Background While immune checkpoint inhibitors (ICI) -induced myocarditis and coronavirus disease 2019 (COVID-19) vaccine-induced myocarditis are considered to be rare; they are both significant side effects, suggested being caused by activation of the immune system against the myocardium. We aimed to assess whether both phenomena share similar presenting characteristics. Methods We included patients diagnosed with either ICI or COVID-19 vaccine-induced myocarditis at our medical center. We performed a retrospective assessment of clinical presentation, blood tests, and advanced echocardiography, including speckle strain. Results We included 18 patients diagnosed with ICI (ICI group) or COVID-19 vaccine (COVID-19 group)-induced myocarditis, and 20 patients with viral myocarditis (Viral group) as a control group. The median age was significantly older in the ICI group (74 years) compared to the COVID-19 and Viral groups (20 and 24 years), p<0.001. The clinical presentation in the COVID-19 group was more similar to the Viral group, presenting mainly with chest pain and fever, while the ICI group presented mainly with dyspnea. ST-elevation was frequent in the COVID-19 and Viral groups and absent in the ICI group, p=0.004. Median peak high sensitivity troponin I values were markedly lower in the ICI group compared to the COVID-19 and Viral groups (619 ng/L vs. 15527 ng/L vs. 7388 ng/L, p=0.004). While the median left ventricular ejection fraction was 60% among all groups, patients in the ICI group presented with mean lower LV global longitudinal strain (−13%) and left atrial conduit strain (17%), compared to the COVID-19 (−17% and 30%) and Viral groups (−18% and 37%), p=0.016 and p=0.001. Conclusions While the suspected mechanism is an activation of the immune system in both ICI and the COVID-19 vaccine-induced myocarditis, we found that the clinical presentation, cardiac biomarkers, and advanced echocardiography of the COVID-19 vaccine, are more similar to viral myocarditis than to ICI-induced myocarditis. Funding Acknowledgement Type of funding sources: None.

This article refers to 'Characteristics, management, and outcomes of patients with left-sided infective endocarditis complicated by heart failure: a substudy of the ESC-EORP EURO-ENDO (European infective endocarditis) registry' by Y. Bohbot et al., published in this issue on pages 1253-1265.