








key: cord-301868-ehck72z2
authors: Jhaveri, Simone; Ahluwalia, Neha; Kaushik, Shubhi; Trachtman, Rebecca; Kowalsky, Shanna; Aydin, Scott; Stern, Kenan
title: Longitudinal Echocardiographic Assessment of Coronary Arteries and Left Ventricular Function Following Multisystem Inflammatory Syndrome in Children (MIS-C)
date: 2020-08-05
journal: J Pediatr
DOI: 10.1016/j.jpeds.2020.08.002
sha: 
doc_id: 301868
cord_uid: ehck72z2

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COVID-19, a disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has accounted for over 460,000 deaths globally as of June 2020.

[1] Children of all ages have been affected, although the clinical manifestations are less severe than adults. In early May, reports emerged from Europe and North America describing a hyperinflammatory condition in children related to SARS-CoV-2 and presenting with some features similar to Kawasaki disease and toxic shock syndrome [2, 3] .

On May 14, 2020, the Centers for Disease Control and Prevention (CDC) recognized this clinical complex as multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 and released a case definition based on clinical and laboratory criteria. [4] MIS-C patients come to medical attention with fever, elevated inflammatory markers, multisystem organ involvement (renal, gastrointestinal, neurologic, dermatologic, cardiac), with evidence of a current or recent SARS-CoV-2 infection or recent close contact with a known or suspected case of COVID-19. In a report describing the experience of MIS-C in New York, 80% of diagnosed children were admitted to the intensive care unit. Of the hospitalized children, 52% had myocardial dysfunction and 9% had coronary artery aneurysms. [5] Management for MIS-C has involved intravenous immunoglobulins, vasoactive agents, anticoagulants and immune-modulating drugs with varied response [6] . To date, reports are limited to description of cardiac findings during hospitalization, however there is paucity of data on the longitudinal follow-up and sequelae in this population. We sought to describe the echocardiographic manifestations of MIS-C including evolution of abnormalities of coronary artery dilation and ventricular systolic function over short-term follow-up after discharge from the hospital.

A single-center retrospective review was conducted on all pediatric patients (<21 years of age) admitted with MIS-C to Mount Sinai Kravis Children's Hospital between April 24 (first admission) and May 16, 2020 who had at least one echocardiogram performed during hospitalization. The determination of diagnosis of MIS-C was based on CDC criteria [4] . Only patients with confirmed SARS-CoV-2 infection J o u r n a l P r e -p r o o f by reverse transcriptase polymerase chain reaction (RT-PCR) and/or serology during hospitalization were included.

All of the patients in our cohort were described previously in three recent multicenter publications [7] [8] [5] that focused on acute presentation and inpatient outcomes. Additionally, 4 patients from this cohort were described in a recent case series [9] . Table (available at www.jpeds.com).

The average LV ejection fraction (EF) at first echocardiogram was 49.5% (range 29-58%). Eight patients (53%) presented with LV dysfunction (EF <55%) ranging from mild to severe (n=2 with EF 50-54%; n=4 with EF 40-49% and n=2 with EF <35%). 10/13 of children (excluding one lost to follow up and one deceased patient) had recovery of cardiac function within one month of the initial study. Three patients continue to have low-normal systolic function (EF=50-55%) and are in ongoing follow-up. (Figure 1, A) Of the four patients (27%) who had RV dysfunction on initial echocardiogram, all but one (deceased) had complete recovery of RV function on follow-up imaging. Two patients had pericardial effusions (small) on initial echocardiograms that resolved. Approximately half (n=8, 53%) of the cohort had mitral regurgitation (mild), all but two resolved over the study period. All patients received therapeutic anticoagulation. Aspirin was started in patients with coronary artery dilation and/or after discontinuation of enoxaparin in patients without dilation.

Coronary artery evaluation was performed in 12 patients (80%) and 10/12 had more than one echocardiogram performed in the study period. Three patients did not have coronary arteries assessing during echocardiography, 2/3 were due to hemodynamically instability, and one patient was the first admission with MIS-C, before the importance of coronary artery assessment was recognized. Of the patients with coronary artery evaluation, one-third (n=4) had coronary involvement (z score >2.5). LMCA aneurysms (1 small, one medium) were seen in two patients; one resolved and one remains persistent at follow-up. (Figure 1, B and Figure 2, A) . LAD aneurysms were seen in three patients (2 small, 1 medium aneurysm). Within 30 days, all patients with LAD involvement had normal z-scores (Figure 1, C) . Only one patient had an aneurysm in the RCA (small) that has remained aneurysmal, albeit slightly smaller on recent echocardiogram (Figure 1, D and Figure 2 , B).

This longitudinal study provides information on short-term echocardiographic outcomes of 15 patients with MIS-C. Although LV dysfunction was common at initial evaluation (53%), significant improvement was seen within a 30-day follow-up period. However, some patients had residual low-normal function at 4-6 weeks follow-up. Our findings are congruent to two larger multicenter studies from New York that showed 53%-65% of patients had evidence of myocardial dysfunction during hospitalization. Follow-up outpatient data on systolic function was not reported. [5] [7] We found that coronary artery abnormalities can be evident in the first two weeks and tend to have a rapid resolution, with only one patient in this study demonstrating persistence of aneurysms. One-third (33%) of our patients (4/12) had coronary aneurysms. This is higher than a recent report by Capone et al, in This study provides short-term longitudinal cardiac information for a small number of patients with MIS-C that may aid in clinical management and counseling of families. Medium and long-term follow-up using echocardiography as well as advanced imaging modalities such as cardiac magnetic resonance and computed tomography will be important to provide comprehensive data. 

An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study

COVID-19 and Kawasaki Disease: Novel Virus and Novel Case

Multisystem Inflammatory Syndrome in Children in New York State

Hyperinflammatory shock in children during COVID-19 pandemic

Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARS-CoV-2 Infection: A Multiinstitutional Study from New York City

Multisystem Inflammatory Syndrome in U.S. Children and Adolescents

Features of COVID-19 post-infectious cytokine release syndrome in children presenting to the emergency department

Diagnosis, treatment, and long-term management of Kawasaki disease: A scientific statement for health professionals from the

Normal Echocardiographic Values for Cardiovascular Structures

A serological assay to detect SARS-CoV-2 seroconversion in humans

Characteristics, Cardiac Involvement, and Outcomes of Multisystem Inflammatory Disease of Childhood (MIS-C) Associated with SARS-CoV-2 Infection

 (7) 80% (12) Corticosteroids administered, % (n) 25% (1) 12.5% (1) 20% (3) Tocilizumab administered, % (n) 100% (4) 62.5% (5) 60% (9) Anakinra administered, % (n) 25% (1) 0% (0) 13.3% (2) Therapeutic anticoagulation % (n) 100 (4)% 100% (8) 100% (15) Remdesivir administered, % (n) 25% (1) 12.5% (1) 20% (3) Plasma therapy administered, % (n) 0% 0% (0) 6.7% (1) ASA during admission, % (n) 50% (2) 0% (0) 13.3% (2) Site of coronary artery involvement (individual patient)1. Mid-LAD, LMCA, mid-RCA 2. LAD 3. LAD 4. LMCA

