Association of early electrical changes with cardiovascular outcomes in immune checkpoint inhibitor myocarditis

• DOI: 10.1016/j.acvd.2022.03.003
• Publication Date: 2022-04-28T01:59:26Z
• Authors: John R. Power; Joachim Alexandre; Arrush Choudhary; Benay Ozbay; Salim S. Hayek; Aarti Asnani; Yuichi Tamura; Mandar Aras; Jennifer Cautela; Franck Thuny; Lauren Gilstrap; Dimitri Arangalage; Steven Ewer; Shi Huang; Anita Deswal; Nicolas L. Palaskas; Daniel Finke; Lorenz H. Lehmann; Stephane Ederhy; Javid Moslehi; Joe-Elie Salem; Charlotte Fenioux; Baptiste Abbar; Yves Allenbach; Shanthini M. Crusz; Arjun K. Ghosh; Tyler Moran; Tyler Mehegan; Lawrence Piro; Wei-Ting Chang; Johnny Chahine; Danette Flint; Ben Stringer; Valérie Gounant; Martin Nicol; Barouyr Baroudjian; Marie-Claire Zimmer; Elvire Mervoyer; Darryl Leong; Ryota Morimoto; Nicolas Piriou; Cecilia Monge; Amy Copeland; Kambiz Ghafourian; Avirup Guha; Sergey Brodsky; Osnat Itzhaki Ben...; Manhal Habib; Grace Dy; Ellen Warner; Michal Laufer-Perl; Lily Koo Lin; Ana Narezkina; Alan Baik; Carrie Lenneman; Pankit Vachhani; Tariq U. Azam; Daniel Perry; Pennelope Blakely; Kazuko Tajiri; Matthew Martini; Joseph Nowatzke; Olusola Ayodeji O...; Andrew Hughes; Lauren A. Baldass...; Milan Patel
• Keywords: Interquartile range

Immune-checkpoint inhibitor-associated myocarditis (ICI-myocarditis) often presents with arrhythmias, but the prognostic value of early electrocardiogram findings is unclear. Although ICI-myocarditis and acute cellular rejection (ACR) following cardiac transplantation use similar treatment strategies, differences in arrhythmia burden are unknown.To evaluate the association of electrocardiogram findings in ICI-myocarditis with myocarditis-related mortality and life-threatening arrhythmia.A total of 125 cases of ICI-myocarditis were identified retrospectively across 49 hospitals worldwide; 50 cases of grade 2R or 3R ACR were included as comparators. Two cardiologists blinded to clinical data interpreted electrocardiograms. Associations between electrocardiogram features, myocarditis-related mortality and the composite of myocarditis-related mortality and life-threatening arrhythmias were examined. Adjusted hazard ratios (aHRs) were calculated.The cohort had 78 (62.4%) men; median (interquartile range) age was 67 (58-76) years. At 30 days, myocarditis-related mortality was 20/124 (16.1%), and 28/124 (22.6%) met the composite endpoint. Patients who developed complete heart block (aHR by subdistribution hazards model [aHR(sh)] 3.29, 95% confidence interval [CI] 1.24-8.68; P=0.02) or life-threatening cardiac arrhythmias (aHR(sh) 6.82, 95% CI: 2.87-16.21; P<0.001) had a higher risk of myocarditis-related mortality. Pathological Q waves (aHR(sh) 3.40, 95% CI: 1.38-8.33; P=0.008), low QRS voltage (aHR(sh) 6.05, 95% CI: 2.10-17.39; P<0.001) and Sokolow-Lyon index (aHR(sh)/mV 0.54, 95% CI: 0.30-0.97; P=0.04) on admission electrocardiogram were also associated with increased risk of myocarditis-related mortality. These associations were mirrored in the composite outcome analysis. Compared with ACR, ICI-myocarditis had a higher incidence of life-threatening cardiac arrhythmias (15/125 [12.0%] vs 1/50 [2%]; P=0.04) and third-degree heart block (19/125 [15.2%] vs 0/50 [0%]; P=0.004).Electrocardiograms in ICI-myocarditis with ventricular tachycardias, heart block, low-voltage and pathological Q waves were associated with myocarditis-related mortality and life-threating arrhythmia. Arrhythmia burden in ICI-myocarditis exceeds that of ACR after heart transplant.