Author + information
- Received May 28, 2019
- Revision received July 25, 2019
- Accepted July 31, 2019
- Published online September 23, 2019.
- Somedeb Ball, MDa,∗,
- Raktim K. Ghosh, MDb,∗,
- Sariya Wongsaengsak, MDa,
- Dhrubajyoti Bandyopadhyay, MDc,
- Gopal Chandra Ghosh, MDd,
- Wilbert S. Aronow, MDe,
- Gregg C. Fonarow, MDf,
- Daniel J. Lenihan, MDg and
- Deepak L. Bhatt, MD, MPHh,∗ (, )@DLBhattMD
- aDepartment of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas
- bDepartment of Cardiology, Case Western Reserve University, Heart and Vascular Institute, MetroHealth Medical Center, Cleveland, Ohio
- cDepartment of Internal Medicine, Icahn School of Medicine at Mount Sinai/Mount Sinai St. Luke's Roosevelt Hospital, New York, New York
- dDepartment of Cardiology, Apollo Gleneagles Hospital, Kolkata, India
- eDivision of Cardiology, Westchester Medical Center and New York Medical College, Valhalla, New York
- fDivision of Cardiovascular Medicine, University of California-Los Angeles, Los Angeles, California
- gCardio-Oncology Center of Excellence, Division of Cardiology, Washington University in St. Louis, St. Louis, Missouri
- hBrigham and Women’s Hospital Heart & Vascular Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Deepak L. Bhatt, Brigham and Women’s Hospital Heart & Vascular Center, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115.
• ICIs are associated with various CVAEs.
• Myocarditis is the most common and most fatal of all immune-related cardiovascular toxicities.
• High-dose corticosteroids are the mainstay of management, guided by severity of adverse events.
• Multidisciplinary initiatives should standardize case definition and surveillance strategies.
Immune checkpoint inhibitors (ICIs) have been an important therapeutic advance in the field of cancer medicine, resulting in a significant improvement in survival of patients with advanced malignancies. Recent reports provided greater insights into the incidence of cardiovascular adverse events (CVAEs) with ICI use. Myocarditis is the most common CVAE associated with ICI. Pericardial diseases, Takotsubo syndrome, arrhythmias, and vasculitis constitute other significant AEs. Physicians should be aware of these infrequent, but potentially fatal toxicities associated with ICIs as their therapeutic use becomes widespread with a myriad of approvals by the U.S. Food and Drug Administration. Management involves prompt administration of high-dose corticosteroids and discontinuation of ICIs in severe myocarditis. This review summarizes the most updated evidence on epidemiology, pathophysiological mechanisms, and management strategies of various CVAEs associated with ICIs. Highlights from recent guidelines published by National Comprehensive Cancer Network on ICI-related CV toxicities have also been incorporated.
- cancer therapeutics-related cardiac dysfunction
- cytotoxic T lymphocyte antigen-4
- programmed cell death ligand 1
- programmed cell death protein 1
↵∗ Drs. Ball and Ghosh contributed equally and are co-first authors.
Dr. Fonarow has been a consultant for Abbott, Amgen, Bayer, Janssen, Medtronic, and Novartis. Dr. Lenihan has been a consultant for Roche, Pfizer, Akcea, Prothena, Boehringer Ingelheim, Bristol-Myers Squibb, and Takeda. Dr. Bhatt has been a member of the Advisory Board for Cardax, Cereno Scientific, Elsevier Practice Update Cardiology, Medscape Cardiology, PhaseBio, and Regado Biosciences; has been a member of the Board of Directors for Boston VA Research Institute, Society of Cardiovascular Patient Care, and TobeSoft; has been the Chair for the American Heart Association Quality Oversight Committee; has been a member of the Data Monitoring Committees for Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi-Sankyo), and Population Health Research Institute; has received honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Vice-Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), HMP Global (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Medtelligence/ReachMD (CME steering committees), Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), and WebMD (CME steering committees); other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), and VA CART Research and Publications Committee (Chair); has received research funding from Abbott, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Idorsia, Ironwood, Ischemix, Lilly, Medtronic, PhaseBio, Pfizer, Regeneron, Roche, Sanofi, Synaptic, and The Medicines Company; has received royalties from Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); has been a site co-investigator for Biotronik, Boston Scientific, St. Jude Medical (now Abbott), and Svelte; has been a trustee for the American College of Cardiology; and has performed unfunded research with FlowCo, Fractyl, Merck, Novo Nordisk, PLx Pharma, and Takeda. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received May 28, 2019.
- Revision received July 25, 2019.
- Accepted July 31, 2019.
- 2019 American College of Cardiology Foundation
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