Background-In patients with severe heart failure and dilated cardiomyopathy, cardiac resynchronization therapy (CRT) improves left ventricular (LV) systolic function associated with LV reverse remodeling and favorable 1-year survival. However, it is unknown whether LV reverse remodeling translates into a better long-term prognosis and what extent of reverse remodeling is clinically relevant, which were investigated in this study. Methods and Results-Patients (nϭ141) with advanced heart failure (meanϮSD age, 64Ϯ11 years; 73% men) who received CRT were followed up for a mean (ϮSD) of 695Ϯ491 days. The extent of reduction in LV end-systolic volume (LVESV) at 3 to 6 months relative to baseline was examined for its predictive value on long-term clinical outcome. The cutoff value for LV reverse remodeling in predicting mortality was derived from the receiver operating characteristic curve. Then the relation between potential predictors of mortality and heart failure hospitalizations were compared by Kaplan-Meier survival analysis, followed by Cox regression analysis. There were 22 (15.6%) deaths, mostly due to heart failure or sudden cardiac death. The receiver operating characteristic curve found that a reduction in LVESV of Ն9.5% had a sensitivity of 70% and specificity of 70% in predicting all-cause mortality and of 87% and 69%, respectively, for cardiovascular mortality. With this cutoff value, there were 87 (61.7%) responders to reverse remodeling. In Kaplan-Meier survival analysis, responders had significantly lower all-cause morality (6.9% versus 30.6%, log-rank 2 ϭ13.26, Pϭ0.0003), cardiovascular mortality (2.3% versus 24.1%, log-rank 2 ϭ17.1, PϽ0.0001), and heart failure events (11.5% versus 33.3%, log-rank 2 ϭ8.71, Pϭ0.0032) than nonresponders. In the Cox regression analysis model, the change in LVESV was the single most important predictor of all-cause (␤ϭ1.048, 95% confidence intervalϭ1.019 to 1.078, Pϭ0.001) and cardiovascular (␤ϭ1.072, 95% confidence intervalϭ1.033 to 1.112, PϽ0.001) mortality. Clinical parameters were unable to predict any outcome event. Conclusions-A reduction in LVESV of 10% signifies clinically relevant reverse remodeling, which is a strong predictor of lower long-term mortality and heart failure events. This study suggests that assessing volumetric changes after an intervention in patients with heart failure provides information predictive of natural history outcomes. (Circulation. 2005;112:1580-1586.)

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