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BACKGROUND: Although perioperative prophylactic glucocorticoids have been used for decades, whether they improve outcomes in infants after heart surgery with cardiopulmonary bypass is unknown. METHODS: We conducted a multicenter, prospective, randomized, placebo-controlled, registry-based trial involving infants (

SARS-CoV-2 infection for most children results in mild or minimal symptoms, though in rare cases severe disease can develop, including a multisystem inflammatory syndrome (MIS-C) with myocarditis. Here, we present longitudinal profiling of immune responses during acute disease and following recovery in children who developed MIS-C, relative to children who experienced more typical symptoms of COVID-19. T cells in acute MIS-C exhibited transient signatures of activation, inflammation, and tissue residency which correlated with cardiac disease severity, while T cells in acute COVID-19 upregulated markers of follicular helper T cells for promoting antibody production. The resultant memory immune response in recovery showed increased frequencies of virus-specific memory T cells with pro-inflammatory functions in children with prior MIS-C compared to COVID-19 while both cohorts generated comparable antibody responses. Together our results reveal distinct effector and memory T cell responses in pediatric SARS-CoV-2 infection delineated by clinical syndrome, and a potential role for tissue-derived T cells in the immune pathology of systemic disease.

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 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 Conclusions: Most cases of suspected COVID-19 vaccine myocarditis occurring in persons

Background The Long-ter M O U tcomes after the Multisystem Inflammatory S yndrome I n C hildren (MUSIC) study aims to characterize the frequency and time course of acute and long-term cardiac and non-cardiac sequelae in multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C), which are currently poorly understood. Methods This multicenter observational cohort study will enroll at least 600 patients Conclusion The MUSIC study, with the largest cohort of MIS-C patients and the longest follow-up period to date, will make an important contribution to our understanding of the acute cardiac and non-cardiac manifestations of MIS-C and the long-term effects of this public health emergency.

BACKGROUND: Trisomy 21 (T21) patients often have elevated pulmonary vascular resistance, which may result in suboptimal cavopulmonary connection (CPC) following Glenn or Fontan operations. The purpose of this study was to assess in a nationwide, multi-institution cohort of CPC patients the impact of T21 on patient morbidity, mortality, and resource utilization. METHODS: A total of 23,271 CPC pediatric patients (2004 – 2019) at 50 U.S. hospitals were evaluated using the Pediatric Health Information System (PHIS) database. Univariable and multivariable regression analyses were used to assess risk-adjusted associations between Down syndrome and other risk factors and postoperative measures of morbidity, mortality, lengths of stay (LOS) and cost of hospitalization. RESULTS: The overall prevalence of T21 among Glenn and Fontan patients was 1.5% (199/13,268) and 0.8% (78/1,003), respectively. Among both CPC cohorts, T21 status significantly increased unadjusted mortality, hospital lengths of stay and total costs of hospitalization compared to non-T21 CPC patients (all P < 0.001). T21 patients also incurred a higher incidence of prolonged mechanical ventilation compared to non-T21 patient in both Glenn and Fontan patients (P < 0.001). Multivariable regression analysis further estimated that T21 patients are associated with a 5.5-fold increase in mortality (P < 0.001) compared to non-T21 patients. Lastly, T21 patients had increased long-term mortality compared to their peers. CONCLUSIONS: Trisomy 21 significantly increases risk-adjusted morbidity, inpatient mortality, long-term mortality and resource utilization following cavopulmonary connections. Further investigation is needed to clarify modifiable patient-level and center-specific risk factors to improve outcomes for T21 patients.

Longitudinal follow-up, resource utilization, and health disparities are top congenital heart research and care priorities. Medicaid claims include longitudinal data on inpatient, outpatient, emergency, pharmacy, rehabilitation, home health utilization, and social determinants of health-including mother-infant pairs.The New York Congenital Heart Surgeons Collaborative for Longitudinal Outcomes and Utilization of Resources linked robust clinical details from locally held state and national registries from 10 of 11 New York congenital heart centers to Medicaid claims, building a novel, statewide mechanism for longitudinal assessment of outcomes, expenditures, and health inequities.The authors included all children 18 years of age undergoing cardiac surgery in The Society of Thoracic Surgeons Congenital Heart Surgery Database or the New York State Pediatric Congenital Cardiac Surgery Registry from 10 of 11 New York centers, 2006 to 2019. Data were linked via iterative, ranked deterministic matching on direct identifiers. Match rates were calculated and compared. Proportions of the linked cohort trackable over 3, 5, and 10 years were described.Of 14,097 registry cases, 59% (n = 8,322) reported Medicaid use. Of these, 7,414 were linked to New York claims, at an 89% match rate. Of matched cases, the authors tracked 79%, 74%, and 65% of children over 3, 5, and 10 years when requiring near-continuous Medicaid enrollment. Allowing more lenient enrollment criteria, the authors tracked 86%, 82%, and 76%, respectively. Mortality over this time was 7.7%, 8.4%, and 10.0%, respectively. Manual validation revealed ∼100% true matches.This establishes a novel statewide data resource for assessment of longitudinal outcome, health expenditure, and disparities for children with congenital heart disease.

We examined cases of operative mortality at a single quaternary academic center for patients undergoing relatively lower-risk (Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Mortality Category 1-3) procedures, as a means of identifying systemic weaknesses and opportunities for quality improvement.A retrospective review of all operative mortality events for patients who underwent a Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Mortality Category 1, 2, or 3 index procedure (2009-2020) at our institution was performed. After a detailed chart review was performed by 2 independent faculty for each case, factors and system deficiencies that contributed to mortality were identified.A total of 42 mortalities were identified. A total of 37 patients (88%) had at least 1 Society of Thoracic Surgeons-designated risk factor, including prior cardiac operations (48%), extracardiac malformations (43%), and preoperative ventilation (33%). Eight patients (19%) had non-Society of Thoracic Surgeons-designated preoperative patient-level variables considered as at potential risk, including severe ventricular dysfunction, pulmonary hypertension, lung hypoplasia, and undiagnosed severe coronary abnormalities. Four patients (10%) had no identified preoperative risk factors. After detailed chart review, 5 broad categories were identified: patient-related factors (n = 33; 78%), postoperative infection (n = 13; 31%), postoperative residual lesions (n = 7; 17%), Fontan physiology failure (n = 4; 10%), and unexplained left ventricular failure after tetralogy of Fallot repair (n = 3; 7%). A total of 74% of patients had at least 1 preoperative, intraoperative, or postoperative system deficiency. A total of 50% of surgeries were urgent or emergency.Operative mortality after Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Mortality Category 1 to 3 procedures is related to the presence of multifactorial risk patterns (Society of Thoracic Surgeons and non-Society of Thoracic Surgeons-designated patient-level risk factors and variables, broad risk categories, system deficiencies, emergency surgery). A multidisciplinary approach to care, with early recognition and treatment of modifiable additional burdens, could reduce this risk.

Little is known about pediatric psychotropic medication use in the emergency department (ED), despite a rise in mental and behavioral health visits. This study describes psychotropic medication use in a nationally representative sample of pediatric mental and behavioral health ED visits over a 14-year period.We conducted a cross-sectional analysis of pediatric (6-17 years) mental and behavioral health ED visits using the National Hospital Ambulatory Medical Care Survey, 2006-2019. We describe administration of psychotropic medications by medication type, diagnosis, and over time. Using multivariable survey weighted logistic regression, we examine associations between medication administration and sociodemographics.A psychotropic medication was administered in 11.4% of the estimated 11,792,860 pediatric mental and behavioral health ED visits in our sample. Benzodiazepines were administered most frequently (4.9% of visits). Visits with anxiety disorders had the highest frequency of psychotropic medication use (26.7%). Visits by Black non-Hispanic patients had a 60% decreased odds of medication administration compared to visits for White non-Hispanic patients. Visits with public compared to private insurance had a 3.5 times increased odds of psychotropic polypharmacy. The proportion of visits in which a psychotropic medication was administered did not change statistically over time.A psychotropic medication was administered in one in ten pediatric mental and behavioral health ED visits. Use differed by sociodemographics but did not change over time. As more youth seek mental and behavioral healthcare in the ED, we must better understand appropriate medication use to ensure quality and equitable care.

Fontan circuit thrombosis is a significant cause of early postoperative morbidity and mortality. Thrombosis incidence and relationship to thromboprophylaxis choice and timing of initiation are not well established. We sought to evaluate the incidence of Fontan circuit thrombosis in the first 30 postoperative days and its relationship to thromboprophylaxis choice and timing. Patients undergoing Fontan surgery, 2006-2016, were reviewed. Fontan circuit thrombosis was defined by sonographic detection of intracardiac or deep venous thrombi. Logistic regression was used to assess relationships between thromboprophylaxis characteristics and thrombosis. One hundred ninety-two patients underwent Fontan. Fontan thrombosis occurred in 19 (10%) patients. 54% were started on aspirin, 27% coumadin, 4% heparin, and 7% none. There was no relationship between thrombosis and baseline anatomy, Fontan type or fenestration. Median time to thromboprophylaxis initiation was 4 days (interquartile range 2-6). Patients not started on thromboprophylaxis had 44.8 times the odds of thrombosis as those on thromboprophylaxis (confidence interval 6.4-311.7, P0.01); no children starting thromboprophylaxis before postoperative day 2 developed thromboses. For every day that thromboprophylaxis was delayed, odds of thrombosis increased by 30% (odds ratio 1.3; CI 1.1-1.6, P0.01). There was no difference in the odds of thrombosis between children taking aspirin vs other thromboprophylaxis types. Odds of early postoperative Fontan circuit thrombosis are increased in patients in whom thromboprophylaxis is delayed beyond the second postoperative day, with no difference in the odds of thrombosis between patients initiated on aspirin vs other thromboprophylaxis. Early aspirin institution post Fontan is recommended to reduce morbidity. Ultra-mini-Abstract: Odds of early postoperative Fontan circuit thrombosis are increased in patients in whom thromboprophylaxis is delayed beyond the second postoperative day, with no difference in the odds of thrombosis between patients initiated on aspirin vs other thromboprophylaxis. Early aspirin institution post Fontan is recommended to reduce morbidity and resource utilization.

The aim of this study was to assess the significance of post-operative troponin levels as a surrogate for left ventricular (LV) dysfunction measured by global longitudinal strain (GLS) in patients with dextro-transposition of the great arteries (d-TGA) who undergo an arterial switch operation (ASO), and to explore the LV GLS recovery in the mid-term follow-up period. Seventy-eight neonates were included, of whom 41 had troponin-I measurements and 37 had troponin-T measurements. The primary outcome of LV GLS was assessed and compared with healthy controls at the pre-operative stage and time of discharge, 3 months, 6 months and 12 months of age. Secondary outcomes included deaths or transplantations and other clinical markers such as length of hospital stay. D-TGA patients had worse LV GLS post-operatively compared to age-matched controls (p 0.01) which improved by 12 months of age (p = 0.53). No association was found between changes in troponin-I or troponin-T levels and LV GLS at the time of discharge (r = 0.4, p = 0.64 and r = -0.5, p = 0.91, respectively). In addition, there were no deaths or transplantations in this cohort over a period of 12 months. LV GLS appears to worsen in the early post-operative period for d-TGA patients who undergo neonatal ASO but this recovers through the first post-operative year. Troponin levels have limited value in predicting early or midterm LV dysfunction and recovery.

Body mass index, race/ethnicity, and payer status are associated with operative mortality in congenital heart disease (CHD). Interactions between these predictors and impacts on longer term outcomes are less well understood. We studied the effect of body mass index, race/ethnicity, and payer on 1-year outcomes following elective CHD surgery and tested the degree to which race/ethnicity and payer explained the effects of body mass index. We hypothesized that body mass index might be a potentially modifiable risk factor for post-operative outcomes. Patients aged 2–25 years who underwent elective CHD surgery at our center from 2010 to 2017 were included. We assessed 1-year unplanned cardiac re-admissions, re-interventions, and mortality. Step-wise, multivariable logistic regression was performed. Of 929 patients, 10.4% were underweight, 14.9% overweight, and 8.5% obese. Non-white race/ethnicity comprised 40.4% and public insurance 29.8%. Only 0.5% died prior to hospital discharge with one additional death in the first post-operative year. Among patients with continuous follow up, unplanned re-admission and re-intervention rates were 14.7% and 12.3%, respectively. In multivariable analyses adjusting for type of surgery and surgeon, obese, overweight, and underweight patients had higher odds of re-admission than normal weight patients (OR 1.40, p=0.026; OR 1.77, p

OBJECTIVE: Despite improvements in operative and perioperative care, the risk of significant morbidity and mortality for children undergoing Fontan procedures persists. Previous investigations have identified peri-Fontan characteristics that may predict early adverse events. The purpose of this study was to identify characteristics from throughout a patient’s lifespan, including all perioperative stages, that might predict early Fontan failure — defined as death, Fontan takedown, or listing for cardiac transplantation before hospital discharge or within 30 postoperative days. METHODS: A single-center retrospective study of all patients undergoing a Fontan procedure was performed. Patient and intervention-related characteristics were examined from birth through Fontan. Data were described using standard summary statistics. Univariable, logistic regression was used to examine associations with early Fontan failure. RESULTS: In total, 191 patients met inclusion criteria. The incidence of early Fontan failure was 4% (n = 8: six deaths, two Fontan takedowns). Neonatal balloon atrial septostomy was the only patient characteristic significantly associated with Fontan failure. Patients who underwent balloon septostomy had 8.5-times higher odds of Fontan failure (CI 2.6 – 28.1, p < 0.001) than those who did not. CONCLUSIONS: Children who require balloon septostomy as neonates remain at higher risk of Fontan takedown, listing for heart transplantation, or death in the early post-Fontan period.

Background Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe life-threatening manifestation of SARS-CoV-2 infection. Acute cardiac dysfunction and resultant cardiogenic shock are common in children with MIS-C. While most children recover rapidly from acute illness, the long-term impact on the myocardium and cardiac function is unknown. Methods In this prospective study, cardiac MRI (CMR) was performed on patients 10 years old. Native T1 and T2 mapping values were compared with 20 children with normal CMR examinations. Results We performed CMRs on 13 subjects at a median age of 13.6 years (interquartile range [IQR] 11.9-16.0) and a median time from hospitalization of 8.2 months (IQR 6.8-9.6). Twelve subjects displayed normal ventricular function with a median left ventricle ejection fraction (LVEF) of 57.2% (IQR 56.1-58.4) and median right ventricular (RV) EF of 53.1% (IQR 52.0-55.7). One subject had low normal EF (52%). There was normal T2 and native T1 as compared to normal controls. There was qualitatively no evidence of edema by T2 weighted imaging. One subject had late gadolinium enhancement (LGE) at the inferior insertion point and mid-ventricular inferolateral region, with normal EF, no evidence of edema or perfusion defects, and normal T1 and T2 times. When stratifying by a history of abnormal LVEF (LVEF

Background Administrative billing data are critical to many initiatives in congenital heart surgery. Mapping algorithms for International Classification of Disease, 10th Revision diagnosis and procedure codes to clinical registry procedure definitions will allow identification of surgical cases and account for patient and procedural factors within administrative data. Our objectives were to develop mapping logic to crosswalk International Classification of Disease, 10th Revision procedure codes to 10 Society of Thoracic Surgeons Congenital Heart Surgery Database benchmark and beta-test the algorithm. Methods Patients undergoing Society of Thoracic Surgeons Congenital Heart Surgery Database benchmark procedures from 2015 to 2019 were identified and served as the gold standard. Cases were linked on direct identifiers to cases from the Pediatric Health Information System Database. Two independent teams developed International Classification of Disease, 10th Revision–based algorithms for cases capture. Algorithms were compared and iteratively refined to optimize sensitivity and specificity. Operative mortalities for cases identified in the administrative versus registry data were compared. Results Overall sensitivity was 91% and specificity was 99% for capture of benchmark operations using International Classification of Diseases 10th Revision codes. Sensitivity was more than 90% in identifying 6 of the 10 individual benchmark procedures and more than 98% sensitive in identifying Fontan, Glenn, and arterial switch with ventricular septal defect procedures. Specificity was more than 98% for all benchmark operations. There were no statistical differences in operative mortality between cases identified in the administrative versus the registry data. Conclusions Novel mapping algorithm for International Classification of Disease, 10th Revision procedure codes enables identification of congenital heart benchmark procedures within administrative billing data. This crosswalk facilitates population-based congenital heart surgical research and quality assessment.

BACKGROUND In spring 2020, a novel hyperinflammatory process associated with severe acute respiratory syndrome coronavirus 2 multisystem inflammatory syndrome in children (MIS-C) was described. The long-term impact remains unknown. We report longitudinal outcomes from a New York interdisciplinary follow-up program. METHODS All children RESULTS In total, 45 children were admitted with MIS-C. The median time to last follow-up was 5.8 months (interquartile range 1.3–6.7). Of those admitted, 76% required intensive care and 64% required vasopressors and/or inotropes. On admission, patients exhibited significant nonspecific inflammation, generalized lymphopenia, and thrombocytopenia. Soluble interleukin (IL) IL-2R, IL-6, IL-10, IL-17, IL-18, and C-X-C Motif Chemokine Ligand 9 were elevated. A total of 80% (n = 36) had at least mild and 44% (n = 20) had moderate-severe echocardiographic abnormalities including coronary abnormalities (9% had a z score of 2–2.5; 7% had a z score > 2.5). Whereas most inflammatory markers normalized by 1 to 4 weeks, 32% (n = 11 of 34) exhibited persistent lymphocytosis, with increased double-negative T cells in 96% of assessed patients (n = 23 of 24). By 1 to 4 weeks, only 18% (n = 7 of 39) had mild echocardiographic findings; all had normal coronaries. At 1 to 4 months, the proportion of double-negative T cells remained elevated in 92% (median 9%). At 4 to 9 months, only 1 child had persistent mild dysfunction. One had mild mitral and/or tricuspid regurgitation. CONCLUSIONS Although the majority of children with MIS-C present critically ill, most inflammatory and cardiac manifestations in our cohort resolved rapidly.

Recent years have seen an exponential increase in the variety of healthcare data captured across numerous sources. However, mechanisms to leverage these data sources to support scientific investigation have remained limited. In 2013 the Pediatric Heart Network (PHN), funded by the National Heart, Lung, and Blood Institute, developed the Integrated CARdiac Data and Outcomes (iCARD) Collaborative with the goals of leveraging available data sources to aid in efficiently planning and conducting PHN studies; supporting integration of PHN data with other sources to foster novel research otherwise not possible; and mentoring young investigators in these areas. This review describes lessons learned through the development of iCARD, initial efforts and scientific output, challenges, and future directions. This information can aid in the use and optimisation of data integration methodologies across other research networks and organisations.

Background:Using existing data from clinical registries to support clinical trials and other prospective studies has the potential to improve research efficiency. However, little has been reported about staff experiences and lessons learned from implementation of this method in pediatric cardiology.Objectives:We describe the process of using existing registry data in the Pediatric Heart Network Residual Lesion Score Study, report stakeholders’ perspectives, and provide recommendations to guide future studies using this methodology.Methods:The Residual Lesion Score Study, a 17-site prospective, observational study, piloted the use of existing local surgical registry data (collected for submission to the Society of Thoracic Surgeons-Congenital Heart Surgery Database) to supplement manual data collection. A survey regarding processes and perceptions was administered to study site and data coordinating center staff.Results:Survey response rate was 98% (54/55). Overall, 57% perceived that using registry data saved research staff time in the current study, and 74% perceived that it would save time in future studies; 55% noted significant upfront time in developing a methodology for extracting registry data. Survey recommendations included simplifying data extraction processes and tailoring to the needs of the study, understanding registry characteristics to maximise data quality and security, and involving all stakeholders in design and implementation processes.Conclusions:Use of existing registry data was perceived to save time and promote efficiency. Consideration must be given to the upfront investment of time and resources needed. Ongoing efforts focussed on automating and centralising data management may aid in further optimising this methodology for future studies.

Background: We report the rationale and design for a peer-evaluation protocol of attending congenital heart surgeon technical skill using direct video observation. Methods: All surgeons contributing data to The Society of Thoracic Surgeons—Congenital Heart Surgery Database (STS-CHSD) are invited to submit videos of themselves operating, to rate peers, or both. Surgeons may submit Norwood procedures, complete atrioventricular canal repairs, and/or arterial switch operations. A HIPPA-compliant website allows secure transmission/evaluation. Videos are anonymously rated using a modified Objective Structured Assessment of Technical Skills score. Ratings are linked to five years of contemporaneous outcome data from the STS-CHSD and surgeon questionnaires. The primary outcome is a composite for major morbidity/mortality. Results: Two hundred seventy-six surgeons from 113 centers are eligible for participation: 83 (30%) surgeons from 53 (45%) centers have agreed to participate, with recruitment ongoing. These surgeons vary considerably in years of experience and outcomes. Participants, both early and late in their careers, describe the process as “very rewarding” and “less time consuming than anticipated.” An initial subset of 10 videos demonstrated excellent interrater reliability (interclass correlation = 0.85). Conclusions: This study proposes to evaluate the technical skills of attending pediatric cardiothoracic surgeons by video observation and peer-review. It is notable that over a quarter of congenital heart surgeons, across a range of experiences, from almost half of United States centers have already agreed to participate. This study also creates a mechanism for peer feedback; we hypothesize that feedback could yield broad and meaningful quality improvement.

OBJECTIVE: To summarize existing literature on neonatal disparities in congenital heart disease surgical outcomes and identify potential policies to address these disparities. FINDING: Disparities in outcomes for neonatal congenital heart surgery were largely published under four domains: race/ethnicity, insurance type, neighborhood/socioeconomic status, and cardiac center characteristics. While existing research identifies associations between these domains and mortality, more nuanced analyses are emerging to understand the mediators between these domains and other non-mortality outcomes, as well as potential interventions and policies to reduce disparities. A broader look into social determinants of health (SDOH), prenatal diagnosis, proximity of birth to a cardiac surgical center, and post-surgical outpatient and neurodevelopmental follow-up may accelerate interventions to mitigate disparities in outcomes. CONCLUSION: Understanding the mechanisms of how SDOH relate to neonatal surgical outcomes is paramount, as disparities research in neonatal congenital heart surgery continues to shift from identification and description, to intervention and policy.

While pediatric SARS-CoV-2 infection is largely spared from severe COVID-19, a small fraction of children develop a life-threatening condition known as MIS-C, which is associated with an aberrant peripheral blood immunophenotype; namely within adaptive immune cell populations. Little is known about how MIS-C impacts memory generation that would be imperative for future SARS-CoV-2 responses. Here, we used high dimensional flow cytometry and TCR sequencing to assess the peripheral blood T cell profile during acute MIS-C (n=17), following recovery (MIS-C-R) up to 9 months post-MIS-C (n=9), and relative to age-matched convalescent, mild pediatric COVID-19 (non-MIS-C; n=5) and uninfected controls (n=3). We also applied antigen-specific analyses to determine the magnitude and functional capacity of SARS-CoV-2-specific T cells in MIS-C-R (n=10) and non-MIS-C children (n=16). Flow cytometry showed unique T cell composition in MIS-C which resolved in recovery: lacking persistence of exhausted CD8+ T cells observed during MIS-C, and reestablishment of the naïve T cell pool. TCR sequencing showed decreased clonal diversity and distinct TCR Vβ usage in acute MIS-C compared to MIS-C-R. Results from antigen-specific analyses show that while T cell memory is similar phenotypically, MIS-C-R children have greater frequencies of SARS-CoV-2-specific CD4+ T cells than non-MIS-C up to 9 months since diagnosis. Meanwhile, SARS-CoV-2-specific CD8+ T cells in MIS-C children were more cytokine-producing, while more cytotoxic in non-MIS-C children. Together, these results reveal a restoration in global T cell phenotype in MIS-C-R children, as well as the robust production of functionally competent SARS-CoV-2 specific T cell memory. This work is supported by grants from NIH (K23 AI141686, 3U01 AI100119-10S1)

Background Many factors affect outcomes after congenital cardiac surgery. Objectives The RLS (Residual Lesion Score) study explored the impact of severity of residual lesions on post-operative outcomes across operations of varying complexity. Methods In a prospective, multicenter, observational study, 17 sites enrolled 1,149 infants undergoing 5 common operations: tetralogy of Fallot repair (n = 250), complete atrioventricular septal defect repair (n = 249), arterial switch operation (n = 251), coarctation or interrupted arch with ventricular septal defect (VSD) repair (n = 150), and Norwood operation (n = 249). The RLS was assigned based on post-operative echocardiography and clinical events: RLS 1 (trivial or no residual lesions), RLS 2 (minor residual lesions), or RLS 3 (reintervention for or major residual lesions before discharge). The primary outcome was days alive and out of hospital within 30 post-operative days (60 for Norwood). Secondary outcomes assessed post-operative course, including major medical events and days in hospital. Results RLS 3 (vs. RLS 1) was an independent risk factor for fewer days alive and out of hospital (p ≤ 0.008) and longer post-operative hospital stay (p ≤ 0.02) for all 5 operations, and for all secondary outcomes after coarctation or interrupted arch with VSD repair and Norwood (p ≤ 0.03). Outcomes for RLS 1 versus 2 did not differ consistently. RLS alone explained 5% (tetralogy of Fallot repair) to 20% (Norwood) of variation in the primary outcome. Conclusions Adjusting for pre-operative factors, residual lesions after congenital cardiac surgery impacted in-hospital outcomes across operative complexity with greatest impact following complex operations. Minor residual lesions had minimal impact. These findings may provide guidance for surgeons when considering short-term risks and benefits of returning to bypass to repair residual lesions.

Duration of mechanical ventilation is an important variable used by German Diagnosis-Related Groups (G-DRG) system to establish cost weight values for reimbursement after congenital heart surgery. Infants are commonly ventilated after open heart surgery. As of year 2015, we strived to achieve early postoperative extubation. This work studies how this approach impacted reimbursement after infant open heart surgery.Data of infants who underwent surgery on cardiopulmonary bypass (CPB) from 2014 to 2018 were reviewed. Successful early extubation was defined as end of mechanical ventilation within 24 hours postoperatively, without reintubation at a later point. Mean cost weight values (case mix index [CMI]) of achieved DRGs were used for estimation of reimbursement. Evolutions over years of early extubation and of reimbursement were compared.A total of 521 infants underwent operations on CPB. Of these, 161 (31%) procedures were of higher risk Society of Thoracic Surgery and the European Association for Cardio-Thoracic Surgery (STAT) categories 3 and 4. Early extubation was achieved in 205 (39%) patients. The rate increased from 14% (year 2014) to 57% (year 2018). Case mix index amounted to 8.87 ± 7.00 after early extubation, and 12.37 ± 7.85 after late extubation:Early extubation could be progressively obtained in the majority of infants. This resulted in lower reimbursement. Surgical complexity was disregarded. The current G-DRG system appears to favor longer mechanical ventilation durations after infant open heart surgery.

Motivated by the shortcoming of current hospital scheduling and capacity planning methods which often model different units in isolation, we introduce the first dynamic multi-day scheduling model that integrates information about capacity usage at more than one location in a hospital. In particular, we analyze the first dynamic model that accounts for patients' length-of-stay and downstream census in scheduling decisions. Via a simple and innovative variable transformation, we show that the optimal number of patients to be allowed in the system is increasing in the state of the system and in the downstream capacity. Moreover, the total system cost exhibits decreasing marginal returns as the capacity increases at any location independently of another location. Through numerical experiments on realistic data, we show that there is substantial value in making integrated scheduling decisions. In contrast, localized decision rules that only focus on a single location of a hospital can result in up to 60% higher expenses.

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 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 Z 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.

BACKGROUND: Low socioeconomic status (SES) has emerged as an important risk factor for higher short-term mortality and neurodevelopmental outcomes in children with hypoplastic left heart syndrome and related anomalies; yet little is known about how SES affects these outcomes over the long-term. METHODS: We linked data from the Single Ventricle Reconstruction trial to US Census Bureau data to analyze the relationship of neighborhood SES tertiles with mortality and transplantation, neurodevelopment, quality of life, and functional status at 5 and 6 years post–Norwood procedure (N = 525). Cox proportional hazards regression and linear regression were used to assess the association of SES with mortality and neurodevelopmental outcomes, respectively. RESULTS: Patients in the lowest SES tertile were more likely to be racial minorities, older at stage 2 and Fontan procedures, and to have more complications and fewer cardiac catheterizations over follow-up (all P < .05) compared with patients in higher SES tertiles. Unadjusted mortality was highest for patients in the lowest SES tertile and lowest in the highest tertile (41% vs 29%, respectively; log-rank P = .027). Adjustment for patient birth and Norwood factors attenuated these differences slightly (P = .055). Patients in the lowest SES tertile reported lower functional status and lower fine motor, problem-solving, adaptive behavior, and communication skills at 6 years (all P < .05). These differences persisted after adjustment for baseline and post-Norwood factors. Quality of life did not differ by SES. CONCLUSIONS: Among patients with hypoplastic left heart syndrome, those with low SES have worse neurodevelopmental and functional status outcomes at 6 years. These differences were not explained by other patient or clinical characteristics.

Approximately, 1.7 million individuals in the United States have been infected with SARS-CoV-2, the virus responsible for the novel coronavirus disease-2019 (COVID-19). This has disproportionately impacted adults, but many children have been infected and hospitalised as well. To date, there is not much information published addressing the cardiac workup and monitoring of children with COVID-19. Here, we share the approach to the cardiac workup and monitoring utilised at a large congenital heart centre in New York City, the epicentre of the COVID-19 pandemic in the United States.

Background/Aims:Registry-based trials have emerged as a potentially cost-saving study methodology. Early estimates of cost savings, however, conflated the benefits associated with registry utilisation and those associated with other aspects of pragmatic trial designs, which might not all be as broadly applicable. In this study, we sought to build a practical tool that investigators could use across disciplines to estimate the ranges of potential cost differences associated with implementing registry-based trials versus standard clinical trials.Methods:We built simulation Markov models to compare unique costs associated with data acquisition, cleaning, and linkage under a registry-based trial design versus a standard clinical trial. We conducted one-way, two-way, and probabilistic sensitivity analyses, varying study characteristics over broad ranges, to determine thresholds at which investigators might optimally select each trial design.Results:Registry-based trials were more cost effective than standard clinical trials 98.6% of the time. Data-related cost savings ranged from $4300 to $600,000 with variation in study characteristics. Cost differences were most reactive to the number of patients in a study, the number of data elements per patient available in a registry, and the speed with which research coordinators could manually abstract data. Registry incorporation resulted in cost savings when as few as 3768 independent data elements were available and when manual data abstraction took as little as 3.4 seconds per data field.Conclusions:Registries offer important resources for investigators. When available, their broad incorporation may help the scientific community reduce the costs of clinical investigation. We offer here a practical tool for investigators to assess potential costs savings.

The aims of this study were (1) to describe the additive risk of performing cardiac surgery in neonates born ≤ 2.0 kg, after accounting for the baseline risks of low birth weight, and (2) to describe the additive risk of being born ≤ 2.0 kg in neonates undergoing cardiac surgery. We used a risk difference analysis in a retrospective cohort, 2006–2016. Neonates born ≤ 2.0 kg undergoing congenital heart surgery during initial postnatal admission were included. Data were standardized alternatingly for birth weight and cardiac surgical risk using national population data to estimate the number of deaths expected had they not required cardiac surgery or were they of normal weight. Of 105 neonates ≤ 2 kg, median birth weight was 1.6 kg (IQR 1.3–1.8 kg). Median gestational age was 33 weeks (IQR 31–35 weeks). Observed operative mortality was 14.3%; 0% for neonates ≤ 1.0 kg (CI 0–33.6%), 20.6% for neonates > 1.0–1.5 kg (CI 8.7–37.9%), and 12.9% for neonates > 1.5–2.0 kg (CI 5.7–23.9%). Among neonates ≤ 2.0 kg not undergoing cardiac surgery, expected mortality was 4.8% (CI 1.6–10.8); cardiac surgery increased the risk of mortality 9.5% (CI 1.7–17.4%). Conversely, the expected risk for normal birth weight neonates undergoing cardiac surgery was 5.7% (CI 2.1–12.0%); low birth weight increased the risk of mortality 8.6% (CI 0.5–16.6%). To continue making advancements in cardiac surgery, we must understand that the rate of mortality observed in normal weight infants is not a realistic target and that, despite advances, the risk attributable to the surgery remains higher among low birth weight patients.

INTRODUCTION: Relative contraindications for adenosine use include heart transplant history and the anti-platelet agent dipyridamole. In an initial prospective study, the safety and efficacy of adenosine to induce atrioventricular (AV) block was demonstrated in pediatric and young adult heart transplant recipients. Over half of this cohort was on dipyridamole, which was suspended before testing. This prospective follow-up study evaluates the safety and efficacy of an adenosine dosing protocol in healthy young patients maintained on dipyridamole after heart transplant. METHODS: After routine cardiac biopsy (4/2016 – 6/2017), a temporary ventricular pacing catheter was placed and adenosine was dosed in stepwise increments until AV block occurred (maximum dose 200mcg/kg up to 12mg). The primary outcome was clinically significant asystole (≥ 12 seconds). Secondary outcomes included dose of adenosine eliciting AV block, AV block duration, dysrhythmias and patient reported symptoms. Incidence and 95% confidence intervals for categorical outcomes were calculated. Paired outcomes were compared to the parent study. RESULTS: Thirty of 39 eligible patients (5 – 24 years) were tested. No patient (0%, CI 0 – 8%) experienced clinically significant asystole. AV block occurred in 29/30 patients (97%, CI 86 – 100%). The median dose causing AV block was 50mcg/kg (vs. 100mcg/kg off dipyridamole; P=0.011). Seventeen patients (57%, CI 39 – 72%) required less adenosine to achieve AV block on dipyridamole; six (20%) required more. AV block occurred only at doses ≥25mcg/kg. Length of block, frequency of atrial/ventricular ectopy and incidence of subjective symptoms after adenosine were not different on dipyridamole. No atrial fibrillation/flutter occurred. CONCLUSION: AV block occurs often at twofold lower adenosine doses in healthy pediatric and young adult heart transplant recipients taking oral dipyridamole, as compared to previous testing of the same cohort off dipyridamole. Results still suggest that initial dosing of 25mcg/kg (max 0.8mg) with stepwise escalation poses low risk of prolonged asystole.

Background The effect of the timing of stage-2-palliation (S2P) on survival through single ventricle palliation remains unknown. This study investigated the optimal timing of S2P that minimizes pre-S2P attrition and maximizes post-S2P survival. Methods The Congenital Heart Surgeons' Society's critical left ventricular outflow tract obstruction cohort was used. Survival analysis was performed using multiphase parametric hazard analysis. Separate risk factors for death after the Norwood and after S2P were identified. Based on the multivariable models, infants were stratified as low, intermediate, or high risk. Cumulative 2-year, post-Norwood survival was predicted. Optimal timing was determined using conditional survival analysis and plotted as 2-year, post-Norwood survival versus age at S2P. Results A Norwood operation was performed in 534 neonates from 21 institutions. The S2P was performed in 71%, at a median age of 5.1 months (IQR: 4.3 to 6.0), and 22% died after Norwood. By 5 years after S2P, 10% of infants had died. For low- and intermediate-risk infants, performing S2P after age 3 months was associated with 89% ± 3% and 82% ± 3% 2-year survival, respectively. Undergoing an interval cardiac reoperation or moderate-severe right ventricular dysfunction before S2P were high-risk features. Among high-risk infants, 2-year survival was 63% ± 5%, and even lower when S2P was performed before age 6 months. Conclusions Performing S2P after age 3 months may optimize survival of low- and intermediate-risk infants. High-risk infants are unlikely to complete three-stage palliation, and early S2P may increase their risk of mortality. We infer that early referral for cardiac transplantation may increase their chance of survival.

Background: In infants requiring 3-stage single-ventricle palliation for hypoplastic left heart syndrome, attrition after the Norwood procedure remains significant. The effect of the timing of stage 2 palliation (S2P), a physician-modifiable factor, on long-term survival is not well understood. We hypothesized that an optimal interval between the Norwood and S2P that both minimizes pre-S2P attrition and maximizes post-S2P survival exists and is associated with individual patient characteristics. Methods: The National Institutes of Health/National Heart, Lung, and Blood Institute Pediatric Heart Network Single Ventricle Reconstruction Trial public data set was used. Transplant-free survival (TFS) was modeled from (1) Norwood to S2P and (2) S2P to 3 years by using parametric hazard analysis. Factors associated with death or heart transplantation were determined for each interval. To account for staged procedures, risk-adjusted, 3-year, post-Norwood TFS (the probability of TFS at 3 years given survival to S2P) was calculated using parametric conditional survival analysis. TFS from the Norwood to S2P was first predicted. TFS after S2P to 3 years was then predicted and adjusted for attrition before S2P by multiplying by the estimate of TFS to S2P. The optimal timing of S2P was determined by generating nomograms of risk-adjusted, 3-year, post-Norwood, TFS versus the interval from the Norwood to S2P. Results: Of 547 included patients, 399 survived to S2P (73%). Of the survivors to S2P, 349 (87%) survived to 3-year follow-up. The median interval from the Norwood to S2P was 5.1 (interquartile range, 4.1–6.0) months. The risk-adjusted, 3-year, TFS was 68±7%. A Norwood-S2P interval of 3 to 6 months was associated with greatest 3-year TFS overall and in patients with few risk factors. In patients with multiple risk factors, TFS was severely compromised, regardless of the timing of S2P and most severely when S2P was performed early. No difference in the optimal timing of S2P existed when stratified by shunt type. Conclusions: In infants with few risk factors, progressing to S2P at 3 to 6 months after the Norwood procedure was associated with maximal TFS. Early S2P did not rescue patients with greater risk factor burdens. Instead, referral for heart transplantation may offer their best chance at long-term survival. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00115934.

To compare treatment failure leading to hospital readmission in children with complicated appendicitis who received oral versus intravenous antibiotics after discharge.Antibiotics are often employed after discharge to prevent treatment failure in children with complicated appendicitis, although existing studies comparing intravenous and oral antibiotics for this purpose are limited.We identified all patients aged 3 to 18 years undergoing appendectomy for complicated appendicitis, who received postdischarge antibiotics at 35 childrens hospitals from 2009 to 2012. Discharge codes were used to identify study subjects from the Pediatric Health Information System database, and chart review confirmed eligibility, treatment assignment, and outcomes. Exposure status was based on outpatient antibiotic therapy, and analysis used optimal and full matching methods to adjust for demographic and clinical characteristics. Treatment failure (defined as an organ-space infection) requiring inpatient readmission was the primary outcome. Secondary outcomes included revisits from any cause to either the inpatient or emergency department setting.In all, 4579 patients were included (median: 99/hospital), and utilization of intravenous antibiotics after discharge ranged from 0% to 91.7% across hospitals. In the matched analysis, the rate of treatment failure was significantly higher for the intravenous group than the oral group [odds ratio (OR) 1.74, 95% confidence interval (CI) 1.05-2.88; risk difference: 4.0%, 95% CI 0.4-7.6%], as was the rate of all-cause revisits (OR 2.11, 95% CI 1.44-3.11; risk difference: 9.4%, 95% CI 4.7-14.2%). The rate of peripherally inserted central catheter line complications was 3.2% in the intravenous group, and drug reactions were rare in both groups (intravenous: 0.7%, oral: 0.5%).Compared with oral antibiotics, use of intravenous antibiotics after discharge in children with complicated appendicitis was associated with higher rates of both treatment failure and all-cause hospital revisits.

Background: Mortality through single-ventricle palliation remains high and the effect of the timing of stage 2 palliation (S2P) is not well understood. We investigated current practice patterns in the timing of S2P across two professional societies and compared them to actual practice patterns from two databases of patients who underwent S2P. Methods: A ten-question survey was distributed to the members of the Congenital Heart Surgeons’ Society (CHSS) and the European Congenital Heart Surgeons’ Association (ECHSA). Results were summarized using descriptive statistics. Surgeon-reported preferences were compared to clinical data from the CHSS Critical Left Ventricular Outflow Tract Obstruction (LVOTO) Registry and the Pediatric Heart Network Single Ventricle Reconstruction (SVR) database. Results: Overall, 38% (88 of 232) of surgeons from 74 institutions responded, of which 70% (62 of 88) were CHSS members and 30% (26 of 88) were ECHSA members. Surgeons reported performing S2P at a median of five months after stage 1 (interquartile range [IQR]: 4.5-6), with no difference between CHSS and ECHSA surgeons. Surgeons reported performing nonelective S2P at a median of 4.5 months after stage 1 (IQR: 3.5-5.5), again with no difference by society. No difference existed between the surgeon-reported preferences and patient data in the Critical LVOTO and SVR databases for the timing of elective (5 vs 5.1 vs 5.3 months, P = .19) or nonelective S2P (4.5 vs 4.6 vs 4.2 months, P = .06). Conclusion: There was a remarkable lack of variation in surgeon preferences regarding the timing of S2P. This may represent a natural standardization of practice across congenital heart surgery, which is notable, given the current lack of guidelines regarding the timing of S2P.

Background Data routinely captured in clinical registries may be leveraged to enhance efficiency of prospective research. The quality of registry data for this purpose has not been studied, however. We evaluated the completeness and accuracy of perioperative data within congenital heart centers' local surgical registries. Methods Within 12 Pediatric Heart Network (PHN) sites, we evaluated 31 perioperative variables (and their subcategories, totaling 113 unique fields) collected via sites' local clinical registries for submission to The Society of Thoracic Surgeons Database, compared with chart review by PHN research coordinators. Both used standard STS definitions. Data were collected on 10 subjects for 2 to 5 procedures/site and adjudicated by the study team. Completeness and accuracy (agreement of registry data with medical record review by PHN coordinator, adjudicated by the study team) were evaluated. Results A total of 56,500 data elements were collected on 500 subjects. With regard to data completeness, 3.1% of data elements were missing from the registry, 0.6% from coordinator-collected data, and 0.4% from both. Overall, registry data accuracy was 98%. In total, 94.7% of data elements were both complete/non-missing and accurate within the registry, although there was variation across data fields and sites. Mean total time for coordinator chart review per site was 49.1 hours versus 7.0 hours for registry query. Conclusions This study suggests that existing surgical registry data constitute a complete, accurate, and efficient information source for prospective research. Variability across data fields and sites also suggest areas for improvement in some areas of data quality.

For decades, physicians have administered corticosteroids in the perioperative period to infants undergoing heart surgery with cardiopulmonary bypass (CPB) to reduce the post-operative systemic inflammatory response to CPB. Some question this practice because steroid efficacy has not been conclusively demonstrated and because some studies indicate that steroids could have harmful effects. STRESS is a randomized, placebo-controlled, double blind, multi-center trial designed to evaluate safety and efficacy of perioperative steroids in infants (age < 1 year) undergoing heart surgery with CPB. Participants (planned enrollment = 1200) are randomized 1:1 to methylprednisolone (30mg/kg) administered into the CPB pump prime versus placebo. The trial is nested within the existing infrastructure of the Society of Thoracic Surgeons Congenital Heart Surgery Database (STS-CHSD). The primary outcome is a global rank score of mortality, major morbidities and hospital length of stay with components ranked commensurate with their clinical severity. Secondary outcomes include several measures of major post-operative morbidity, post-operative hospital length of stay and steroid-related safety outcomes including prevalence of hyperglycemia and post-operative infectious complications. STRESS will be one of the largest trials ever conducted in children with heart disease and will answer a decades old question related to safety and efficacy of perioperative steroids in infants undergoing heart surgery with CPB. The pragmatic “trial within a registry” design may provide a mechanism for conducting low cost, high efficiency trials in a heretofore-understudied patient population. Trial Registration Number

BACKGROUND: Travel distance to surgical centers may be increased when coverage restrictions prevent children with congenital heart disease (CHD) from receiving care at out-of-state congenital heart surgery centers. We estimated the minimum travel distance to congenital heart surgery centers among publicly insured infants with time-sensitive CHD surgical needs, under two different scenarios: if they were and were not restricted to in-state centers. METHODS AND RESULTS: Using 2012 Medicaid Analytic extract data from 40 states, we identified 4,598 infants with CHD that require surgery in the first year of life. We calculated the minimum travel distance between patients’ homes and the nearest cardiac surgery center, assuming patients were and were not restricted to in-state centers. We used linear regression to identify demographic predictors of distance under both scenarios. When patients were not restricted to in-state centers, mean minimum travel distance was 43.7 miles, compared to 54.1 miles when they were restricted. For 5.9% of patients, the difference in travel distance under the two scenarios exceeded 50 miles. In six states, the difference in mean minimum travel distance exceeded 20 miles. Under both scenarios, distance was positively predicted by rural status, residence in middle-income zip codes, and white/non-Hispanic or American Indian/Alaskan Native race/ethnicity. CONCLUSIONS: For some publicly insured infants with severe CHD, facilitating the receipt of out-of-state care could mitigate access barriers. Existing efforts to regionalize care at fewer centers should be designed to avoid exacerbating access barriers among publicly insured CHD patients.