Electrocardiographic features of immune checkpoint inhibitor associated myocarditis

Daniel A. Zlotoff, Malek Z.O. Hassan, Amna Zafar, Raza M. Alvi, Magid Awadalla, Syed S. Mahmood, Lili Zhang, Carol L. Chen, Stephane Ederhy, Ana Barac, Dahlia Banerji, Maeve Jones-O'connor, Sean P. Murphy, Merna Armanious, Brian J. Forrestal, Michael C. Kirchberger, Otavio R. Coelho-Filho, Muhammad A. Rizvi, Gagan Sahni, Anant MandawatCarlo G. Tocchetti, Sarah Hartmann, Hannah K. Gilman, Eduardo Zatarain-Nicolás, Michael Mahmoudi, Dipti Gupta, Ryan Sullivan, Sarju Ganatra, Eric H. Yang, Lucie M. Heinzerling, Franck Thuny, Leyre Zubiri, Kerry L. Reynolds, Justine V. Cohen, Alexander R. Lyon, John Groarke, Paaladinesh Thavendiranathan, Anju Nohria, Michael G. Fradley, Tomas G. Neilan

Research output: Contribution to journalArticlepeer-review

Abstract

Background Myocarditis is a highly morbid complication of immune checkpoint inhibitor (ICI) use that remains inadequately characterized. The QRS duration and the QTc interval are standardized electrocardiographic measures that are prolonged in other cardiac conditions; however, there are no data on their utility in ICI myocarditis. Methods From an international registry, ECG parameters were compared between 140 myocarditis cases and 179 controls across multiple time points (pre-ICI, on ICI prior to myocarditis, and at the time of myocarditis). The association between ECG values and major adverse cardiac events (MACE) was also tested. Results Both the QRS duration and QTc interval were similar between cases and controls prior to myocarditis. When compared with controls on an ICI (93±19 ms) or to baseline prior to myocarditis (97±19 ms), the QRS duration prolonged with myocarditis (110±22 ms, p<0.001 and p=0.009, respectively). In contrast, the QTc interval at the time of myocarditis (435±39 ms) was not increased compared with pre-myocarditis baseline (422±27 ms, p=0.42). A prolonged QRS duration conferred an increased risk of subsequent MACE (HR 3.28, 95% CI 1.98 to 5.62, p<0.001). After adjustment, each 10 ms increase in the QRS duration conferred a 1.3-fold increase in the odds of MACE (95% CI 1.07 to 1.61, p=0.011). Conversely, there was no association between the QTc interval and MACE among men (HR 1.33, 95% CI 0.70 to 2.53, p=0.38) or women (HR 1.48, 95% CI 0.61 to 3.58, p=0.39). Conclusions The QRS duration is increased in ICI myocarditis and is associated with increased MACE risk. Use of this widely available ECG parameter may aid in ICI myocarditis diagnosis and risk-stratification.

Original languageEnglish (US)
Article numbere002007
JournalJournal for ImmunoTherapy of Cancer
Volume9
Issue number3
DOIs
StatePublished - Mar 2 2021

Keywords

  • autoimmunity
  • immune tolerance
  • immunotherapy
  • inflammation
  • self tolerance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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