Echocardiographic Indicators Associated with Adverse Clinical Course and Cardiac Sequelae in Multisystem Inflammatory Syndrome in Children with COVID-19

Sanil, Yamuna; Misra, Amrit; Safa, Raya; Blake, Jennifer M.; Eddine, Ahmad Charaf; Balakrishnan, Preetha; Garcia, Richard U.; Taylor, Rachel; Dentel, John N.; Ang, Jocelyn; Cashen, Katherine; Heidemann, Sabrina M.; Bauerfield, Christian; Sethuraman, Usha; Farooqi, Ahmad; Aggarwal, Sanjeev; Singh, Gautam

Background Multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C) causes significant cardiovascular involvement, which can be a determinant of clinical course and outcome. We aimed to investigate whether echocardiographic measures of ventricular function were independently associated with adverse clinical course and cardiac sequaele in MIS-C. Methods In a longitudinal observational study of 54 MIS-C patients (mean age 6.8 ± 4.4 years, 46% male, 56% African American), measures of ventricular function and morphometry at initial presentation, pre-discharge, and median of 3 and 10 week follow-up were retrospectively analyzed, and were compared to 108 84 age and gender matched normal controls. The magnitude of strain is expressed as an absolute value. Risk stratification for adverse clinical course and outcomes were analyzed between the tertiles of clinical and echo data using ANOVA, univariate and multivariate regression. Results Median LV apical 4-chamber longitudinal (LVA4LS) and global longitudinal strain (LVGLS) at the initial presentation were significantly decreased in MIS-C compared to normal cohort (16.2% and 15.1% vs. 22.3% and 22.0% respectively, p<0.01). Patients in the lowest LVA4LS tertile (<13%) had significantly higher CRP and hs-Troponin, need for intensive care (ICU), mechanical life support, and longer hospital length of stay (LOS) compared to those in the highest tertile (>18.5%) (p<0.01). Initial LVA4LS and LVGLS were normal in 13 of 54 and 10 of 39 patients respectively. There was no mortality. In multivariate regression, only LVA4LS was associated with both the need for ICU and LOS. At median 10 week follow-up to date, 7 of 36 patients (19%) and 6 of 25 patients (24%) had abnormal LVA4LS and LVGLS respectively. Initial LVA4LS<16.2% indicated abnormal LVA4LS at follow-up with 100% sensitivity. Conclusion Impaired LVGLS and LVA4LS at initial presentation independently indicate a higher risk of adverse acute clinical course and persistent subclinical LV dysfunction at 10 weeks follow-up, suggesting they could be applied to identify higher risk children with MIS-C.