Background: Congenital heart disease (CHD) accounts for approximately 40% of deaths in United States (US) children with birth defects. Previous US data from 1999-2006 demonstrated an overall decrease in CHD mortality. Our study aimed to assess current trends in US mortality related to CHD from infancy to adulthood over the last 19 years and determine differences by sex and race/ethnicity. Methods: We conducted an analysis of death certificates from 1999-2017 to calculate annual CHD mortality by age at death, race/ethnicity, and sex. Population estimates used as denominators in mortality rate calculations for infants were based on National Center for Health Statistics live birth data. Mortality rates in individuals ≥1 year of age utilized US Census Bureau bridged-race estimates as denominators for population estimates. We characterized temporal trends in all-cause mortality, mortality resulting directly due to and related to CHD by age, race/ethnicity, and sex using joinpoint regression. Results: There were 47.7 million deaths with 1 in 814 deaths due to CHD (n=58,599). While all-cause mortality decreased 16.4% across all ages, mortality resulting from CHD declined 39.4% overall. The mean annual decrease in CHD mortality was 2.6%, with the largest decrease for those age >65 years. The age-adjusted mortality rate decreased from 1.37 to 0.83 per 100,000. Males had higher mortality due to CHD than females throughout the study, although both sexes declined at a similar rate (~40% overall), with a 3-4% annual decrease between 1999 and 2009, followed by a slower annual decrease of 1.4% through 2017. Mortality resulting from CHD significantly declined among all races/ethnicities studied, although disparities in mortality persisted for non-Hispanic blacks versus non-Hispanic whites (mean annual decrease 2.3% versus 2.6%, respectively; age-adjusted mortality rate 1.67 to 1.05 versus 1.35 to 0.80 per 100,000, respectively). Conclusions: While overall US mortality due to CHD has decreased over the last 19 years, disparities in mortality persist for males compared to females and for non-Hispanic blacks compared to non-Hispanic whites. Determining factors that contribute to these disparities such as access to quality care, timely diagnosis, and maintenance of insurance will be important moving into the next decade.

Objective Acute maternal hyperoxygenation (AMH) results in increased fetal left heart blood flow. Our aim was to perform a pilot study to determine the safety, feasibility and direction and magnitude of effect of chronic maternal hyperoxygenation (CMH) on mitral and aortic valve annular dimensions in fetuses with left heart hypoplasia (LHH) after CMH. Methods

BACKGROUND: Data on anxiety, depression, and attention-deficit/hyperactivity disorder (ADHD) are lacking for youth with congenital heart disease (CHD), particularly those with simple CHD. This study aims to characterize these disorders in youth with CHD compared to those without CHD. METHODS: A comparative cross-sectional study was conducted by using the electronic medical records of a large tertiary care hospital between 2011 and 2016. Inclusion criteria were youth aged 4 to 17 years with >1 hospitalization or emergency department visits. Exclusion criteria were patients with arrhythmias or treatment with clonidine and/or benzodiazepines. The primary predictor variable was CHD type: simple, complex nonsingle ventricle, and complex single ventricle. The primary outcome variable was a diagnosis and/or medication for anxiety and/or depression or ADHD. Data were analyzed by using logistic regression (Stata v15; Stata Corp, College Station, TX). RESULTS: We identified 118 785 patients, 1164 with CHD. Overall, 18.2% (n = 212) of patients with CHD had a diagnosis or medication for anxiety or depression, compared with 5.2% (n = 6088) of those without CHD. All youth with CHD had significantly higher odds of anxiety and/or depression or ADHD. Children aged 4 to 9 years with simple CHD had ∼5 times higher odds (odds ratio: 5.23; 95% confidence interval: 3.87–7.07) and those with complex single ventricle CHD had ∼7 times higher odds (odds ratio: 7.46; 95% confidence interval: 3.70–15.07) of diagnosis or treatment for anxiety and/or depression. Minority and uninsured youth were significantly less likely to be diagnosed or treated for anxiety and/or depression or ADHD, regardless of disease severity. CONCLUSIONS: Youth with CHD of all severities have significantly higher odds of anxiety and/or depression and ADHD compared to those without CHD. Screening for these conditions should be considered in all patients with CHD.

ASD closure is safe and effective in patients over 40 years of age with minimal complications. The procedure resulted in a decrease in the RV size that was accompanied by improvement in clinical symptoms. Our findings suggest that device closure of ASDs in adult patients >40 years of age should be the first option of management.

Aberrant left-right patterning in the developing human embryo can lead to a broad spectrum of congenital malformations. The causes of most laterality defects are not known, with variants in established genes accounting for <20% of cases. We sought to characterize the genetic spectrum of these conditions by performing whole-exome sequencing of 323 unrelated laterality cases. We investigated the role of rare, predicted-damaging variation in 1726 putative laterality candidate genes derived from model organisms, pathway analyses, and human phenotypes. We also evaluated the contribution of homo/hemizygous exon deletions and gene-based burden of rare variation. A total of 28 candidate variants (26 rare predicted-damaging variants and 2 hemizygous deletions) were identified, including variants in genes known to cause heterotaxy and primary ciliary dyskinesia (ACVR2B, NODAL, ZIC3, DNAI1, DNAH5, HYDIN, MMP21), and genes without a human phenotype association, but with prior evidence for a role in embryonic laterality or cardiac development. Sanger validation of the latter variants in probands and their parents revealed no de novo variants, but apparent transmitted heterozygous (ROCK2, ISL1, SMAD2), and hemizygous (RAI2, RIPPLY1) variant patterns. Collectively, these variants account for 7.1% of our study subjects. We also observe evidence for an excess burden of rare, predicted loss-of-function variation in PXDNL and BMS1-two genes relevant to the broader laterality phenotype. These findings highlight potential new genes in the development of laterality defects, and suggest extensive locus heterogeneity and complex genetic models in this class of birth defects.

Little is known about the efficacy and safety of the 40 mm Amplatzer septal occluder (ASO). Thirty-three patients (22 female, 11 male) with a large secundum atrial septal defect (ASD) underwent attempted device closure using the 40 mm ASO at a median age of 40 years (range, 14-81 years) and median weight of 65 kg (range, 48-98 kg). The median size of the ASD measured on 2D transesophageal echocardiography (27 patients) or intracardiac echocardiography (6 patients) was 30.5 mm (range, 24-39 mm) and the median balloon-stretched diameter was 37.7 mm (range, 32-43.7 mm). The median Qp:Qs ratio was 3.2:1 (range, 1.4-6.2). The attempt was unsuccessful in five patients; two had device embolization and one had left atrial wall perforation due to the sheath; all three required emergent surgery. The attempt was successful in the 28 remaining patients, resulting in complete immediate closure in 14 and a trivial residual shunt in 14. Fluoroscopy time ranged from 8.6 to 37.8 min (median, 12.2 min). At 24-hr follow-up, 2D transthoracic echocardiography with color flow Doppler revealed complete closure in 23 patients, and 5 had a trivial residual shunt. There were no complications encountered in patients who received the device. On follow-up, all patients are doing well. We conclude that the 40 mm ASO is safe and effective in most patients with a large ASD up to a diameter of 39 mm. However, the use of this device requires careful attention as the procedure may be unsuccessful or the device may embolize.

It is now expected that most individuals with congenital heart disease will survive to adulthood, including those with complex heart conditions. Maintaining lifelong medical care requires those with congenital heart disease to eventually transfer from pediatric to adult‐oriented health care systems. Developing health care transition skills and gaining independence in managing one’s own health care is imperative to this process and to ongoing medical and psychosocial success. This scientific statement reviews the recent evidence regarding transition and provides resources, components, and suggestions for development of congenital heart disease transition programs with the goals of improving patient knowledge, self‐management, and self‐efficacy skills to the level they are capable to eventually integrate smoothly into adult‐oriented health care. Specifically, the scientific statement updates 3 sections relevant to transition programming. First, there is a review of specific factors to consider, including social determinants of health, psychosocial well‐being, and neurocognitive status. The second section reviews costs of inadequate transition including the public health burden and the impairment in individual quality of life. Finally, the last section discusses considerations and suggestions for transition program design including communication platforms, a family‐centered approach, and individual models. Although this scientific statement reviews recent literature surrounding transitions of care for individuals with congenital heart disease there remain significant knowledge gaps. As a field, we have yet to determine ideal timing and methods of transition, and barriers to transition and transfer remain, particularly for the underserved populations. The consequences of poor health care transition are great and garnering outcomes and information through organized, multifaceted, collaborative approaches to transition is critical to improving the lifelong care of individuals with congenital heart disease.

Background: Prenatal detection (PND) has benefits for infants with hypoplastic left heart syndrome (HLHS) and transposition of the great arteries (TGA), but associations between sociodemographic and geographic factors with PND have not been sufficiently explored. This study evaluated whether socioeconomic quartile (SEQ), public insurance, race and ethnicity, rural residence, and distance of residence (distance and driving time from a cardiac surgical center) are associated with the PND or timing of PND, with a secondary aim to analyze differences between the United States and Canada. Methods: In this retrospective cohort study, fetuses and infants <2 months of age with HLHS or TGA admitted between 2012 and 2016 to participating Fetal Heart Society Research Collaborative institutions in the United States and Canada were included. SEQ, rural residence, and distance of residence were derived using maternal census tract from the maternal address at first visit. Subjects were assigned a SEQ z score using the neighborhood summary score or Canadian Chan index and separated into quartiles. Insurance type and self-reported race and ethnicity were obtained from medical charts. We evaluated associations among SEQ, insurance type, race and ethnicity, rural residence, and distance of residence with PND of HLHS and TGA (aggregate and individually) using bivariate analysis with adjusted associations for confounding variables and cluster analysis for centers. Results: Data on 1862 subjects (HLHS: n=1171, 92% PND; TGA: n=691, 58% PND) were submitted by 21 centers (19 in the United States). In the United States, lower SEQ was associated with lower PND in HLHS and TGA, with the strongest association in the lower SEQ of pregnancies with fetal TGA (quartile 1, 0.78 [95% CI, 0.64–0.85], quartile 2, 0.77 [95% CI, 0.64–0.93], quartile 3, 0.83 [95% CI, 0.69–1.00], quartile 4, reference). Hispanic ethnicity (relative risk, 0.85 [95% CI, 0.72–0.99]) and rural residence (relative risk, 0.78 [95% CI, 0.64–0.95]) were also associated with lower PND in TGA. Lower SEQ was associated with later PND overall; in the United States, rural residence and public insurance were also associated with later PND. Conclusions: We demonstrate that lower SEQ, Hispanic ethnicity, and rural residence are associated with decreased PND for TGA, with lower SEQ also being associated with decreased PND for HLHS. Future work to increase PND should be considered in these specific populations.