Anemia at Initial Presentation Is Associated with Myocardial Abnormalities Detected by Cardiac Magnetic Resonance Imaging > 6 Weeks After Multisystem Inflammatory Syndrome in Children (MIS-C)

Background: Multisystem inflammatory syndrome in children (MIS-C) often presents with features similar to that of myocarditis and with evidence of myocardial injury. This has raised concern about persistent myocarditis following MIS-C which can be assessed by cardiac MRI (CMR). We aim to study if the initial clinical presentation, laboratory abnormalities, immunotherapy, and persistence of symptoms during follow up are predictive of persistent myocarditis on CMR after being diagnosed with MIS-C.

Methods: A retrospective cohort study was performed including all patients <21 years old who had a CMR > 6 weeks after MIS-C diagnosis at our institution. The primary outcome was myocarditis on CMR by revised Lake Louise criteria and secondary composite outcome included at least 1 CMR abnormality using tissue characterization techniques (extracellular volume >30%, myocardial T2 values >60 ms, or late gadolinium enhancement). These CMR findings identify evidence of myocardial injury, edema, and scar, respectively.

Results: There were a total of 49 patients with MIS-C included in the analysis (31 male, 63%) with median age of 11.4 years (8.8, 15.6). CMR was performed at a median of 3.6 months (IQR 2.9, 4.5) after diagnosis and a total of 3/49 (6%) patients met criteria for myocarditis on CMR. At least 1 CMR abnormality was found in 8/49 (16%) patients. The cohort overall commonly presented with left ventricular ejection fraction <55% by 2D echocardiography in 27/49 (55%), coronary artery dilation 23/49 (47%), and the need for inotropic support 21/49 (43%) patients. Among symptoms at presentation, inflammatory markers, cardiac biomarkers, immunomodulatory therapies, length of hospitalization, and persistence of symptoms, only lower trough hemoglobin during presentation was associated with evidence of myocardial injury, edema, or fibrosis on CMR performed at 3.4 (2.8, 4.4) months following MISC diagnosis (Table). A receiver operating characteristic curve analysis using lowest hemoglobin at MIS-C diagnosis to predict CMR abnormality > 6 weeks after MIS-C showed an area under the curve of 0.83 (Figure).

Conclusion: MIS-C is followed by subacute myocarditis detected on CMR in 6% of the study patient cohort, despite significant myocardial involvement at initial presentation. A lower trough hemoglobin at the time of MIS-C diagnosis is associated with persistent myocardial abnormalities detected on CMR during follow-up. CMR using parametric mapping technique is helpful in detecting myocarditis and subclinical myocardial abnormalities in the assessment of children following MIS-C. Longitudinal follow-up is necessary to reveal clinical significance of abnormalities detected on CMR in this study population.