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Concept: Congenital heart defect

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Ebstein’s anomaly is a rare congenital heart malformation characterised by adherence of the septal and posterior leaflets of the tricuspid valve to the underlying myocardium. Associated abnormalities of left ventricular morphology and function including left ventricular noncompaction (LVNC) have been observed. An association between Ebstein’s anomaly with LVNC and mutations in the sarcomeric protein gene MYH7, encoding β-myosin heavy chain, has been shown by recent studies. This might represent a specific subtype of Ebstein’s anomaly with a Mendelian inheritance pattern. In this review we discuss the association of MYH7 mutations with Ebstein’s anomaly and LVNC and its implications for the clinical care for patients and their family members.

Concepts: Gene, Genetics, Evolution, Heart, Right ventricle, Tricuspid valve, Congenital heart defect, Ebstein's anomaly

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OBJECTIVE: To evaluate the scale and clinical importance of loss to follow-up of past patients with serious congenital heart disease, using a common malformation as an example. To better understand the antecedents of loss to specialist follow-up and patients' attitudes to returning. DESIGN: Cohort study using NHS number functionality. Content and thematic analysis of telephone interviews of subset contacted after loss to follow-up. PATIENTS, INTERVENTION AND SETTING: Longitudinal follow-up of complete consecutive list of all 1085 UK patients with repair of tetralogy of Fallot from single institution 1964-2009. MAIN OUTCOME MEASURES: Survival, freedom from late pulmonary valve replacement, loss to specialist follow-up, shortfall in late surgical revisions related to loss to follow-up. Patients' narrative about loss to follow-up. RESULTS: 216 (24%) of patients known to be currently alive appear not to be registered with specialist clinics; some are seen in general cardiology clinics. Their median age is 32 years and median duration of loss to follow-up is 22 years; most had been lost before Adult Congenital services had been consolidated in their present form. 48% of the late deaths to date have occurred in patients not under specialist follow-up. None of those lost to specialist follow-up has had secondary pulmonary valve replacement while 188 patients under specialist care have. Patients lost to specialist follow-up who were contacted by telephone had no knowledge of its availability. CONCLUSIONS: Loss to specialist follow-up, typically originating many years ago, impacts patient management.

Concepts: Cohort study, Longitudinal study, Hospital, Heart, Congenital disorder, Congenital heart defect, Congenital heart disease, Tetralogy of Fallot

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The Pediatric Cardiac Genomics Consortium (PCGC) designed the Congenital Heart Disease Genetic Network Study to provide phenotype and genotype data for a large congenital heart defects (CHDs) cohort. This article describes the PCGC cohort, overall and by major types of CHDs (e.g., conotruncal defects) and subtypes of conotrucal heart defects (e.g., tetralogy of Fallot) and left ventricular outflow tract obstructions (e.g., hypoplastic left heart syndrome). Cases with CHDs were recruited through ten sites, 2010-2014. Information on cases (N = 9,727) and their parents was collected through interviews and medical record abstraction. Four case characteristics, eleven parental characteristics, and thirteen parent-reported neurodevelopment outcomes were summarized using counts and frequencies and compared across CHD types and subtypes. Eleven percent of cases had a genetic diagnosis. Among cases without a genetic diagnosis, the majority had conotruncal heart defects (40%) or left ventricular outflow tract obstruction (21%). Across CHD types, there were significant differences (p<0.05) in the distribution of all four case characteristics (e.g., sex), four parental characteristics (e.g., maternal pregestational diabetes), and five neurodevelopmental outcomes (e.g., learning disabilities). Several characteristics (e.g., sex) were also significantly different across CHD subtypes. The PCGC cohort is one of the largest CHD cohorts available for the study of genetic determinants of risk and outcomes. The majority of cases do not have a genetic diagnosis. This description of the PCGC cohort, including differences across CHD types and subtypes, provides a reference work for investigators who are interested in collaborating with or using publically available resources from the PCGC.

Concepts: Gene, Heart, Hypertrophic cardiomyopathy, Down syndrome, Congenital heart defect, Congenital heart disease, Tetralogy of Fallot, Hypoplastic left heart syndrome

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Previous studies have yielded inconsistent results for the effects of periconceptional multivitamins containing folic acid and of folic acid food fortification on congenital heart defects (CHDs).

Concepts: Folic acid, Food fortification, Congenital heart defect, Congenital heart disease

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There is no consensus in current practice guidelines whether IVF/ICSI conception represents an indication for performing a fetal echocardiogram. The aim of the study is to assess whether CHD occurs more often with the use of in-vitro-fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) techniques as compared to spontaneous pregnancies.

Concepts: Pregnancy, Fetus, Fertility, Congenital heart defect, Congenital heart disease

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Valve-sparing aortic root reconstruction (VSRR) is an accepted method to treat patients with aortic root dilation. The role of the VSRR is less well defined for patients with bicuspid aortic valve, severe aortic valve insufficiency, congenital heart defects, and type A aortic dissection. We studied the clinical outcome of patients who underwent VSRR for expanded indications.

Concepts: Aortic aneurysm, Aortic dissection, Aorta, Congenital heart defect, Congenital heart disease, Aortic valve, Aortic insufficiency, Bicuspid aortic valve

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Abstract Objective. In general the analytical epidemiological studies evaluated cases with congenital heart defects together. However, different congenital heart defect entities have different etiology, and in the vast majority of patients the underlying causes are unclear. Thus the objective of the study was to evaluate the possible etiological factors in the origin of single ventricular septal defect (VSD) after surgical intervention or lethal outcome, i.e. as homogeneous as possible. Method. In the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities acute and chronic maternal diseases with related drug treatments and pregnancy supplements in early pregnancy were evaluated in the mothers of 1,661 cases with isolated/single VSD and their 2,534 matched and 38,151 all controls without defect, and 19,833 malformed controls with other isolated non-cardiac defect. Results. There was a higher risk of VSD in the children of mothers with high fever related influenza during the critical period of VSD and this risk was limited by antifever therapy. In addition paroxysmal supraventricular tachycardia and epilepsy treated with anticonvulsant drugs associated with higher risk of VSD. Finally the high doses of folic acid alone in early pregnancy Conclusions. H high fever related maternal diseases may have a role in the origin of VSD which is preventable with antifever drug therapy, and the high doses of folic acid in early pregnancy were able to reduce the risk of VSD.

Concepts: Epidemiology, Down syndrome, Congenital heart defect, Congenital heart disease, Ventricular septal defect

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OPINION STATEMENT: Ebstein anomaly (EA) is a rare congenital heart defect that may not be detected until late in adolescence or adulthood. Since the original description in a 19-year-old laborer with severe tricuspid valve (TV) regurgitation in 1866, our understanding of this rare condition has increased to the recognition that it is an abnormality not only of the TV, but also of the right ventricle (RV). EA is the result of failure of delamination of the TV leaflets from the interventricular septum, resulting in adherence of the leaflets to the underlying myocardium. This results in a wide variety of abnormalities, including apical and posterior displacement of the dilated TV annulus; dilation of the “atrialized” portion of the RV; and fenestrations, redundancy, and tethering of the anterior leaflet of the TV. The malformed TV is usually regurgitant, but may rarely be stenotic. The clinical manifestations of EA in the adult depend on several factors, including the extent of TV leaflet distortion, degree of tricuspid regurgitation (TR), right atrial pressure, and presence of a right-to-left atrial level shunt. Over the past several decades, advances in diagnostic imaging and surgical techniques have contributed to our current management of this challenging congenital heart defect.

Concepts: Heart, Right ventricle, Ventricle, Right atrium, Tricuspid valve, Congenital heart defect, Congenital heart disease, Ebstein's anomaly

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Context:Paragangliomas are a type of neuroendocrine tumor that has been reported to be present in patients with cyanotic congenital heart disease. This report documents the first case of a patient with successful resection of a sympathetic paraganglioma in the setting of unrepaired tetralogy of Fallot, the most common cause of cyanotic heart disease, with pulmonary atresia.Objective:We present a 33-yr-old woman with hypertensive crises from a paraganglioma who presented for surgical resection.Patient and Methods:The patient’s preoperative workup was consistent with a functioning sympathetic paraganglioma. Preoperative transesophageal echocardiogram displayed normal ventricular function, moderate-severe right ventricular hypertrophy, severe right ventricular hypertension, an overriding aorta, bidirectional shunting, pulmonary atresia, and aortopulmonary collaterals.Results:The patient underwent a successful laparoscopic resection of a functioning 7-cm paraganglioma after careful preoperative preparation and intraoperative monitoring. Pathology returned as a well-defined, partially hemorrhagic mass measuring 7.0 × 4.5 × 4.5 cm adjacent to and compressing the adrenal gland.Conclusion:Surgical resection of paraganglioma tumors in rare patients such as this one is appropriate; however, surgery requires meticulous perioperative management with a multidisciplinary approach. Future studies are needed to determine whether there is a link between neuroendocrine tumors and cyanotic congenital heart disease.

Concepts: Oncology, Hypertension, Cardiology, Heart, Blood pressure, Congenital heart defect, Congenital heart disease, Tetralogy of Fallot

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Previous studies have shown that copy-number variants (CNVs) contribute to the risk of complex developmental phenotypes. However, the contribution of global CNV burden to the risk of sporadic congenital heart disease (CHD) remains incompletely defined. We generated genome-wide CNV data by using Illumina 660W-Quad SNP arrays in 2,256 individuals with CHD, 283 trio CHD-affected families, and 1,538 controls. We found association of rare genic deletions with CHD risk (odds ratio [OR] = 1.8, p = 0.0008). Rare deletions in study participants with CHD had higher gene content (p = 0.001) with higher haploinsufficiency scores (p = 0.03) than they did in controls, and they were enriched with Wnt-signaling genes (p = 1 × 10(-5)). Recurrent 15q11.2 deletions were associated with CHD risk (OR = 8.2, p = 0.02). Rare de novo CNVs were observed in ~5% of CHD trios; 10 out of 11 occurred on the paternally transmitted chromosome (p = 0.01). Some of the rare de novo CNVs spanned genes known to be involved in heart development (e.g., HAND2 and GJA5). Rare genic deletions contribute ~4% of the population-attributable risk of sporadic CHD. Second to previously described CNVs at 1q21.1, deletions at 15q11.2 and those implicating Wnt signaling are the most significant contributors to the risk of sporadic CHD. Rare de novo CNVs identified in CHD trios exhibit paternal origin bias.

Concepts: Gene, Copy number variation, Chromosome, Heart, Congenital heart defect, Congenital heart disease, Odds, Trio