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:
- 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.
- 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.
- 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.
- Other adverse effects associated with ICIs include atrial and ventricular tachyarrhythmias and bradyarrhythmias, cardiomyopathy, pericarditis, and vasculitis.
- 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.
- There are no specific recommendations for monitoring for ICI-related cardiovascular toxicities. Timing and frequency of evaluations should be individualized.
- 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.
- 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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