OBJECTIVE : Despite the well-established benefits of cardiac resynchronization therapy (CRT) in heart failure (HF) patients with left ventricular ejection fraction (LVEF) ≤35%, many patients with less reduced EF remain refractory to optimized medical treatment and at high risk of morbidity and mortality. The objective of the study is to evaluate the effects of CRT in optimally treated patients with New York Heart Association (NYHA) classes II-IV, LVEF of 36-45%, and left bundle branch (LBBB), including clinical, structural and biochemical response. METHODS : A selected group of HF patients have been implanted with CRT-P devices and were followed up for 6 months at 4, 12 and 24 weeks. Clinical assessment included NYHA class, quality of life and 6-min walk distance (6 MWD) test. Echocardiographic assessment included LV dimensions and function and left atrial volume. Serum N-terminal pro b-type natriuretic peptide (NT-ProBNP) was measured at the same intervals. RESULTS : This prospective single center study included 23 patients. NYHA functional class significantly improved after CRT-P (p < 0.0001), associated with improvement in QOL (p < 0.0001) and 6 MWD, which increased, from 145.7 ± 20.1 m to 219.5 ± 42.2 m (p < 0.0001). Mean QRS duration showed significant shortening from 164.4 ± 13.2 ms to 126.4 ± 13.6 ms (p < 0.0001). CRT induced reverse remodeling with reduction in both left ventricular end diastolic diameter (LVEDD) from 68.95 ± 5.05 mm to 62.8 ± 4.47 mm, p = 0.0002 and left ventricular end systolic diameter (LVESD) from 54.1 ± 4.5 mm to 46.5 ± 4.1 mm, p < 0.0001, and significant increase in LVEF (from 40.3 ± 2.8 to 48.3 ± 4.2 mm, p < 0.0001). The biochemical response to CRT showed significant reduction in serum NT-ProBNP from 1025.6 ± 363.1 pg/ml to 594.9 ± 263.5 pg/ml (p < 0.0001). CONCLUSIONS : Symptomatic HF patients on maximal optimized medical treatment who have LBBB and baseline LVEF 35-45% appeared to derive significant clinical and structural benefit from CRT.