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Cardiac resynchronization therapy (CRT) elicits more beneficial effects on left-ventricular (LV) structure and function, and long-term clinical outcomes in nonischemic heart failure patients. Rates of β-blocker use in recent heart failure trials are higher than in CRT trials and this may influence the response to CRT. This study examined the long-term effects of CRT on LV structure and function in New York Heart Association class III–IV β-blocker-treated patients.One hundred and four (41 ischemic and 63 nonischemic) CRT patients, who were receiving β-blockers before and throughout 12 months following device implantation, were retrospectively selected. Variations in echocardiographic parameters recorded before, and 6 and 12 months after CRT were analyzed.Selected patients were all stable on β-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (97%) and diuretics (97%) before implantation. CRT was associated with significant improvements in LV morphological and systo-diastolic functional parameters at 6 months, with further improvements between 6 and 12 months seen in nonischemic patients only. Accordingly, rates of echocardiographic response to CRT were similar at 6 months but significantly higher in nonischemic patients after 1 year. The degree of reduction in LV diameters and volumes, and of increase in ejection fraction, was significantly larger in nonischemic patients at both 6 and 12 months. In addition, a significant reduction in LV mass and severity of mitral regurgitation was more evident in nonischemic patients both 6 and 12 months following CRT.Ischemic aetiology of heart failure is associated with less favorable long-term effects of CRT on LV structure and function despite the systematic use of β-blockers.