Electrocardiographic features of immune checkpoint inhibitor associated myocarditis

• Published in: Journal for immunotherapy of cancer Vol. 9; no. 3; p. e002007
• Main Authors: Zlotoff, Daniel A, Hassan, Malek Z O, Zafar, Amna, Alvi, Raza M, Awadalla, Magid, Mahmood, Syed S, Zhang, Lili, Chen, Carol L, Ederhy, Stephane, Barac, Ana, Banerji, Dahlia, Jones-O'Connor, Maeve, Murphy, Sean P, Armanious, Merna, Forrestal, Brian J, Kirchberger, Michael C, Coelho-Filho, Otavio R, Rizvi, Muhammad A, Sahni, Gagan, Mandawat, Anant, Tocchetti, Carlo G, Hartmann, Sarah, Gilman, Hannah K, Zatarain-Nicolás, Eduardo, Mahmoudi, Michael, Gupta, Dipti, Sullivan, Ryan, Ganatra, Sarju, Yang, Eric H, Heinzerling, Lucie M, Thuny, Franck, Zubiri, Leyre, Reynolds, Kerry L, Cohen, Justine V, Lyon, Alexander R, Groarke, John, Thavendiranathan, Paaladinesh, Nohria, Anju, Fradley, Michael G, Neilan, Tomas G
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01-03-2021; BMJ Publishing Group
• Series: Original research
• Subjects: Action Potentials - drug effects; Aged; Aged, 80 and over; Biopsy; Body mass index; Cancer; Cardiac arrhythmia; Cardiovascular disease; Clinical/Translational Cancer Immunotherapy; Electrocardiography; Female; Heart Conduction System - drug effects; Heart Conduction System - physiopathology; Heart failure; Heart Rate - drug effects; Humans; Immune Checkpoint Inhibitors - adverse effects; Immunotherapy; Life Sciences; Lung cancer; Male; Melanoma; Middle Aged; Mortality; Myocarditis; Myocarditis - chemically induced; Myocarditis - diagnosis; Myocarditis - physiopathology; Patients; Predictive Value of Tests; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Statistical analysis; Time Factors; immune tolerance; autoimmunity; self tolerance; inflammation; immunotherapy
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1136/jitc-2020-002007

BackgroundMyocarditis 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.MethodsFrom 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.ResultsBoth 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).ConclusionsThe 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.