Electrocardiographic features of immune checkpoint inhibitor associated myocarditis

Zlotoff DA, Hassan MZ, Zafar A, Alvi RM, Awadalla M, Mahmood SS, Zhang L, Chen CL, Ederhy S, Barac A, Banerji D, Jones-O'connor M, Murphy SP, Armanious M, Forrestal BJ, Kirchberger M, Coelho-Filho OR, Rizvi MA, Sahni G, Mandawat A, Tocchetti CG, Hartmann S, Gilman HK, Zatarain-Nicolás E, Mahmoudi M, Gupta D, Sullivan R, Ganatra S, Yang EH, Heinzerling LM, Thuny F, Zubiri L, Reynolds KL, Cohen JV, Lyon AR, Groarke J, Thavendiranathan P, Nohria A, Fradley MG, Neilan TG (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Book Volume: 9

Article Number: e002007

Journal Issue: 3

DOI: 10.1136/jitc-2020-002007

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.

Authors with CRIS profile

Involved external institutions

Hospital General Universitario Gregorio Marañón Spain (ES) Weill Cornell Medicine United States (USA) (US) University of California Los Angeles (UCLA) United States (USA) (US) Mount Sinai Health System United States (USA) (US) Massachusetts General Hospital United States (USA) (US) Lahey Hospital & Medical Center United States (USA) (US) H. Lee Moffitt Cancer Center & Research Institute United States (USA) (US) University of Southampton United Kingdom (GB) Brigham and Women's Hospital (BWH) United States (USA) (US) Hôpitaux Universitaires Paris-Ouest France (FR) MedStar Washington Hospital Center United States (USA) (US) Universidade Estadual de Campinas (UNICAMP) / University of Campinas Brazil (BR) Albert Einstein College of Medicine United States (USA) (US) Lehigh Valley Health Network United States (USA) (US) University of Toronto Canada (CA) Emory University United States (USA) (US) Klinikum der Universität München Germany (DE) Penn Medicine United States (USA) (US) Aix-Marseille University / Aix-Marseille Université France (FR) Università degli Studi di Napoli Federico II Italy (IT) Imperial College London / The Imperial College of Science, Technology and Medicine United Kingdom (GB)

How to cite

APA:

Zlotoff, D.A., Hassan, M.Z., Zafar, A., Alvi, R.M., Awadalla, M., Mahmood, S.S.,... Neilan, T.G. (2021). Electrocardiographic features of immune checkpoint inhibitor associated myocarditis. Journal for ImmunoTherapy of Cancer, 9(3). https://doi.org/10.1136/jitc-2020-002007

MLA:

Zlotoff, Daniel A., et al. "Electrocardiographic features of immune checkpoint inhibitor associated myocarditis." Journal for ImmunoTherapy of Cancer 9.3 (2021).

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