the stretch quantifier for endocardial engraved zones (SQUEEZ) algorithm. Cardiac venous anatomy was mapped to individualized American Heart Association (AHA) bull’s-eye plots to identify the optimal venous target and compared with acute hemodynamic response (AHR) in each coronary venous target using an LV pressure wire.ResultsFifteen data sets were evaluable. CT-SQUEEZ–derived targets produced a similar mean AHR compared with the best achievable AHR (20.4% ± 13.7% vs 24.9% ± 11.1%; P = .36). SQUEEZ-derived guidance produced a positive AHR in 92% of target segments, and pacing in a CT-SQUEEZ target vein produced a greater clinical response rate vs nontarget segments (90% vs 60%).ConclusionPreprocedural CT-SQUEEZ–derived target selection may be a valuable tool to predict the optimal venous site for LV lead placement in patients undergoing CRT upgrade.