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Post-MIS-C cardiovascular outcomes: a systematic review

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Abstract

Limited knowledge and variability in findings exist regarding the resolution of cardiovascular outcomes following Multisystem Inflammatory Syndrome in Children (MIS-C). We conducted a systematic review to estimate the frequency of cardiovascular outcomes following MIS-C. A systematic search was conducted in Pubmed/Medline, Scopus, Embase, SciELO, LILACS, Cochrane Library, Web of Science, and medRxiv were searched up to February 2024. We included studies reporting cardiovascular events that began in acute MIS-C and persisted after discharge. Screening and data extraction were performed by independent reviewers. We performed a random-effects meta-analysis and assessed the certainty of the evidence using the GRADE approach. Eighty-four studies (n = 4,778) were included; seven had a comparator group. The frequency of cardiovascular outcomes—including coronary abnormalities (Z-score ≥ 2), left ventricle ejection fraction < 55%, diastolic dysfunction, myocarditis, and pericardial effusion—decreased over time, with most resolving by 6 to 9 months. However, cardiac magnetic resonance imaging studies identified myocardial edema and/or fibrosis persisting up to 12 months, and two studies reported coronary abnormalities at 18- to 24-month follow-up. Evidence certainty was very low. Compared to children with COVID-19 or healthy controls, MIS-C showed more cardiovascular events and greater subclinical myocardial dysfunction, as assessed by strain analysis, during a 6-month follow-up. Compared with other etiologies of myocarditis, MIS-C myocarditis was associated with better cardiovascular outcomes but shorter exercise duration and lower aerobic capacity on stress testing. Conclusions: Cardiovascular outcomes following MIS-C improved over time, but certain subclinical cardiac abnormalities persisted up to 12 to 24 months. These findings may support long-term follow-up after MIS-C.
Trial registration: Protocol registration number: PROSPERO, CRD42022336784.
What is Known:
Multisystem Inflammatory Syndrome in Children (MIS-C) may lead to persistent cardiovascular complications. However, studies show variability in their findings, with heterogeneous follow-up durations—including limited long-term data—small sample sizes, and data mostly originating from single-center experiences in high-income countries.
What is New:
• Cardiovascular outcomes following MIS-C improved over time across global reports, most resolving by 6–9 months; however, advanced non-invasive methods have identified subclinical cardiac abnormalities up to 12–24 months. This may support the development of evidence-based follow-up recommendations after MIS-C.
Title
Post-MIS-C cardiovascular outcomes: a systematic review
Authors
Giancarlo Alvarado-Gamarra
Katherine Alcala-Marcos
Carlos R. Celis
Pía Balmaceda-Nieto
Luigi Cieza
Cristian Morán-Mariños
Pamela Grados-Espinoza
Carlos Alva-Díaz
Lucie Ecker
Theresa J. Ochoa
Luis Miguel Franchi
Leigh M. Howard
Carlos G. Grijalva
Claudio F. Lanata
Publication date
01-03-2026
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Pediatrics / Issue 3/2026
Print ISSN: 0340-6199
Electronic ISSN: 1432-1076
DOI
https://doi.org/10.1007/s00431-026-06798-6
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