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Echo Findings in Pediatric Multisystem Inflammatory Syndrome in COVID-19
Quick Takes
- In this study, MIS-C behaves differently from classic Kawasaki disease, with greater incidence of myocardial injury and sparing of the coronary arteries.
- Even with preserved systolic function, there are subtle changes in diastolic function and strain parameters to suggest myocardial injury.
- In short-term follow-up, there is normalization of systolic function but persistence of diastolic dysfunction.
Study Questions:
What are the echocardiographic manifestations of multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19), as compared to classic Kawasaki disease (KD)?
Methods:
This was a retrospective, single-center study of pediatric COVID-19 patients admitted to the Children’s Hospital of Philadelphia between April and June 2020, who received a clinical diagnosis of MIS-C. Exclusion criteria were pre-existing cardiac disease, acute respiratory distress syndrome, need for extracorporeal membrane oxygenation, and prior treatment with chemotherapy. There were two prepandemic control groups: one with 20 age-matched healthy children and one with 20 classic KD patients. Echocardiography was performed in the acute phase of MIS-C and KD, with follow-up in the subacute period in the MIS-C group. Echocardiography included standard measurements per the American Society of Echocardiography, coronary artery size, and strain via speckle tracking analysis. Strain parameters included left ventricular (LV) deformation during systole (e.g., global longitudinal strain), diastole (e.g., longitudinal early diastolic strain), left atrial strain, and right ventricular (RV) strain. MIS-C patients were further divided into positive (+) versus negative (-) myocardial injury based on biomarkers (B-type natriuretic peptide >500 pg/ml and troponin I >0.03 ng/ml).
Results:
A total of 28 MIS-C patients were included in the study. They were age-matched to the control group but significantly older (median age: 11.4 years vs. 3.1 years; p < 0.001) and more obese (mean body mass index 22.5 kg/m2 vs. 16.0 kg/m2, p < 0.001) than KD patients. Myocardial injury was present in 17/28 (61%) MIS-C patients.
Coronary artery echocardiography: Only 1/28 (4%) MIS-C patients had coronary ectasia (which resolved at early follow-up) and none had segmental aneurysms versus 4/20 (20%) KD patients with coronary abnormalities in the acute phase.
Functional echocardiographic assessment: MIS-C patients had lower LV systolic ejection fractions (EFs) than controls (57% [range 48-61] vs. 64% [range 61-66], p < 0.001), more LV diastolic dysfunction, and lower peak left atrial strain and RV free wall strain (all p < 0.001). MIS-C patients also had worse LV systolic and diastolic function than the KD group (all strain parameters, p < 0.05) and cardiogenic shock was far more frequent (85 vs. 5% incidence). Myocardial injury (+) MIS-C patients were even more affected than myocardial injury (-) patients, with respect to all functional echo parameters.
Follow-up echocardiography was done for 20 of the 28 MIS-C patients at 5.2 ± 3 days. Most had improvement in LVEF (median 64% from 54%, p < 0.001), but persistent diastolic dysfunction and depressed global longitudinal strain (GLS).
Conclusions:
In this study, myocardial injury was a prominent feature of MIS-C, with elevation in biomarkers in 61% of children. Systolic and diastolic function were both abnormal in the acute phase, while diastolic dysfunction, as measured by multiple strain parameters, was more likely to persist. Echocardiographic abnormalities were more severe in patients with evidence of myocardial injury. The study also demonstrates significant differences in the cardiac manifestations of MIS-C versus classic KD. Systolic and diastolic dysfunction were more prominent in MIS-C than KD, whereas the opposite was true for coronary artery involvement, with abnormalities present in only 4% of MIS-C patients and normalization at early follow-up.
Perspective:
This pilot study describes a detailed echocardiographic assessment of a cohort of pediatric patients with MIS-C, a novel and rare manifestation of COVID-19 occurring in <1% of children. Even though the sample size is small, it remains an impressive number of cases obtained within a short time frame at a single tertiary-care center. While the authors acknowledge a lack of long-term follow-up, they express a need for more rapid data dissemination. Contrary to initial reports, the study indicates that MIS-C has only limited overlap with KD, including far less coronary artery involvement. However, systolic and diastolic dysfunction may be more common, and the latter may persist even after recovery of systolic EF. The authors attribute this to a myocarditis-like state, based on elevation of cardiac biomarkers, but this will require confirmation by cardiac magnetic resonance and/or biopsy in future studies. Long-term outcomes and risk/benefit ratio of various therapeutic agents will be critical to define if MIS-C continues to be a manifestation of novel coronavirus infection.
Clinical Topics: Congenital Heart Disease and Pediatric Cardiology, COVID-19 Hub, Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Congenital Heart Disease, CHD and Pediatrics and Imaging, CHD and Pediatrics and Prevention, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Echocardiography/Ultrasound
Keywords: Coronavirus, COVID-19, Diagnostic Imaging, Diastole, Echocardiography, Heart Failure, Inflammation, Mucocutaneous Lymph Node Syndrome, Myocarditis, Natriuretic Peptide, Brain, Pediatrics, Pediatric Obesity, severe acute respiratory syndrome coronavirus 2, Shock, Cardiogenic, Systole, Troponin I
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