key: cord-0948519-3r9nqv6r authors: Kelly, Michael S.; Valle, Christopher W.; Fernandes, Neil D.; Cummings, Brian M.; Lahoud-Rahme, Manuella; Chiu, Joanne S. title: Multisystem Inflammatory Syndrome in Children (MIS-C): Cardiac Biomarker Profiles and Echocardiographic Findings in the Acute and Recovery Phases date: 2020-08-11 journal: J Am Soc Echocardiogr DOI: 10.1016/j.echo.2020.08.008 sha: 91b53c0a048ccd6d5fc4c89a41f23fd1cb5c1adc doc_id: 948519 cord_uid: 3r9nqv6r nan The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been unrelenting in disease burden worldwide with increasing recognition of Multisystem Inflammatory Syndrome in Children (MIS-C) [1] [2] [3] [4] [5] [6] [7] . While cardiac manifestations are reported in , the relationship between cardiac biomarkers and echocardiographic abnormalities and its evolution during illness remains unclear. We present our single institution experience of cardiac manifestations in MIS-C describing changes in cardiac biomarkers and echocardiographic findings across a spectrum of illness severity. This cohort included all patients meeting the CDC or WHO case definitions of MIS-C admitted between May 1, 2020 through June 5, 2020, with follow-up through June 24, 2020. Echocardiograms were performed on the Philips Ie33 standard machine (Philips Healthcare, Andover, MA). Two-dimensional left ventricular ejection fraction (LVEF) was calculated by 5/6 area length method. Cardiac magnetic resonance imaging (MRI) evaluation of late gadolinium enhancement was performed by single-shot survey images. Data are presented as median (range) except as otherwise noted. Twelve children met the inclusion criteria with a median age of 3.5 years (2 months -21 years); 3/12 (25%) were female. All patients tested positive for SARS-CoV-2 either by nasopharyngeal PCR or serology. Laboratory evidence of inflammation was common, as was treatment with immunomodulatory therapies. Serological evidence of myocardial injury was common. Elevated high sensitivity troponin T (hsTropT) and N-terminal pro B-type natriuretic peptide (NT-proBNP) were seen in 9/12 (75%) and 9/11 (82%) patients respectively (Table 1) . Cardiac MRI was performed following the acute phase of illness prior to discharge on two patients who required mechanical support with extracorporeal membrane oxygenation (ECMO). One patient with echocardiographic findings of mildly dilated left main and left anterior descending coronary arteries had on MRI subtle mid-myocardial late gadolinium enhancement in the septum and inferior left ventricle (LV), normal function (LVEF = 60%, right ventricular ejection function (RVEF) = 59%), and a small pericardial effusion. The second patient had no coronary abnormalities by echocardiogram with MRI demonstrating no signs of myocarditis, infiltration, or scar, with normal function (LVEF = 55%, RVEF = 53%) and a small pericardial effusion. While inpatient, 42 echocardiograms were performed (3 echocardiograms per patient [1 -7] ), with echocardiographic abnormalities observed in 8/12 patients (75%). The most common echocardiographic abnormality was reduced LVEF (<55%), noted in 7/12 patients (58%). Median lowest observed LVEF was 54% (14 -70%), with severely reduced LVEF (<30%) seen in 3/12 patients (25%) and mildly reduced LVEF (40-55%) seen in 4/12 (33%) patients. Regional wall motion abnormalities were seen in 3/12 (25%) patients, and qualitative right ventricular (RV) dysfunction was present in 4/12 patients (33%). Coronary changes were observed in 5/12 patients (42%) including lack of distal tapering of the left anterior descending (LAD) (3/12, 25%), LAD dilation (1/12, 8%), and small saccular aneurysm of the right coronary artery (1/12, 8%). All observed effusions were small (4/12, 33%) without evidence of tamponade. Mild or moderate mitral regurgitation was seen in 3/12 (25%) patients, and 2/12 (17%) patients had mild or moderate tricuspid regurgitation. At discharge, echocardiographic abnormalities persisted in 6/8 patients (75%) including small saccular aneurysm of the right coronary artery (1/8, 13%), small pericardial effusion (1/8, 13%) , mild LV dilation with normal LVEF (2/8, 25%), mild RV dilation and dysfunction (1/8, 13%), mild mitral regurgitation (2/8, 25%) and mild tricuspid regurgitation (1/8, 13%). All patients had normal LVEF at discharge. Marked cardiac biomarker elevation was seen, and all patients with LVEF <55% had either a peak hsTropT value of >100 pg/L or a peak NT-proBNP of >1000 ng/mL (Figure 1 ). Of the children with no abnormalities seen on echocardiogram, none had a peak hsTropT >100 (26.5 [<6 -37] pg/mL) and 1/4 (25%) had a peak NT-proBNP >1000 (565 [248 -2613] pg/mL). Follow-up visits and echocardiograms were available for 10/12 (83%) patients (median 16.5 days from discharge [8 -26] ) given that one patient transferred care to another institution while the other is awaiting cardiology follow up. All other patients were asymptomatic at followup with normalization of cardiac biomarkers. All echocardiographic abnormalities resolved with no new abnormalities detected. We describe the evolution of cardiac biomarker elevation and echocardiographic findings in MIS-C patients. The spectrum of cardiac involvement seen in our cohort is similar to large MIS-C case series published in the US 5, 6 with further detail in this report on specific findings during both the acute phase and in recovery. In comparing children with less severe to those with J o u r n a l P r e -p r o o f more severe echocardiographic involvement, elevated cardiac biomarkers were observed to parallel increased severity of echocardiography abnormalities. Based on our observation, while myocardial injury appears common in MIS-C, significant cardiac biomarker elevation (hsTropT >100 pg/L and/or NT-proBNP >5000 ng/mL) may be more indicative of concerning echocardiographic findings associated with illness severity including reduced LVEF. Reduced LVEF without significant biomarker elevation was not seen in our cohort, which may play a role in determining triage and disease trajectory in this emerging process. We report the observed findings in our institutional cohort with a limitation being the need for larger data cohorts with statistical analysis to determine true correlation. Our experience supports previous reports that children with MIS-C across a spectrum of illness severity appear to recover quickly with normalization of cardiac function. Further investigation studying the correlation among cardiac biomarkers, clinical outcomes and echocardiographic data remains urgent to better understand the comprehensive cardiac involvement in MIS-C patients. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. All authors declare no conflicts of interest and no competing interests. Ethics approval: Study was reviewed and approved by our institutional research board (2020P001114). Data is not currently available on any publically available data repositories. Hyperinflammatory Shock in Children During COVID-19 Pandemic Acute Heart Failure in Multisystem Inflammatory Syndrome in Children (MIS-C) in the Context of Global SARS-CoV-2 Pandemic An Outbreak of Severe Kawasaki-like Disease at the Italian Epicentre of the SARS-CoV-2 Epidemic: An Observational Cohort Study Kawasaki-like Multisystem Inflammatory Syndrome in Children During the covid-19 Pandemic Multisystem Inflammatory Syndrome in Children in New York State PIMS-TS): Cardiac Features, Management and Short-Term Outcomes at a UK Tertiary Paediatric Hospital Abnormal (%) Median Maximum Value Erythrocyte Sedimentation Rate (<13 mm/hr) 9/10 (90%) 50 mm/hr <500 ng/mL) 11/12 (92%) 2523 ng/mL N-terminal pro-B-type natriuretic peptide (<500 pg/mL) 9/11 (82%) 2121 pg/mL Erythrocyte Sedimentation Rate (<13 mm/hr) 9/10 (90%) 50 mm/hr <500 ng/mL) 11/12 (92%) 2523 ng/mL N-terminal pro-B-type natriuretic peptide