Heart failure in cancer: role of checkpoint inhibitors

The introduction of immune checkpoint inhibitors have greatly improved clinical outcomes in several cancer types, revolutionizing the management of a wide variety of tumors endowed with poor prognosis. Despite its success, high grade immune related adverse events were observed in patients treated with checkpoint inhibitors. While cardiotoxicity was largely underestimated in initial studies, numerous reports of fulminant myocarditis and fatal heart failure (HF) have been recently described. In this review we discuss possible mechanisms involved in cardiac toxicity triggered by inhibition of cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) pathway, the most prominent checkpoint inhibitors available in the clinic. Major cardiovascular events associated with checkpoint inhibitors adds another layer of complexity in cancer therapy and urges for an interdisciplinary approach between oncologists, cardiologists, and immunologist.