Case-control association study of congenital heart disease from a tertiary paediatric cardiac centre from North India.

BACKGROUND: Congenital Heart diseases (CHDs) account for 1/3rd of all congenital birth defects. Etiopathogenesis of CHDs remain elusive despite extensive investigations globally. Phenotypic heterogeneity witnessed in this developmental disorder reiterate gene-environment interactions with periconceptional factors as risk conferring; and genetic analysis of both sporadic and familial forms of CHD suggest its multigenic basis. Significant association of de novo and inherited variants have been observed. Approximately 1/5th of CHDs are documented in the ethnically distinct Indian population but genetic insights have been very limited. This pilot case-control based association study was undertaken to investigate the status of Caucasian SNPs in a north Indian cohort. METHOD: A total of 306 CHD cases sub-classified into n = 198 acyanotic and n = 108 cyanotic types were recruited from a dedicated tertiary paediatric cardiac centre in Palwal, Haryana. 23 SNPs primarily prioritized from Genome-wide association studies (GWAS) on Caucasians were genotyped using Agena MassARRAY Technology and test of association was performed with adequately numbered controls. RESULTS: Fifty percent of the studied SNPs were substantially associated in either allelic, genotypic or sub-phenotype categories validating their strong correlation with disease manifestation. Of note, strongest allelic association was observed for rs73118372 in CRELD1 (p < 0.0001) on Chr3, rs28711516 in MYH6 (p = 0.00083) and rs735712 in MYH7 (p = 0.0009) both on Chr 14 and were also significantly associated with acyanotic, and cyanotic categories separately. rs28711516 (p = 0.003) and rs735712 (p = 0.002) also showed genotypic association. Strongest association was observed with rs735712(p = 0.003) in VSD and maximum association was observed for ASD sub-phenotypes. CONCLUSIONS: Caucasian findings were partly replicated in the north Indian population. The findings suggest the contribution of genetic, environmental and sociodemographic factors, warranting continued investigations in this study population.

The study of expression levels of DNA methylation regulators in patients affected with congenital heart defects (CHDs).

BACKGROUND: Congenial heart defects (CHDs) have multifactorial etiology with complex interplay of genetic and environmental factors. Environmental impact can have epigenetic mechanism of CHD development. Many studies have reported the causal association between CHD and distinct DNA methylation profile which is one of the key epigenetic events, which has vital role in normal embryonic development. The products of DNMT1, DNMT3A, DNMT3B, and MBD2 are important regulators of DNA methylation process. Changes in the expression of these genes are implicated in congenital structural cardiac defects. Hence, in this proof-of-concept study, we have compared the expression levels of these genes in the blood samples of healthy controls and CHD cases while investigating the etiology of CHD. METHODS: In this study with 48 CHD cases and 47 healthy controls, total RNA was isolated from the whole blood samples using TRI reagent. Quantitative RT PCR (qRT-PCR) was used to analyze the mRNA levels of DNMT1, DNMT3A, DNMT3B, and MBD2. The expression levels have been analyzed by relative quantification. RESULTS: We observed that DNMT3B (fold change = -2.563; p = .0018) and DNMT3A (fold change = -2.169; p = .05) were significantly downregulated in CHD patients, whereas the expression of DNMT1 and MBD2 was not significantly different between cases and controls. CONCLUSIONS: Lower expression of de novo methyltransferases, namely, DNMT3B and DNMT3A in CHD cases, may be an important contributor to the mechanism of CHD pathogenesis. Further studies with age-matched controls and analysis of global DNA methylation profile are required to investigate the proposed causal association.

Acyanotic Truncus Arteriosus: Not a Misnomer But a True Rarity.

Truncus arteriosus, also referred to as common arterial trunk (CAT), is generally classified as a cyanotic congenital heart disease characterized by a single arterial trunk arising from the heart and supplying both pulmonary and systemic circulations. Cyanosis exists by virtue of it being an admixture lesion. We report a 13-year-old boy diagnosed to have type 1 CAT who was acyanotic at presentation and had all features of an operable lesion even at this age. He underwent a successful repair with closure of the subtruncal VSD and insertion of a hand-sewn valved right ventricle-to-pulmonary artery conduit made of bovine pericardium and Gore-Tex membrane.

Pseudoaneurysm following a neonatal coarctation repair; a dreadful complication.

Aneurysms of descending thoracic aorta following surgical repair of coarctation have been reported in literature. Almost always, they are seen in repairs involving prosthetic patch aortoplasty. We report a neonate who underwent resection and an extended end to end anastomosis repair of coarctation and subsequently developed a huge pseudoaneurysm at a 3-month follow-up. He underwent a repair of the same through a sternotomy approach under hypothermic low flow cardiopulmonary bypass. An autologous pericardial patch aortoplasty was done successfully.

Timing of congenital cardiac surgery in children who turned COVID-19 positive.

We report a series of four patients with CHD who tested positive for COVID-19, got treated, and underwent cardiac surgery in the same sitting. All had an uneventful perioperative course similar to COVID-19-negative patients. We conclude that children with asymptomatic or mild COVID-19 disease may be subjected to surgery as early as within 1 week since COVID-19 negative.

Isolated left subclavian with a compensatory ductus in a child with Tetralogy of Fallot.

Tetralogy of Fallot is a cyanotic heart disease wherein aortopulmonary collaterals serve as source of pulmonary blood flow to maintain oxygenation. We report an incidentally detected isolated left subclavian artery supplying a compensatory ductus in a child with Tetralogy of Fallot that effectively contributed as a de novo palliative systemic to pulmonary artery shunt. Clinically, the entity could not be suspected, as the child did not have symptoms suggestive of arterial insufficiency of the left arm or weak pulses or neurological symptoms. The child underwent successful intracardiac repair with a reimplantation of left subclavian artery to left common carotid artery.

Exploring the Role of Maternal Nutritional Epigenetics in Congenital Heart Disease.

Congenital heart disease (CHD) is one of the major debilitating birth defects resulting in significant impact on neonatal and child mortality globally. The etiology of CHD is complex and multifactorial. Many causative genes responsible for CHDs have been identified from the familial forms previously. Still, the non-Mendelian inheritance and predominant sporadic cases have stimulated research to understand the epigenetic basis and environmental impact on the incidence of CHD. The fetal epigenetic programming affecting cardiac development is susceptible to the availability of key dietary factors during the crucial periconceptional period. This article highlights the need and importance of in-depth research in the new emerging area of maternal nutritional epigenetics and CHD. It summarizes the current research and underlines the limitations in these types of studies. This review will benefit the future research on nutrition as a modifiable environmental factor to decrease the incidence of CHD.

Transesophageal Echocardiography Reveals a Missed Right Atrial Aneurysm in a Patient with Atrial Septal Defect and Mitral Valve Prolapse.

Right atrial (RA) aneurysms are rare entities reported in the literature. Affected patients are usually asymptomatic, but sometimes, they tend to present with arrhythmias or even heart failure if big. They may form a nidus for thrombus formation and subsequent thromboembolic complications. We report a coincidental finding of a RA aneurysm in a 22-year-old female with the atrial septal defect and mitral valve prolapse, causing moderate mitral regurgitation. The aneurysm was detected incidentally on transesophageal echo after anesthetic induction for elective surgery of the primary pathology. The mitral valve was repaired, and the atrial septal defect was closed. The aneurysm was excised in toto and RA wall repaired.

Explanting the migrated hepatic stent in the right atrium by modified vena caval inflow occlusion.

Stenting of hepatic veins can be a long lasting solution for Budd-Chiari syndrome. These stents could very rarely migrate into the right atrium. During surgical retrieval, cardiopulmonary bypass (CPB) can be avoided if vena caval inflow occlusion (VCIO) is used. A hybrid alternative of VCIO by using a balloon to occlude the inferior vena cava was done to retrieve the stent thus avoiding CPB and total circulatory arrest.

Transesophageal Echocardiography in a Distal Aortopulmonary Window.

Aortopulmonary window (APW) is a relatively rare cardiac lesion representing approximately 0.2%-0.4% of all cardiac malformation. It is a cardiac abnormality that results from abnormal communication between the proximal aorta and the main pulmonary artery in the presence of two normally separated aortic and pulmonary valves. In the past, the diagnostic and surgical approach to APW was almost always preceded by cardiac catheterization. With recent advances in noninvasive approach and techniques of two-dimensional echocardiography diagnosis of the defect and associated anomalies are facilitated without a cath study. We report a 4-month-old infant with a distal APW who was referred to our center for surgical repair. We emphasize the usage of transesophageal echocardiography as a valuable intraoperative tool which not only confirms the preoperative diagnosis but also helps in assessing the surgical repair of an APW.

Isolated Double-chambered Right Ventricle with Intact Interventricular Septum.

Double-chambered right ventricle (DCRV) is a developmental cardiac anomaly in which anomalous muscle bundles divide the right ventricular (RV) cavity into two chambers. It is usually associated with other congenital cardiac defects, of which ventricular septal defect is the most common association. Isolated DCRV with an intact interventricular septum is very rarely reported. It manifests itself usually in adolescence and adults as the obstruction progresses gradually. It is important to recognize this anomaly as it can progress to severe RV failure if unaddressed. We report a 13-year-old male who presented to us with an isolated DCRV. He successfully underwent a resection of the RV cavity anomalous muscle bundles. We also stress on the utility of transesophageal echocardiography intraoperatively which accurately delineates the location of the muscle bundles and helps in evaluating the adequacy of resection postsurgery.