Electrocardiographic features of immune checkpoint inhibitor associated myocarditis

• Type of Material: Article
• Authors: Daniel A Zlotoff, Massachusetts General Hospital; Malek ZO Hassan, Massachusetts General Hospital; Amna Zafar, Massachusetts General Hospital; Raza M Alvi, Massachusetts General Hospital; Magid Awadalla, Massachusetts General Hospital; Syed S Mahmood, NewYork Presbyterian Hosp Weill Cornell Med NewYork-Presbyterian Hospital, Weill Cornell Medicine; Lili Zhang, Montefiore Medical Center, New York; Carol L Chen, Memorial Sloan Kettering Cancer Center; Stephane Ederhy, Hopitaux Universitaires Est Parisien; Ana Barac, MedStar Washington Hospital Center; Dahlia Banerji, Massachusetts General Hospital; Maeve Jones-O'Connor, Massachusetts General Hospital; Sean P Murphy, Massachusetts General Hospital; Merna Armanious, H. Lee Moffitt Cancer Center & Research Institute; Brian J Forrestal, MedStar Washington Hospital Center; Michael C Kirchberger, Friedrich Alexander Univ Erlangen Nurnberg FAU; Otavio R Coelho-Filho, University of Campinas, Brazil; Muhammad A Rizvi, Lehigh Valley Hospital; Gagan Sahni, Mount Sinai Medical Center, New York; Anant Mandawat, Emory University; Carlo G Tocchetti, Università degli Studi di Napoli Federico II; Sarah Hartmann, Massachusetts General Hospital; Hannah K Gilman, Massachusetts General Hospital; Eduardo Zatarain-Nicolas, Hospital General Universitario Gregorio Marañón; Michael Mahmoudi, University of Southampton; Dipti Gupta, Memorial Sloan Kettering Cancer Center; Ryan Sullivan, Massachusetts General Hospital; Sarju Ganatra, Lahey Hospital and Medical Center, Massachusetts; Eric H Yang, University of California Los Angeles; Lucie M Heinzerling, LMU Klinikum, Germany; Franck Thuny, Aix-Marseille University, France; Leyre Zubiri, Massachusetts General Hospital; Kerry L Reynolds, Massachusetts General Hospital; Justine Cohen, University of Pennsylvania; Alexander R Lyon, Royal Brompton Hospital; John Groarke, Brigham and Women's Hospital, Massachusetts; Paaladinesh Thavendiranathan, University of Toronto; Anju Nohria, Brigham and Women's Hospital, Massachusetts; Michaek G Fradley, H. Lee Moffitt Cancer Center & Research Institute; Tomas G Neilan, Massachusetts General Hospital
• Language: English
• Date: 2021-01-01
• Publisher: BMJ PUBLISHING GROUP
• Publication Version: Final Published Version
• Copyright Statement: © Author(s) (or their employer(s)) 2021
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1136/jitc-2020-002007
• Title of Journal or Parent Work: JOURNAL FOR IMMUNOTHERAPY OF CANCER
• Volume: 9
• Issue: 3
• Grant/Funding Information: This work was supported by the National Institutes of Health (P30CA008748 to DG and CLC; R01HL137562, R01HL130539, and K24HL150238 to TGN; and T32HL007208-39 to DAZ).
• Keywords: Oncology; Science & Technology; Immunology; autoimmunity; immune tolerance; inflammation; immunotherapy; self tolerance; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Radiology; Health Sciences, Medicine and Surgery; Health Sciences, Oncology

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.