Identifying novel data-driven subgroups in congenital heart disease using multi-modal measures of brain structure.

Individuals with congenital heart disease (CHD) have an increased risk of neurodevelopmental impairments. Given the hypothesized complexity linking genomics, atypical brain structure, cardiac diagnoses and their management, and neurodevelopmental outcomes, unsupervised methods may provide unique insight into neurodevelopmental variability in CHD. Using data from the Pediatric Cardiac Genomics Consortium Brain and Genes study, we identified data-driven subgroups of individuals with CHD from measures of brain structure.

Achieving an Optimal Outcome After Stage 1 Palliation for Hypoplastic Left Heart Syndrome and Variants: Frequency, Associated Factors, and Subsequent Outcomes.

Background: We sought to measure frequency of achieving an optimal outcome after stage 1 palliation (S1P) for hypoplastic left heart syndrome and variants, determine factors associated with optimal outcomes, and compare outcomes after stage 2 palliation (S2P) using the National Pediatric Cardiology Quality Improvement Collaborative database (2008-2016).

Methods And Results: This is a retrospective cohort study with optimal outcome defined a priori as meeting all of the following: (1) discharge after S1P in <19 days (top quartile), (2) no red flag or major event readmissions before S2P, and (3) performing S2P between 90 and 240 days of age. Optimal outcome was achieved in 256 of 2182 patients (11.

Preoperative Hemodynamics Impact the Benefit of Fenestration on Fontan Postoperative Length of Stay.

Background: Utilization of Fontan fenestration varies considerably by center.

Objectives: Using a multicenter Pediatric Heart Network dataset linking surgical and preoperative hemodynamic variables, the authors evaluated factors associated with use of Fontan fenestration and the impact of fenestration on post-Fontan length of stay (LOS).

Methods: Patients 2 to 6 years old at Fontan surgery from 2010 to 2020 with catheterization<1 year prior were included.

Precision in Norwood Shunt Sizing: Single Ventricle Reconstruction Trial Public Dataset Analysis.

Background: Morbidity and mortality after the Norwood procedure remains high. Shunt size selection is not standardized and the impact of shunt size on outcomes is poorly understood. The Single Ventricle Reconstruction trial randomized infants to modified Blalock-Taussig-Thomas shunt (MBTTS) or right ventricle-to-pulmonary artery shunt at the Norwood procedure.

Apixaban for Prevention of Thromboembolism in Pediatric Heart Disease.

Background: Children with heart disease frequently require anticoagulation for thromboprophylaxis. Current standard of care (SOC), vitamin K antagonists or low-molecular-weight heparin, has significant disadvantages.

Objectives: The authors sought to describe safety, pharmacokinetics (PK), pharmacodynamics, and efficacy of apixaban, an oral, direct factor Xa inhibitor, for prevention of thromboembolism in children with congenital or acquired heart disease.

Longitudinal Follow-Up of Children With HLHS and Association Between Norwood Shunt Type and Long-Term Outcomes: The SVR III Study.

Objective: In the SVR trial (Single Ventricle Reconstruction), newborns with hypoplastic left heart syndrome were randomly assigned to receive a modified Blalock-Taussig-Thomas shunt (mBTTS) or a right ventricle-to-pulmonary artery shunt (RVPAS) at Norwood operation. Transplant-free survival was superior in the RVPAS group at 1 year, but no longer differed by treatment group at 6 years; both treatment groups had accumulated important morbidities. In the third follow-up of this cohort (SVRIII [Long-Term Outcomes of Children With Hypoplastic Left Heart Syndrome and the Impact of Norwood Shunt Type]), we measured longitudinal outcomes and their risk factors through 12 years of age.

Neonatal Depression Is Associated With 1-Year Mortality in Critical Congenital Heart Disease.

Background Low 5-minute Apgar scores (AS) are predictive of term and preterm neonatal mortality but have not been well studied in the critical congenital heart disease (CCHD) population. We analyzed US national vital statistics data to evaluate the association between neonatal depression (AS 0-3) and 1-year mortality in CCHD. Methods and Results We performed a retrospective cohort study using 2014 to 2018 Centers for Disease Control and Prevention cohort-linked birth certificate and infant death records.

Defining Expectations for Infants With Hypoplastic Left Heart Syndrome Who Survive Initial Surgical Palliation.

Background: Overall one-year non-mortality outcomes for surgically palliated hypoplastic left heart syndrome (HLHS) patients remain understudied. Using the metric Days Alive and Outside of Hospital (DAOH), the present study sought to characterize expectations for surgically palliated patients' first year of life.

Methods: The Pediatric Health Information System database was used to identify by code all HLHS patients who underwent surgical palliation (Norwood/hybrid and/or heart transplantation [HTx]) during their index neonatal admission and were successfully discharged alive (n  =  2227) and for whom one-year DAOH could be calculated.

Evidence-Based Assessment of Congenital Heart Disease Genes to Enable Returning Results in a Genomic Study.

Background: Congenital heart disease (CHD) is the most common major congenital anomaly and causes significant morbidity and mortality. Epidemiologic evidence supports a role of genetics in the development of CHD. Genetic diagnoses can inform prognosis and clinical management.

The impact of the COVID-19 pandemic on individuals with Fontan circulation: Focus on gaps in care.

Background: Gaps in subspecialty cardiology care could potentially delay identification and care for multi-organ complications common in patients with Fontan circulation. This study analyzed the frequency of gaps in care for individuals with Fontan circulation during the COVID-19 pandemic and associated demographic and clinical factors.

Methods: This retrospective study evaluated individuals with Fontan circulation followed at our center since 2010.

Severe Maternal Morbidity in Pregnancies Complicated by Fetal Congenital Heart Disease.

Background: Maternal risk factors for fetal congenital heart disease (CHD) may also be associated with delivery complications in the mother.

Objectives: This study aimed to determine the prevalence of and risk factors for severe maternal morbidity (SMM) and maternal hospital transfer in pregnancies complicated by fetal CHD.

Methods: A population-based retrospective cohort study utilizing linked Ohio birth certificates and birth defect data for all live births from 2011 to 2015 was performed.

Association Between Seasonal Fontan Timing, Viral Infection Burden, and Post-Operative Length of Stay.

The Fontan procedure (FP) is typically a semi-elective surgery performed between 2 and 5 years of age to complete staged single ventricle palliation. Optimal timing for the FP, particularly in relation to seasonal infectious burden, remains unclear. We queried the Pediatric Health Information System (PHIS) database for all admissions for viral respiratory infections (VRI) from January 2006 to September 2015 and separately for all admissions with a primary procedure code of FP.

Analysis of commonly expressed genes between first trimester fetal heart and placenta cell types in the context of congenital heart disease.

Congenital heart disease (CHD) is often associated with fetal growth abnormalities. During the first trimester of pregnancy, the heart and placenta develop concurrently, and share key developmental pathways. It is hypothesized that defective morphogenesis of either organ is synergistically linked.

Prevalence of Genetic Diagnoses in a Cohort With Valvar Pulmonary Stenosis.

Background: Valvar pulmonary stenosis (vPS) accounts for 8% to 12% of congenital heart disease cases. Multiple genetic syndromes are associated with vPS, most commonly Noonan syndrome, but the cause is unknown in most cases. We analyzed genomic data from a large cohort with vPS to determine the prevalence of genetic diagnosis.

Management of Neonates Admitted With Tetralogy of Fallot: Changing Patterns Across the United States.

Background: This study describes the evolving in-hospital management strategies for neonates who are diagnosed with tetralogy of Fallot (ToF).

Methods: The Pediatric Health Information System (PHIS) database was used to identify admitted patients aged 0 to 1 month old with ToF from 2010 through 2019; era 1, 2010 through 2014; and era 2, 2015 through 2019. International Classification of Diseases codes were used to identify related interventions that occurred during this admission but not necessarily as a neonate: full repair, systemic-to-pulmonary shunt, and percutaneous stent in the right ventricular outflow tract and/or patent ductus arteriosus.

Height Versus Body Surface Area to Normalize Cardiovascular Measurements in Children Using the Pediatric Heart Network Echocardiographic Z-Score Database.

Normalizing cardiovascular measurements for body size allows for comparison among children of different ages and for distinguishing pathologic changes from normal physiologic growth. Because of growing interest to use height for normalization, the aim of this study was to develop height-based normalization models and compare them to body surface area (BSA)-based normalization for aortic and left ventricular (LV) measurements. The study population consisted of healthy, non-obese children between 2 and 18 years of age enrolled in the Pediatric Heart Network Echo Z-Score Project.

Altered erythropoiesis in newborns with congenital heart disease.

Background: Fetal hypoxia has been implicated in fetal growth restriction in congenital heart disease (CHD) and leads to stress erythropoiesis in utero. The objective is to assess erythropoiesis and its association with growth in newborns with CHD.

Methods: Fetuses with prenatally diagnosed CHD from 2013 to 2018 were retrospectively reviewed.

Socioeconomic Status and Long-term Outcomes in Single Ventricle Heart Disease.

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 ( = 525). Cox proportional hazards regression and linear regression were used to assess the association of SES with mortality and neurodevelopmental outcomes, respectively.

Abnormalities of placental development and function are associated with the different fetal growth patterns of hypoplastic left heart syndrome and transposition of the great arteries.

Background: Birthweight is a critical predictor of congenital heart disease (CHD) surgical outcomes. Hypoplastic left heart syndrome (HLHS) is cyanotic CHD with known fetal growth restriction and placental abnormalities. Transposition of the great arteries (TGA) is cyanotic CHD with normal fetal growth.

Recruitment, retention, and adherence in a clinical trial: The Pediatric Heart Network's Marfan Trial experience.

Background/aims: The Pediatric Heart Network Marfan Trial was a randomized trial comparing atenolol versus losartan on aortic root dilation in 608 children and young adults with Marfan syndrome. Barriers to enrollment included a limited pool of eligible participants, restrictive entry criteria, and a diverse age range that required pediatric and adult expertise. Retention was complicated by a 3-year commitment to a complex study and medication regimen.

Author Correction: Left atrial dysfunction in sickle cell anemia is associated with diffuse myocardial fibrosis, increased right ventricular pressure and reduced exercise capacity.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.