Background:Pro-inflammatory cytokines contribute to the pathophysiology of heart failure (HF) and are up-regulated in affected patients. We investigated whether pro-inflammatory cytokines might predict the response to cardiac resynchronization therapy (CRT).Methods and Results:Plasma levels of tumor necrosis factor-α (TNF-α) and interleukin-6 were assessed in 91 patients before CRT. Response to CRT was defined as a decrease ≥15% in left ventricular end-systolic volume (LVESV) at 6 months. Baseline TNF-α did correlate with LVESV reduction (P=0.001) after CRT. The subject group was divided according to tertiles of TNF-α. From the lower to the upper tertile LVESV (–31±28%, –17±17%, –9±22%) and LV end-diastolic volume (–23±25%, –14±16%, –4±18%) were progressively less reduced after CRT (P<0.001). The proportion of responders to CRT was 70%, 42% and 33%, according to the lower, intermediate and upper tertile of TNF-α distribution (P=0.01). Serious cardiac events (cardiac death, HF hospitalization or urgent heart transplantation) occurred in 63% of patients in the upper tertile vs. 32% and 17% in the intermediate and lower tertiles, respectively, during a median follow-up of 47 months (P<0.001).Conclusions:Circulating TNF-α predicts the degree of LV reverse remodeling after CRT and may contribute to the early identification of those patients at higher risk of events after device implantation. (Circ J 2014; 78: 2232–2239)