Ongoing Myocardial Damage in Chronic Heart Failure is Related to Activated Tumor Necrosis Factor and Fas/Fas Ligand System

BACKGROUND: Elevated concentrations of cardiac troponin T and heart-type fatty acid-binding protein (H-FABP) identify patients with chronic heart failure (CHF) and ongoing myocardial damage (OMD) who are at increased risk for future cardiac events. Cardiomyocyte necrosis and/or apoptosis via activated tumor necrosis factor (TNF) and the Fas/Fas ligand (FasL) system may be related to the development of OMD. METHODS AND RESULTS: The serum concentrations of H-FABP, a sensitive marker of membrane damage of cardiomyocytes, soluble Fas (sFas) and TNF-alpha were measured in 38 patients with CHF. The concentrations of H-FABP, TNF-alpha and s-Fas in patients with New York Heart Association (NYHA) III + IV were all significantly higher than in those patients in NYHA II (H-FABP; III + IV 9.3+/-5.9 vs II 5.1+/-1.8 ng/ml, p=0.003, TNF-alpha; III + IV 10.5+/-3.8 vs II 8.0+/-2.7 pg/ml, p=0.02, sFas; III + IV 3.36+/-1.37 vs II 2.58 +/-0.84 ng/ml, p=0.03). Increased concentrations of H-FABP significantly correlated with the concentrations of TNF- alpha (r=0.57, p=0.0001) and sFas (r=0.69, p<0.0001), independent of renal function. CONCLUSION: OMD detected by H-FABP, a marker of membrane damage, is related to activated TNF and the Fas/FasL system, which suggests a pathophysiological role of cardiomyocyte necrosis and/or apoptosis in patients with worsening heart failure.