Case Report: An association of left ventricular outflow tract obstruction with 5p deletions.

Introduction: 5p deletion syndrome, also called Cri-du-chat syndrome 5p is a rare genetic syndrome with reports up to 36% of patients are associated with congenital heart defects. We investigated the association between left outflow tract obstruction and Cri-du-chat syndrome.

Methods: A retrospective review of the abnormal microarray cases with congenital heart defects in Children's Hospital of Pittsburgh and the Cytogenomics of Cardiovascular Malformations Consortium.

Double outlet right ventricle.

This review article addresses the history, morphology, anatomy, medical management, and different surgical options for patients with double outlet right ventricle.

A Multicenter Analysis of Abnormal Chromosomal Microarray Findings in Congenital Heart Disease.

Background Chromosomal microarray analysis (CMA) provides an opportunity to understand genetic causes of congenital heart disease (CHD). The methods for describing cardiac phenotypes in patients with CMA abnormalities have been inconsistent, which may complicate clinical interpretation of abnormal testing results and hinder a more complete understanding of genotype-phenotype relationships. Methods and Results Patients with CHD and abnormal clinical CMA were accrued from 9 pediatric cardiac centers.

Spatial transcriptome profiling uncovers metabolic regulation of left-right patterning.

Left-right patterning disturbance can cause severe birth defects, but it remains least understood of the three body axes. We uncovered an unexpected role for metabolic regulation in left-right patterning. Analysis of the first spatial transcriptome profile of left-right patterning revealed global activation of glycolysis, accompanied by right-sided expression of and genes regulating insulin growth factor signaling.

Risk Factors Associated With Pressure Injury in Critically Ill Children With Congenital Heart Disease.

Background: Children with congenital heart disease have unique risk factors associated with the pathophysiology of an abnormal heart; hence, this population is most likely at increased risk of acquiring a pressure injury during hospitalization. Few studies have included patients with congenital heart disease or examined the factors unique to these patients.

Objective: To identify risk factors associated with pressure injury development in children with congenital heart disease.

Contribution of LRP1 in Human Congenital Heart Disease Correlates with Its Roles in the Outflow Tract and Atrioventricular Cushion Development.

Due to the prevalence of congenital heart disease in the human population, determining the role of variants in congenital heart disease (CHD) can give a better understanding of the cause of the disorder. A homozygous missense mutation in the LDL receptor-related protein 1 () in mice was shown to cause congenital heart defects, including atrioventricular septal defect (AVSD) and double outlet right ventricle (DORV). Integrative analysis of publicly available single-cell RNA sequencing (scRNA-seq) datasets and spatial transcriptomics of human and mouse hearts indicated that is predominantly expressed in mesenchymal cells and mainly located in the developing outflow tract and atrioventricular cushion.

A Pipeline to Characterize Structural Heart Defects in the Fetal Mouse.

Congenital heart diseases (CHDs) are major causes of infant death in the United States. In the 1980s and earlier, most patients with moderate or severe CHD died before adulthood, with the maximum mortality during the first week of life. Remarkable advances in surgical techniques, diagnostic approaches, and medical management have led to marked improvements in outcomes.

Uncompensated mitochondrial oxidative stress underlies heart failure in an iPSC-derived model of congenital heart disease.

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease with 30% mortality from heart failure (HF) in the first year of life, but the cause of early HF remains unknown. Induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CM) from patients with HLHS showed that early HF is associated with increased apoptosis, mitochondrial respiration defects, and redox stress from abnormal mitochondrial permeability transition pore (mPTP) opening and failed antioxidant response. In contrast, iPSC-CM from patients without early HF showed normal respiration with elevated antioxidant response.

Common deletion variants causing protocadherin-α deficiency contribute to the complex genetics of BAV and left-sided congenital heart disease.

Bicuspid aortic valve (BAV) with ~1%-2% prevalence is the most common congenital heart defect (CHD). It frequently results in valve disease and aorta dilation and is a major cause of adult cardiac surgery. BAV is genetically linked to rare left-heart obstructions (left ventricular outflow tract obstructions [LVOTOs]), including hypoplastic left heart syndrome (HLHS) and coarctation of the aorta (CoA).

Mitochondrial Respiration Defects in Single-Ventricle Congenital Heart Disease.

Congenital heart disease (CHD) with single-ventricle (SV) physiology is now survivable with a three-stage surgical course ending with Fontan palliation. However, 10-year transplant-free survival remains at 39-50%, with ventricular dysfunction progressing to heart failure (HF) being a common sequela. For SV-CHD patients who develop HF, undergoing the surgical course would not be helpful and could even be detrimental.

Endocytic Protein Defects in the Neural Crest Cell Lineage and Its Pathway Are Associated with Congenital Heart Defects.

Endocytic trafficking is an under-appreciated pathway in cardiac development. Several genes related to endocytic trafficking have been uncovered in a mutagenic ENU screen, in which mutations led to congenital heart defects (CHDs). In this article, we review the relationship between these genes (including and ) and cardiac neural crest cells (CNCCs) during cardiac development.

Mucociliary Clearance Scans Show Infants Undergoing Congenital Cardiac Surgery Have Poor Airway Clearance Function.

Infants undergoing congenital cardiac surgery with cardiopulmonary bypass are at high risk for respiratory complications. As impaired airway mucociliary clearance (MCC) can potentially contribute to pulmonary morbidity, our study objective was to measure airway clearance in infants undergoing congenital cardiac surgery and examine correlation with clinical covariables that may impair airway clearance function. Airway clearance in infants was measured over 30 min using inhaled nebulized Technetium 99m sulfur colloid administered either via a nasal cannula or the endotracheal tube in intubated infants.

A Membrane-Tethered Ubiquitination Pathway Regulates Hedgehog Signaling and Heart Development.

The etiology of congenital heart defects (CHDs), which are among the most common human birth defects, is poorly understood because of its complex genetic architecture. Here, we show that two genes implicated in CHDs, Megf8 and Mgrn1, interact genetically and biochemically to regulate the strength of Hedgehog signaling in target cells. MEGF8, a transmembrane protein, and MGRN1, a RING superfamily E3 ligase, assemble to form a receptor-like ubiquitin ligase complex that catalyzes the ubiquitination and degradation of the Hedgehog pathway transducer Smoothened.

Mutation of LRP1 in cardiac neural crest cells causes congenital heart defects by perturbing outflow lengthening.

The recent recovery of mutations in vesicular trafficking genes causing congenital heart disease (CHD) revealed an unexpected role for the endocytic pathway. We now show that mice with a C4232R missense mutation in Low density lipoprotein receptor related protein 1 (LRP1) exhibit atrioventricular septal defects with double outlet right ventricle. Lrp1 mice exhibit shortened outflow tracts (OFT) and dysmorphic hypocellular cushions with reduced proliferation and increased apoptosis.

Early conversion of classic Fontan conversion may decrease term morbidity: single centre outcomes.

Background: The initial classic Fontan utilising a direct right atrial appendage to pulmonary artery anastomosis led to numerous complications. Adults with such complications may benefit from conversion to a total cavo-pulmonary connection, the current standard palliation for children with univentricular hearts.

Methods: A single institution, retrospective chart review was conducted for all Fontan conversion procedures performed from July, 1999 through January, 2017.

Deposition studies of aerosol delivery by nasal cannula to infants.

Aim: Nasal cannulas are used to provide oxygen support for infants and have been considered as a means for delivering aerosols to the lungs. To measure mucociliary clearance in the lungs of infants with congenital heart defects, we delivered radiopharmaceutical aerosols via a nasal cannula. Here we report on the pulmonary and nasal deposition of these aerosols.

The Risk of Thromboembolic Complications in Fontan Patients with Atrial Flutter/Fibrillation Treated with Electrical Cardioversion.

Atrial flutter or fibrillation (AFF) remains a major chronic complication of the Fontan procedure. This complication further predisposes this patient population to thromboembolic events. However, the incidence of thromboembolic complications in Fontan patients with AFF prior to or acutely after electrical cardioversion is unknown.

Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left ventricular non-compaction.

Objectives: We evaluated the role of Cypher/ZASP in the pathogenesis of dilated cardiomyopathy (DCM) with or without isolated non-compaction of the left ventricular myocardium (INLVM).

Background: Dilated cardiomyopathy, characterized by left ventricular dilation and systolic dysfunction with signs of heart failure, is genetically transmitted in 30% to 40% of cases. Genetic heterogeneity has been identified with mutations in multiple cytoskeletal and sarcomeric genes causing the phenotype.

Mutations in the muscle LIM protein and alpha-actinin-2 genes in dilated cardiomyopathy and endocardial fibroelastosis.

Dilated cardiomyopathy (DCM) is a major cause of morbidity and mortality. Two genes have been identified for the X-linked forms (dystrophin and tafazzin), while mutations in multiple genes cause autosomal dominant DCM. Muscle LIM protein (MLP) is a member of the cysteine-rich protein (CRP) family and has been implicated in both myogenesis and sarcomere assembly.

Intrauterine diagnosis of heterotaxy syndrome.

Background: Heterotaxy syndrome, including right isomerism and left isomerism, is characterized by an abnormal symmetry of the viscera and veins and is frequently associated with complex cardiac anomalies. We sought to define the feasibility of in utero diagnosis and the postnatal outcome.

Methods: Patients with heterotaxy syndrome were identified from 579 fetal echocardiograms performed from January 1994 to December 1998.