Changes and Prognostic Impact of Apoptotic and Inflammatory Cytokines in Patients Treated with Cardiac Resynchronization Therapy

OBJECTIVES: In patients with heart failure, increased apoptosis, inflammation and activation of the transforming growth factor (TGF)-β cytokine system have been documented. The aim of the present study was to establish (i) whether cytokine concentrations decrease in patients who respond to cardiac resynchronization therapy (CRT), and (ii) whether pre-implant values have any prognostic value. METHODS: Eighty-one CRT candidates were prospectively studied. The success of CRT was assessed based on clinical and echocardiographic improvement 6 months after implantation. Mortality was assessed 2 years after implantation. Blood samples were drawn before and 6 months after implantation. Serum concentrations of Fas, TNF-related apoptosis-inducing ligand, tumor necrosis factor (TNF)-α, TNF-receptor 1, TGF-β1 and interleukin (IL)-6 were measured using ELISA. RESULTS: At 6 months, 46 (56.8%) patients were classified as responders and 35 (43.2%) as nonresponders. Neither group differed with respect to baseline characteristics. In responders, the concentrations of IL-6, TNF-α and TGF-β1 decreased significantly. In nonresponders, the concentration of TGF-β1 even increased significantly. In multivariate analysis, the concentration of TGF-β1 was a significant predictor of death during follow-up. CONCLUSIONS: The response to CRT implantation was associated with a decrease of TGF-β1, IL-6 and TNF-α. Higher pre-implant concentrations of TGF-1β were independently associated with a poor prognosis in CRT patients.