The role of TNF-α, Fas/Fas ligand system and NT-proBNP in the early detection of asymptomatic left ventricular dysfunction in cancer patients treated with anthracyclines

Abstract

Background: Anthracycline-induced cardiotoxicity typically presents as congestive heart failure (CHF). As immuno-inflammatory activation and apoptosis are important mechanisms in the process of heart failure, the use of biomarkers that could detect cardiovascular toxicity before the clinical presentation is of great importance. We studied whether sTNF-a, sTNF-RI, sTNF-RII, Fas/FasLigand system and NT-proBNP associate with early cardiac dysfunction in patients receiving cardiotoxic drugs. Methods: Two groups of breast cancer patients—group A with metastatic disease under chemotherapy with epirubicin and group B with no residual disease under a less cardiotoxic regimen—as well as healthy women were included in this prosprective study. NT-proBNP, sTNF-a, sTNF-RI, sTNF-RII, sFas, sFas-Ligand and left ventricular ejection fraction (LVEF) were determined in all patients before and after the completion of chemotherapy. Results: In Group A, an increase in sFas levels (p < 0.001), a decrease in the sFasL levels (p = 0.010), an NT-proBNP increase (p <0.001) and a significant reduction of LVEF (p < 0.001) was recorded post-chemotherapy. The decrease in LVEF correlated significantly with the increase in sFas, the decrease in sFasL and the rise in NT-proBNP levels. In Group B, TNF-RI levels were higher (p = 0.024) and mean sFas-L levels lower (p = 0.021) post chemotherapy with no LVEF drop. Two of group A (7.6%) patients developed symptomatic CHF 12 and 14 months respectively after the end of chemotherapy. Conclusion: SFas, sFas-L and NT-proBNP correlate with reductions in LVEF and could be used as sensitive biochemical indices for the detection of asymptomatic left ventricular dysfunction in cancer patients under cardiotoxic chemotherapy.

Keywords

• Anthracyclines
• Cardiotoxicity
• TNF-α
• Fas/Fas ligand
• NT-proBNP