Acute Cardiovascular Manifestations in 286 Children With Multisystem Inflammatory Syndrome Associated With COVID-19 Infection in Europe

Abstract

Background: The aim of the study was to document cardiovascular clinical findings, cardiac imaging and laboratory markers in children presenting with the novel multisystem inflammatory syndrome (MIS-C) associated with COVID-19 infection. Methods: A real-time internet-based survey endorsed by the Association for European Paediatric and Congenital Cardiologists (AEPC) Working Groups for Cardiac Imaging and Cardiovascular Intensive Care. Inclusion criteria was children 0-18 years admitted to hospital between February 1 and June 6, 2020 with diagnosis of an inflammatory syndrome and acute cardiovascular complications. Results: A total of 286 children from 55 centers in 17 European countries were included. The median age was 8.4 years (IQR 3.8-12.4 years) and 67% were males. The most common cardiovascular complications were shock, cardiac arrhythmias, pericardial effusion and coronary artery dilatation. Reduced left ventricular ejection fraction was present in over half of the patients and a vast majority of children had raised cardiac troponin (cTnT) when checked. The biochemical markers of inflammation were raised in majority of patients on admission: elevated CRP, serum ferritin, procalcitonin, NT-proBNP, IL-6 level and D-dimers. There was a statistically significant correlation between degree of elevation in cardiac and biochemical parameters and need for intensive care support (p <0.05). Polymerase chain reaction (PCR) for SARS-CoV-2 was positive in 33.6% while IgM and IgG antibodies were positive in 15.7% and IgG 43.6 % cases, respectively when checked. One child died in the study cohort. Conclusions: Cardiac involvement is common in children with multisystem inflammatory syndrome associated with Covid-19 pandemic. A majority of children have significantly raised levels of NT pro-BNP, ferritin, D-dimers and cardiac troponin in addition to high CRP and procalcitonin levels. Compared to adults with Covid-19, mortality in children with MIS-C is uncommon despite multi-system involvement, very elevated inflammatory markers and need for intensive care support.

Detailed Assessment of Left Ventricular Function in Multisystem Inflammatory Syndrome in Children, Using Strain Analysis

“…Most published MIS-C case series have assessed for myocardial function with LV EF alone and have reported depressed EF in 38-58% of patients. 6 , 11 , 12 , 13 , 17 , 18 , 19 , 20 , 21 We found that an additional 8% of patients were identified as having impaired LV systolic function using strain measurements compared to EF alone. Among MIS-C patients with normal initial EF, 27% of patients had depressed peak circumferential systolic strain, and, in the setting of the high incidence of elevated troponin and BNP, the percentage of patients with myocardial involvement in MIS-C may be higher than what has been reported using EF alone.…”

“…5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 The most common cardiac manifestation of MIS-C is depressed myocardial function. 6 , 11 , 12 , 13 , 17 , 18 , 19 , 20 , 21 In this single center cohort study, impaired LV systolic function was common with 40% of patients having depressed ejection fraction and 48% demonstrating a decrease in at least one component of systolic strain. Notably, even among MIS-C patients with normal EF, strain assessment showed evidence of impaired LV systolic and diastolic function compared with healthy controls.…”

“…Though limited, MRI data in children with MIS-C has demonstrated both diffuse and sub-epicardial myocardial edema patterns. 19 , 21 While subendocardial myocardial damage in ischemic heart disease has been associated with early reduction in longitudinal strain, it is possible that the unique inflammatory milieu and pattern of myocardial damage results in greater reduction in circumferential shortening as approximately 60% of circumferentially oriented myofibers are located in the mid-muscular layer. 30 , 34 This highlights the importance of further evaluation into the etiology of myocardial dysfunction in this new disease process and to the potential utility of acquiring both longitudinal and circumferential strain in this population.…”

“… 11 , 12 , 13 , 14 , 17 In the case series published to date, 38-58% have presented with depressed left ventricular (LV) systolic function based on ejection fraction (EF) and a significant number have presented with cardiogenic shock. 6 , 11 , 12 , 13 , 17 , 18 , 19 , 20 , 21 Notably, the mechanism of LV dysfunction is yet to be fully elucidated. The trajectory of recovery of systolic function and response to anti-inflammatory medications are also not fully described, though initial reports suggest most patients have normalization of systolic function in the initial 7-10 days after presentation.…”

“…The trajectory of recovery of systolic function and response to anti-inflammatory medications are also not fully described, though initial reports suggest most patients have normalization of systolic function in the initial 7-10 days after presentation. 6 , 13 , 14 , 18 , 19 , 20 , 21 …”