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Advances in Experimental Medicine and... 2024Tricuspid atresia (TA) is a rare congenital heart condition that presents with a complete absence of the right atrioventricular valve. Because of the rarity of familial...
Tricuspid atresia (TA) is a rare congenital heart condition that presents with a complete absence of the right atrioventricular valve. Because of the rarity of familial and/or isolated cases of TA, little is known about the potential genetic abnormalities contributing to this condition. Potential responsible chromosomal abnormalities were identified in exploratory studies and include deletions in 22q11, 4q31, 8p23, and 3p as well as trisomies 13 and 18. In parallel, potential culprit genes include the ZFPM2, HEY2, NFATC1, NKX2-5, MYH6, and KLF13 genes. The aim of this chapter is to expose the genetic components that are potentially involved in the pathogenesis of TA in humans. The large variability in phenotypes and genotypes among cases of TA suggests a genetic network that involves many components yet to be unraveled.
Topics: Humans; Chromosome Aberrations; Phenotype; Tricuspid Atresia; Univentricular Heart
PubMed: 38884756
DOI: 10.1007/978-3-031-44087-8_54 -
Advances in Experimental Medicine and... 2024The development of a fully functional four-chambered heart is critically dependent on the correct formation of the structures that separate the atrial and ventricular... (Review)
Review
The development of a fully functional four-chambered heart is critically dependent on the correct formation of the structures that separate the atrial and ventricular chambers. Perturbation of this process typically results in defects that allow mixing of oxygenated and deoxygenated blood. Atrioventricular septal defects (AVSD) form a class of congenital heart malformations that are characterized by the presence of a primary atrial septal defect (pASD), a common atrioventricular valve (cAVV), and frequently also a ventricular septal defect (VSD). While AVSD were historically considered to result from failure of the endocardial atrioventricular cushions to properly develop and fuse, more recent studies have determined that inhibition of the development of other components of the atrioventricular mesenchymal complex can lead to AVSDs as well. The role of the dorsal mesenchymal protrusion (DMP) in AVSD pathogenesis has been well-documented in studies using animal models for AVSDs, and in addition, preliminary data suggest that the mesenchymal cap situated on the leading edge of the primary atrial septum may be involved in certain situations as well. In this chapter, we review what is currently known about the molecular mechanisms and animal models that are associated with the pathogenesis of AVSD.
Topics: Animals; Heart Septal Defects; Disease Models, Animal; Humans; Signal Transduction; Heart Septal Defects, Atrial; Heart Septal Defects, Ventricular
PubMed: 38884733
DOI: 10.1007/978-3-031-44087-8_31 -
Advances in Experimental Medicine and... 2024Atrioventricular septal defects (AVSDs) consist of a number of cardiac malformations that result from abnormal development of the endocardial cushions. AVSDs occur in...
Atrioventricular septal defects (AVSDs) consist of a number of cardiac malformations that result from abnormal development of the endocardial cushions. AVSDs occur in 0.19 of 1000 live births and constitute 4-5 % of congenital heart defects. AVSDs can be categorized as incomplete (or partial) or complete, and intermediate or transitional.
Topics: Humans; Heart Septal Defects
PubMed: 38884731
DOI: 10.1007/978-3-031-44087-8_29 -
Advances in Experimental Medicine and... 2024Ventricular septal defects (VSDs) are recognized as one of the commonest congenital heart diseases (CHD), accounting for up to 40% of all cardiac malformations, and...
Ventricular septal defects (VSDs) are recognized as one of the commonest congenital heart diseases (CHD), accounting for up to 40% of all cardiac malformations, and occur as isolated CHDs as well as together with other cardiac and extracardiac congenital malformations in individual patients and families. The genetic etiology of VSD is complex and extraordinarily heterogeneous. Chromosomal abnormalities such as aneuploidy and structural variations as well as rare point mutations in various genes have been reported to be associated with this cardiac defect. This includes both well-defined syndromes with known genetic cause (e.g., DiGeorge syndrome and Holt-Oram syndrome) and so far undefined syndromic forms characterized by unspecific symptoms. Mutations in genes encoding cardiac transcription factors (e.g., NKX2-5 and GATA4) and signaling molecules (e.g., CFC1) have been most frequently found in VSD cases. Moreover, new high-resolution methods such as comparative genomic hybridization enabled the discovery of a high number of different copy number variations, leading to gain or loss of chromosomal regions often containing multiple genes, in patients with VSD. In this chapter, we will describe the broad genetic heterogeneity observed in VSD patients considering recent advances in this field.
Topics: Humans; Chromosome Aberrations; DNA Copy Number Variations; Genetic Predisposition to Disease; Heart Septal Defects, Ventricular; Mutation; Transcription Factors
PubMed: 38884729
DOI: 10.1007/978-3-031-44087-8_27 -
Advances in Experimental Medicine and... 2024The relative simplicity of the clinical presentation and management of an atrial septal defect belies the complexity of the developmental pathogenesis. Here, we describe... (Review)
Review
The relative simplicity of the clinical presentation and management of an atrial septal defect belies the complexity of the developmental pathogenesis. Here, we describe the anatomic development of the atrial septum and the venous return to the atrial chambers. Experimental models suggest how mutations and naturally occurring genetic variation could affect developmental steps to cause a defect within the oval fossa, the so-called secundum defect, or other interatrial communications, such as the sinus venosus defect or ostium primum defect.
Topics: Heart Septal Defects, Atrial; Animals; Humans; Disease Models, Animal; Mutation; Atrial Septum; Signal Transduction
PubMed: 38884727
DOI: 10.1007/978-3-031-44087-8_25 -
Advances in Experimental Medicine and... 2024Although atrial septal defects (ASD) can be subdivided based on their anatomical location, an essential aspect of human genetics and genetic counseling is distinguishing... (Review)
Review
Although atrial septal defects (ASD) can be subdivided based on their anatomical location, an essential aspect of human genetics and genetic counseling is distinguishing between isolated and familiar cases without extracardiac features and syndromic cases with the co-occurrence of extracardiac abnormalities, such as developmental delay. Isolated or familial cases tend to show genetic alterations in genes related to important cardiac transcription factors and genes encoding for sarcomeric proteins. By contrast, the spectrum of genes with genetic alterations observed in syndromic cases is diverse. Currently, it points to different pathways and gene networks relevant to the dysregulation of cardiomyogenesis and ASD pathogenesis. Therefore, this chapter reflects the current knowledge and highlights stable associations observed in human genetics studies. It gives an overview of the different types of genetic alterations in these subtypes, including common associations based on genome-wide association studies (GWAS), and it highlights the most frequently observed syndromes associated with ASD pathogenesis.
Topics: Humans; Heart Septal Defects, Atrial; Genome-Wide Association Study; Genetic Predisposition to Disease; Mutation
PubMed: 38884726
DOI: 10.1007/978-3-031-44087-8_24 -
Advances in Experimental Medicine and... 2024Atrial septal defects (ASDs) occur in 1 of 1500 live births and constitute 6-10% of congenital heart defects. There is a female-to-male predominance of 2 to 1. According... (Review)
Review
Atrial septal defects (ASDs) occur in 1 of 1500 live births and constitute 6-10% of congenital heart defects. There is a female-to-male predominance of 2 to 1. According to their embryological origins, we can differentiate five different types of ASDs (see Fig. 23.1).
Topics: Humans; Heart Septal Defects, Atrial; Female; Male
PubMed: 38884725
DOI: 10.1007/978-3-031-44087-8_23 -
Journal of Thoracic Disease May 2024Left atrioventricular valvular regurgitation (LAVVR) recurrence after partial and transitional atrioventricular septal defect (AVSD) repair is the main risk factor...
BACKGROUND
Left atrioventricular valvular regurgitation (LAVVR) recurrence after partial and transitional atrioventricular septal defect (AVSD) repair is the main risk factor associated with reoperation or mortality. The purpose of this study was to identify risk factors associated with the recurrence of LAVVR after surgical repair of transitional and partial AVSD at a single institution.
METHODS
A hundred and fifty-seven patients who underwent anatomical repair for partial and transitional AVSD from January 2013 to December 2021 were included in our institutional database. Demographic characteristics, operative information, comorbidities, complications, and outcomes were retrieved from electronic medical records. Echocardiographic evaluations included cardiac dimensions, the degree of LAVVR, and the anatomy of the atrioventricular valve.
RESULTS
After a median follow-up period of 5.8 years, 40 patients had recurrent moderate or even more severe LAVVR. Compared with patients without recurrent LAVVR, those experiencing LAVVR recurrence were more likely to have larger preoperative left atrial (LA) size and larger left ventricular (LV) size after standardization, larger left atrioventricular valve (LAVV) cleft width, higher proportions of preoperative moderate or even more severe LAVVR, and immediately postoperative mild to moderate or even more severe LAVVR. Univariate Cox regression analysis showed that age at first repair, height, LA size after standardization, LV size after standardization, the severity of preoperative LAVVR, immediately postoperative LAVVR, and the LAVV cleft width more than 1cm were risk factors for recurrent LAVVR (P<0.05 for all). Multivariable Cox regression analysis showed that mild to moderate or even more severe LAVVR postoperatively [hazard ratio (HR) 9.53, 95% confidence interval (CI): 3.78-24.01; P<0.001], the width of LAVV cleft more than 1 cm (HR: 3.90, 95% CI: 1.80-8.48; P<0.001) and age at first repair (HR: 0.45, 95% CI: 0.31-0.66; P<0.001) were independently associated with the recurrence of LAVVR.
CONCLUSIONS
The width of LAVV cleft, mild to moderate or even more severe LAVVR immediately after surgery, and age at initial surgery are risk factors for recurrent LAVVR. The presence of recurrent LAVVR necessitates proactive surveillance to facilitate timely reintervention.
PubMed: 38883679
DOI: 10.21037/jtd-23-1694 -
Pediatric Cardiology Jun 2024This study aimed to compare the long-term clinical outcomes and costs between using either transesophageal echocardiography (TEE) or X-ray fluoroscopy for Percutaneous...
Comparison of Long-Term Clinical Outcomes and Costs Between Transesophageal Echocardiography-Guided and X-ray-Guided Percutaneous Atrial Septal Defect Closure in Children.
This study aimed to compare the long-term clinical outcomes and costs between using either transesophageal echocardiography (TEE) or X-ray fluoroscopy for Percutaneous atrial septal defect (ASD) closure in children. An analysis was conducted on clinical data from children undergoing TEE-guided (n = 168) and X-ray-guided (n = 139) percutaneous ASD closure. Demographic characteristics, technical indices, acute complications, follow-up outcomes, and costs were compared between the groups. The results are that TEE-guided closure demonstrated shorter surgical times (20.3 ± 7.6 min vs. 32.8 ± 7.9 min, P < 0.001) and lower procedural costs ($3093.3 ± 451.5 vs. $3589.1 ± 219.4, P < 0.001) compared to X-ray guidance. Initial successful closure rates were similar between the groups (TEE: 98.2%, XR: 97.1%, P = 0.691). TEE guidance also resulted in fewer acute complications and reduced radiation exposure. TEE-guided percutaneous ASD closure offers advantages in terms of shorter surgical times, lower procedural costs, and reduced radiation exposure compared to X-ray guidance. These findings support the preference for TEE guidance in pediatric ASD closure procedures, with potential implications for improving patient outcomes and reducing healthcare costs.
PubMed: 38880798
DOI: 10.1007/s00246-024-03539-0 -
International Journal of Cardiology Jun 2024The purpose of this study was to analyse the association between stannum exposure during pregnancy and congenital heart diseases in offspring.
BACKGROUND
The purpose of this study was to analyse the association between stannum exposure during pregnancy and congenital heart diseases in offspring.
METHODS
Based on a prospective birth cohort study conducted in Gansu Maternal and Child Health Hospital from 2010 to 2012, 14,359 pregnant women were followed up using a nested case-control study method. 97 pregnant women whose offspring were diagnosed with CHDs were used as the case group, and 194 pregnant women whose offspring did not suffer from congenital heart diseases were used as the control group in a ratio of 1:2 according to their age and place of birth. Inductively coupled plasma mass spectrometry was used to determine elemental stannum in blood samples from pregnant women hospitalized for delivery and in fetal cord blood samples. Multifactorial logistic regression analysis was used to assess the association between stannum and offspring CHDs.
RESULTS
There was a moderate positive correlation between the concentration of stannum in pregnant women's blood and that in umbilical cord blood. A higher concentrations of maternal blood stannum level was associated with a greater risk of CHDs (aOR 3.409, 95%CI 1.785-6.826), isolated CHDs (aOR 4.044, 95%CI 1.803-9.070), multiple CHDs (aOR 2.625, 95%CI 1.137-6.061), patent ductus arteriosus (aOR 2.882, 95%CI 1.443-5.756), atrial septal defects (aOR 3.067, 95%CI 1.406-6.690), ventricular septal defects (aOR 7.414, 95%CI 1.414-38.874). There was a correlation between the maternal and cord blood sample suggesting stannum crosses the placenta.
PubMed: 38880423
DOI: 10.1016/j.ijcard.2024.132270