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Background: The present study was designed to evaluate the respective value of left ventricular (LV) reverse remodeling (changes in LV end-systolic volume relative to baseline (ΔLVESV)) or LV performance improvement (ΔLV ejection fraction (ΔLVEF) or ΔGlobal longitudinal strain (GLS)) to predict long-term outcome in a prospective cohort of consecutive patients receiving routine cardiac resynchronization therapy (CRT)., Methods: One hundred and seventy heart failure patients (NYHA classes II-IV, LVEF ≤ 35%, QRS width ≥ 120 ms) underwent echocardiography before and 9 months after CRT. The relationships between ΔLVESV, ΔLVEF, ΔGLS and outcome (all-cause mortality and/or CHF hospitalization, overall mortality, cardiovascular mortality, CHF hospitalization) were investigated., Results: During a median follow-up of 32 months, 20 patients died and 27 were hospitalized for heart failure. ΔLVESV, ΔLVEF or ΔGLS were significantly associated with all-cause mortality or CHF hospitalization (adjusted hazard's ratio (HR) per standard deviation 0.58 (0.43-0.77), 0.39 (0.27-0.57) or 0.55 (0.37-0.83) respectively, all p < 0.01) and all other endpoints (all p < 0.01). Patients with ΔLVESV≥15%, ΔLVEF ≥ 10% and ΔGLS ≥ 1% had a reduced risk of mortality or CHF hospitalization (adjusted HR=0.25 (0.12-0.51), p < 0.001, adjusted HR = 0.26 (0.13-0.54), p < 0.001 and adjusted HR 0.38 (0.19-0.75), p = 0.006 respectively). Overall performance of multivariate models was better using ΔLVESV or ΔLVEF compared with ΔGLS. Interobserver agreement was excellent for ΔLVESV (Intraclass correlation coefficient - ICC-0.91) and ΔGLS (ICC 0.90) but modest for ΔLVEF (ICC 0.76) in a sample of 20 patients from the study population., Conclusions: LV reverse remodeling assessed by ΔLVESV is a strong and reproducible predictor of outcome following CRT. Compared with ΔLVESV, ΔLVEF and ΔGLS have important shortcomings: poorer reproducibility or lower predictive value., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)