Post-MIS-C cardiovascular outcomes: a systematic review

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.