key: cord-0866718-hm7vih1u authors: Bews, Hilary; Bryson, Ashley; Bortoluzzi, Tessa; Tam, James W.; Jassal, Davinder S. title: COVID-19 vaccination induced myopericarditis: an imager’s perspective date: 2022-01-29 journal: CJC Open DOI: 10.1016/j.cjco.2022.01.007 sha: 4694d7818e66e7914d224c60cdb85a938643f1c2 doc_id: 866718 cord_uid: hm7vih1u COVID-19 vaccine induced myocarditis is a rare adverse event in the current pandemic. The following is a case series of 10 individuals with COVID-19 vaccine related myocarditis confirmed by cardiac MRI (CMR). In this cohort of predominantly males with a mean age of 23 years, chest discomfort and positive cardiac biomarkers occurred at a median of 3 days after the second COVID-19 vaccine dose. Although systolic function was relatively preserved on noninvasive cardiac imaging, there was evidence of delayed enhancement on CMR confirming myocarditis. As COVID-19 vaccine induced myocarditis has a relatively benign clinical course, the benefits of vaccination still by far outweigh this small risk. COVID-19 vaccine induced myocarditis is a rare adverse event in the current pandemic. The following is a case series of 10 individuals with COVID-19 vaccine related myocarditis confirmed by cardiac MRI (CMR). In this cohort of predominantly males with a mean age of 23 years, chest discomfort and positive cardiac biomarkers occurred at a median of 3 days after the second COVID-19 vaccine dose. Although systolic function was relatively preserved on noninvasive cardiac imaging, there was evidence of delayed enhancement on CMR confirming myocarditis. As COVID-19 vaccine induced myocarditis has a relatively benign clinical course, the benefits of vaccination still by far outweigh this small risk. The COVID-19 pandemic has resulted in unprecedented morbidity and mortality, and has had economic and social implications that will continue to last for decades to come. In response to the pandemic, two mRNA vaccines were developed by Pfizer and Moderna, respectively, and approved by Health Canada in December 2020. Since this time, a small number of case reports have described the rare occurrence of myocarditis after COVID-19 vaccination, raising the confirmation of this rare vaccine related adverse event. We report a case series of 10 patients diagnosed with COVID-19 vaccine related myocarditis by cardiac MRI (CMR). Table S1 ). The mean age of affected individuals was 23 years (range 18-45 years). A total of 9 cases occurred in males, 2 of whom were female to male transgender individuals currently on testosterone therapy. The median time from vaccination to hospital presentation was 3 days (range 2-20 days) and 90% presented after the second vaccine dose. None of the 10 individuals had a previous history of pericarditis nor myocarditis. The most common presenting symptom was pleuritic chest pain with no evidence of a pericardial rub. The mean hsTnT level was 846 ng/L (normal 0 -14 ng/L) and the mean CRP level was 39 mg/L (range 3 -92 mg/L; normal < 5 mg/L). The most common finding on electrocardiography included subtle diffuse ST abnormalities. All 10 individuals had negative COVID-19 PCR testing on admission. On transthoracic echocardiography (TTE), the mean left ventricular ejection fraction (LVEF) was 56% with mild regional wall motion abnormalities (range 45%-60%; supplementary Table S2 ). There was no evidence of a pericardial effusion on TTE imaging. While the location of wall motion abnormalities did vary between cases, the basal to mid inferior and inferolateral walls were overwhelmingly affected. Diastolic function, left ventricular filling pressures, and right J o u r n a l P r e -p r o o f ventricular structure and function were normal. In a subset of 4 patients, global longitudinal strain (GLS) was performed ( Figure 1A) and was reduced in a primarily epicardial distribution, with an average value of -13.7 (supplementary Table S2 ). The CMR studies were completed, on average, 10.3 days after TTE (range 0 -52 days). All patients demonstrated a preserved or borderline reduced LVEF on CMR (supplementary Table S3 ). On CMR, regional wall motion abnormalities were only observed in 1 patient with no evidence of a pericardial effusion. All 10 patients demonstrated late gadolinium enhancement (LGE) in a sub-epicardial or mid-myocardial distribution, most commonly affecting the inferior, inferolateral, and lateral walls as detailed in supplementary Table S3 (Figures 1B-C) . LGE of the pericardium was not observed. All patients were admitted to hospital for work-up of myocarditis and monitoring, with a median stay of 4.5 days (range 3 -6 days). The majority of cases were treated with ibuprofen and colchicine for acute pericarditis, and although 2 patients required additional therapy for recurrent chest pain, no adverse events including arrhythmias, heart failure, cardiogenic shock or death were noted in any of the 10 cases. 4 Finally, a delayed hypersensitivity reaction has been proposed, with sensitization occurring after the first dose of COVID-19 vaccination. 6 In one case series, the 3 patients diagnosed with myocarditis following the first COVID-19 vaccine dose had all recovered from prior natural SARS-CoV-2 infection, suggesting an alternate sensitization event. 6 Of note, our patient who presented after the first vaccine dose did not have a previously documented SARS- Similar to previous case series, our findings confirm that COVID-19 vaccine related myocarditis disproportionately affects young males, primarily after the second vaccine dose. 4, 6 In phase I/II studies, a stronger immunologic response was observed after the second vaccine dose, which may explain this finding. 7 The overrepresentation of male cases likely relates to a complex J o u r n a l P r e -p r o o f interplay between sex differences in hormonal factors, including a role of testosterone in the inhibition of anti-inflammatory cells and stimulation of a Th1 immune response. 4 The 2 transgender female to male patients on testosterone therapy in our case series support this theory. The echocardiographic and CMR findings of a normal or borderline reduced LVEF in our case series was consistent with previous reports. 8 Of interest, although the majority of our patients were treated for acute pericarditis with anti-inflammatory agents and colchicine, there was no evidence of a pericardial effusion nor delayed enhancement of the pericardium on TTE and CMR imaging. Despite the observation of mild regional wall motion abnormalities affecting the mid to basal inferior and inferolateral walls on TTE in the acute setting, most patients did not demonstrate wall motion abnormalities on CMR. This may be, in part, due to the delayed CMR imaging of approximately 10 days after the acute presentation. All of our patients demonstrated LGE, primarily affecting the inferior, inferolateral, and lateral walls. This distribution coincides with findings reported by Shaw et al. 8 In addition to CMR, we report novel abnormal epicardial GLS values in all 3 patients who had this parameter measured, suggesting that GLS may be an additional noninvasive tool for the identification of COVID-19 vaccine related myocarditis. vaccination. In this case series, young males were more commonly affected, particularly after the second mRNA vaccine dose. As COVID-19 vaccine induced myocarditis has a relatively benign clinical course, the benefits of vaccination still by far outweigh this small risk. Brighton collaboration, myocarditis/pericarditis case definition. The Task Force for Global Health Myocarditis after BNT162b2 mRNA Vaccine against Covid-19 in Israel Myocarditis and Pericarditis After COVID-19 mRNA Vaccination: Practical Considerations for Care Providers Myocarditis With COVID-19 mRNA Vaccines Safety of the BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting Myocarditis Following Immunization With mRNA COVID-19 Vaccines in Members of the US Military Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults Possible Association Between COVID-19 Vaccine and Myocarditis: Clinical and CMR Findings