Cardiovascular Toxicities of Immune Checkpoint Inhibitors

Ball S, Ghosh RK, Wongsaengsak S, et al.
Cardiovascular Toxicities of Immune Checkpoint Inhibitors: JACC Review Topic of the Week. J Am Coll Cardiol 2019;74:1714-1727.

The following are key points to remember from this JACC Review Topic of the Week on the cardiovascular toxicities of immune checkpoint inhibitors:

  1. Immune checkpoint inhibitors (ICIs) block immune tolerance signal-mediated cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD1), or programmed cell death ligand 1 (PDL-1), leading to potentiation of the patient’s immune system against tumor cells.
  2. The indications for immune checkpoint inhibitors are growing, encompassing various malignancies extending from melanoma, renal cell carcinoma, breast cancer, Hodgkin’s lymphoma, colorectal cancer, and others.
  3. Myocarditis is the most common manifestation of ICI cardiovascular toxicity, occurs in 1% of patients, and is more likely in those receiving dual-blockade. Fifteen percent are fulminant, and have 50% mortality. ICI-related myocarditis typically occurs within 30 days of drug initiation.
  4. Other adverse effects associated with ICIs include atrial and ventricular tachyarrhythmias and bradyarrhythmias, cardiomyopathy, pericarditis, and vasculitis.
  5. The pathophysiologic mechanisms of ICI-related cardiovascular toxicity are unknown, but thought to be related to clonal expansion of T-lymphocytes with receptors against shared common antigens across tumor cells and affected tissues.
  6. There are no specific recommendations for monitoring for ICI-related cardiovascular toxicities. Timing and frequency of evaluations should be individualized.
  7. The diagnosis of ICI-related myocarditis relies on an overall clinical assessment including a history, physical exam, electrocardiogram, biomarkers, and imaging. Cardiac magnetic resonance imaging typically demonstrates myocardial inflammation and necrosis. Endomyocardial biopsy can confirm the diagnosis, but is rarely necessary.
  8. While based on anecdotal evidence, the management recommendations for ICI-related toxicities focuses on early recognition, cessation of ICI, supportive care, corticosteroid and other immunosuppressive therapies including plasmapheresis, intravenous immunoglobulin, anti-thymocyte globulin, myphenolate mofetil, tacrolimus, infliximab, and abatacept.

Clinical Topics: Arrhythmias and Clinical EP, Cardio-Oncology, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Pericardial Disease, Prevention, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Heart Failure and Cardiac Biomarkers, Magnetic Resonance Imaging

Keywords: Antilymphocyte Serum, Atrial Fibrillation, Bradycardia, Breast Neoplasms, Carcinoma, Renal Cell, Cardiac Imaging Techniques, Cardiomyopathies, Cardiotoxicity, Colorectal Neoplasms, CTLA-4 Antigen, Electrocardiography, Hodgkin Disease, Immune Tolerance, Immunoglobulins, Intravenous, Inflammation, Lymphoma, Magnetic Resonance Imaging, Melanoma, Myocarditis, Pericarditis, Primary Prevention, Tachycardia, Tacrolimus, T-Lymphocytes, Vasculitis

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