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Review
July 7, 2021

Clinical Strategy for the Diagnosis and Treatment of Immune Checkpoint Inhibitor–Associated Myocarditis: A Narrative Review

Author Affiliations
  • 1Department of Cardiology, Angiology, and Pneumology, Cardio-Oncology Unit, Heidelberg University Hospital, Heidelberg, Germany
  • 2German Centre for Cardiovascular Research, partner site Heidelberg/Mannheim, Heidelberg, Germany
  • 3German Cancer Research Centre, Heidelberg, Germany
  • 4Aix-Marseille University, University Mediterranean Center of Cardio-Oncology, Unit of Heart Failure and Valvular Heart Diseases, Center for Cardiovascular and Nutrition Research, Nord Hospital, Assistance Publique-Hôpitaux de Marseille, France
  • 5Groupe Méditerranéen de Cardio-Oncologie, Marseille, France
  • 6Oncosafety Network of the Early Phases Cancer Trials Center, Marseille, France
  • 7Department of Cardiology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston
  • 8Department of Medicine, Division of Cardiology, University of California, San Francisco
  • 9Cardio-Oncology Program, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
  • 10Department of Internal Medicine and Clinical Immunology, Sorbonne Université, Pitié-Salpêtrière University Hospital, Paris, France
  • 11Sorbonne Université, Institut National de la Santé et de la Recherche Médicale, Association Institut de Myologie, Centre de Recherche en Myologie, UMRS974, Paris, France
  • 12Department of Pharmacology, Normandie University, University of Caen Normandy, PICARO Cardio-oncology Program, Signalisation, Électrophysiologie et Imagerie des Lésions d'Ischémie-Reperfusion Myocardique, Caen, France
  • 13Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
  • 14Department of Internal Medicine III, University of Kiel, Kiel, Germany
  • 15German Center for Cardiovascular Research, partner site Hamburg/Kiel/Lübeck, Kiel, Germany
  • 16CardioVascular Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
  • 17Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, affiliated with the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
  • 18Sorbonne Université, ACTION Study Group, Institut National de la Santé et de la Recherche Médicale, Institut de Cardiologie, Hôpital Pitié-Salpêtrière (Assistance Publique-Hôpitaux de Paris), Paris, France
  • 19Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor
  • 20Hôpitaux Universitaires Paris-Est, Assistance Publique-Hôpitaux de Paris, Hôpital Saint Antoine, Service de Cardiologie, Unico, Unité de Cardio-Oncologie, Groupe de Recherche Clinique en Cardio-Oncologie, Université Pierre et Marie Curie, Paris, France
  • 21Department of Pharmacology, Sorbonne Université, Assistance Publique-Hôpitaux de Paris, UNICO-GRECO Cardio-Oncology Program, Pitié-Salpêtrière Hospital, Paris, France
JAMA Cardiol. 2021;6(11):1329-1337. doi:10.1001/jamacardio.2021.2241
Abstract

Importance  In the last decade, immune checkpoint inhibitors (ICIs) have been approved for the treatment of many cancer types. Immune checkpoint inhibitor–associated myocarditis has emerged as a significant and potentially fatal adverse effect. Recognizing, diagnosing, and treating ICI-associated myocarditis poses new challenges for the practicing clinician. Here, the current literature on ICI-associated myocarditis is reviewed.

Observations  Clinical presentation and cardiac pathological findings are highly variable in patients with ICI-associated myocarditis. Although endomyocardial biopsy is the criterion standard diagnostic test, a combination of clinical suspicion, cardiac biomarkers (specifically troponin), and cardiac imaging, in addition to biopsy, is often needed to support the diagnosis. Importantly, the combination of a cytotoxic T-lymphocyte–associated protein 4 inhibitor with a programmed cell death protein 1 or programmed death-ligand 1 inhibitor increases the risk of developing ICI-associated myocarditis.

Conclusion and Relevance  This review aims to provide a standardized diagnostic and therapeutic approach for patients with suspected ICI-associated myocarditis. A complete history of recent cancer treatments and physical examination in combination with cardiac biomarkers, cardiac imaging, and endomyocardial biopsy represent a pragmatic diagnostic approach for most cases of ICI-associated myocarditis. The addition of novel biomarkers or imaging modalities is an area of active research and should be evaluated in larger cohorts.

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