Concept: Congenital heart disease
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.
Structural genetic changes, especially copy number variants (CNVs), represent a major source of genetic variation contributing to human disease. Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease, but to date little is known about the role of CNVs in the etiology of TOF. Using high-resolution genome-wide microarrays and stringent calling methods, we investigated rare CNVs in a prospectively recruited cohort of 433 unrelated adults with TOF and/or pulmonary atresia at a single centre. We excluded those with recognized syndromes, including 22q11.2 deletion syndrome. We identified candidate genes for TOF based on converging evidence between rare CNVs that overlapped the same gene in unrelated individuals and from pathway analyses comparing rare CNVs in TOF cases to those in epidemiologic controls. Even after excluding the 53 (10.7%) subjects with 22q11.2 deletions, we found that adults with TOF had a greater burden of large rare genic CNVs compared to controls (8.82% vs. 4.33%, p = 0.0117). Six loci showed evidence for recurrence in TOF or related congenital heart disease, including typical 1q21.1 duplications in four (1.18%) of 340 Caucasian probands. The rare CNVs implicated novel candidate genes of interest for TOF, including PLXNA2, a gene involved in semaphorin signaling. Independent pathway analyses highlighted developmental processes as potential contributors to the pathogenesis of TOF. These results indicate that individually rare CNVs are collectively significant contributors to the genetic burden of TOF. Further, the data provide new evidence for dosage sensitive genes in PLXNA2-semaphorin signaling and related developmental processes in human cardiovascular development, consistent with previous animal models.
A high incidence of orofacial clefts is reported in China, but no data has shown the relation between cleft types and the incidence of other defects so far. The aim of this study is to assess the incidence of congenital heart diseases and other organic defects associated with different types of orofacial clefts.
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).
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.
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.
- Current treatment options in cardiovascular medicine
- Published about 5 years ago
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.
Sympathetic Paraganglioma in a Patient with Unrepaired Tetralogy of Fallot: A Case Report and Review of the Literature.
- The Journal of clinical endocrinology and metabolism
- Published about 5 years ago
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.
Giant occipitoparietal encephaloceles are rare forms of neurodevelopmental defects whose etiologies remain uncertain. Their occurrence can lead to variable neurological outcomes depending on the extent of cerebral cortex involved and the ability to repair the defect. In addition, encephaloceles may be associated with various genetic syndromes and familial inheritance. Here, the authors describe a unique constellation of malformations associated with the case of a giant occipitoparietal meningoencephalocele with herniation of cortical tissue and continuity with the ventricular system. The patient had a cleft lip and palate, hemivertebrae of the thoracic spine, a patent ductus arteriosus, a ventricular septal defect, and coarctation of the aorta. To identify the genetic underpinnings of these malformations, fluorescence in situ hybridization and microarray analysis were performed and revealed an 80.65-kb gain within chromosome band 2p11.2. Duplications of this region involving RMND5A, whose product contains a C-terminal to lis homology (LisH) domain, have not previously been associated with a defined phenotype but may present insight into encephalocele formation. Surgical repair and follow-up for the neurological malformations are also discussed.
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.