Kawasaki Disease in the Time of COVID-19 and MIS-C: The International Kawasaki Disease Registry.

BACKGROUND: Patients with multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) have overlapping clinical features. We compared demographics, clinical presentation, management, and outcomes of patients according to evidence of previous SARS-CoV-2 infection. METHODS: The International Kawasaki Disease Registry (IKDR) enrolled KD and MIS-C patients from sites in North, Central, and South America, Europe, Asia, and the Middle East. Evidence of previous infection was defined as: Positive (household contact or positive polymerase chain reaction [PCR]/serology), Possible (suggestive clinical features of MIS-C and/or KD with negative PCR or serology but not both), Negative (negative PCR and serology and no known exposure), and Unknown (incomplete testing and no known exposure). RESULTS: Of 2345 enrolled patients SARS-CoV-2 status was Positive for 1541 (66%) patients, Possible for 89 (4%), Negative for 404 (17%) and Unknown for 311 (13%). Clinical outcomes varied significantly among the groups, with more patients in the Positive/Possible groups presenting with shock, having admission to intensive care, receiving inotropic support, and having longer hospital stays. Regarding cardiac abnormalities, patients in the Positive/Possible groups had a higher prevalence of left ventricular dysfunction, and patients in the Negative and Unknown groups had more severe coronary artery abnormalities. CONCLUSIONS: There appears to be a spectrum of clinical features from MIS-C to KD with a great deal of heterogeneity, and one primary differentiating factor is evidence for previous acute SARS-CoV-2 infection/exposure. SARS-CoV-2 Positive/Possible patients had more severe presentations and required more intensive management, with a greater likelihood of ventricular dysfunction but less severe coronary artery adverse outcomes, in keeping with MIS-C.

Cardiac Biomarkers Aid in Differentiation of Kawasaki Disease from Multisystem Inflammatory Syndrome in Children Associated with COVID-19.

Kawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 show clinical overlap and both lack definitive diagnostic testing, making differentiation challenging. We sought to determine how cardiac biomarkers might differentiate KD from MIS-C. The International Kawasaki Disease Registry enrolled contemporaneous KD and MIS-C pediatric patients from 42 sites from January 2020 through June 2022. The study population included 118 KD patients who met American Heart Association KD criteria and compared them to 946 MIS-C patients who met 2020 Centers for Disease Control and Prevention case definition. All included patients had at least one measurement of amino-terminal prohormone brain natriuretic peptide (NTproBNP) or cardiac troponin I (TnI), and echocardiography. Regression analyses were used to determine associations between cardiac biomarker levels, diagnosis, and cardiac involvement. Higher NTproBNP (≥ 1500 ng/L) and TnI (≥ 20 ng/L) at presentation were associated with MIS-C versus KD with specificity of 77 and 89%, respectively. Higher biomarker levels were associated with shock and intensive care unit admission; higher NTproBNP was associated with longer hospital length of stay. Lower left ventricular ejection fraction, more pronounced for MIS-C, was also associated with higher biomarker levels. Coronary artery involvement was not associated with either biomarker. Higher NTproBNP and TnI levels are suggestive of MIS-C versus KD and may be clinically useful in their differentiation. Consideration might be given to their inclusion in the routine evaluation of both conditions.

Neighborhood Social Vulnerability and Interstage Weight Gain: Evaluating the Role of a Home Monitoring Program.

Background Poor interstage weight gain is a risk factor for adverse outcomes in infants with hypoplastic left heart syndrome. We sought to examine the association of neighborhood social vulnerability and interstage weight gain and determine if this association is modified by enrollment in our institution's Infant Single Ventricle Management and Monitoring Program (ISVMP). Methods and Results We performed a retrospective single-center study of infants with hypoplastic left heart syndrome before (2007-2010) and after (2011-2020) introduction of the ISVMP. The primary outcome was interstage weight gain, and the secondary outcome was interstage growth failure. Multivariable linear and logistic regression models were used to examine the association between the Social Vulnerability Index and the outcomes. We introduced an interaction term into the models to test for effect modification by the ISVMP. We evaluated 217 ISVMP infants and 111 pre-ISVMP historical controls. The Social Vulnerability Index was associated with interstage growth failure (P=0.001); however, enrollment in the ISVMP strongly attenuated this association (P=0.04). Pre-ISVMP, as well as high- and middle-vulnerability infants gained 4 g/d less and were significantly more likely to experience growth failure than low-vulnerability infants (high versus low: adjusted odds ratio [aOR], 12.5 [95% CI, 2.5-62.2]; middle versus low: aOR, 7.8 [95% CI, 2.0-31.2]). After the introduction of the ISVMP, outcomes did not differ by Social Vulnerability Index tertile. Infants with middle and high Social Vulnerability Index scores who were enrolled in the ISVMP gained 4 g/d and 2 g/d more, respectively, than pre-ISVMP controls. Conclusions In infants with hypoplastic left heart syndrome, high social vulnerability is a risk factor for poor interstage weight gain. However, enrollment in the ISVMP significantly reduces growth disparities.

Feasibility of Digital Stethoscopes in Telecardiology Visits for Interstage Monitoring in Infants with Palliated Congenital Heart Disease.

Infants with staged surgical palliation for congenital heart disease are at high-risk for interstage morbidity and mortality. Interstage telecardiology visits (TCV) have been effective in identifying clinical concerns and preventing unnecessary emergency department visits in this high-risk population. We aimed to assess the feasibility of implementing auscultation with digital stethoscopes (DSs) during TCV and the potential impact on interstage care in our Infant Single Ventricle Monitoring & Management Program. In addition to standard home-monitoring practice for TCV, caregivers received training on use of a DS (Eko CORE attachment assembled with Classic II Infant Littman stethoscope). Sound quality of the DS and comparability to in-person auscultation were evaluated based on two providers' subjective assessment. We also evaluated provider and caregiver acceptability of the DS. From 7/2021 to 6/2022, the DS was used during 52 TCVs in 16 patients (median TCVs/patient: 3; range: 1-8), including 7 with hypoplastic left heart syndrome. Quality of heart sounds and murmur auscultation were subjectively equivalent to in-person findings with excellent inter-rater agreement (98%). All providers and caregivers reported ease of use and confidence in evaluation with the DS. In 12% (6/52) of TCVs, the DS provided additional significant information compared to a routine TCV; this expedited life-saving care in two patients. There were no missed events or deaths. Use of a DS during TCV was feasible in this fragile cohort and effective in identifying clinical concerns with no missed events. Longer term use of this technology will further establish its role in telecardiology.

Association of Home Monitoring and Unanticipated Interstage Readmissions in Infants With Hypoplastic Left Heart Syndrome.

Background The impact of home monitoring on unanticipated interstage readmissions in infants with hypoplastic left heart syndrome has not been previously studied. We sought to examine the association of our institution's Infant Single Ventricle Management and Monitoring Program (ISVMP) with readmission frequency, cumulative readmission days, and readmission illness severity and to identify patient-level risk factors for readmission. Methods and Results We performed a retrospective single-center cohort study comparing infants with hypoplastic left heart syndrome enrolled in ISVMP (December 2010-December 2019) to historical controls (January 2007-November 2010). The primary outcome was number of readmissions per interstage days. Secondary outcomes were cumulative interstage readmission days and occurrence of severe readmissions. Inverse probability weighted and multivariable generalized linear models were used to examine the association between ISVMP and the outcomes. We compared 198 infants in the ISVMP to 128 historical controls. Infants in the ISVMP had more than double the risk of interstage readmission compared with controls (adjusted incidence rate ratio, 2.38 [95% CI, 1.50-3.78]; P=0.0003). There was no difference in cumulative interstage readmission days (adjusted incidence rate ratio, 1.02 [95% CI, 0.69-1.50]; P=0.90); however, infants in the ISVMP were less likely to have severe readmissions (adjusted odds ratio, 0.28 [95% CI, 0.11-0.68]; P=0.005). Other factors independently associated with number of readmissions included residing closer to our center, younger gestational age, genetic syndrome, and discharge on exclusive enteral feeds. Conclusions Infants in the ISVMP had more frequent readmissions but comparable readmission days and fewer severe unanticipated readmissions. These findings suggest that home monitoring can reduce interstage morbidity without increasing readmission days.

Examination of Adverse Reactions After COVID-19 Vaccination Among Patients With a History of Multisystem Inflammatory Syndrome in Children.

Importance: Data are limited regarding adverse reactions after COVID-19 vaccination in patients with a history of multisystem inflammatory syndrome in children (MIS-C). The lack of vaccine safety data in this unique population may cause hesitancy and concern for many families and health care professionals. Objective: To describe adverse reactions following COVID-19 vaccination in patients with a history of MIS-C. Design, Setting, and Participants: In this multicenter cross-sectional study including 22 North American centers participating in a National Heart, Lung, and Blood Institute, National Institutes of Health-sponsored study, Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children (MUSIC), patients with a prior diagnosis of MIS-C who were eligible for COVID-19 vaccination (age ≥5 years; ≥90 days after MIS-C diagnosis) were surveyed between December 13, 2021, and February 18, 2022, regarding COVID-19 vaccination status and adverse reactions. Exposures: COVID-19 vaccination after MIS-C diagnosis. Main Outcomes and Measures: The main outcome was adverse reactions following COVID-19 vaccination. Comparisons were made using the Wilcoxon rank sum test for continuous variables and the χ2 or Fisher exact test for categorical variables. Results: Of 385 vaccine-eligible patients who were surveyed, 185 (48.1%) received at least 1 vaccine dose; 136 of the vaccinated patients (73.5%) were male, and the median age was 12.2 years (IQR, 9.5-14.7 years). Among vaccinated patients, 1 (0.5%) identified as American Indian/Alaska Native, non-Hispanic; 9 (4.9%) as Asian, non-Hispanic; 45 (24.3%) as Black, non-Hispanic; 59 (31.9%) as Hispanic or Latino; 53 (28.6%) as White, non-Hispanic; 2 (1.1%) as multiracial, non-Hispanic; and 2 (1.1%) as other, non-Hispanic; 14 (7.6%) had unknown or undeclared race and ethnicity. The median time from MIS-C diagnosis to first vaccine dose was 9.0 months (IQR, 5.1-11.9 months); 31 patients (16.8%) received 1 dose, 142 (76.8%) received 2 doses, and 12 (6.5%) received 3 doses. Almost all patients received the BNT162b2 vaccine (347 of 351 vaccine doses [98.9%]). Minor adverse reactions were observed in 90 patients (48.6%) and were most often arm soreness (62 patients [33.5%]) and/or fatigue (32 [17.3%]). In 32 patients (17.3%), adverse reactions were treated with medications, most commonly acetaminophen (21 patients [11.4%]) or ibuprofen (11 [5.9%]). Four patients (2.2%) sought medical evaluation, but none required testing or hospitalization. There were no patients with any serious adverse events, including myocarditis or recurrence of MIS-C. Conclusions and Relevance: In this cross-sectional study of patients with a history of MIS-C, no serious adverse events were reported after COVID-19 vaccination. These findings suggest that the safety profile of COVID-19 vaccination administered at least 90 days following MIS-C diagnosis appears to be similar to that in the general population.

Initial Experience with Telemedicine for Interstage Monitoring in Infants with Palliated Congenital Heart Disease.

Infants with staged surgical palliation for congenital heart disease are at high-risk for interstage morbidity and mortality; home monitoring programs have mitigated these risks. In 2019, we instituted telemedicine (TM) in our established Infant Single Ventricle Monitoring Program. All consecutive patients discharged following neonatal operation/intervention were monitored until subsequent stage 2 surgical palliation. We offered TM (synchronous video) visits as part of regularly scheduled follow-up, replacing at least one in-person primary care visit with a TM cardiologist visit. We tracked emergency department (ED) visits, hospitalizations, how TM identified clinical concerns, and whether use of TM prevented unnecessary ED visits or expedited in-person assessment. We assessed caregiver and clinician satisfaction. Between 8/2019 and 5/2020, we conducted 60 TM visits for 29 patients. Of 31 eligible patients, 2 families (6.9%) declined. Median monitoring time was 199 days (range 75-264) and median number of TM visits/patient was 2 (range 1-5). In 6 visits (10%), significant clinical findings were identified which avoided an ED visit. Five TM visits led to expedited outpatient assessments, of which 1 patient required hospitalization. There were no missed events or deaths. Median ED visits/patient/month were significantly lower compared to the same calendar period of the prior year (0.0 (0-2.5) vs. 0.4 (0-3.7), p = 0.0004). Caregivers and clinicians expressed high levels of satisfaction with TM. TM for this high-risk population is feasible and effective in identifying clinical concerns and preventing unnecessary ED visits. TM was particularly effective during the COVID-19 pandemic, allowing for easy adaptation of care to ensure patient safety in this fragile cohort.

Neurologic complications of infective endocarditis in children.

OBJECTIVES: To define the frequency and characteristics of acute neurologic complications in children hospitalised with infective endocarditis and to identify risk factors for neurologic complications. STUDY DESIGN: Retrospective cohort study of children aged 0-18 years hospitalised at a tertiary children's hospital from 1 January, 2008 to 31 December, 2017 with infective endocarditis. RESULTS: Sixty-eight children met Duke criteria for infective endocarditis (43 definite and 25 possible). Twenty-three (34%) had identified neurologic complications, including intracranial haemorrhage (25%, 17/68) and ischaemic stroke (25%, 17/68). Neurologic symptoms began a median of 4.5 days after infective endocarditis symptom onset (interquartile range 1, 25 days), though five children were asymptomatic and diagnosed on screening neuroimaging only. Overall, only 56% (38/68) underwent neuroimaging during acute hospitalisation, so additional asymptomatic neurologic complications may have been missed. Children with identified neurologic complications compared to those without were older (48 versus 22% ≥ 13 years old, p = 0.031), more often had definite rather than possible infective endocarditis (96 versus 47%, p < 0.001), mobile vegetations >10mm (30 versus 11%, p = 0.048), and vegetations with the potential for systemic embolisation (65 versus 29%, p = 0.004). Six children died (9%), all of whom had neurologic complications. CONCLUSIONS: Neurologic complications of infective endocarditis were common (34%) and associated with mortality. The true frequency of neurologic complications was likely higher because asymptomatic cases may have been missed without screening neuroimaging. Moving forward, we advocate that all children with infective endocarditis have neurologic consultation, examination, and screening neuroimaging. Additional prospective studies are needed to determine whether early identification of neurologic abnormalities may direct management and ultimately reduce neurologic morbidity and overall mortality.

Clinically Suspected Myocarditis Temporally Related to COVID-19 Vaccination in Adolescents and Young Adults: Suspected Myocarditis After COVID-19 Vaccination.

BACKGROUND: Understanding the clinical course and short-term outcomes of suspected myocarditis after the coronavirus disease 2019 (COVID-19) vaccination has important public health implications in the decision to vaccinate youth. METHODS: We retrospectively collected data on patients <21 years old presenting before July 4, 2021, with suspected myocarditis within 30 days of COVID-19 vaccination. Lake Louise criteria were used for cardiac MRI findings. Myocarditis cases were classified as confirmed or probable on the basis of the Centers for Disease Control and Prevention definitions. RESULTS: We report on 139 adolescents and young adults with 140 episodes of suspected myocarditis (49 confirmed, 91 probable) at 26 centers. Most patients were male (n=126, 90.6%) and White (n=92, 66.2%); 29 (20.9%) were Hispanic; and the median age was 15.8 years (range, 12.1-20.3; interquartile range [IQR], 14.5-17.0). Suspected myocarditis occurred in 136 patients (97.8%) after the mRNA vaccine, with 131 (94.2%) after the Pfizer-BioNTech vaccine; 128 (91.4%) occurred after the second dose. Symptoms started at a median of 2 days (range, 0-22; IQR, 1-3) after vaccination. The most common symptom was chest pain (99.3%). Patients were treated with nonsteroidal anti-inflammatory drugs (81.3%), intravenous immunoglobulin (21.6%), glucocorticoids (21.6%), colchicine (7.9%), or no anti-inflammatory therapies (8.6%). Twenty-six patients (18.7%) were in the intensive care unit, 2 were treated with inotropic/vasoactive support, and none required extracorporeal membrane oxygenation or died. Median hospital stay was 2 days (range, 0-10; IQR, 2-3). All patients had elevated troponin I (n=111, 8.12 ng/mL; IQR, 3.50-15.90) or T (n=28, 0.61 ng/mL; IQR, 0.25-1.30); 69.8% had abnormal ECGs and arrhythmias (7 with nonsustained ventricular tachycardia); and 18.7% had left ventricular ejection fraction <55% on echocardiogram. Of 97 patients who underwent cardiac MRI at a median 5 days (range, 0-88; IQR, 3-17) from symptom onset, 75 (77.3%) had abnormal findings: 74 (76.3%) had late gadolinium enhancement, 54 (55.7%) had myocardial edema, and 49 (50.5%) met Lake Louise criteria. Among 26 patients with left ventricular ejection fraction <55% on echocardiogram, all with follow-up had normalized function (n=25). CONCLUSIONS: Most cases of suspected COVID-19 vaccine myocarditis occurring in persons <21 years have a mild clinical course with rapid resolution of symptoms. Abnormal findings on cardiac MRI were frequent. Future studies should evaluate risk factors, mechanisms, and long-term outcomes.

Comparison Between Currently Recommended Long-Term Medical Management of Coronary Artery Aneurysms After Kawasaki Disease and Actual Reported Management in the Last Two Decades.

In the 2017 American Heart Association (AHA) Kawasaki disease (KD) guidelines, risk levels (RLs) for long-term management are defined by both maximal and current coronary artery (CA) dimensions normalized as z-scores. We sought to determine the degree to which current recommended practice differs from past actual practice, highlighting areas for knowledge translation efforts. The International KD Registry (IKDR) included 1651 patients with CA aneurysms (z-score > 2.5) from 1999 to 2016. Patients were classified by AHA RL using maximum CA z-score (RL 3 = small, RL 4 = medium, RL 5 = large/giant) and subcategorized based on decreases over time. Medical management provided was compared to recommendations. Low-dose acetylsalicylic acid (ASA) use ranged from 86 (RL 3.1) to 95% (RL 5.1) for RLs where use was "indicated." Dual antiplatelet therapy (ASA + clopidogrel) use ranged from 16% for RL 5.2 to 9% for RL 5.4. Recommended anticoagulation (warfarin or low molecular weight heparin) use was 65% for RL 5.1, while 12% were on triple therapy (anticoagulation + dual antiplatelet). Optional statin use ranged from 2 to 8% depending on RL. Optional beta-blocker use was 2-25% for RL 5, and 0-5% for RLs 3 and 4 where it is not recommended. Generally, past practice was consistent with the latest AHA guidelines, taking into account the flexible wording of recommendations based on the limited evidence, as well as unmeasured patient-specific factors. In addition to strengthening the overall evidence base, knowledge translation efforts may be needed to address variation in thromboprophylaxis management.

Evidence of thrombotic microangiopathy in children with SARS-CoV-2 across the spectrum of clinical presentations.

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.

Decreasing Interstage Mortality After the Norwood Procedure: A 30-Year Experience.

Background The superior cavo-pulmonary connection was introduced at our institution in 1988 for infants undergoing surgery for hypoplastic left heart syndrome. Patients with hypoplastic left heart syndrome remain at high risk for mortality in the time period between the Norwood procedure and the superior cavo-pulmonary connection. The primary objectives of this study were to compare interstage mortality across 4 eras and analyze factors that may impact interstage mortality. Methods and Results Patients with hypoplastic left heart syndrome who underwent the Norwood procedure, were discharged from the hospital, and were eligible for superior cavo-pulmonary connection between January 1, 1988, and December 31, 2017, were included. The study period was divided into 4 eras based on changes in operative or medical management. Mortality rates were estimated with 95% CIs. Adjusted and unadjusted logistic regression models were used to identify risk factors for mortality. There were 1111 patients who met the inclusion criteria. Overall, interstage mortality was 120/1111 (10.8%). Interstage mortality was significantly lower in era 4 relative to era 1 (4.6% versus 13.4%; P=0.02) during the time that age at the superior cavo-pulmonary connection was the lowest (135 days; P<0.01) and the interstage monitoring program was introduced. In addition, use of the right ventricle to pulmonary artery shunt was associated with decreased interstage mortality (P=0.02) and was more routinely practiced in era 4. Conclusions During this 30-year experience, the risk of interstage mortality decreased significantly in the most recent era. Factors that coincide with this finding include younger age at superior cavo-pulmonary connection, introduction of an interstage monitoring program, and increased use of the right ventricle to pulmonary artery shunt.

Management of Multisystem Inflammatory Syndrome in Children Associated With COVID-19: A Survey From the International Kawasaki Disease Registry.

BACKGROUND: Since April 2020, there have been numerous reports of children presenting with systemic inflammation, often in critical condition, and with evidence of recent infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This condition, since defined as the multisystem inflammatory syndrome in children (MIS-C), is assumed to be a delayed immune response to coronavirus disease 2019 (COVID-19), and there are frequently cardiac manifestations of ventricular dysfunction and/or coronary artery dilation. METHODS: We surveyed the inpatient MIS-C management approaches of the members of the International Kawasaki Disease Registry across 38 institutions and 11 countries. RESULTS: Among the respondents, 56% reported using immunomodulatory treatment for all MIS-C patients, regardless of presentation. Every respondent reported use of intravenous immunoglobulin (IVIG), including 53% administering IVIG in all patients. Steroids were most often used for patients with severe clinical presentation or lack of response to IVIG, and only a minority used steroids in all patients (14%). Acetylsalicylic acid was frequently used among respondents (91%), including anti-inflammatory and/or antiplatelet dosing. Respondents reported use of prophylactic anticoagulation, especially in patients at higher risk for venous thromboembolism, and therapeutic anticoagulation, particularly for patients with giant coronary artery aneurysms. CONCLUSIONS: There is variation in management of MIS-C patients, with suboptimal evidence to assess superiority of the various treatments; evidence-based gaps in knowledge should be addressed through worldwide collaboration to optimize treatment strategies.

CONTEXTE: Depuis avril 2020, de nombreux cas d'enfants présentant une inflammation généralisée, se trouvant souvent dans un état critique et montrant des signes d'une infection récente au coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2), ont été signalés. On pense que cet état, désigné depuis sous le nom de syndrome inflammatoire multisystémique de l'enfant (SIME), pourrait être une réponse immunitaire tardive au virus de la maladie à coronavirus 2019 (COVID-19); les patients présentent souvent des manifestations cardiaques associées à une dysfonction ventriculaire ou à une dilatation des artères coronaires. MÉTHODOLOGIE: Nous avons mené un sondage sur les stratégies de prise en charge du SIME en milieu hospitalier auprès des membres du registre international de la maladie de Kawasaki, qui sont rattachés à 38 établissements répartis dans 11 pays. RÉSULTATS: Au total, 56 % des répondants ont déclaré opter pour un traitement immunomodulateur pour tous les patients présentant un SIME, quelles qu'en soient les manifestations. Tous les répondants ont déclaré avoir recours à l'administration d'immunoglobulines par voie intraveineuse, 53 % d'entre eux utilisant ce traitement chez tous les patients. Les stéroïdes étaient plus souvent utilisés chez les patients présentant des symptômes cliniques graves ou ne répondant pas aux immunoglobulines administrées par voie intraveineuse; seule une minorité de répondants ont déclaré utiliser des stéroïdes chez tous les patients (14 %). Les répondants utilisaient aussi fréquemment l'acide acétylsalicylique (91 %), à des doses anti-inflammatoires ou antiplaquettaires. Ils ont en outre déclaré avoir recours à des anticoagulants en prophylaxie, en particulier chez les patients présentant un risque élevé de thromboembolie veineuse, et à une anticoagulothérapie chez les patients présentant des anévrismes coronaires géants. CONCLUSIONS: La prise en charge des patients présentant un SIME varie d'un médecin à l'autre, et les données permettant d'évaluer la supériorité des divers traitements employés sont insuffisantes; il conviendrait donc de mettre en place des initiatives de collaboration afin de combler les lacunes des connaissances et d'optimiser les stratégies thérapeutiques.

Echocardiographic Findings in Pediatric Multisystem Inflammatory Syndrome Associated With COVID-19 in the United States.

BACKGROUND: Centers from Europe and United States have reported an exceedingly high number of children with a severe inflammatory syndrome in the setting of coronavirus disease 2019, which has been termed multisystem inflammatory syndrome in children (MIS-C). OBJECTIVES: This study aimed to analyze echocardiographic manifestations in MIS-C. METHODS: A total of 28 MIS-C, 20 healthy control subjects and 20 classic Kawasaki disease (KD) patients were retrospectively reviewed. The study reviewed echocardiographic parameters in the acute phase of the MIS-C and KD groups, and during the subacute period in the MIS-C group (interval 5.2 ± 3 days). RESULTS: Only 1 case in the MIS-C group (4%) manifested coronary artery dilatation (z score = 3.15) in the acute phase, showing resolution during early follow-up. Left ventricular (LV) systolic and diastolic function measured by deformation parameters were worse in patients with MIS-C compared with KD. Moreover, MIS-C patients with myocardial injury were more affected than those without myocardial injury with respect to all functional parameters. The strongest parameters to predict myocardial injury in MIS-C were global longitudinal strain, global circumferential strain, peak left atrial strain, and peak longitudinal strain of right ventricular free wall (odds ratios: 1.45 [95% confidence interval (CI): 1.08 to 1.95], 1.39 [95% CI: 1.04 to 1.88], 0.84 [95% CI: 0.73 to 0.96], and 1.59 [95% CI: 1.09 to 2.34], respectively). The preserved LV ejection fraction (EF) group in MIS-C showed diastolic dysfunction. During the 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.

Medium-Term Complications Associated With Coronary Artery Aneurysms After Kawasaki Disease: A Study From the International Kawasaki Disease Registry.

Background Coronary artery aneurysms (CAAs) may occur after Kawasaki disease (KD) and lead to important morbidity and mortality. As CAA in patients with KD are rare and heterogeneous lesions, prognostication and risk stratification are difficult. We sought to derive the cumulative risk and associated factors for cardiovascular complications in patients with CAAs after KD. Methods and Results A 34-institution international registry of 1651 patients with KD who had CAAs (maximum CAA Z score ≥2.5) was used. Time-to-event analyses were performed using the Kaplan-Meier method and Cox proportional hazard models for risk factor analysis. In patients with CAA Z scores ≥10, the cumulative incidence of luminal narrowing (>50% of lumen diameter), coronary artery thrombosis, and composite major adverse cardiovascular complications at 10 years was 20±3%, 18±2%, and 14±2%, respectively. No complications were observed in patients with a CAA Z score <10. Higher CAA Z score and a greater number of coronary artery branches affected were associated with increased risk of all types of complications. At 10 years, normalization of luminal diameter was noted in 99±4% of patients with small (2.5≤Z<5.0), 92±1% with medium (5.0≤Z<10), and 57±3% with large CAAs (Z≥10). CAAs in the left anterior descending and circumflex coronary artery branches were more likely to normalize. Risk factor analysis of coronary artery branch level outcomes was performed with a total of 893 affected branches with Z score ≥10 in 440 patients. In multivariable regression models, hazards of luminal narrowing and thrombosis were higher for patients with CAAs of the right coronary artery and left anterior descending branches, those with CAAs that had complex architecture (other than isolated aneurysms), and those with CAAs with Z scores ≥20. Conclusions For patients with CAA after KD, medium-term risk of complications is confined to those with maximum CAA Z scores ≥10. Further risk stratification and close follow-up, including advanced imaging, in patients with large CAAs is warranted.

Standardization of the Perioperative Management for Neonates Undergoing the Norwood Operation for Hypoplastic Left Heart Syndrome and Related Heart Defects.

OBJECTIVES: 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. DESIGN: Quality improvement project. SETTING: High volume cardiac center, tertiary care children's hospital. PATIENTS: Neonates undergoing Norwood operation. INTERVENTIONS: 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. MEASUREMENTS AND MAIN RESULTS: 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). CONCLUSIONS: 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.

Low-Molecular-Weight Heparin vs Warfarin for Thromboprophylaxis in Children With Coronary Artery Aneurysms After Kawasaki Disease: A Pragmatic Registry Trial.

BACKGROUND: The substantial risk of thrombosis in large coronary artery aneurysms (CAAs) (maximum z-score ≥ 10) after Kawasaki disease (KD) mandates effective thromboprophylaxis. We sought to determine the effectiveness of anticoagulation (low-molecular-weight heparin [LMWH] or warfarin) for thromboprophylaxis in large CAAs. METHODS: Data from 383 patients enrolled in the International KD Registry (IKDR) were used. Time-to-event analysis was used to account for differences in treatment duration and follow-up. RESULTS: From diagnosis onward (96% received acetylsalicylic acid concomitantly), 114 patients received LMWH (median duration 6.2 months, interquartile range [IQR] 2.5-12.7), 80 warfarin (median duration 2.2 years, IQR 0.9-7.1), and 189 no anticoagulation. Cumulative incidence of coronary artery thrombosis with LMWH was 5.7 ± 3.0%, with warfarin 6.7 ± 3.7%, and with no anticoagulation 20.6 ± 3.0% (P < 0.001) at 2.5 years after the start of thromboprophylaxis (LMWH vs warfarin HR 1.5, 95% confidence interval [CI] 0.4-5.1; P = 0.56). A total of 51/63 patients with coronary artery thrombosis received secondary thromboprophylaxis (ie, thromboprophylaxis after a previous thrombus): 27 LMWH, 24 warfarin. There were no differences in incidence of further coronary artery thrombosis between strategies (HR 2.9, 95% CI 0.6-13.5; P = 0.19). Severe bleeding complications were generally rare (1.6 events per 100 patient-years) and were noted equally for patients on LMWH and warfarin (HR 2.3, 95% CI 0.6-8.9; P = 0.25). CONCLUSIONS: LMWH and warfarin appear to have equivalent effectiveness for preventing thrombosis in large CAAs after KD, although event rates for secondary thromboprophylaxis and safety outcomes were low. Based on our findings, all patients with CAA z-score ≥ 10 should receive anticoagulation, but the choice of agent might be informed by secondary risk factors and patient preferences.