Neighborhood Childhood Opportunity, Race/Ethnicity, and Surgical Outcomes in Children With Congenital Heart Disease.

BACKGROUND: Racial and ethnic disparities in outcomes for children with congenital heart disease (CHD) coexist with disparities in educational, environmental, and economic opportunity. OBJECTIVES: We sought to determine the associations between childhood opportunity, race/ethnicity, and pediatric CHD surgery outcomes. METHODS: Pediatric Health Information System encounters aged <18 years from 2016 to 2022 with International Classification of Diseases-10th edition codes for CHD and cardiac surgery were linked to ZIP code-level Childhood Opportunity Index (COI), a score of neighborhood educational, environmental, and socioeconomic conditions. The associations of race/ethnicity and COI with in-hospital surgical death were modeled with generalized estimating equations and formal mediation analysis. Neonatal survival after discharge was modeled by Cox proportional hazards. RESULTS: Of 54,666 encounters at 47 centers, non-Hispanic Black (Black) (OR: 1.20; P = 0.01), Asian (OR: 1.75; P < 0.001), and Other (OR: 1.50; P < 0.001) groups had increased adjusted mortality vs non-Hispanic Whites. The lowest COI quintile had increased in-hospital mortality in unadjusted and partially adjusted models (OR: 1.29; P = 0.004), but not fully adjusted models (OR: 1.14; P = 0.13). COI partially mediated the effect of race/ethnicity on in-hospital mortality between 2.6% (P = 0.64) and 16.8% (P = 0.029), depending on model specification. In neonatal multivariable survival analysis (n = 13,987; median follow-up: 0.70 years), the lowest COI quintile had poorer survival (HR: 1.21; P = 0.04). CONCLUSIONS: Children in the lowest COI quintile are at risk for poor outcomes after CHD surgery. Disproportionally increased mortality in Black, Asian, and Other populations may be partially mediated by COI. Targeted investment in low COI neighborhoods may improve outcomes after hospital discharge. Identification of unmeasured factors to explain persistent risk attributed to race/ethnicity is an important area of future exploration.

Midterm Outcomes and Cardiac Magnetic Resonance Imaging following Multisystem Inflammatory Syndrome in Children.

At midterm follow-up visits performed at a median of 7 months (IQR 6.0-8.4 months), 16 patients with multisystem inflammatory syndrome in children had resolution of left ventricular dysfunction and most had resolution of coronary aneurysms. On cardiovascular magnetic resonance imaging, no patients had late gadolinium enhancement.

Multisystem Inflammatory Syndrome in Children Associated with Severe Acute Respiratory Syndrome Coronavirus 2 Infection (MIS-C): A Multi-institutional Study from New York City.

OBJECTIVE: To assess clinical characteristics and outcomes of severe acute respiratory syndrome coronavirus 2-associated multisystem inflammatory syndrome in children (MIS-C). STUDY DESIGN: Children with MIS-C admitted to pediatric intensive care units in New York City between April 23 and May 23, 2020, were included. Demographic and clinical data were collected. RESULTS: Of 33 children with MIS-C, the median age was 10 years; 61% were male; 45% were Hispanic/Latino; and 39% were black. Comorbidities were present in 45%. Fever (93%) and vomiting (69%) were the most common presenting symptoms. Depressed left ventricular ejection fraction was found in 63% of patients with median ejection fraction of 46.6% (IQR, 39.5-52.8). C-reactive protein, procalcitonin, d-dimer, and pro-B-type natriuretic peptide levels were elevated in all patients. For treatment, intravenous immunoglobulin was used in 18 (54%), corticosteroids in 17 (51%), tocilizumab in 12 (36%), remdesivir in 7 (21%), vasopressors in 17 (51%), mechanical ventilation in 5 (15%), extracorporeal membrane oxygenation in 1 (3%), and intra-aortic balloon pump in 1 (3%). The left ventricular ejection fraction normalized in 95% of those with a depressed ejection fraction. All patients were discharged home with median duration of pediatric intensive care unit stay of 4.7 days (IQR, 4-8 days) and a hospital stay of 7.8 days (IQR, 6.0-10.1 days). One patient (3%) died after withdrawal of care secondary to stroke while on extracorporeal membrane oxygenation. CONCLUSIONS: Critically ill children with coronavirus disease-2019-associated MIS-C have a spectrum of severity broader than described previously but still require careful supportive intensive care. Rapid, complete clinical and myocardial recovery was almost universal.

De novo mutations in histone-modifying genes in congenital heart disease.

Congenital heart disease (CHD) is the most frequent birth defect, affecting 0.8% of live births. Many cases occur sporadically and impair reproductive fitness, suggesting a role for de novo mutations. Here we compare the incidence of de novo mutations in 362 severe CHD cases and 264 controls by analysing exome sequencing of parent-offspring trios. CHD cases show a significant excess of protein-altering de novo mutations in genes expressed in the developing heart, with an odds ratio of 7.5 for damaging (premature termination, frameshift, splice site) mutations. Similar odds ratios are seen across the main classes of severe CHD. We find a marked excess of de novo mutations in genes involved in the production, removal or reading of histone 3 lysine 4 (H3K4) methylation, or ubiquitination of H2BK120, which is required for H3K4 methylation. There are also two de novo mutations in SMAD2, which regulates H3K27 methylation in the embryonic left-right organizer. The combination of both activating (H3K4 methylation) and inactivating (H3K27 methylation) chromatin marks characterizes 'poised' promoters and enhancers, which regulate expression of key developmental genes. These findings implicate de novo point mutations in several hundreds of genes that collectively contribute to approximately 10% of severe CHD.

What are we missing? Arrhythmia detection in the pediatric intensive care unit.

OBJECTIVES: To test the hypothesis that instituting a process of routine daily review of rhythm alarms in non-cardiac patients in the pediatric intensive care unit would yield clinically important disturbances that would otherwise go undetected. STUDY DESIGN: A prospective observational study was performed over a consecutive 28-day period. Total bedside monitor alarms, rhythm alarms, and heart rate (HR) trends were recorded. Rhythm alarm recordings were reviewed independently by two study team members. Medical records for patients with critical arrhythmias were reviewed to evaluate for prior knowledge of the event and to correlate with clinical data. RESULTS: We evaluated 86 patients (343 patient-days). There were 54,656 total monitor alarms (159.3 alarms/patient-day), of which 19,970 (37%) were rhythm alarms, including 4032 (20%) critical arrhythmias. Fifty-six percent of the critical alarms were artifactual. Seventeen of the 1786 ventricular tachycardia alarms represented true episodes that occurred in 5 patients. Two patients' care were altered as a result of detection of the arrhythmia in the review process. Eight hundred sixty-five (98%) of the 883 true critical alarms reviewed were for extreme HR. Eighty-three percent (5172) of the 6239 true non-critical alarms reviewed were HR alarms. CONCLUSIONS: Daily review of rhythm alarms improves detection of clinically relevant arrhythmias in non-cardiac pediatric intensive care unit patients.

Acute kidney injury after surgery for congenital heart disease.

BACKGROUND: The RIFLE criteria (risk, injury, failure, loss, and end-stage kidney disease) have been used to assess acute kidney injury (AKI) in various populations of critically ill children. There are limited reports of AKI using RIFLE criteria in large pediatric populations undergoing congenital heart disease surgery. METHODS: Records of patients 18 years and younger who underwent surgery for congenital heart disease between January 2006 and November 2009 were reviewed. The RIFLE score was determined for each patient postoperatively. Multivariate logistic regression analyses were performed to determine risk factors for AKI and the association with clinical outcomes, with subanalyses of patients 1 month of age or younger. RESULTS: Data for 458 patients (median age, 7.6 months) were collected and analyzed. Evidence of AKI was demonstrated in 234 patients (51%), the vast majority of whom recovered within 48 hours. Younger age, higher RACHS-1 (risk-adjusted classification for congenital heart surgery) category, and longer cardiopulmonary bypass time were associated with development of AKI. Acute kidney injury was associated with longer duration of ventilation and lengths of intensive care unit and hospital stay. Incidence of AKI in patients 1 month of age or younger was 60.9%, of which more than half required greater than 72 hours to recover. In patients 1 month of age or younger, use of cardiopulmonary bypass, lower preoperative serum creatinine, and higher preoperative blood urea nitrogen were associated with AKI, and AKI was the only factor associated with longer intensive care unit and hospital lengths of stay. CONCLUSIONS: Incidence of AKI based on RIFLE criteria in patients undergoing congenital heart disease surgery is higher than previously reported. Risk factors include age 1 month or younger and use of cardiopulmonary bypass. Acute kidney injury is associated with longer lengths of stay.

Web-based survey of current trends in hemodynamic monitoring after congenital heart surgery.

Strategies for monitoring patients recovering after congenital heart surgery have evolved considerably as technology continues to progress. Monitoring techniques traditionally centered around the comprehensive physical examination have been replaced by a number of revolutionary technologies developed to objectively evaluate various components of the cardiovascular system. Despite scant evidence that these methodologies actually improve outcomes, some have been embraced by clinicians. We developed an Internet survey designed to describe current practices of clinicians who care for patients after congenital heart surgery. There were 162 respondents to our survey with the majority from the United States. The views of cardiologists, intensivists, those dual trained in both cardiology and critical care medicine, and surgeons are all robustly represented in the results. Serial lactate monitoring was the strategy that was utilized most often by respondents (94%), followed by multisite near-infrared spectrometry (NIRS, 67%). There were 78% who utilized the combination of serial lactate and NIRS monitoring. Serial lactate monitoring was the technique that was thought to best represent cardiovascular well-being after heart surgery (40%). The results of this survey suggest that despite the paucity of evidence that clinical outcomes of patients recovering after congenital heart surgery are improved by any of these monitoring techniques, there is almost universal acceptance to monitor patients with serial lactate monitoring, NIRS monitoring, or a combination of these techniques.

Successful treatment of a neonate with persistent vancomycin-resistant enterococcal bacteremia with a daptomycin-containing regimen.

Infections caused by vancomycin-resistant enterococci (VRE) may be difficult to treat because of the limited armamentarium of antimicrobial agents. The difficulty is compounded in pediatric patients in general and neonates in particular because many of the newer antimicrobials have not been studied or approved for children. We report a 3-week-old infant who developed enterococcal bacteremia on post-operative day 10 after a surgical palliation for complex congenital heart disease that was complicated by acute renal failure. Despite removal of vascular catheters and antimicrobial regimens that included linezolid, quinupristin/dalfopristin, ampicillin/sulbactam, rifampin, and gentamicin, bacteremia persisted. It was not cleared until daptomycin (in combination with doxycycline) was started. This is the first case of successful treatment of probable endocarditis due to VRE in a neonate using a daptomycin-containing regimen.

Comparison of cisatracurium and vecuronium by infusion in neonates and small infants after congenital heart surgery.

BACKGROUND: Neonates and infants often require extended periods of mechanical ventilation facilitated by sedation and neuromuscular blockade. METHODS: Twenty-three patients aged younger than 2 yr were randomly assigned to receive either cisatracurium or vecuronium infusions postoperatively in a double-blinded fashion after undergoing congenital heart surgery. The infusion was titrated to maintain one twitch of a train-of-four. The times to full spontaneous recovery of train-of-four without fade, extubation, intensive care unit discharge, and hospital discharge were documented after drug discontinuation. Sparse sampling after termination of the infusion and a one-compartment model were used for pharmacokinetic analysis. The Mann-Whitney U test and Student t test were used to compare data between groups. RESULTS: There were no significant differences between groups with respect to demographic data or duration of postoperative neuromuscular blockade infusion. The median recovery time for train-of-four for cisatracurium (30 min) was less than that for vecuronium (180 min) (P < 0.05). Three patients in the vecuronium group had prolonged train-of-four recovery: Two had long elimination half-lives for vecuronium, and one had a high concentration of 3-OH vecuronium. There were no differences in extubation times, intensive care unit stays, or hospital stays between groups. CONCLUSIONS: Our results parallel data from adults demonstrating a markedly shorter recovery of neuromuscular transmission after cisatracurium compared with vecuronium. Decreased clearance of vecuronium and the accumulation of 3-OH vecuronium may contribute to prolonged spontaneous recovery times. Cisatracurium is associated with faster spontaneous recovery of neuromuscular function compared with vecuronium but not with any differences in intermediate outcome measures in neonates and infants.

Extracorporeal membrane oxygenation for pneumonitis after a Glenn palliation.

A five-month old male with a single ventricle palliated with a bidirectional cavopulmonary anastomosis developed severe respiratory insufficiency from respiratory syncytial virus (RSV) pneumonitis. He was successfully rescued with extracorporeal membrane oxygenation (ECMO) therapy and recovered with minimal morbidity.