Ventricular septal defects (VSD) with outflow tract (OFT) malalignment are a common group of congenital heart diseases with varying severity. The developmental process of these defects is challenging to understand due to the complex nature of cardiac morphogenesis and the difficulties in visualizing the temporal and spatial changes that occur during pathogenesis. However, recent advancements in imaging techniques, such as high-resolution episcopic microscopy, have provided valuable insights into the normal septation of ventricular chambers and OFT alignment. Building upon this knowledge, we have utilized lightsheet microscopy, another innovative imaging method, to further investigate the developmental processes that lead to abnormal formation of the ventricular septum and the malalignment of arterial roots with the ventricular chambers. Our study highlights endocardial cushion hypoplasia and insufficient rotation of the outflow tract as two interrelated central factors contributing to the pathogenesis of these defects. This finding has the potential to enhance our understanding of the etiology of congenital heart diseases and may contribute to the development of improved diagnostic and therapeutic strategies in the future.

Ventricular septal defects (VSDs) are a prevalent congenital heart anomaly demanding safe and lasting interventions. This paper explores the application of Invengenx® bovine pericardial patch (Tisgenx, Irvine, California), a promising biomaterial, in VSD repair. We present two case studies: a seven-month-old infant and a three-year-old child undergoing VSD closure using autologous and bovine pericardial patches, respectively. Both patients tolerated the procedures well, experiencing no intra-operative complications and demonstrating excellent postoperative recovery. Echocardiography postoperatively showed no complications and improved clinical outcomes. Notably, the pericardial patches exhibited excellent integration and suture retention, highlighting their durability and compatibility with the growing heart. These cases establish the feasibility and effectiveness of the Invengenx® pericardial patch for VSD repair. The favorable outcomes in terms of safety and efficacy support the potential of this biomaterial as a valuable alternative in pediatric cardiac surgery, particularly for complex VSDs or patients with contraindications to synthetic patches. Further research is crucial to unlock the full potential of bovine pericardium as a durable and advantageous option for VSD repair in a broader range of pediatric patients.

UNASSIGNED: A multidisciplinary team approach, careful hemostasis, and factor replacement therapy are important in the perioperative management of hemophiliac patients undergoing pediatric cardiac surgery.
UNASSIGNED: The combination of congenital heart diseases (CHD) and hemophilia is rare; furthermore, heart surgery and perioperative management of such cases is challenging. This report illustrates the challenges of pediatric cardiac surgery in an infant with both hemophilia B and CHD. Multidisciplinary team approach, careful hemostasis, and factor replacement therapy were key to success without hemorrhagic complications before, during and after surgery.

The feasibility of percutaneous closure ventricular septal defects (VSD) in children has been previously proven. However, data on long-term outcomes are limited. We aim to evaluate the long-term outcome of our experience with percutaneous closure of VSD using various occluders.
Retrospective institutional analysis of children who underwent transcatheter closure of perimembranous and muscular VSDs between September 2012 and February 2020. Patient demographics, procedural, and long-term follow-up data were comprehensively analyzed. Patients who lost to follow-up within two years post-procedure were excluded.
We identified 75 patients (54.7% males) with a median of 66 months (IQR, 46-96). The closure success rate at one year was 95.7%. Complete heart block was detected in two patients early post-procedure and resolved with steroids. The VSDs were perimembranous (52%), muscular (33.33%), and residual (14.67%). Implanted devices were Pfm Nit-Occlud LeˆVSD Coil (42.7%), HyperionTM VSD Muscular Occluder (28%), Amplatzer VSD muscular occluder (10.7%), Amplatzer Duct Occluder (14.7%), Occlutech Muscular VSD Occluder (2.7%), and Amplatzer Duct Occluder II (1.3%). No new arrhythmia or valve regurgitation was detected after two years post-procedure. Persisted complications on long-term follow-up included: residual shunting in 3(4%), mild tricuspid regurgitation in 2(2.7%), and aortic regurgitation in 2(2.7%), with one immediate post-catheterization mild aortic regurgitation worsened during follow-up, requiring surgical repair of VSD three years after device implantation. No deaths were reported.
Long-term outcomes of pediatric transcatheter VSD closure using different devices are satisfactory. Post-procedural adverse events are limited, but long-term surveillance is necessary to monitor their progression.

We present a case of holoprosencephaly (HPE) with cyclopia and proboscis. The mother was a 35-year-old, G1P1 with no known comorbid conditions, not in a consanguineous marriage, and with no history of illicit drug use. On a routine antenatal ultrasound scan, features of alobar HPE, proboscis, and other anomalies were identified. The mother was counseled about the condition and as per their consent, the pregnancy was terminated. After labor induction, she gave birth to a female neonate weighing 1,000 g. The newborn\'s Apgar score could not be calculated. In the initial physical examination, an eye and a 3.5-cm proboscis were seen in the middle of the forehead. The newborn had no nose, and the outer ears were normal. On postmortem examination, alobar HPE, polydactyly, ventricular septal defect, and myelomeningocele were confirmed. This case report highlights the importance of attention to these details during antenatal scans for early detection in order to reduce the maternal and neonatal health burden. The pictures presented in this article were taken after obtaining parental consent.

Both percutaneous and perventricular device closures of perimembranous ventricular septal defects (Pm-VSDs) are alternatives to surgical procedures，but they all present certain drawbacks.
To report our clinical experiences and midterm follow-up results of minimally invasive peratrial device closure of Pm-VSDs under the guidance of transesophageal echocardiography(TEE) in patients <12 months of age.
Between January 2015 and December 2020，268 patients <12 months of age with Pm-VSDs underwent peratrial device closure in our institute. The procedure was performed under TEE guidance via a small right subaxillary incision. The delivery pathways is established by manipulating the hollow probe, and then the device is installed.
A total of 263 cases (98.1%) underwent successful closure, whereas five cases failed and were converted to cardiopulmonary bypass operation via the original incision during the procedure. The mean age was 9.5 ± 2.0 months and the mean body weight was 8.8 ± 1.4 kg. The mean diameter of the VSD was 4.4 ± 0.5 mm. One patient (0.4%) underwent a second thoracotomy for postoperative intercostal hemorrhage on the second day after surgery. The mean diameter of the occluder size was 5.5 ± 0.6 mm. During the follow-up (4.3 ± 1.4 y), there was no mortality, no new aortic valve regurgitation and atrioventricular block.
Peratrial device closure of Pm-VSDs via the right subaxillary route under TEE guidance is safe and effective at midterm follow-up, confirming this is an valuable alternative method for patients <12 months of age.

(1) Background: The interaction between single nucleotide variants (SNVs) associated with congenital heart diseases (CHDs) and their gene methylation status has not been well researched. The aim of the present study was to determine if there is a relationship between the methy lation status (MS) of genes and the allelic variants associated with CHDs. (2) Methods: Seven SNVs of the genes AXIN1, TBX1, TBX20, and MTHFR were selected from the literature. DNA extraction, genotyping, and a methylation analysis were performed on healthy subjects and subjects with CHDs. (3) Results: Twenty-two subjects with CHDs were selected as the case group (15 with ventricular septal defects (VSDs) and 7 with atrial septal defects (ASDs)), and 44 healthy subjects comprised the control group. The MTHFR and AXIN1 genes were hypermethylated in the control group when compared to the case group. When analyzed separately, those with atrial septum defects exhibited greater methylation, except for the gene MTHFR where there were no differences. Only the alternate alleles of MTHFR showed a significantly different methylation status in those without cardiopathy. (4) Conclusions: The MTHFR and AXIN genes were hypermethylated in the control group; however, only the alternate alleles of MTHFR (rs1801133 and rs1801131) showed a significantly different methylation status.

Membranous ventricular septal aneurysm (VSA) is an uncommon cardiac abnormality, potentially leading to several cardiac complications such as aortic valve prolapse, arrhythmias, and aneurysm rupture. A young competitive soccer player presented for a post-COVID sports cardiology assessment, denying any previous cardiological evaluations. On transthoracic echocardiography, a membranous VSA was incidentally found with no other cardiac abnormality nor hemodynamic impairment associated. A well-oriented anamnesis guided by echocardiographic findings revealed that a ventricular septal defect was diagnosed at birth with spontaneous closure at 4 years old. From that moment, no further follow-up was performed. Before granting cardiological approval to competitive sport, transesophageal echocardiography and Holter electrocardiogram were performed to confirm the absence of interventricular shunt and any other cardiac abnormality or arrhythmias associated with VSA. This case highlights the value of an accurate and comprehensive clinical and echocardiographic evaluation when performing a cardiological sports assessment, even in a young asymptomatic athlete.

This study attempted to learn the association between maternal betaine-homocysteine methyltransferase (BHMT) gene polymorphisms, maternal dietary habits, and their interactions with the risk of ventricular septal defects (VSD) in offspring. A total of 426 mothers of VSD children and 740 control mothers were included in the study. Logistic regression was used to evaluate the level of associations and interaction effects. Our study suggested that mothers reporting excessive intake of smoked foods (aOR = 2.44, 95%CI: 1.89-3.13), barbecued foods (aOR = 1.86, 95%CI: 1.39-2.48), fried foods (aOR = 1.93, 95%CI: 1.51-2.46), and pickled vegetables (aOR = 2.50, 95%CI: 1.92-3.25) were at a significantly higher risk of VSD in offspring, instead, mothers reporting regular intake of fresh fruits (aOR = 0.47, 95%CI: 0.36-0.62), fish and shrimp (aOR = 0.35, 95%CI: 0.28-0.44), fresh eggs, (aOR = 0.56, 95%CI: 0.45-0.71), beans (aOR = 0.68, 95%CI: 0.56-0.83), and milk products (aOR = 0.67, 95%CI: 0.56-0.80) were at a lower risk of VSD in offspring. In addition, maternal BHMT gene polymorphisms at rs1316753 (CG vs. CC: aOR = 2.01, 95%CI: 1.43-2.83) and rs1915706 (CT vs. TT: (aOR = 1.81, 95%CI: 1.33-2.46) were significantly associated with increased risk of VSD in offspring. Furthermore, a significant interaction between BHMT polymorphisms and maternal bean intake was identified in the study. In conclusion, Maternal BHMT polymorphisms at rs1316753 and rs1915706, dietary habits as well as their interaction were observed to be significantly associated with the risk of VSD in offspring.

BACKGROUND: Ventricular septal defects (VSDs) are one of the leading causes of death due to cardiac anomalies during the first months of life. The prevalence of VSD in neonates is reported up to 4%. Despite the remarkable progress in medication, treatment and surgical procedure for VSDs, the genetic etiology of VSDs is still in infancy because of the complex genetic and environmental interactions.
METHODS: Three hundred fifty subjects (200 VSD children and 150 healthy controls) were recruited from different pediatric cardiac units. Pediatric clinical and demographic data were collected. A total of six variants, rs1017 (ISL1), rs7240256 (NFATc1), rs36208048 (VEGF), variant of HEY2, rs11067075 (TBX5) and rs1801133 (MTHFR) genes were genotyped by tetra-ARMS PCR and PCR-RFLP methods.
RESULTS: The results showed that in cases, the rs1017 (g.16138A > T) variant in the ISL1 gene has an allele frequency of 0.42 and 0.58 respectively for the T and A alleles, and 0.75 and 0.25 respectively in the controls. The frequencies of the AA, TA and TT genotypes were, 52%, 11% and 37% in cases versus 21%, 8% and 71% respectively in the controls. For the NFATc1 variant rs7240256, minor allele frequency (MAF) was 0.43 in cases while 0.23 in controls. For the variant in the VEGF gene, genotype frequencies were 0% (A), 32% (CA) and 68% (CC) in cases and 0.0%, 33% and 67% respectively in controls. The allele frequency of C and A were 0.84 and 0.16 in cases and 0.83 and 0.17 respectively in controls. The TBX5 polymorphism rs11067075 (g.51682G > T) had an allelic frequency of 0.44 and 0.56 respectively for T and G alleles in cases, versus 0.26 and 0.74 in the controls. We did not detect the presence of the HEY2 gene variant (g.126117350A > C) in our pediatric cohort. For the rs1801133 (g.14783C > T) variant in the MTHFR gene, the genotype frequencies were 25% (CC), 62% (CT) and 13% (TT) in cases, versus 88%, 10% and 2% in controls. The ISL1, NFATc1, TBX5 and MTHFR variants were found to be in association with VSD in the Pakistani pediatric cohort whilst the VEGF and HEY2 variants were completely absent in our cohort.
CONCLUSIONS: We propose that a wider programme of genetic screening of the Pakistani population for genetic markers in heart development genes would be helpful in reducing the risk of VSDs.