Association between EKG Alterations and Clinical Outcomes in Immune Checkpoint Inhibitor-Associated Myocarditis

Abstract

Background Immune checkpoint inhibitors (ICIs) have revolutionized oncologic care. Myocarditis is an uncommon but frequently fatal complication of ICI use. There is need for improved methods of detection and risk stratification of ICI myocarditis. Both the QRS duration and the QTc interval on EKG are widely used, standardized, and easily interpretable measures; there are no data on the utility of these measures among patients with ICI myocarditis. Hypothesis We hypothesized that ICI myocarditis is associated with EKG abnormalities and that such abnormalities would correlate with worse clinical outcomes. Methods From a multicenter international registry, we compared the PR interval, QRS duration, and QTc interval from 110 ICI myocarditis cases and 178 controls. Where available, we measured these parameters from cases and controls prior to starting ICI and also while on ICI but prior to the development of myocarditis (for cases). The association between EKG measures and major adverse cardiac events (MACE) was tested. Cases and controls were compared using the pair-wise Wilcoxon rank-sum test with Bonferroni correction, MACE Kaplan-Meier curves were compared with the log-rank test, and hazard ratios (HR) were determined using the Cox proportional hazards model. Results The PR interval, QRS duration, and QTc interval were similar between cases and controls both prior to ICI and after initiation of ICI but prior to myocarditis (in cases). At presentation with myocarditis, cases had a similar PR interval, but longer QRS duration (107±22 ms vs 91±19 ms; p 110 ms conferred a 2.6-fold increased risk of MACE (95% confidence interval [CI] 1.5-4.4; p 450 ms also conferred a 2.6-fold increased risk (95% CI 1.3-5.1; p=0.003; figure B). Conclusions Increases in QRS duration and QTc interval, but not PR interval, were observed in ICI myocarditis and were each associated with increased risk of MACE. Measurement of these standardized and widely available parameters may be helpful in diagnosing ICI myocarditis and identifying those with ICI myocarditis at elevated risk of MACE.