Cardiotoxicity of Novel Targeted Chemotherapeutic Agents

With the continuing development of newer targeted therapies in oncology, it is necessary to understand their potential cardiovascular side effects. In this review, we discuss the association of novel targeted agents and left ventricular systolic dysfunction.

Within the last 5 years, multiple new agents have been developed to target specific cancer pathways and found to have off-targeted cardiotoxicity. The most recent example is the recognition of myocarditis caused by immune checkpoint inhibitors. The development of targeted cancer therapies has revolutionized oncology, but many of these agents are inherently toxic to the cardiovascular system. Nearly all vascular endothelial growth factor (VEGF) inhibitors cause cardiotoxicity to varying degrees. Epidermal growth factor receptor (EGFR) inhibitors developed since the discovery of trastuzumab are significantly less cardiotoxic than their predecessor, but still convene risk. BCR-ABL tyrosine kinase inhibitors (TKI), once thought to pose significant risk as a class effect, appear to only be cardiotoxic if they have anti-VEGF activity. The newer generation of proteasome inhibitors such as carfilzomib appears to have significant cardiotoxicity, with almost 5% of patients developing symptomatic heart failure (HF). Immune checkpoint inhibitors can very rarely cause rapidly fatal myocarditis. As of now, there are no sufficient guidelines to direct clinical care for patients on these new classes of agents, but this is likely to change as more data and clinical experience accumulate.