Cardiovascular Toxicity Associated With Immune Checkpoint Inhibitor Therapy: A Comprehensive Review

Abstract

Immune checkpoint inhibitors (ICIs), a significant breakthrough treatment of cancer, exert their function through enhancing the immune system’s ability to recognize and attack cancer cells. However, these revolutionary cancer treatments have been associated with a range of immune-related adverse effects, including cardiovascular toxicity. The most commonly reported cardiovascular toxicities associated with ICIs are myocarditis, pericarditis, arrhythmias, and vasculitis. These cardiovascular manifestations are often severe and can lead to life-threatening complications. Therefore, prompt identification and management of these toxicities is critical, and a multidisciplinary teamwork by cardiologists and oncologists are required to ensure optimal patient outcomes. In this review, we summarize the current knowledge on the mechanisms underlying ICI-associated cardiovascular toxicity, clinical presentations of these toxicities, potential risk factors, diagnosis, management, and surveillance strategies during ICI therapy. While ICIs have already transformed cancer treatment, further research is needed to better understand and manage their immune-related cardiovascular effects, and possibly, to identify biomarkers which can predict the occurrence of these cardiovascular complications.

Isolated Pericardial Effusion Without Associated Myocarditis in a Small-Cell Lung Cancer Patient Undergoing Atezolizumab Therapy

“…A consequence of reactivating immune surveillance is a myriad of irAEs, including cardiotoxicity. The pathophysiology of these adverse events is poorly understood, but one proposed mechanism suggests cross-reactivity related to molecular mimicry [ 4 ]. Examples of cardiotoxicity include cardiac arrest, heart failure, myocarditis, and pericardial disease.…”

“…Examples of cardiotoxicity include cardiac arrest, heart failure, myocarditis, and pericardial disease. Although pericardial disease is especially rare, occurring at a rate of 0.36%, the associated mortality rate is high accounting for anywhere from 13-21% of fatalities [4][5][6][7]. The time course for ICI-related pericardial disease is usually within 30 days of treatment [8], presenting as dyspnea, chest pain, and hemodynamic instability [8,9], with dyspnea being the most common symptom [10].…”

Recurrent Pericardial Effusion in a Patient With Delayed Progression of Melanoma Treated With Immune Checkpoint Inhibitors

“…These T cells destroy malignant cells; however, they may also target healthy cardiac tissue. Another proposed mechanism suggests that molecular mimicry induces cardiac tissue autoimmunity [4]. Cardiotoxic irAEs presenting as pericardial disease are uncommon, representing approximately 0.36% of reported toxicities [5].…”

“…Based on prior research, the majority of toxicities occur within one year; however, reports have shown that they can also occur years after initiation of ICIs [3]. Due to this, several studies recommend performing routine cardiac surveillance in patients receiving ICIs, including a baseline cardiovascular assessment [3,4].…”