Electrocardiographic features of immune checkpoint inhibitor associated myocarditis.

MedStar author(s):
Citation: Journal for Immunotherapy of Cancer. 9(3), 2021 03.PMID: 33653803Institution: MedStar Heart & Vascular Institute | MedStar Washington Hospital CenterDepartment: Medicine/Pulmonary-Critical CareForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: *Action Potentials/de [Drug Effects] | *Electrocardiography | *Heart Conduction System/de [Drug Effects] | *Heart Rate/de [Drug Effects] | *Immune Checkpoint Inhibitors/ae [Adverse Effects] | *Myocarditis/di [Diagnosis] | Aged | Aged, 80 and over | Female | Heart Conduction System/pp [Physiopathology] | Humans | Male | Middle Aged | Myocarditis/ci [Chemically Induced] | Myocarditis/pp [Physiopathology] | Predictive Value of Tests | Registries | Retrospective Studies | Risk Assessment | Risk Factors | Time FactorsYear: 2021ISSN:
  • 2051-1426
Name of journal: Journal for immunotherapy of cancerAbstract: 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.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. Copyright (c) Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.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).All authors: Alvi RM, Armanious M, Awadalla M, Banerji D, Barac A, Chen CL, Coelho-Filho OR, Cohen JV, Ederhy S, Forrestal BJ, Fradley MG, Ganatra S, Gilman HK, Groarke J, Gupta D, Hartmann S, Hassan MZO, Heinzerling LM, Jones-O'Connor M, Kirchberger MC, Lyon AR, Mahmood SS, Mahmoudi M, Mandawat A, Murphy SP, Neilan TG, Nohria A, Reynolds KL, Rizvi MA, Sahni G, Sullivan R, Thavendiranathan P, Thuny F, Tocchetti CG, Yang EH, Zafar A, Zatarain-Nicolas E, Zhang L, Zlotoff DA, Zubiri LOriginally published: Journal for Immunotherapy of Cancer. 9(3), 2021 Mar.Fiscal year: FY2021Fiscal year of original publication: FY2021Digital Object Identifier: Date added to catalog: 2021-03-10
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Journal Article MedStar Authors Catalog Article 33653803 Available 33653803

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.

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. Copyright (c) Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

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).

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