Narrowing the Survival Gap: Trends in Survival of Individuals with Down Syndrome with and without Congenital Heart Defects Born 1979 to 2018.

OBJECTIVE: To evaluate the hypothesis that childhood survival for individuals with Down syndrome (DS) and congenital heart defects (CHDs) has improved in recent years, approaching the survival of those with DS without CHDs. STUDY DESIGN: Individuals with DS born from 1979 to 2018 were identified through the Metropolitan Atlanta Congenital Defects Program, a population-based birth defects surveillance system administered by the Centers for Disease Control and Prevention. Survival analysis was performed to evaluate predictors of mortality for those with DS. RESULTS: The cohort included 1671 individuals with DS; 764 had associated CHDs. The 5-year survival in those with DS with CHD improved steadily among individuals born in the 1980s through the 2010s (from 85% to 93%; P = .01), but remained stable (96% to 95%; P = .97) in those with DS without CHDs. The presence of a CHD was not associated with mortality through 5 years of age for those born 2010 or later (hazard ratio, 2.63; 95% CI, 0.95-8.37). In multivariable analyses, atrioventricular septal defects were associated with early (<1 year) and late (>5 year) mortality, whereas ventricular septal defects were associated with intermediate (1-5 years) mortality and atrial septal defects with late mortality, when adjusting for other risk factors. CONCLUSIONS: The gap in 5-year survival between children with DS with and without CHDs has improved over the last 4 decades. Survival after 5 years remains lower for those with CHDs, although longer follow-up is needed to determine if this difference lessens for those born in the more recent years.

Cardiac Magnetic Resonance Findings of Coronavirus Disease 2019 (COVID-19) Vaccine-Associated Myopericarditis at Intermediate Follow-Up: A Comparison with Classic Myocarditis.

OBJECTIVE: To report intermediate cardiac magnetic resonance (CMR) findings of coronavirus disease 2019 (COVID-19) vaccine-associated myopericarditis (C-VAM) and compare with classic myocarditis. STUDY DESIGN: Retrospective cohort study including children diagnosed with C-VAM from May 2021 through December 2021 with early and intermediate CMR. Patients with classic myocarditis from January 2015 through December 2021 and intermediate CMR were included for comparison. RESULTS: There were 8 patients with C-VAM and 20 with classic myocarditis. Among those with C-VAM, CMR performed at a median 3 days (IQR 3, 7) revealed 2 of 8 patients with left ventricular ejection fraction <55%, 7 of 7 patients receiving contrast with late gadolinium enhancement (LGE), and 5 of 8 patients with elevated native T1 values. Borderline T2 values suggestive of myocardial edema were present in 6 of 8 patients. Follow-up CMRs performed at a median 107 days (IQR 97, 177) showed normal ventricular systolic function, T1, and T2 values; 3 of 7 patients had LGE. At intermediate follow-up, patients with C-VAM had fewer myocardial segments with LGE than patients with classic myocarditis (4/119 vs 42/340, P = .004). Patients with C-VAM also had a lower frequency of LGE (42.9 vs 75.0%) and lower percentage of left ventricular ejection fraction <55% compared with classic myocarditis (0.0 vs 30.0%), although these differences were not statistically significant. Five patients with classic myocarditis did not receive an early CMR, leading to some selection bias in study design. CONCLUSIONS: Patients with C-VAM had no evidence of active inflammation or ventricular dysfunction on intermediate CMR, although a minority had persistent LGE. Intermediate findings in C-VAM revealed less LGE burden compared with classic myocarditis.

Cardiac Magnetic Resonance Findings after Multisystem Inflammatory Syndrome in Children.

OBJECTIVE: To describe the cardiac magnetic resonance (MR) findings of children recovered from multisystem inflammatory syndrome in children (MIS-C) longer than 3 months after acute illness. STUDY DESIGN: We performed a retrospective cohort study of children hospitalized with MIS-C at a single institution receiving cardiac MR imaging between July 2020 and May 2021. Patient demographics, echocardiogram data from diagnosis through follow-up, and cardiac MR data obtained at approximately 3 months after hospitalization were recorded. RESULTS: In total, 51 children with a median age of 11.3 years were included; 80% of patients had left ventricular ejection fraction <55%, 65% of patients developed valvular regurgitation, and 20% of patients developed coronary artery dilation during acute illness. Cardiac MR was performed at a median time of 105 days after diagnosis; 8% of patients had left ventricular ejection fraction <55%; 1 patient had residual valvular regurgitation; and 2 patients had residual coronary artery dilation. Two of 51 patients were found to have late gadolinium enhancement, T1 mapping abnormalities, and abnormal or borderline extracellular volume calculations suggesting myocardial fibrosis. No patient had T2 mapping abnormalities corresponding with edema, and no patient met the modified Lake Louise criteria for acute myocarditis; 10 of 51 patients had isolated elevated T1 values. CONCLUSIONS: At 3-5 months following diagnosis, cardiac MR reveals no evidence of acute myocarditis as described by the modified Lake Louise criteria in patients with MIS-C. Two patients were observed to have myocardial fibrosis without regional wall motion abnormalities, and 10 had isolated imaging changes (elevated T1 values) in the absence of macroscopic fibrosis.

Multisystem Inflammatory Syndrome in Children: Survey of Protocols for Early Hospital Evaluation and Management.

OBJECTIVE: To describe the similarities and differences in the evaluation and treatment of multisystem inflammatory syndrome in children (MIS-C) at hospitals in the US. STUDY DESIGN: We conducted a cross-sectional survey from June 16 to July 16, 2020, of US children's hospitals regarding protocols for management of patients with MIS-C. Elements included characteristics of the hospital, clinical definition of MIS-C, evaluation, treatment, and follow-up. We summarized key findings and compared results from centers in which >5 patients had been treated vs those in which ≤5 patients had been treated. RESULTS: In all, 40 centers of varying size and experience with MIS-C participated in this protocol survey. Overall, 21 of 40 centers required only 1 day of fever for MIS-C to be considered. In the evaluation of patients, there was often a tiered approach. Intravenous immunoglobulin was the most widely recommended medication to treat MIS-C (98% of centers). Corticosteroids were listed in 93% of protocols primarily for moderate or severe cases. Aspirin was commonly recommended for mild cases, whereas heparin or low molecular weight heparin were to be used primarily in severe cases. In severe cases, anakinra and vasopressors frequently were recommended; 39 of 40 centers recommended follow-up with cardiology. There were similar findings between centers in which >5 patients vs ≤5 patients had been managed. Supplemental materials containing hospital protocols are provided. CONCLUSIONS: There are many similarities yet key differences between hospital protocols for MIS-C. These findings can help healthcare providers learn from others regarding options for managing MIS-C.

Multisystem Inflammatory Syndrome in Children Associated with Severe Acute Respiratory Syndrome Coronavirus 2: A Systematic Review.

OBJECTIVE: To develop a more comprehensive description of multisystem inflammatory syndrome in children (MIS-C), a novel syndrome linked to severe acute respiratory syndrome coronavirus 2, by conducting a systematic analysis of studies from different settings that used various inclusion criteria. STUDY DESIGN: MIS-C studies were identified by searching PubMed and Embase as well as preprint repositories and article references to identify studies of MIS-C cases published from April 25, 2020, through June 29, 2020. MIS-C study metadata were assessed and information on case demographics, clinical symptoms, laboratory measurements, treatments, and outcomes were summarized and contrasted between studies. RESULTS: Eight studies were identified representing a total of 440 MIS-C cases. Inclusion criteria varied by study: 3 studies selected patients diagnosed with Kawasaki disease, 2 required cardiovascular involvement, and 3 had broader multisystem inclusion criteria. Median age of patients by study ranged from 7.3 to 10 years, and 59% of patients were male. Across all studies, the proportion of patients with positive results for severe acute respiratory syndrome coronavirus 2 reverse transcriptase-polymerase chain reaction tests ranged from 13% to 69% and for serology, from 75% to 100%. Patients with MIS-C had high prevalence of gastrointestinal (87%), dermatologic/mucocutaneous (73%), and cardiovascular (71%) symptoms. Prevalence of cardiovascular, neurologic, and respiratory system involvement significantly differed by study inclusion criteria. All studies reported elevated C-reactive protein, interleukin-6, and fibrinogen levels for at least 75% of patients in each study. CONCLUSIONS: This systematic review of MIS-C studies assists with understanding this newly identified syndrome and may be useful in developing a refined, universal case definition of MIS-C.

Coronavirus Disease 2019 Infection in Children with Pre-Existing Heart Disease.

We present 7 children with congenital heart disease and coronavirus disease 2019. Of these, 5 were younger than 1 year of age and 3 had atrioventricular canal defect and trisomy 21. All 7 developed acute decompensation, with 1 death in an 18-year-old with hypertrophic cardiomyopathy and other comorbidities.

Improved National Outcomes Achieved in a Cardiac Learning Health Collaborative Based on Early Performance Level.

OBJECTIVE: Within the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC), a learning health network developed to improve outcomes for patients with hypoplastic left heart syndrome and variants, we assessed which centers contributed to reductions in mortality and growth failure. STUDY DESIGN: Centers within the NPC-QIC were divided into tertiles based on early performance for mortality and separately for growth failure. These groups were evaluated for improvement from the early to late time period and compared with the other groups in the late time period. RESULTS: Mortality was 3.8% for the high-performing, 7.6% for the medium-performing, and 14.4% for the low-performing groups in the early time period. Only the low-performing group had a significant change (P < .001) from the early to late period. In the late period, there was no difference in mortality between the high- (5.7%), medium- (7%), and low- (4.6%) performing centers (P = .5). Growth failure occurred in 13.9% for the high-performing, 21.9% for the medium-performing, and 32.8% for the low-performing groups in the early time period. Only the low-performing group had a significant change (P < .001) over time. In the late period, there was no significant difference in growth failure between the high- (19.8%), medium- (21.5%), and low- (13.5%) performing groups (P = .054). CONCLUSIONS: Improvements in the NPC-QIC mortality and growth measures are primarily driven by improvement in those performing the worst in these areas initially without compromising the success of high-performing centers. Focus for improvement may vary by center based on performance.

Assessment of Growth 6 Years after the Norwood Procedure.

At 6 years of age, patients with hypoplastic left heart syndrome had mean age-adjusted z-scores for weight and height below the normative population, and body mass index was similar to the normative population. Males had the greatest increase in z-scores for body mass index. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00115934.

Quality improvement in screening for critical congenital heart disease.

OBJECTIVES: Screening for critical congenital heart disease with pulse oximetry requires healthcare providers to decipher a previously published algorithm, a feature that raises concerns about quality of interpretation of pulse oximetry results. We hypothesized that this method would be prone to error and a computer-based tool would lead to a more accurate interpretation of the screening results. STUDY DESIGN: In this randomized crossover study, healthcare providers with prior experience using pulse oximetry received 2 sets of 10 mock screening scenarios and were asked to interpret the results of each scenario as "pass," "fail," or "retest." Participants were randomized to use either the paper algorithm or computer-based tool for the first set of 10 scenarios and the alternative method for the second set. We used Wilcoxon rank sum tests to compare the accuracy of interpretation using the 2 methods. RESULTS: The 102 participants answered 81.6% of the scenarios correctly when manually interpreting the algorithm vs 98.3% correct when using the computer-based tool (P < .001). These differences were most pronounced for the "fail" scenarios (65.4% manual vs 96.7% computer, P < .001) and the "retest" scenarios (80.7% manual vs 98.7% computer, P < .001), but were also significant for the "pass" scenarios (94.1% manual vs 99.0% computer, P < .001). CONCLUSIONS: Use of a manual algorithm for the interpretation of results in screening for critical congenital heart disease with pulse oximetry is susceptible to human error. Implementation of a computer-based tool to aid in the interpretation of the results may lead to improved accuracy and quality.

Racial and ethnic disparities in post-operative mortality following congenital heart surgery.

OBJECTIVES: This study assessed racial/ethnic disparities in post-operative mortality after surgery for congenital heart disease (CHD) and explored whether disparities persist after adjusting for access to care. STUDY DESIGN: We used the Pediatric Health Information System database to perform a retrospective cohort study of 44,017 patients with 49,833 CHD surgery encounters in 2004-2008 at 41 children's hospitals. We used χ(2) analysis to compare unadjusted mortality rates by race/ethnicity (non-Hispanic white, non-Hispanic black, Hispanic) and constructed Poisson regression models to determine adjusted mortality risk ratios (RRs) and 95% CIs. RESULTS: In-hospital post-operative mortality rate was 3.4%; non-Hispanic whites had the lowest mortality rate (2.8%), followed by non-Hispanic blacks (3.6%) and Hispanics (3.9%) (P < .0001). After adjusting for age, sex, genetic syndrome, and surgery risk category, the RR of death was 1.32 for non-Hispanic blacks (CI, 1.14-1.52) and 1.21 for Hispanics (CI, 1.07-1.37), both compared with non-Hispanic whites. After adjusting for access to care (insurance type and hospital of surgery), these estimates did not appreciably change (non-Hispanic blacks: RR, 1.27; CI, 1.09-1.47; Hispanics: RR, 1.22; CI, 1.05-1.41). CONCLUSIONS: There are notable racial/ethnic disparities in post-operative mortality after CHD surgery that do not appear to be explained by differences in access to care.

Associations between maternal fever and influenza and congenital heart defects.

OBJECTIVE: To examine associations between maternal reports of prenatal fever or influenza and congenital heart defects (CHDs), and to evaluate whether those associations varied with antipyretic use. STUDY DESIGN: We analyzed case infants with CHD (n = 2361) and control infants without CHD (n = 3435) from the Baltimore-Washington Infant Study (1981-1989). Participating mothers were asked whether they experienced a "fever of 101°F or higher," had "influenza (flu)," or used an antipyretic agent (ie, acetaminophen, salicylate, or nonsteroidal anti-inflammatory drug) during the period extending from 3 months before pregnancy through the end of the third month of pregnancy. We used logistic regression to compute ORs and 95% CIs while controlling for potential confounders. RESULTS: There were significant associations between fever and influenza and specific CHDs, namely right-sided obstructive defects (fever: OR, 2.04; 95% CI, 1.27 to 3.27; influenza: OR, 1.75; 95% CI, 1.16 to 2.62) and atrioventricular septal defects in infants with Down syndrome (fever: OR, 1.92; 95% CI, 1.10 to 3.38; influenza: OR, 1.66; 95% CI, 1.04 to 2.63). Maternal antipyretic use in the setting of fever or influenza tended to decrease these associations. CONCLUSIONS: Prenatal maternal fever or influenza may be associated with right-sided obstructive lesions in all infants and with atrioventricular septal defects in infants with Down syndrome. The use of antipyretics might attenuate such associations.