Cardiotoxicity of Immune Checkpoint Inhibitors

Abstract

Purpose of Review Immune checkpoint inhibitors (ICIs) have improved the survival of several cancers. However, they may cause a wide range of immune-related adverse events (irAEs). While most irAEs are manageable with temporary cessation of ICI and immunosuppression, cardiovascular toxicity can be associated with high rates of morbidity and mortality. As ICIs evolve to include high-risk patients with preexisting cardiovascular risk factors and disease, the risk and relevance of ICI-associated cardiotoxicity may be even higher. Recent Findings Several cardiovascular toxicities such as myocarditis, stress cardiomyopathy, and pericardial disease have been reported in association with ICIs. Recent findings also suggest an increased risk of atherosclerosis with ICI use. ICI-associated myocarditis usually occurs early after initiation and can be fulminant. A high index of suspicion is required for timely diagnosis. Prompt treatment with high-dose corticosteroids is shown to improve outcomes. Summary Although the overall incidence is rare, ICI cardiotoxicity, particularly myocarditis, is associated with significant morbidity and mortality, making it a major therapy-limiting adverse event. Early recognition and prompt treatment with the cessation of ICI therapy and initiation of high-dose corticosteroids are crucial to improve outcomes. Cardio-oncologists will need to play an important role not just in the management of acute cardiotoxicity but also to reduce the risk of long-term sequelae.

Cardiotoxicity of Non-Anthracycline Cancer Chemotherapy Agents

“…The presentation of ICI-associated myocarditis may vary from mild symptoms such as fatigue and myalgia to more severe such as chest pain, dyspnea due to heart failure, pulmonary edema, arrhythmias, and sudden cardiac death [ 24 , 25 , 27 , 32 , 33 ]. In a multi-center study of 140 patients, 35 of which developed ICI-associated myocarditis, the median time of onset was 34 days (IQR 21–75 days) after the first ICI administration.…”

“…Immunohistochemistry reveals CD3+, CD4+ and CD68+ positive T cell markers [ 24 ]. It should be performed in patients with negative or ambiguous imaging results but high clinical suspicion, although focal distribution may reduce its sensitivity [ 32 ].…”

Eurasian clinical guidelines for cardiovascular complications of cancer treatments: diagnosis, prevention and treatment (2022)

“…Терапия ИКТ может сопровождаться целым рядом иммуноопосредованных осложнений, в том числе сердечно-сосудистых [409,410,411]. Зарегистрированные проявления кардиотоксичности ИКТ включают миокардит, перикардит, аритмии и нарушения АВ проводимости (вероятнее всего, как проявление миокардита), сердечную недостаточность невоспалительного генеза, синдром Такоцубо, артериальную гипотонию, васкулит, внезапную смерть и острый коронарный синдром (ОКС) [412,413,408]. Наиболее клинически значимым считается миокардит, поскольку он может представлять непосредственную угрозу жизни пациента.…”

“…Наиболее клинически значимым считается миокардит, поскольку он может представлять непосредственную угрозу жизни пациента. Хотя частота миокардита невелика, однако почти в половине случаев он ассоциирован с тяжелыми жизнеугрожающими осложнениями смертью [47,409,412,414].…”

Cardiac Toxicity Associated with Cancer Immunotherapy and Biological Drugs

“…The consequence might be the activation of focal or systemic autoimmune phenomena underlying the clinical picture of immune-related adverse events. Moreover, in animal models, both CTLA-4 and PD-1 demonstrated a protective effect against immune-mediated cardiac damage [ 106 , 107 ].…”