Cardiotoxicity Induced by Immune Checkpoint Inhibitors: What a Cardio-Oncology Team Should Know and Do

SIMPLE SUMMARY: Immune checkpoint inhibitors, including monoclonal antibodies directed against the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway or the cytotoxic T-lymphocyte antigen-4 (CTLA-4) pathway and the most recent lymphocyte-activation gene 3 (LAG-3)—blocking antibody, currently represent the standard of care for the treatment of a large number of solid tumors. However, the development of immune-related adverse events can limit the use of these beneficial agents in the clinical setting. It is of crucial importance to identify predictive biomarkers for those patients most likely benefiting from immunotherapy. ABSTRACT: Immune checkpoint inhibitors (ICIs) have revolutionized the therapeutic scenario for several malignancies. However, they can be responsible for immune-related adverse events (irAEs), involving several organs, with a pooled incidence ranging between 54% and 76%. The frequency of cardiovascular system involvement is <1%. Among the cardiovascular irAEs, myocarditis is the most common and the most dangerous but other, less common manifestations of ICI-related cardiotoxicity include pericardial disease, arrhythmias, Takotsubo-like syndrome, and acute myocardial infarction, all of which remain poorly explored. Both oncologists and cardiologists, as well as the patients, should be aware of the possible occurrence of one or more of these complications, which in some cases are fatal, in order to implement effective strategies of cardiac surveillance. In this review, we summarize the latest studies and recommendations on the pathogenesis, clinical manifestation, diagnosis, and management of ICI-related cardiotoxicity in order to realize a complete and updated overview on the main aspects of ICI-related cardiotoxicity, from surveillance to diagnosis to management, useful for both oncologists and cardiologists in their clinical practice. In particular, in the first part of the review, we realize a description of the pathogenetic mechanisms and risk factors of the main cardiovascular irAEs. Then, we focus on the management of ICI-related cardiotoxicity by analyzing five main points: (1) identifying and evaluating the type and severity of the cardiotoxicity; (2) deciding whether to withhold ICI therapy; (3) initiating steroid and immunosuppressive therapy; (4) starting conventional cardiac treatment; and (5) restarting ICI therapy. Finally, we discuss the existing evidence on surveillance for ICI-related cardiotoxicity and propose a surveillance strategy for both short- and long-term cardiotoxicity, according to the most recent guidelines.