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Background Although rare, classic viral myocarditis in the pediatric population is a disease that carries significant morbidity and mortality. Since 2020, myocarditis has been a common component of multisystem inflammatory syndrome in children (MIS‐C) following SARS‐CoV‐2 infection. In 2021, myocarditis related to mRNA COVID‐19 vaccines was recognized as a rare adverse event. This study aims to compare classic, MIS‐C, and COVID‐19 vaccine‐related myocarditis with regard to clinical presentation, course, and outcomes. Methods and Results In this retrospective cohort study, we compared patients aged <21 years hospitalized at our institution with classic viral myocarditis from 2015 to 2019, MIS‐C myocarditis from March 2020 to February 2021, and vaccine‐related myocarditis from May 2021 to June 2021. Of 201 total participants, 43 patients had classic myocarditis, 149 had MIS‐C myocarditis, and 9 had vaccine‐related myocarditis. At presentation, ejection fraction was lowest for those with classic myocarditis, with ejection fraction <55% present in 58% of patients. Nearly all patients with MIS‐C myocarditis (n=139, 93%) and all patients with vaccine‐related myocarditis (n=9, 100%) had normal left ventricular ejection fraction at the time of discharge compared with 70% (n=30) of the classic myocarditis group ( P <0.001). At 3 months after discharge, of the 21 children discharged with depressed ejection fraction, none of the 10 children with MIS‐C myocarditis had residual dysfunction compared with 3 of the 11 (27%) patients in the classic myocarditis group. Conclusions Compared with classic myocarditis, those with MIS‐C myocarditis had better clinical outcomes, including rapid recovery of cardiac function. Patients with vaccine‐related myocarditis had prompt resolution of symptoms and improvement of cardiac function.

Background: Although rare, myocarditis in the pediatric population is a disease process that carries significant morbidity and mortality. Prior to the SARS-CoV-2 related (COVID-19) pandemic, enteroviruses were the most common cause of classic myocarditis. However, since 2020, myocarditis linked to multisystem inflammatory syndrome in children (MIS-C) is now common. In recent months, myocarditis related to COVID-19 vaccines has also been described. This study aims to compare these three different types of myocarditis with regards to clinical presentation, course, and outcomes. Methods: In this retrospective cohort study, we included all patients <21 years of age hospitalized at our institution with classic viral myocarditis from 2015-2019, MIS-C myocarditis from 3/2020-2/2021 and COVID-19 vaccine-related myocarditis from 5/2021-6/2021. We compared demographics, initial symptomatology, treatment, laboratory data, and echocardiogram findings. Results: Of 201 total participants, 43 patients had classic myocarditis, 149 had MIS-C myocarditis, and 9 had COVID-19 vaccine-related myocarditis. Peak troponin was highest in the classic myocarditis group, whereas the MIS-C myocarditis group had the highest recorded brain natriuretic peptide (BNP). There were significant differences in time to recovery of normal left ventricular ejection fraction (LVEF) for the three groups: nearly all patients with MIS-C myocarditis (n=139, 93%) and all patients with COVID-19 vaccine-related myocarditis (n=9, 100%) had normal LVEF at the time of discharge, but a lower proportion of the classic myocarditis group (n=30, 70%) had a normal LVEF at discharge (p<0.001). Three months post-discharge, 18 of 40 children (45%) in the classic myocarditis group still required heart failure treatment, whereas only one of the MIS-C myocarditis patients and none of the COVID-19 vaccine-associated myocarditis patients did. Conclusions: Compared to those with classic myocarditis, those with MIS-C myocarditis had more significant hematologic derangements and worse inflammation at presentation, but had better clinical outcomes, including rapid recovery of cardiac function. Patients with COVID-19 vaccine-related myocarditis had similar clinical presentation to patients with classic myocarditis, but their pattern of recovery was similar to those with MIS-C, with prompt resolution of symptoms and improvement of cardiac function. Long-term follow-up should focus on cardiac and non-cardiac consequences of myocarditis associated with COVID-19 illness and vaccination. Key Words: MIS-C, myocarditis, COVID-19, mRNA vaccine

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Background: In the absence of evidence-based therapies for Multisystem Inflammatory Syndrome in Children (MIS-C), we aimed to describe the similarities and differences in the evaluation and treatment of MIS-C at hospitals in the United States. Methods: We conducted a cross-sectional survey from June 16 to July 16, 2020 of U.S. pediatric hospitals regarding protocols for patients with MIS-C. Elements included hospital characteristics, clinical definition of MIS-C, evaluation, treatment, and follow-up. We summarized key findings and compared results from centers that had treated >5 patients vs. those that had treated <5 patients. Results: Forty centers of varying size and experience with MIS-C participated. About half (21/40) of centers required only 1 day of fever for MIS-C to be considered. In the evaluation of patients, there was often a tiered approach. Intravenous immunoglobulin was the most widely used medication to treat MIS-C (98% of centers). Corticosteroids were listed in 93% of protocols for primarily the moderate or severe cases. Aspirin was commonly used including for mild cases, whereas heparin or low molecular weight heparin were used primarily in severe cases. In severe cases, anakinra and vasopressors were frequently recommended. Nearly all centers (39/40) recommended follow up with cardiology. There were similar findings between centers that had treated >5 patients vs. those that had treated <5 patients. A supplement containing hospital protocols is provided. Conclusion: There are many similarities yet some key differences between hospital protocols for MIS-C. These findings can help healthcare providers learn from others regarding options for managing MIS-C patients.

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Objective: To report intermediate cardiac magnetic resonance (CMR) findings of COVID-19 vaccine associated myocarditis (C-VAM) and compare to classic myocarditis (CM) and multisystem inflammatory syndrome in children (MIS-C). Study Design: Retrospective cohort study including children diagnosed with C-VAM from 5/2021 through 12/2021 with early and intermediate CMR. Patients with CM and MIS-C with intermediate CMR were included for comparison. Results: There were 8 patients with C-VAM, 20 with CM, and 61 with MIS-C. Among those with C-VAM, CMR performed at median 3 days (IQR 3, 7) revealed 2/8 patients with left ventricular ejection fraction (LVEF)<55%, 7/7 patients with late gadolinium enhancement (LGE), and 5/8 patients with elevated native T1 values. Borderline T2 values suggestive of myocardial edema were present in 6/8. Follow-up CMRs performed at median 107 days (IQR 97, 177) showed normal ventricular systolic function, T1, and T2 values; 3/7 patients had LGE. At intermediate follow up the C-VAM group had a lower percentage of LVEF<55% compared to CM and MIS-C (0.0 vs 30.0 vs 6.6%, respectively, p=0.018) and an intermediate degree of LGE (42.9 vs 75.0 vs 3.3%, respectively, p<0.001). Pairwise comparisons showed fewer myocardial segments with LGE in the C-VAM group versus CM (4/119 vs 42/340, p=0.004) and more segments with LGE than MIS-C (4/119 vs 2/1020, p=0.0014). Conclusion: Patients with C-VAM had no evidence of active inflammation or ventricular dysfunction on intermediate CMR although a minority had persistent LGE. Intermediate findings in C-VAM may be favorable compared to CM though LGE is more common compared to MIS-C.

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