Biomarkers for the detection of apparent and subclinical cancer therapy-related cardiotoxicity

Abstract

Progress in cancer therapy over the past decades improved long-term survival but increased cancer therapy-related cardiotoxicity. Many novel treatment options have been implemented with yet incompletely characterized cardiovascular side effects including heart failure, coronary artery disease, arrhythmias, valvular disease, venous thromboembolism and myocarditis. Diagnosis of potential cardiotoxic side effects is essential for an optimal treatment but remains challenging. Cardiac biomarkers troponin and brain natriuretic peptide/N-terminal proBNP (BNP/NT-proBNP) have been extensively studied in heart failure and acute coronary syndromes. Emerging evidence implicates a significant role in the detection of cardiotoxicity and guidance of therapy in cancer patients. Elevated troponin or BNP/NT-proBNP levels were associated with increased all-cause mortality in cancer patients and have been shown to predict manifest heart failure. BNP/NT-proBNP may be useful for the prediction of cancer therapy-related heart failure and response to heart failure therapy in adult and pediatric cancer patients while troponin can indicate acute myocardial infarction in patients with cancer therapy-related risk for coronary artery disease. Furthermore, troponin may be used for the identification of immune checkpoint inhibitor-related myocarditis with very high sensitivity. Finally, even D-dimer levels have been shown to improve risk stratification and diagnosis in cancer-associated venous thromboembolism. This review aims to summarize the current knowledge about biomarkers in cancer therapy-related cardiotoxicity. We also outline possible clinical recommendations for the detection and treatment of subclinical and clinically apparent cardiotoxic effects using biomarkers.

Keywords: Biomarker; brain natriuretic peptide (BNP); cardio-oncology; cardiotoxicity; troponin.

Figure 1

Biomarkers in different forms of cancer therapy-related cardiotoxicity. Various forms of cancer therapy exhibit cardiotoxic side effects. Troponin may serve as a marker for acute coronary syndrome in patients receiving radiotherapy, fluoropyrimidines, platinum-based antineoplastic drugs or vascular endothelial growth factor receptor inhibitors. In addition, assessment of serum troponin in suspected immune checkpoint inhibitor-related myocarditis can be recommended. D-dimer levels may indicate cancer- or cancer therapy-related venous thromboembolism. BNP/NT-proBNP is associated with cancer therapy-related heart failure induced by anthracyclines, HER2 inhibitors, alkylating agents, tyrosine kinase inhibitors and proteasome inhibitors. This figure was created using SMART Servier Medical Art templates (https://smart.servier.com/). ACS, acute coronary syndrome; VEGF, vascular endothelial growth factor receptor; VTE, venous thromboembolism; NT-proBNP, N-terminal pro brain natriuretic peptide; HF, heart failure; HER2, human epidermal growth factor receptor 2.