<p>Most children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have mild or minimal disease, with a small proportion developing severe disease or multisystem inflammatory syndrome in children (MIS-C). Complement-mediated thrombotic microangiopathy (TMA) has been associated with SARS-CoV-2 infection in adults but has not been studied in the pediatric population. We hypothesized that complement activation plays an important role in SARS-CoV-2 infection in children and sought to understand if TMA was present in these patients. We enrolled 50 hospitalized pediatric patients with acute SARS-CoV-2 infection (n = 21, minimal coronavirus disease 2019 [COVID-19]; n = 11, severe COVID-19) or MIS-C (n = 18). As a biomarker of complement activation and TMA, soluble C5b9 (sC5b9, normal 247 ng/mL) was measured in plasma, and elevations were found in patients with minimal disease (median, 392 ng/mL; interquartile range [IQR], 244-622 ng/mL), severe disease (median, 646 ng/mL; IQR, 203-728 ng/mL), and MIS-C (median, 630 ng/mL; IQR, 359-932 ng/mL) compared with 26 healthy control subjects (median, 57 ng/mL; IQR, 9-163 ng/mL; P < .001). Higher sC5b9 levels were associated with higher serum creatinine (P = .01) but not age. Of the 19 patients for whom complete clinical criteria were available, 17 (89%) met criteria for TMA. A high proportion of tested children with SARS-CoV-2 infection had evidence of complement activation and met clinical and diagnostic criteria for TMA. Future studies are needed to determine if hospitalized children with SARS-CoV-2 should be screened for TMA, if TMA-directed management is helpful, and if there are any short- or long-term clinical consequences of complement activation and endothelial damage in children with COVID-19 or MIS-C.</p>
<p><strong>BACKGROUND: </strong>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).</p>
<p><strong>OBJECTIVES: </strong>This study aimed to analyze echocardiographic manifestations in MIS-C.</p>
<p><strong>METHODS: </strong>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).</p>
<p><strong>RESULTS: </strong>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.</p>
<p><strong>CONCLUSIONS: </strong>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.</p>
<p><strong>CONDENSED ABSTRACT: </strong>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.</p>
<p><strong>OBJECTIVES: </strong>In-hospital complications after the Norwood operation for single ventricle heart defects account for the majority of morbidity and mortality. Inpatient care variation occurs within and across centers. This multidisciplinary quality improvement project standardized perioperative management in a large referral center.</p>
<p><strong>DESIGN: </strong>Quality improvement project.</p>
<p><strong>SETTING: </strong>High volume cardiac center, tertiary care children's hospital.</p>
<p><strong>PATIENTS: </strong>Neonates undergoing Norwood operation.</p>
<p><strong>INTERVENTIONS: </strong>The quality improvement team developed and implemented a clinical guideline (preoperative admission to 48 hr after surgery). The composite process metric, Guideline Adherence Score, contained 13 recommendations in the guideline that reflected consistent care for all patients.</p>
<p><strong>MEASUREMENTS AND MAIN RESULTS: </strong>One-hundred two consecutive neonates who underwent Norwood operation (January 1, 2013, to July 12, 2016) before guideline implementation were compared with 50 consecutive neonates after guideline implementation (July 13, 2016, to May 4, 2018). No preguideline operations met the goal Guideline Adherence Score. In the first 6 months after guideline implementation, 10 of 12 operations achieved goal Guideline Adherence Score and continued through implementation, reaching 100% for the last 10 operations. Statistical process control analysis demonstrated less variability and decreased hours of postoperative mechanical ventilation and cardiac ICU length of stay during implementation. There were no statistically significant differences in major hospital complications or in 30-day mortality. A higher percentage of patients were extubated by postoperative day 2 after guideline implementation (67% [30/47] vs 41% [41/99], respectively; p = 0.01). Of these patients, reintubation within 72 hours of extubation significantly decreased after guideline implementation (0% [0/30] vs 17% [7/41] patients, respectively; p = 0.02).</p>
<p><strong>CONCLUSIONS: </strong>This initiative successfully implemented a standardized perioperative care guideline for neonates undergoing the Norwood operation at a large center. Positive statistical process control centerline shifts in Guideline Adherence Score, length of postoperative mechanical ventilation, and cardiac ICU length of stay were demonstrated. A higher percentage were successfully extubated by postoperative day 2. Establishment of standard processes can lead to best practices to decrease major adverse events.</p>
<p><strong>INTRODUCTION: </strong>Interstage mortality causes are often unknown in infants with shunt-dependent univentricular defects. For 2 years, screening catheterisation was encouraged before neonatal discharge to determine if routine evaluation improved interstage outcomes.</p>
<p><strong>METHODS: </strong>Retrospective single-centre review of home monitoring programme from December, 2010 to June, 2012. Composite scores were created for physical examination/echocardiography risk factors; catheterisation risk factors; and interstage adverse events. Composite scores were compared between usual care and screening catheterisation groups. The ability of each risk factor composite to predict interstage adverse events, individually and in combination, was assessed with sensitivity, specificity, and receiver operating characteristic curves.</p>
<p><strong>RESULTS: </strong>There were 27 usual care and 32 screening catheterisation patients. There were no significant differences between groups except rates of catheterisation before discharge (29.6 versus 100%, p < 0.001). Usual care patients who underwent catheterisation for clinical indications had higher intervention rates (37.5 versus 3.1%, p = 0.004). Physical examination/echocardiography risk factor frequency was similar, but usual care patients with catheterisation had a higher catheterisation risk factor frequency. Interstage adverse event frequency was similar (48.2 versus 53.1%, p = 0.7). For interstage adverse event prediction, sensitivity for the physical examination/echocardiography, catheterisation, and either risk factor composites was 53.3, 72, and 80%, respectively; specificity was 59, 60, and 48%. The area under the receiver operating characteristic curve was 0.56, 0.66, and 0.64.</p>
<p><strong>CONCLUSION: </strong>Screening catheterisation evaluation offered slightly increased sensitivity and specificity, but no difference in interstage adverse event frequency. Given this small advantage versus known risks, screening catheterisations are no longer encouraged.</p>