Tumor Necrosis Factor-α Predicts Response to Cardiac Resynchronization Therapy in Patients With Chronic Heart Failure

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-alpha (TNF-alpha) 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-alpha did correlate with LVESV reduction (P=0.001) after CRT. The subject group was divided according to tertiles of TNF-alpha. 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-alpha 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-alpha 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.