Pediatric ECG standards have been defined without echocardiographic confirmation of normal anatomy. The Pediatric Heart Network Normal Echocardiogram Z-score Project provides a racially diverse group of healthy children with normal echocardiograms. We hypothesized that ECG and echocardiographic measures of left ventricular (LV) dimensions are sufficiently correlated in healthy children to imply a clinically meaningful relationship.
View Article and Find Full Text PDFBackground: Known genetic causes of congenital heart disease (CHD) explain <40% of CHD cases, and interpreting the clinical significance of variants with uncertain functional impact remains challenging. We aim to improve diagnostic classification of variants in patients with CHD by assessing the impact of noncanonical splice region variants on RNA splicing.
Methods: We tested de novo variants from trio studies of 2649 CHD probands and their parents, as well as rare (allele frequency, <2×10) variants from 4472 CHD probands in the Pediatric Cardiac Genetics Consortium through a combined computational and in vitro approach.
The well-established manifestation of mitochondrial mutations in functional cardiac disease (e.g., mitochondrial cardiomyopathy) prompted the hypothesis that mitochondrial DNA (mtDNA) sequence and/or copy number (mtDNAcn) variation contribute to cardiac defects in congenital heart disease (CHD).
View Article and Find Full Text PDFReproducibility in medical research has been a long-standing issue. More recently, the COVID-19 pandemic has publicly underlined this fact as the retraction of several studies reached out to general media audiences. A significant number of these retractions occurred after in-depth scrutiny of the methodology and results by the scientific community.
View Article and Find Full Text PDFObjective: To evaluate the association of systolic blood pressure percentile, race, and body mass index with left ventricular hypertrophy on electrocardiogram and echocardiogram to define populations at risk.
Study Design: This is a retrospective cross-sectional study design utilising a data analytics tool (Tableau) combining electrocardiogram and echocardiogram databases from 2003 to 2020. Customized queries identified patients aged 2-18 years who had an outpatient electrocardiogram and echocardiogram on the same date with available systolic blood pressure and body measurements.
Background: Little is known about geographical variation in infant mortality due to congenital heart disease (CHD) and the social determinants of health that might mediate such variation. We aimed to examine US county-level estimates of infant mortality due to CHD to understand geographical patterns and factors that might influence variation in mortality.
Methods: This US population-based cohort study used linked livebirth-infant death cohort files from the US National Center for Health Statistics from Jan 1, 2006, to Dec 31, 2015.
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).
Impaired exercise following Fontan is a surrogate of morbidity. Single-center longitudinal data exist, but there is a lack of contemporary multi-center data. Ramp cycle ergometry was re-performed in consented participants who had originally participated in the Pediatric Heart Network's Fontan cross-sectional study.
View Article and Find Full Text PDFBackground: De novo genic and copy number variants are enriched in patients with congenital heart disease, particularly those with extra-cardiac anomalies. The impact of de novo damaging variants on outcomes following cardiac repair is unknown.
Methods: We studied 2517 patients with congenital heart disease who had undergone whole-exome sequencing as part of the CHD GENES study (Congenital Heart Disease Genetic Network).
Objective: To describe epidemiologic data from the Sudden Death in the Young (SDY) Case Registry. Understanding the scope of SDY may optimize prevention efforts.
Study Design: We analyzed sudden, unexpected deaths of infants (<365 days) and children (1-17 years) from a population-based registry of 8 states/jurisdictions in 2015 and 9 in 2016.
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.
View Article and Find Full Text PDFA genetic etiology is identified for one-third of patients with congenital heart disease (CHD), with 8% of cases attributable to coding de novo variants (DNVs). To assess the contribution of noncoding DNVs to CHD, we compared genome sequences from 749 CHD probands and their parents with those from 1,611 unaffected trios. Neural network prediction of noncoding DNV transcriptional impact identified a burden of DNVs in individuals with CHD (n = 2,238 DNVs) compared to controls (n = 4,177; P = 8.
View Article and Find Full Text PDFRecent 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.
View Article and Find Full Text PDFBackground/Aims Identifying predictors of recruitment success in clinical trials, particularly prior to study launch, could contribute to higher study completion rates and improved scientific return on investment. This article evaluates the performance of clinical trials funded by the National Heart, Lung, and Blood Institute that began recruitment before and after implementation of National Heart, Lung, and Blood Institute's 2009 Accrual Policy and identifies study-related factors that predict recruitment success. Methods A retrospective analysis of National Heart, Lung, and Blood Institute's cardiovascular clinical trials with initial funding from 1996 to 2012 was performed to assess recruitment success.
View Article and Find Full Text PDFCirc Arrhythm Electrophysiol
July 2018
Background: Interpretation of pediatric ECGs is limited by lack of accurate sex- and race-specific normal reference values obtained with modern technology for all ages. We sought to obtain contemporary digital ECG measurements in healthy children from North America, to evaluate the effects of sex and race, and to compare our results to commonly used published datasets.
Methods: Digital ECGs (12-lead) were retrospectively collected for children ≤18 years old with normal echocardiograms at 19 centers in the Pediatric Heart Network.
Ectopic atrial tachycardia (EAT) is common in surgically repaired congenital heart disease (CHD) and carries the potential for significant hemodynamic compromise. Our objective was to determine the incidence, and risk factors of EAT after CHD surgery. Prospective study of patients that underwent surgery for CHD from February to October 2016 was performed.
View Article and Find Full Text PDFCongenital heart disease (CHD) is the leading cause of mortality from birth defects. Here, exome sequencing of a single cohort of 2,871 CHD probands, including 2,645 parent-offspring trios, implicated rare inherited mutations in 1.8%, including a recessive founder mutation in GDF1 accounting for ∼5% of severe CHD in Ashkenazim, recessive genotypes in MYH6 accounting for ∼11% of Shone complex, and dominant FLT4 mutations accounting for 2.
View Article and Find Full Text PDFJ Cardiovasc Electrophysiol
January 2018
Introduction: Genetic testing for congenital long QT syndrome (LQTS) has become common. Recent studies have shown that some variants labelled as pathogenic might be misclassified due to sparse case reports and relatively common allele frequencies (AF) in the general population. This study aims to evaluate the presence of LQTS-associated variants in the Genome Aggregation Database (gnomAD) population, and assess the functional impact of these variants.
View Article and Find Full Text PDFBackground: The Fontan operation results in a circulation that is dependent on low pulmonary vascular resistance to maintain an adequate cardiac output. Medical therapies that lower pulmonary vascular resistance may augment cardiac output and improve long-term outcomes.
Objectives: This phase I/II clinical trial conducted by the Pediatric Heart Network was designed to evaluate short-term safety, pharmacokinetics (PK), and preliminary efficacy of udenafil in adolescents following Fontan.