Heart Failure in Relation to Anthracyclines and Other Chemotherapies

Anthracyclines are the cornerstone of therapy for a wide range of solid and hematologic malignancies; however, their use is limited by the risk of chemotherapy-induced cardiotoxicity leading to cardiomyopathy and heart failure. The incidence of cardiotoxicity in the literature depends on the definition being used, anthracycline dose, duration of follow-up, and surveillance methods used to identify cardiac injury. The reported risk of clinical heart failure has been around 2% to 4% with low-dose anthracycline regimens, whereas the incidence of cardiac injury defined by an abnormal increase in cardiac biomarkers has been reported as high as 35%. Multiple mechanisms have been proposed for anthracycline cardiotoxicity, including the deleterious effects of oxidative stress and reactive oxygen species and the inhibition of topoisomerase II beta, which leads to cardiomyocyte death. In addition, genetic susceptibility is an emerging field that is currently generating active research. The risk factors associated with anthracycline cardiotoxicity include lifetime cumulative dose, age, prior cardiac dysfunction, and the presence of cardiovascular risk factors, in particular hypertension. In this review, we summarize the incidence, mechanisms, and risk factors for anthracycline-mediated left ventricular dysfunction and discuss the role of risk stratification and early detection in patient management.