Forms Of Congenital Heart Disease Research Articles

Eisenmenger Syndrome: Pathophysiology, Clinical Manifestations, and Contemporary Management Approaches in Advanced Cardiopulmonary Disease

Eisenmenger syndrome, a complex and severe form of congenital heart disease, results from prolonged left-to-right shunting due to underlying cardiac defects such as ventricular septal defects, atrial septal defects, or patent ductus arteriosus, ultimately leading to irreversible pulmonary arterial hypertension and a reversal of the initial shunt. This syndrome represents the most severe spectrum of pulmonary vascular disease associated with congenital heart defects and is characterized by hypoxemia, erythrocytosis, and systemic cyanosis. Despite advances in early diagnosis and intervention in congenital heart disease, Eisenmenger syndrome remains a significant concern due to the irreversible nature of pulmonary vascular changes and associated multisystem complications. This article provides a comprehensive review of the pathophysiology, clinical manifestations, and the role of pharmacologic and non-pharmacologic therapies, including advanced palliative care, to improve patient quality of life. Emerging therapies such as endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostacyclin analogs show promise in symptom management, though surgical interventions, such as heart-lung transplantation, remain reserved for selected cases. Given the high mortality associated with Eisenmenger syndrome, a multidisciplinary approach is critical in managing complications, improving patient outcomes, and supporting functional status.

Electrophysiologic Considerations in Adult Patients with Ebstein's Anomaly.

Ebstein's anomaly (EA) is a rare cyanotic form of congenital heart disease (CHD) characterized by apical displacement of the tricuspid valve, with resultant hemodynamic and electrical manifestations. The severity of symptoms is determined by the degree of apical displacement and deformity and incompetence of the tricuspid valve. As a result, patients with EA can be severely symptomatic during infancy and childhood or can be incidentally discovered in the sixth or seventh decade of life. Hallmarks of Ebstein's anomaly include progressive cyanosis, right-sided heart failure, and tachyarrhythmias, among which tachyarrhythmias (most commonly atrial, but also ventricular) are the most common presenting symptoms in Ebstein's anomaly patients during adulthood. This review aims to provide insight into the genetic and electrophysiological (EP) basis underlying the tachyarrhythmias encountered when managing patients with EA.

Abstract 4135928: Externally Validated Deep Learning Model for Patent Ductus Arteriosus Detection by Echocardiography in Preterm Infants

Introduction: Patent ductus arteriosus (PDA) is a common form of congenital heart disease in premature infants and a source of significant morbidity. Echocardiography is the mainstay modality for diagnosis and monitoring but is resource-intensive and requires expertise for interpretation. Aims: To develop and externally validate a deep learning model to identify PDA in preterm infants by echocardiography. Methods: We trained, validated, and tested a convolutional neural network to detect PDA in raw echocardiogram clips from infants (gestational age <37 weeks) with and without PDAs and no significant additional congenital heart disease at the Medical University of South Carolina (MUSC). For training and validation, we employed a 12-fold cross-validation procedure. Experienced cardiologists defined the ground truth labels. We assessed classification performance on an internal model naïve dataset using the area under the receiver operator curve (AUROC), sensitivity, specificity, positive predictive value, and negative predictive value. For external multicenter testing, we used studies from Children’s Hospital of Orange County (CHOC) and Boston Children’s Hospital (BCH), both of which utilize a different ultrasound system vendor. Results: Training and validation were completed using 1,145 color/color-compare clips (661 clips with PDA and 484 no PDA) from 66 patients. The internal test dataset consisted of 142 clips from 16 patients. The external CHOC and BCH cohorts consisted of 146 clips from 50 patients and 294 clips from 68 patients, respectively. Model performance was similar for internal and external testing (Table 1). Conclusions: Our deep learning model detected the presence of PDA with acceptable performance. This performance generalized well across multiple institutions and ultrasound vendors. This work shows promise for the future development of an automated tool for PDA diagnosis enabling the democratization of pediatric cardiology resources.

Abstract Mo088: RBFOX2 haploinsufficiency impairs cardiomyocyte adhesion and contractility through faulty RNA metabolism

Background: Hypoplastic left heart syndrome (HLHS) is a severe form of congenital heart disease that is uniformly lethal if left untreated. Protein damaging mutations in one allele of RBFOX2, a highly conserved RNA binding protein, are enriched in HLHS patients, suggesting they are causal. However, it remains unclear how RBFOX2 haploinsufficiency contributes to disease pathogenesis as heterozygous animal models appear healthy. Methods: We generated and characterized RBFOX2 heterozygous and null human induced pluripotent stem cells (hiPSCs) and assessed their phenotypes in differentiated cardiomyocytes (iPSC-CMs) in 2D culture. To learn if altered function might be revealed in a more native microenvironment, we also generated 3D engineered heart tissues (EHTs) from RBFOX2 heterozygous hiPSC-CMs. To delineate the underlying molecular mechanisms, we performed bulk RNA-seq to reveal differential gene expression (DGE) and alternative splicing events (ASEs) between the different genetic cohorts and eCLIP-seq to detect RNAs directly bound by RBFOX2 in the CM lineage. Results: We observed dose-dependent reductions in cell adhesion, size, maturation, respiration, calcium handling, and action potential duration with no significant effect on proliferation in 2D culture. Although myofibril alignment and contractility were completely abolished in null hiPSC-CMs, these features were surprisingly preserved in heterozygous cells. However, in EHTs, we found that RBFOX2 is haploinsufficient for tissue maturation and contractility, suggesting that myocardial-intrinsic defects contribute to RBFOX2 -mediated HLHS. Integration of DGE, ASEs and eCLIP-seq datasets uncovered significant enrichment of DGE and/or ASEs of RBFOX2-bound and unbound transcripts involved in cell adhesion between the extracellular matrix (ECM) and the actin cytoskeleton/sarcomere network. Included in the direct targets with altered expression and alternative splicing was the ECM ligand FIBRONECTIN 1 ( FN1 ), which when downregulated was previously associated with HLHS. Conclusions: Our data suggest that RBFOX2 sits atop an expression and splicing hierarchy that promotes optimal CM cell growth, adhesion, and contractility that protects the heart from HLHS pathogenesis.

PA-VSD Without MAPCA(s): Review of Long-Term Outcomes and Reinterventions.

Pulmonary atresia with ventricular septal defect without major aortopulmonary collateral arteries (MAPCAs) is an uncommon form of congenital heart disease. As more patients with congenital heart disease live to adulthood, the objective of this article was to review the long-term results of this specific population. A review of the PubMed database was performed using pertinent key words (pulmonary atresia, tetralogy of Fallot, conduit, right ventricle-pulmonary artery) concentrating on studies from 1990-present and published in English. Most studies of pulmonary atresia-ventricular septal defect patients included those with and without MAPCAs. Analysis included examination of the entire cohort, consideration of the proportion of patients with MAPCAs, and any subgroup analysis of the patients without MAPCAs. Survival is approximately 80% at ten years and is improved with complete repair and larger pulmonary arteries. Some studies have found genetic syndromes and extracardiac anomalies to impact survival, while others have not. Incomplete repair has been shown to be associated with worse survival. Independent of initial management strategy, patients with pulmonary atresia and ventricular septal defects without MAPCAs require repeat intervention on the right ventricular outflow tract. Hypoplastic pulmonary arteries have been shown to be a risk factor for reintervention, and decreased conduit durability has been shown with younger age at implantation of conduit. Long-term outcomes have improved for patients with pulmonary atresia-ventricular septal defect without MAPCAs, with complete repair and adequate pulmonary arteries favorable for survival. Long-term outcomes include reinterventions, both catheter-based and surgical, predominantly on the right ventricular outflow tract.

Scimitar Syndrome in a Pediatric Cohort.

Scimitar syndrome is a rare form of congenital heart disease (CHD) characterized by anomalous pulmonary venous drainage of the right lung to the inferior vena cava. We describe the presentation, diagnosis, therapeutic management and long-term follow-up of 10 pediatric patients with Scimitar Syndrome. We performed a retrospective observational study of all pediatric patients from our institution with scimitar syndrome (March 1996-July 2023). Patients underwent systematic evaluation including medical and family history, chest x-ray, 12-lead electrocardiogram, echocardiogram, angiography and/or computed tomography; or magnetic resonance angiography. Ten patients with scimitar syndrome were included. The median age at diagnosis was 10.4 [0.1-150.2] months and the median follow-up time was 7.7 [1.3-15.3] years. Eight patients presented with aortopulmonary collateral arteries which were embolized. Two patients had dual connections to the inferior vena cava and left atrium; embolization of the inferior vena cava connection was only feasible in one of them. No patients underwent surgery of the scimitar vein. Three patients had surgical correction of CHDs. There were no deaths related to scimitar syndrome during follow-up. All patients with scimitar syndrome need prompt cardiovascular evaluation and follow-up. Our study demonstrates that a conservative approach with aortopulmonary collateral artery embolization, scimitar vein embolization when dual drainage to the left atrium is identified, along with correction of concomitant CHDs might have good results in patients with scimitar syndrome in order to postpone surgical correction of the anomalous pulmonary venous return to an older age when clinically or hemodynamically indicated. Further studies with longer-term follow-up and a larger sample size are needed to more effectively determine treatment strategy.

HEART FAILURE WITH PRESERVED EJECTION FRACTION (HFPEF) IN A PATIENT WITH RECENT TAVI AND NUMEROUS CORONARY FISTULAS OF THE LEFT CORONARY ARTERY DRAINING INTO THE VENTRICULAR CAVITY

Abstract Coronary fistula is a rare form of congenital heart disease and is defined as an abnormal connection between a coronary branch and a cardiac chamber or a large intrathoracic vessel without the interposition of the capillary circulation. The right coronary artery is the most common site of origin for coronary fistula. Other sites include the left anterior descending artery and left circumflex artery. The clinical presentation and the natural history can be extremely variable depending on the patient‘s age, fistula size, and anatomy. Small to medium–sized coronary fistulas may be asymptomatic. Large fistulas can manifest with angina pectoris due to myocardial ischemia secondary to the coronary steal phenomenon. Shunting through large fistulas can have hemodynamic consequences secondary to volume overload in the pulmonary or systemic circulation, leading to symptoms and signs of heart failure. We describe the case of an 83–year–old woman recently undergoing TAVI and suffering from primary myelofibrosis requiring periodic transfusions. Pre–TAVI coronary angiography showed coronary vessels free from significant hemodynamic lesions and multiple coronary–ventricular fistulas draining into the left ventricle. Total body aortic CT angiography did not reveal other abnormal vascular connections. One month after the aortic valve correction procedure, the patient presented with heart failure (HfpEF). At a recent follow–up visit, diuretic therapy was discontinued due to the successful correction of aortic valve disease and normal ejection fraction. Due to further anemization from the underlying hematologic condition, the patient underwent blood transfusion with worsening of dyspnea despite correction of hemoglobin levels. Discontinuation of diuretic therapy and transfusion of red blood cell units resulted in volume overload with worsening clinical condition. The presence of multiple coronary fistulas precluded an interventional approach, but therapeutic optimization and reintroduction of diuretic therapy restored the patient‘s hemodynamic compensation. Usually fistulas drain into the low–pressure venous circulation like right ventricle and right atrium. This case represents a rare instance of multiple left coronary fistulas draining into the left ventricle (only 3% of cases). Aortic valve correction may have further reduced left ventricular telediastolic pressures, worsening the shunt of coronary fistulas resulting in heart failure due to volume overload.

NOT JUST A SIMPLE FEVER: DIAGNOSIS OF COMPLICATED INFECTIVE ENDOCARDITIS ON BICUSPID AORTIC VALVE IN A YOUNG MAN

Abstract Bicuspid aortic valve is the most common form of congenital heart disease (prevalence of 0.5 to 2.0%). These patients develop infective endocarditis at significantly higher rates than the general population; furthermore, they are at increased risk of developing infective endocarditis at a younger age owing to intrinsic factors of the aortic valve, but demonstrate better long–term survival after surgical treatment. This case report concerns a 33–year–old caucasian man who presented to the emergency department for persistent fever. He had no significant past medical history, except for a known bicuspid aortic (type 0) valve. The laboratory test demonstrated an active infection and blood cultures were positive, so we performed a transthoracic echocardiogram showing a mobile mass on the aortic valve, associated to a severe aortic regurgitation. Hence, we decided to perform a transesophageal echocardiogram that documented a bicuspid aortic valve with an extensive endocarditic vegetation on anterior leaflet, cusp prolapse and a non–homogenous peri–valvular area, involving the mitral–aortic junction, compatible with abscess. Perivalvular extension of infective endocarditis is the most frequent cause of uncontrolled infection and is associated with a poor prognosis so, as suggested by ESC Guidelines, this clinical case represented an indication for early surgery. The patient was transferred to cardiac surgery department where he underwent surgery. Extensive debridement of the endocarditic lesion was performed; the mitral–aortic junction was reconstructed by suturing a double patch of heterologous pericardium. The defect resulting from the debridement beneath the left coronary ostium was also reconstructed using an additional sutured pericardial patch; then, an Inspiris Resilia size 23 prosthesis was implanted. Transesophageal echocardiography revealed good functioning of the aortic valve prosthesis with mild mitral insufficiency. Meanwhile, blood cultures resulted positive for Staphylococcus Aureus coagulase–negative, so specific antibiotic therapy was started.

Mesenchymal Stem Cells improve phenotype of induced pluripotent stem cell (iPSC)-derived cardiomyocytes in Hypoplastic Left Heart Syndrome

Hypoplastic left heart syndrome (HLHS) is a clinically and anatomically severe form of congenital heart disease (CHD). We previously demonstrated that genetic variants in the alpha myosin heavy chain (MYH6) gene are significantly associated with HLHS as well as poor outcomes in patients. Additionally, induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) carrying an MYH6-R443P head domain variant demonstrated an impaired CM phenotype including dysmorphic sarcomere structure, altered contractility, and upregulated MYH7 expression. Mesenchymal stem cells (MSCs) and their secretome are currently being explored as a potential therapeutic for cardiac injury. In this study, a possible treatment strategy for iPSC-CMs with a MYH6 tail domain variant was examined through investigation of co-culturing umbilical cord tissue derived MSCs from a healthy newborn. iPSC-CMs from an unaffected family member were included as a normal control to compare cellular RNA and protein changes observed in the MYH6-E1584K line. The MYH6-E1584K variant line demonstrated significant upregulation of sarcomere, calcium channel, and inflammation/immune related gene expression in both mRNA and protein levels. Co-culturing with MSCs rescued expression of several genes and was confirmed through label free proteomic analysis. Co-culturing iPSC-CMs with MSCs also significantly improved contraction (contraction maximum displacement and velocity) in MYH6-E1584K iPSC-CMs. Finally, measurements of microRNA, cytokines, and exosomes secreted into cultured media indicated significant changes. This study suggests that MSC secreted factors improve CM expression and function and may elucidate a new mechanistic target for patients with HLHS. AHW/HHI Innovation Pilot Award. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Surgical Outcomes in Patients Undergoing a Double Switch Operation for Corrected Transposition

BackgroundCongenitally corrected transposition of the great arteries (CC-TGA) is a rare and complex form of congenital heart disease. Results of physiologic repair proved disappointing due to late right ventricular dysfunction and/or tricuspid regurgitation. The current study was performed to evaluate surgical outcomes in patients undergoing a double switch for CC-TGA. MethodsThis was a retrospective review of 121 patients who underwent a double switch over a 2-decade time frame (2002-2023). Patients were a median age of 32 months. Before the double switch, 49 of 121 patients (40%) had undergone left ventricular retraining. ResultsSixty-seven patients underwent an arterial switch, and 54 underwent a Rastelli procedure. There were 4 in-hospital deaths (3.3%), including 3 who had a Rastelli procedure (5.6%) and 1 who had an arterial switch (1.5%). At a median follow-up of 30 months, there were 4 late deaths (2 Rastelli and 2 arterial switch). Combined early and late mortality was 9.3% for the Rastelli and 4.5% for arterial switch. Combined mortality was 2.0% for patients who required left ventricular retraining vs 9.7% for those who did not. For the 117 patients discharged from the hospital, 93% have normal or low-normal left ventricular function, and 96% have mild or less neoaortic insufficiency. ConclusionsSurgical outcomes in patients undergoing a double switch procedure have been excellent both in the short- and midterm. However, the Rastelli procedure was associated with a more than 2-fold increase in mortality risk compared with the arterial switch.

Fetal left and right ventricular strain parameters using speckle tracking in congenital heart diseases.

Assessment of fetal ventricular function is mostly subjective, and currently, for the objective assessment left ventricular shortening fraction is obtained. However, this by itself is not very reliable. Hence, more tools that can provide an objective assessment are needed to increase the confidence of functional assessment. Speckle tracking imaging can provide one such tool. In this study we sought to establish the normative value of global longitudinal and circumferential strain for our fetal patients and for two major forms of congenital heart diseases, namely atrioventricular canal defects (AVC) and uncorrected dextro-transposition of the great arteries (dTGA) to act as a benchmark. The study was completed via a single center retrospective analysis on 72 fetal echocardiograms (26 normal, 15 dTGA, and 31 AVC). Tomtec Arena™ echocardiography analysis software was used for analysis. In normal fetuses, mean left ventricular (LV) global longitudinal strain (GLS) was - 22.6% (95% CI -24, -21.1) and mean right ventricular (RV) GLS was - 22.1% (95% CI -23.6, -20.6). In AVC patients LV GLS was-26.6% (95% CI -28,-25.3) and mean RV GLS was - 26.5% (95% CI -27.9,-25.2). In dTGA patients LV GLS was - 22.9% (95% CI of -24.8, -21) and RV GLS was - 21.3% (95% CI was - 23.4, -20.8). There was good intra-rater reliability though poor to fair inter-rater reliability. Notwithstanding its current limitations, strain imaging can provide useful information that can increase confidence of cardiac functional assessment in fetal patients. However, to be reliable across the board, further automation and standardization is required.

Association study of FLT4 and HYDIN single nucleotide polymorphisms with atrial septal defect susceptibility in the Han Chinese population of Southwest China

BackgroundAtrial septal defect (ASD) is a common form of congenital heart disease. Although several genes related to ASD have been found, the genetic factors of ASD remain unclear. This study aimed to evaluate the correlation between 10 candidate single nucleotide polymorphisms (SNPs) and sporadic atrial septal defects.MethodsBased on the results of 34 individual whole exome sequences, 10 candidate SNPs were selected. In total, 489 ASD samples and 420 normal samples were collected. The 10 SNPs in the case group and the control group were identified through Snapshot genotyping technology. The χ2-test and unconditional regression model were used to evaluate the relationship between ASD and each candidate SNP. Haploview software was used to perform linkage disequilibrium and haplotype analysis.ResultsThe χ2 results showed that the FLT4 rs383985 (P = 0.003, OR = 1.115–1.773), HYDIN rs7198975 (P = 0.04621, OR = 1.003–1.461), and HYDIN rs1774266 (P = 0.04621, OR = 1.003–1.461) alleles were significantly different between the control group and the case group (P < 0.05). Only the association with the FLT4 polymorphism was statistically significant after adjustment for multiple comparisons.ConclusionThese findings suggest that a possible molecular pathogenesis associated with sporadic ASD is worth exploring in future studies.

ЗНАЧЕНИЕ ИММУНОЛОГИЧЕСКОГО СКРИНИНГА В ПРОГНОЗИРОВАНИИ ИНФЕКЦИОННЫХ ОСЛОЖНЕНИЙ КАРДИОХИРУРГИИ

Incidence of infectious complications in children with congenital heart disease, especially with cyanotic and complex defects, is higher than in the population, which is associated with both hemodynamic and immune disorders. Various types of primary immunodeficiencies in congenital heart disease and the dependence of immune disorders on the morphology of the defect, the severity of circulatory failure and arterial hypoxemia are described. The importance of diagnosing immunological disorders is emphasized to reduce the risk of infectious complications of cardiac surgery, reduce mortality and improve the outcomes of surgical interventions for congenital heart disease. The prognostic value of immune disorders identified by the TREC/KREC method for infectious complications of cardiac surgery has not been studied. The purpose of this research was to assess the possibility of predicting infectious complications of cardiac surgery in children with congenital heart disease based on screening using the TREC/KREC method. Material and methods used: preoperatively, 200 children with congenital heart disease aged 3 days to 12 months old were examined. Instrumental and laboratory methods were used including immunological screening for TREC/KREC DNA. Results: 123 (62.4%) were diagnosed with “acyanotic” congenital heart disease, 74 (37.5%) with various cyanotic congenital heart diseases and 10 (5%) with congenital heart diseases with Down syndrome, Di George syndrome, Williams syndrome or multiple malformations. 184 (92%) underwent various cardiac surgical interventions. Violations of T-cell immunity according to preoperative TREC/KREC screening were observed in 23.5% of cases including in all children with syndromic forms of congenital heart disease, multiple malformations, and significantly more often in cyanotic congenital heart disease, conotruncal defects, and those admitted in critical conditions. Infectious complications of cardiac surgery were observed significantly more often in this group than in children with normal T-cell immunity (in 36% and 3.6%, respectively). Conclusion: the prognostic value of TREC/KREC screening for targeted preparation and postoperative management in order to prevent infectious complications of cardiac surgery has been confirmed.

Variants of the promoter of MYH6 gene in congenital isolated and sporadic patent ductus arteriosus: case-control study and cellular functional analyses.

Patent ductus arteriosus (PDA) is a common form of congenital heart disease. The MYH6 gene has important effects on cardiovascular growth and development, but the effect of variants in the MYH6 gene promoter on ductus arteriosus is unknown. DNA was extracted from blood samples of 721 subjects (428 patients with isolated and sporadic PDA and 293 healthy controls) and analyzed by sequencing for MYH6 gene promoter region variants. Cellular function experiments with three cell lines (HEK-293, HL-1, and H9C2 cells) and bioinformatics analyses were performed to verify their effects on gene expression. In the MYH6 gene promoter, 11 variants were identified. Four variants were found only in patients with PDA and 2 of them (g.3434G>C and g.4524C>T) were novel. Electrophoretic mobility shift assay showed that the transcription factors bound by the promoter variants were significantly altered in comparison to the wild-type in all three cell lines. Dual luciferase reporter showed that all the 4 variants reduced the transcriptional activity of the MYH6 gene promoter (P < 0.05). Prediction of transcription factors bound by the variants indicated that these variants alter the transcription factor binding sites. These pathological alterations most likely affect the contraction of the smooth muscle of ductus arteriosus, leading to PDA. This study is the first to focus on variants at the promoter region of the MYH6 gene in PDA patients with cellular function tests. Therefore, this study provides new insights to understand the genetic basis and facilitates further studies on the mechanism of PDA formation.

Results of the Double Switch Operation in Patients Who Previously Underwent Left Ventricular Retraining.

Congenitally corrected transposition of the great arteries (CC-TGA) is a complex form of congenital heart disease that has numerous subtypes. While most patients with CC-TGA have a large ventricular septal defect (VSD) and pulmonary stenosis, there are some patients who have either no VSD or a highly restrictive VSD. These patients will require left ventricular (LV) retraining prior to double switch. The purpose of this study was to review our experience with the double switch procedure in patients who had previously undergone LV retraining. This was a retrospective review of a single institution experience with the double switch procedure in patients who had undergone LV retraining (2002-present). Forty-five patients underwent double switch following LV retraining. Of these, 39 had an arterial switch with hemi-Mustard/bidirectional Glenn and six had a Senning. The median cross-clamp time was 135 min (range 71-272) and median bypass time was 202 min (range 140-430 min). Median hospital length of stay was eight days (range 4-108). There were no in-hospital deaths. Median duration of follow-up was 30 months (range 0-175). One patient subsequently underwent heart transplantation and died 65 months following double switch. At follow-up, 41 of the 44 survivors (93%) have normal or low normal LV function and 40 of the 44 survivors (91%) have no or trace mitral regurgitation. The data demonstrate early and mid-term survival of 100% and 97%. Ninety-three percent had preserved LV function. These results suggest that patients with CC-TGA who undergo LV retraining and double switch can have excellent clinical outcomes.

Un-diagnosed coarctation of the aorta in a 27-year-old adult with a rare presentation: a rare case report

Introduction and importance: Coarctation of the aorta (COA) is a rare form of congenital heart disease that is typically diagnosed in children. COA is known to present with hypertension, weak or absent femoral pulses, heart failure in older patients, but the presentation of COA as calf atrophy is extremely rare. This article reports the successful surgical repair of a 27-year-old adult with undiagnosed COA. Case presentation: A 27-year-old-male has presented with calf atrophy, which was diagnosed as COA transthoracic echocardiography and computed tomography angiography indicate COA, which is treated with successful surgical repair. Clinical discussion: COA is typically diagnosed in children with a rare incidence in adults. Calf atrophy is an extremely rare presentation and uncommon. He has calf atrophy, which led to the diagnosis of COA in 27 years. The presentation in this medium-aged population with this rare manifestation gives our case significance to be one of the unique reported cases. Conclusion: COA is uncommon to be found in adults and the presentation with calf atrophy is even rare. The authors revealed that COA can be found in adults and with an unexpected manifestation and highlights the significance of early detection, and timely referral to a specialist can enable proper management, which includes surgical correction.

The detailed profile of congenital heart diseases in 254 children with Down syndrome in Saudi Arabia

BackgroundDown syndrome is the most common chromosomal abnormality in humans. It is associated with several congenital anomalies, including a spectrum of congenital heart diseases. Understanding the true prevalence and distribution of congenital heart diseases is essential for health resource planning, outcomes, and family counseling.This study aimed to assess the prevalence and distribution of congenital heart disease in children with Down syndrome. It is a retrospective cohort review that included all patients treated at King Abdulaziz University Hospital. Frequencies were estimated using the SPSS software and comparisons were made using Student’s t test.ResultsThe ages of the 254 subjects ranged from less than 1 year to 53 years. Of these, 44.5% were female and 40.6% were Saudi nationals. Congenital heart disease was present in 66.5% with a significant difference between Saudi nationals 44.6%) and non-Saudi nationals 71.5% (P = 0.01). The atrioventricular septal defect was the most common pathology, representing 33.1% of all congenital heart diseases followed by perimembranous ventricular septal defect 18.9%, and right ventricular pathology 10.2%.ConclusionThe prevalence of congenital heart diseases in Saudi children with Down Syndrome is similar to that reported worldwide. Septal defects and right-sided pathologies are the dominant forms of congenital heart diseases, with atrioventricular septal defect and perimembranous ventricular septal defect representing the most common pathologies.

Clinical Presentation and Therapy of d-Transposition of the Great Arteries.

d-Transposition of the great arteries (d-TGA) is the most common form of congenital heart disease that presents with cyanosis in a newborn. The aorta arises from the right ventricle and the pulmonary artery arises from the left ventricle. It constitutes 3-5% of all congenital heart defects. In a simple d-TGA (about two-thirds of patients), there is no other cardiac abnormality other than a patent foramen ovale (PFO) and a patent ductus arteriosus (PDA). In a complex d-TGA additional cardiac abnormalities such as VSD, pulmonary stenosis or coronary abnormalities are present. About one-third to 40% of patients with d-TGA have an associated ventricular septal defect. Among patients with d-TGA, 6% of those with intact ventricular septum and 31% of those with ventricular septal defect have associated pulmonary stenosis. Coronary abnormalities are of importance with regard to the complexity of surgical repair.

Tetralogy of Fallot: variants of MYH6 gene promoter and cellular functional analyses.

Tetralogy of Fallot (TOF) is a common form of congenital heart disease. The MYH6 gene has important effects on cardiovascular growth and development. In 608 subjects, including 315 TOF patients, we investigated the MYH6 gene promoter variants and verified the effect on gene expression by using cellular functional experiments with three cell lines (HEK-293, HL-1, and H9C2 cells) and bioinformatics analysis. In the MYH6 gene promoter, 12 variants were identified from 608 subjects. Five variants were found only in patients with TOF and two of them (g.3384G>T and g.4518T>C) were novel. Electrophoretic mobility shift assay with three cell lines (HEK-293, HL-1, and H9C2) showed significant changes in the transcription factors bound by the promoter variants compared to the wild-type. Dual luciferase reporter showed that four of the five variants reduced the transcriptional activity of the MYH6 gene promoter (p < 0.05). This study is the first to test the cellular function of variants in the promoter region of the MYH6 gene in patients with TOF, which provides new insights into the genetic basis of TOF and provides a basis for further study of the mechanism of TOF formation. DNA from 608 human subjects was sequenced for MYH6 gene promoter region variants with five variants found only in TOF patients and two were novel. EMSA and dual luciferase reporter experiments in three cell lines found these variants pathological. Prediction by JASPAR database indicated that these variants alter the transcription factor binding sites. The study, for the first time, confirmed that there are variants at the MYH6 gene promoter region and these variants alter the cellular function. The variants found in this study suggest the possible pathological role in the formation of TOF.

Arch watch: current approaches and opportunities for improvement.

Coarctation of the aorta (CoA) is a ductus arteriosus (DA)-dependent form of congenital heart disease (CHD) characterized by narrowing in the region of the aortic isthmus. CoA is a challenging diagnosis to make prenatally and is the critical cardiac lesion most likely to go undetected on the pulse oximetry-based newborn critical CHD screen. When undetected CoA causes obstruction to blood flow, life-threatening cardiovascular collapse may result, with a high burden of morbidity and mortality. Hemodynamic monitoring practices during DA closure (known as an "arch watch") vary across institutions and existing tools are often insensitive to developing arch obstruction. Novel measures of tissue oxygenation and oxygen deprivation may improve sensitivity and specificity for identifying evolving hemodynamic compromise in the newborn with CoA. We explore the benefits and limitations of existing and new tools to monitor the physiological changes of the aorta as the DA closes in infants at risk of CoA.