Immune checkpoint inhibitor-associated cardiovascular toxicities: A review

Abstract

Immune checkpoint inhibitors (ICIs) have revolutionary effects on therapeutic strategies for multiple malignancies. Their efficacy depends on their ability to reactivate the host immune system to fight cancer cells. However, adverse reactions to ICIs are common and involve several organs, limiting their use in clinical practice. Although the incidence of cardiovascular toxicity is relatively low, it is associated with serious consequences and high mortality rates. The primary cardiovascular toxicities include myocarditis, pericarditis, Takotsubo syndrome, arrhythmia, vasculitis, acute coronary syndrome, and venous thromboembolism. Currently, the mechanism underlying ICI-associated cardiovascular toxicity remains unclear and underexplored. The diagnosis and monitoring of ICI-associated cardiovascular toxicities mainly include the following indicators: symptoms, signs, laboratory examination, electrocardiography, imaging, and pathology. Treatments are based on the grade of cardiovascular toxicity and mainly include drug withdrawal, corticosteroid therapy, immunosuppressants, and conventional cardiac treatment. This review focuses on the incidence, underlying mechanisms, clinical manifestations, diagnoses, and treatment strategies.

Keywords: Cardiovascular toxicities; Immune checkpoint inhibitors; Immunotherapy; Multidisciplinary treatments; Myocarditis.

Fig. 1

Schematic diagram of immune checkpoint inhibitors blocking T cell activation. Abbreviations: APC, antigen-presenting cell; CTLA-4, cytotoxic T lymphocyte antigen-4; ICI, immune checkpoint inhibitor; MHC, major histocompatibility complex; PD-1, programmed death-1; PD-L1, programmed death ligand-1; TCR, T cell receptor; LAG-3, lymphocyte activation gene-3. Figure created with BioRender.com.

Fig. 2

The spectrum of cardiovascular toxicities associated with immune checkpoint inhibitors. Figure created with BioRender.com.

Fig. 3

Overview of diagnosis and treatments for ICI-associated cardiovascular toxicities. Abbreviations: ICI, Immune checkpoint inhibitor; CK, creatine kinase; CK-MB, creatine kinase-MB; BNP, B-type natriuretic peptide; NTpro-BNP, N-terminal pro-BNP; TNT, troponin T; ECG, electrocardiogram; CT, computed tomography; MRI, magnetic resonance imaging; MDT, multi-disciplinary treatment. Figure created with BioRender.com.