Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: A Systematic Review

Int J Mol Sci. 2022 Sep 19;23(18):10948. doi: 10.3390/ijms231810948.


Immune checkpoint inhibitors (ICIs) are an important advancement in the field of cancer treatment, significantly improving the survival of patients with a series of advanced malignancies, like melanoma, non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and Hodgkin lymphoma. ICIs act upon T lymphocytes and antigen-presenting cells, targeting programmed cell death protein 1 (PD1), programmed cell death protein ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), breaking the immune tolerance of the T cells against malignant cells and enhancing the body's own immune response. A variety of cardiac-adverse effects are associated with ICI-based treatment, including pericarditis, arrhythmias, cardiomyopathy, and acute coronary syndrome, with myocarditis being the most studied due to its often-unexpected onset and severity. Overall, Myocarditis is rare but presents an immune-related adverse event (irAE) that has a high fatality rate. Considering the rising number of oncological patients treated with ICIs and the severity of their potential adverse effects, a good understanding and continuous investigation of cardiac irAEs is of the utmost importance. This systematic review aimed to revise recent publications (between 2016-2022) on ICI-induced cardiac toxicities and highlight the therapeutical approach and evolution in the selected cases.

Keywords: arrythmia; cardiomyopathy; immune checkpoint inhibitors; myocarditis; pericarditis.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Antineoplastic Agents, Immunological* / therapeutic use
  • Apoptosis Regulatory Proteins
  • B7-H1 Antigen
  • CTLA-4 Antigen
  • Carcinoma, Hepatocellular* / chemically induced
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Cardiotoxicity / etiology
  • Drug-Related Side Effects and Adverse Reactions*
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects
  • Ligands
  • Liver Neoplasms* / chemically induced
  • Lung Neoplasms* / drug therapy
  • Myocarditis* / chemically induced
  • Programmed Cell Death 1 Receptor


  • Antineoplastic Agents, Immunological
  • Apoptosis Regulatory Proteins
  • B7-H1 Antigen
  • CTLA-4 Antigen
  • Immune Checkpoint Inhibitors
  • Ligands
  • Programmed Cell Death 1 Receptor

Grants and funding

The APC was funded by authors and “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca.