Myocarditis in the Setting of Cancer Therapeutics: Proposed Case Definitions for Emerging Clinical Syndromes in Cardio-Oncology

Marc P. Bonaca, Benjamin A. Olenchock, Joe Elie Salem, Stephen D. Wiviott, Stephane Ederhy, Ariel Cohen, Garrick C. Stewart, Toni K. Choueiri, Marcelo Di Carli, Yves Allenbach, Dharam J. Kumbhani, Lucie Heinzerling, Laleh Amiri-Kordestani, Alexander R. Lyon, Paaladinesh Thavendiranathan, Robert Padera, Andrew Lichtman, Peter P. Liu, Douglas B. Johnson, Javid Moslehi

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Recent developments in cancer therapeutics have improved outcomes but have also been associated with cardiovascular complications. Therapies harnessing the immune system have been associated with an immune-mediated myocardial injury described as myocarditis. Immune checkpoint inhibitors are one such therapy with an increasing number of case and cohort reports describing a clinical syndrome of immune checkpoint inhibitor-associated myocarditis. Although the full spectrum of immune checkpoint inhibitor-associated cardiovascular disease still needs to be fully defined, described cases of myocarditis range from syndromes with mild signs and symptoms to fatal events. These observations in the clinical setting stand in contrast to outcomes from randomized clinical trials in which myocarditis is a rare event that is investigator reported and lacking in a specific case definition. The complexities associated with diagnosis, as well as the heterogeneous clinical presentation of immune checkpoint inhibitor-associated myocarditis, have made ascertainment and identification of myocarditis with high specificity challenging in clinical trials and other data sets, limiting the ability to better understand the incidence, outcomes, and predictors of these rare events. Therefore, establishing a uniform definition of myocarditis for application in clinical trials of cancer immunotherapies will enable greater understanding of these events. We propose an operational definition of cancer therapy-associated myocarditis that may facilitate case ascertainment and report and therefore may enhance the understanding of the incidence, outcomes, and risk factors of this novel clinical syndrome.

Original languageEnglish (US)
Pages (from-to)80-91
Number of pages12
JournalCirculation
Volume140
Issue number1
DOIs
StatePublished - Jul 2 2019

Keywords

  • adjudication
  • cardiovascular disease
  • immunosuppressive agents
  • immunotherapy
  • myocarditis
  • oncology, medical

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Bonaca, M. P., Olenchock, B. A., Salem, J. E., Wiviott, S. D., Ederhy, S., Cohen, A., Stewart, G. C., Choueiri, T. K., Di Carli, M., Allenbach, Y., Kumbhani, D. J., Heinzerling, L., Amiri-Kordestani, L., Lyon, A. R., Thavendiranathan, P., Padera, R., Lichtman, A., Liu, P. P., Johnson, D. B., & Moslehi, J. (2019). Myocarditis in the Setting of Cancer Therapeutics: Proposed Case Definitions for Emerging Clinical Syndromes in Cardio-Oncology. Circulation, 140(1), 80-91. https://doi.org/10.1161/CIRCULATIONAHA.118.034497