Background Centers from Europe and United States have reported an exceedingly high number of children with a severe inflammatory syndrome in the setting of COVID-19, which has been termed multisystem inflammatory syndrome in children (MIS-C). Objectives This study aimed to analyze echocardiographic manifestations in MIS-C. Methods We retrospectively reviewed 28 MIS-C, 20 healthy controls and 20 classic Kawasaki disease (KD) patients. We reviewed echocardiographic parameters in acute phase of MIS-C and KD groups, and during subacute period in MIS-C group (interval: 5.2 ± 3 days). Results Only 1 case in MIS-C (4%) manifested coronary artery dilatation (z score=3.15) in acute phase, showing resolution during early follow up. Left ventricular (LV) systolic and diastolic function measured by deformation parameters, were worse in MIS-C compared to KD. Moreover, MIS-C patients with myocardial injury (+) were more affected than myocardial injury (-) MIS-C with respect to all functional parameters. The strongest parameters to predict myocardial injury in MIS-C were global longitudinal strain (GLS), global circumferential strain (GCS), peak left atrial strain (LAS) and peak longitudinal strain of right ventricular free wall (RVFWLS) (Odds ratio: 1.45 (1.08-1.95), 1.39 (1.04-1.88), 0.84 (0.73-0.96), 1.59 (1.09-2.34) respectively). The preserved LVEF group in MIS-C showed diastolic dysfunction. During subacute period, LVEF returned to normal (median: from 54% to 64%, p<0.001) but diastolic dysfunction persisted. Conclusions Unlike classic KD, coronary arteries may be spared in early MIS-C, however, myocardial injury is common. Even preserved EF patients showed subtle changes in myocardial deformation, suggesting subclinical myocardial injury. During an abbreviated follow-up, there was good recovery of systolic function but persistence of diastolic dysfunction and no coronary aneurysms. Condensed abstract Multisystem inflammatory syndrome in children (MIS-C) is an illness that resembles Kawasaki Disease (KD) or toxic shock, reported in children with a recent history of COVID-19 infection. This study analyzed echocardiographic manifestations of this illness. In our cohort of 28 MIS-C patients, left ventricular systolic and diastolic function were worse than in classic KD. These functional parameters correlated with biomarkers of myocardial injury. However, coronary arteries were typically spared. The strongest predictors of myocardial injury were global longitudinal strain, right ventricular strain, and left atrial strain. During subacute period, there was good recovery of systolic function, but diastolic dysfunction persisted.

Background In multisystem inflammatory syndrome in children, there is paucity of longitudinal data on cardiac outcomes. We analyzed cardiac outcomes 3 to 4 months after initial presentation using echocardiography and cardiac magnetic resonance imaging. Methods and Results We included 60 controls and 60 cases of multisystem inflammatory syndrome in children. Conventional echocardiograms and deformation parameters were analyzed at 4 time points: (1) acute phase (n=60), (2) subacute phase (n=50; median, 3 days after initial echocardiography), (3) 1‐month follow‐up (n=39; median, 22 days), and (4) 3‐ to 4‐month follow‐up (n=25; median, 91 days). Fourteen consecutive cardiac magnetic resonance imaging studies were reviewed for myocardial edema or fibrosis during subacute (n=5) and follow‐up (n=9) stages. In acute phase, myocardial injury was defined as troponin‐I level ≥0.09 ng/mL (>3 times normal) or brain‐type natriuretic peptide >800 pg/mL. All deformation parameters, including left ventricular global longitudinal strain, peak left atrial strain, longitudinal early diastolic strain rate, and right ventricular free wall strain, recovered quickly within the first week, followed by continued improvement and complete normalization by 3 months. Median time to normalization of both global longitudinal strain and left atrial strain was 6 days (95% CI, 3–9 days). Myocardial injury at presentation (70% of multisystem inflammatory syndrome in children cases) did not affect short‐term outcomes. Four patients (7%) had small coronary aneurysms at presentation, all of which resolved. Only 1 of 9 patients had residual edema but no fibrosis by cardiac magnetic resonance imaging. Conclusions Our short‐term study suggests that functional recovery and coronary outcomes are good in multisystem inflammatory syndrome in children. Use of sensitive deformation parameters provides further reassurance that there is no persistent subclinical dysfunction after 3 months.

Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that causes cardiac contractile dysfunction, whereas inactivation of MIF improves cardiac function in experimental animal models of sepsis. We used cultured cardiomyocytes to determine whether MIF-induced contractile dysfunction was mediated in part by myocyte apoptosis and to identify MIF-activated intracellular signaling pathways in this process. MIF treatment significantly increased myocyte apoptosis in a dose-dependent manner to 15.5+/-3.9% and 26.0+/-7.1% TUNEL positive nuclei (20 and 30 ng/ml MIF for 24h) vs control (3.7+/-0.9%). This effect was attenuated by inactivation of MIF with the chemical inhibitor, ISO-1. MIF-induced cleavage of caspase 3 and reduction of Bcl-xL/Bax were similarly attenuated by ISO-1 pre-treatment. MIF stimulated the rapid, transient phosphorylation of stress kinases, p38MAPK and JNK. Thus, MIF induces cardiomyocyte apoptosis by activating stress kinases and mitochondria-associated apoptotic mechanisms, whereas inactivation of MIF pro-inflammatory activity improves cardiomyocyte survival.