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Clinical course and follow-up of pediatric patients with COVID-19 vaccine-associated myocarditis compared to non–vaccine-associated myocarditis within the prospective multicenter registry—“MYKKE” - 07/12/23

Doi : 10.1016/j.ahj.2023.11.006 
Nele Rolfs, MD a, b, , Cynthia Huber, MSc c, Eicke Schwarzkopf, MA a, b, Dirk Mentzer, MD d, Brigitte Keller-Stanislawski, MD d, Bernd Opgen-Rhein, MD a, b, Wiebke Frede, MD e, Axel Rentzsch, MD f, Tobias Hecht, MD g, Martin Boehne, MD, PhD h, Maria Grafmann, MD i, Daniela Kiski, MD j, Iva Graumann, MD k, Rudi Foth, MD l, Inga Voges, MD, PhD m, n, Ulrich Schweigmann, MD o, Bettina Ruf, MD p, Marcus Fischer, MD q, Gesa Wiegand, MD r, Karin Klingel, MD, PhD s, Thomas Pickardt, PhD t, Tim Friede, PhD c, Daniel Messroghli, MD, PhD b, u, v, Stephan Schubert, MD, PhD g, v, Franziska Seidel, MD a, b, v
on Behalf of the

MYKKE Consortium

a Department of Congenital Heart Disease – Pediatric Cardiology, Deutsches Herzzentrum der Charité, Berlin, Germany 
b Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany 
c Medical Statistics, Universitätsmedizin Goettingen, Goettingen, Germany 
d Paul-Ehrlich-Institut – Federal Institute for Vaccines and Biomedicines, Langen, Germany 
e Pediatric Cardiology and Congenital Heart Defects, Center for Pediatrics, University Hospital Heidelberg, Heidelberg, Germany 
f Department of Pediatric Cardiology, Saarland University Hospital, Homburg (Saar), Germany 
g Center of Congenital Heart Disease and Pediatric Cardiology, Heart- and Diabetes Center NRW and University Clinic of Ruhr-University Bochum, Bad Oeynhausen, Germany 
h Department of Pediatric Cardiology and Intensive Care Medicine, Hannover Medical School, Hannover, Germany 
i Department of Pediatric Cardiology, Children's Heart Clinic, University Heart & Vascular Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 
j Department of Pediatric Cardiology, University Hospital Muenster, Muenster, Germany 
k Department of Pediatrics, Martin-Luther-Universität Halle-Wittenberg, Halle, Germany 
l Department of Pediatric Cardiology, Universitätsmedizin Goettingen, Goettingen, Germany 
m Department of Congenital Heart Disease and Pediatric Cardiology, University Hospital Schleswig-Holstein, Kiel, Germany 
n DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Luebeck/Kiel, Kiel, Germany 
o Pediatric Cardiology, Olgahospital, Stuttgart, Germany 
p Department of Pediatric Cardiology, German Heart Center Munich, Munich, Germany 
q Department of Pediatric Cardiology and Pediatric Intensive Care, Ludwig Maximilians University of Munich, Munich, Germany 
r Department of Pediatric Cardiology, University Hospital Tuebingen, Tuebingen, Germany 
s Cardiopathology, Institute for Pathology, University Hospital Tuebingen, Tuebingen, Germany 
t Competence Network for Congenital Heart Defects, Berlin, Germany 
u Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Berlin, Germany 
v DZHK (German Center for Cardiovascular Research), Berlin, Germany 

Reprint requests: Nele Rolfs, MD, Department of Congenital Heart Disease – Pediatric Cardiology, Deutsches Herzzentrum der Charité, Augustenburger Platz 1, 13353 Berlin, Germany.Department of Congenital Heart Disease – Pediatric CardiologyDeutsches Herzzentrum der CharitéAugustenburger Platz 1Berlin13353Germany

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ABSTRACT

Background

Since the onset of widespread COVID-19 vaccination, increased incidence of COVID-19 vaccine-associated myocarditis (VA-myocarditis) has been noted, particularly in male adolescents.

Methods

Patients <18 years with suspected myocarditis following COVID-19 vaccination within 21 days were enrolled in the PedMYCVAC cohort, a substudy within the prospective multicenter registry for pediatric myocarditis “MYKKE.” Clinical data at initial admission, 3- and 9-months follow-up were monitored and compared to pediatric patients with confirmed non–vaccine-associated myocarditis (NVA-myocarditis) adjusting for various baseline characteristics.

Results

From July 2021 to December 2022, 56 patients with VA-myocarditis across 15 centers were enrolled (median age 16.3 years, 91% male). Initially, 11 patients (20%) had mildly reduced left ventricular ejection fraction (LVEF; 45%-54%). No incidents of severe heart failure, transplantation or death were observed. Of 49 patients at 3-months follow-up (median (IQR) 94 (63-118) days), residual symptoms were registered in 14 patients (29%), most commonly atypical intermittent chest pain and fatigue. Diagnostic abnormalities remained in 23 patients (47%). Of 21 patients at 9-months follow-up (259 (218-319) days), all were free of symptoms and diagnostic abnormalities remained in 9 patients (43%). These residuals were mostly residual late gadolinium enhancement in magnetic resonance imaging. Patients with NVA-myocarditis (n=108) more often had symptoms of heart failure (P = .003), arrhythmias (P = .031), left ventricular dilatation (P = .045), lower LVEF (P < .001) and major cardiac adverse events (P = .102).

Conclusions

Course of COVID-19 vaccine-associated myocarditis in pediatric patients seems to be mild and differs from non–vaccine-associated myocarditis. Due to a considerable number of residual symptoms and diagnostic abnormalities at follow-up, further studies are needed to define its long-term implications.

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Abbreviations : ARVC, BMI, BSA, CMRI, COVID-19, CRP, ECG, EMB, GLM, Hs-cTnT, HTX, IL-1RA, IQR, LGE, LVEF, LVEDD, LVEDV, LVNC, MACE, MCS, MRNA, NYHA, NSAIDs, NSVT, NT-proBNP, NVA-myocarditis, VA-myocarditis


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