Original Investigation
Phenotypic Heterogeneity of Fulminant COVID-19--Related Myocarditis in Adults

https://doi.org/10.1016/j.jacc.2022.04.056Get rights and content
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Abstract

Background

Adults who have been infected with SARS-CoV-2 can develop a multisystem inflammatory syndrome (MIS-A), including fulminant myocarditis. Yet, several patients fail to meet MIS-A criteria, suggesting the existence of distinct phenotypes in fulminant COVID-19–related myocarditis.

Objectives

This study sought to compare the characteristics and clinical outcome between patients with fulminant COVID-19–related myocarditis fulfilling MIS-A criteria (MIS-A+) or not (MIS-A−).

Methods

A monocentric retrospective analysis of consecutive fulminant COVID-19–related myocarditis in a 26-bed intensive care unit (ICU).

Results

Between March 2020 and June 2021, 38 patients required ICU admission (male 66%; mean age 32 ± 15 years) for suspected fulminant COVID-19–related myocarditis. In-ICU treatment for organ failure included dobutamine 79%, norepinephrine 60%, mechanical ventilation 50%, venoarterial extracorporeal membrane oxygenation 42%, and renal replacement therapy 29%. In-hospital mortality was 13%. Twenty-five patients (66%) met the MIS-A criteria. MIS-A− patients compared with MIS-A+ patients were characterized by a shorter delay between COVID-19 symptoms onset and myocarditis, a lower left ventricular ejection fraction, and a higher rate of in-ICU organ failure, and were more likely to require mechanical circulatory support with venoarterial extracorporeal membrane oxygenation (92% vs 16%; P < 0.0001). In-hospital mortality was higher in MIS-A− patients (31% vs 4%). MIS-A+ had higher circulating levels of interleukin (IL)-22, IL-17, and tumor necrosis factor-α (TNF-α), whereas MIS-A− had higher interferon-α2 (IFN-α2) and IL-8 levels. RNA polymerase III autoantibodies were present in 7 of 13 MIS-A− patients (54%) but in none of the MIS-A+ patients.

Conclusion

MIS-A+ and MIS-A− fulminant COVID-19–related myocarditis patients have 2 distinct phenotypes with different clinical presentations, prognosis, and immunological profiles. Differentiating these 2 phenotypes is relevant for patients’ management and further understanding of their pathophysiology.

Key Words

COVID-19
cytokines
fulminant myocarditis
multisystem inflammatory syndrome
RNA polymerase III autoantibodies
SARS-CoV-2
VA-ECMO

Abbreviations and Acronyms

CMR
cardiac magnetic resonance imaging
ELISA
enzyme-linked immunosorbent assay
EMB
endomyocardial biopsy
ICU
intensive care unit
IFN
interferon
IgG
immunoglobulin G
IL
interleukin
LVEF
left ventricular ejection fraction
MIS
multisystem inflammatory syndrome
MIS-A
multisystem inflammatory syndrome in adults
MIS-C
multisystem inflammatory syndrome in children
PCA
principal component analysis
RT-PCR
reverse transcription polymerase chain reaction
SARS-CoV-2
severe acute respiratory syndrome-coronavirus-2
TNF
tumor necrosis factor
VA-ECMO
venoarterial extracorporeal membrane oxygenation

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Listen to this manuscript's audio summary by Editor-in-Chief Dr Valentin Fuster on www.jacc.org/journal/jacc.

Andrew Civitello, MD, served as Guest Associate Editor for this paper. Christie M. Ballantyne, MD, served as Guest Editor-in-Chief for this paper.

The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.

∗

Drs Barhoum and Pineton de Chambrun contributed equally to this work as first authors.

†

Drs Gorochov and Hékimian jointly coordinated the study as senior authors.

© 2022 by the American College of Cardiology Foundation. Published by Elsevier.