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Purpose: We tested the impact of dyssynchrony measured by cross-correlation analysis (XCA) in relation to long-term outcome and compared this method to other parameters of longitudinal dyssynchrony. In addition, we investigated the predictive ability of XCA according to QRS. Method: 131 consecutive patients with standard criteria for CRT were prospectively enrolled from two centres. Mechanical dyssynchrony was determined from TDI velocity curves by time-to-peak opposing wall delay OWD ≥ 80 ms, Yu index ≥ 32 ms and maximal activation delay (AD-max) > 35 ms. AD-max was calculated by XCA from the TDI-derived myocardial acceleration curves. Outcome was defined as death or left ventricular assist device (LVAD) implantation and modeled using Cox proportional hazards regression. Follow-up was truncated at 1460 days.Results: Of 121 patients (92%) with adequate image quality, 29 patients died and 1 received LVAD implantation. AD-max > 35 ms was independently associated with survival; HR 2.7, 95% CI [1.14–6.18], (P=0.02). AD-max performed significantly better than Yu index and OWD (P < 0.05, all). Patients without dyssynchrony and QRS between 120-150 ms showed a particularly poor survival when compared to groups with dyssynchrony (for AD-max > 35 ms and QRS between 120 ms - 150 ms; HR [CI 95% ] = 3.9 [1.13–13.6], P = 0.03 and for AD-max > 35 ms and QRS > 150 ms; HR [CI 95% ] = 4.3 [1.65–11.2], P< 0.003).Conclusion: Mechanical dyssynchrony assessed by XCA was predictive of long-term survival after CRT and superior to TDI-derived indices of longitudinal dyssynchrony. Furthermore, patients without dyssynchrony and QRS between 120- 150 ms had a particularly poor prognosis. These results indicate a valuable role for assesment of longitudinal dyssynchrony by XCA in selection of CRT candidates.