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Frontiers in Physiology 2022Congenital heart defects (CHD) include structural abnormalities of the heart or/and great vessels that are present at birth. CHD affects around 1% of all newborns... (Review)
Review
Congenital heart defects (CHD) include structural abnormalities of the heart or/and great vessels that are present at birth. CHD affects around 1% of all newborns worldwide. Tetralogy of Fallot (TOF) is the most prevalent cyanotic congenital cardiac abnormality, affecting three out of every 10,000 live infants with a prevalence rate of 5-10% of all congenital cardiac defects. The four hallmark characteristics of TOF are: right ventricular hypertrophy, pulmonary stenosis, ventricular septal defect, and overriding aorta. Approximately 20% of cases of TOF are associated with a known disease or chromosomal abnormality, with the remaining 80% of TOF cases being non-syndromic, with no known aetiology. Relatively few TOF patients have been studied, and little is known about critical causative genes for non-syndromic TOF. However, rare genetic variants have been identified as significant risk factors for CHD, and are likely to cause some cases of TOF. Therefore, this review aims to provide an update on well-characterized genes and the most recent variants identified for non-syndromic TOF.
PubMed: 36277185
DOI: 10.3389/fphys.2022.1012665 -
Frontiers in Pediatrics 2020The pathognomonic feature of tetralogy of Fallot (ToF) is the antero-cephalad deviation of the outlet septum in combination with an abnormal arrangement of the...
The pathognomonic feature of tetralogy of Fallot (ToF) is the antero-cephalad deviation of the outlet septum in combination with an abnormal arrangement of the septoparietal trabeculations. The aim of this article was to study perinatal hearts using Polarized Light Imaging (PLI) in order to investigate the deep alignment of cardiomyocytes that bond the different components of the ventricular outflow tracts both together and to the rest of the ventricular mass, thus furthering the classic description of ToF. 10 perinatal hearts with ToF and 10 perinatal hearts with no detectable cardiac anomalies (control) were studied using PLI. The orientation of the myocardial cells was extracted and studied at high resolution. Virtual dissections in multiple section planes were used to explore each ventricular structure. Contrary to the specimens of the control group, for all ToF specimens studied, the deep latitudinal alignment of the cardiomyocytes bonds together the left part of the Outlet septum (OS) S to the anterior wall of the left ventricle. In addition, the right end of the muscular OS bonds directly on the right ventricular wall (RVW) superior to the attachment of the ventriculo infundibular fold (VIF). Thus, the OS is a bridge between the lateral RVW and the anterior left ventricular wall. The VIF, RVW, and OS define an "inverted U" that roofs the cone between the interventricular communication and the overriding aorta. The opening angle and the length of the branches of this "inverted U" depend however on three components: the size of the OS, the size of the VIF, and the distance between the points of insertion of the OS and VIF into the RVW. The variation of these three components accounts for a significant part of the diversity observed in the anatomical presentations of ToF in the perinatal period.
PubMed: 33072668
DOI: 10.3389/fped.2020.503054 -
Annals of Biomedical Engineering Dec 2021Mechanical forces are essential for proper growth and remodeling of the primitive pharyngeal arch arteries (PAAs) into the great vessels of the heart. Despite general...
Mechanical forces are essential for proper growth and remodeling of the primitive pharyngeal arch arteries (PAAs) into the great vessels of the heart. Despite general acknowledgement of a hemodynamic-malformation link, the direct correlation between hemodynamics and PAA morphogenesis remains poorly understood. The elusiveness is largely due to difficulty in performing isolated hemodynamic perturbations and quantifying changes in-vivo. Previous in-vivo arch artery occlusion/ablation experiments either did not isolate the effects of hemodynamics, did not analyze the results in a 3D context or did not consider the effects of varying degrees of occlusion. Here, we overcome these limitations by combining minimally invasive occlusion experiments in the avian embryo with 3D anatomical models of development and in-silico testing of experimental phenomenon. We detail morphological and hemodynamic changes 24 hours post vessel occlusion. 3D anatomical models showed that occlusion geometries had more circular cross-sectional areas and more elongated arches than their control counterparts. Computational fluid dynamics revealed a marked change in wall shear stress-morphology trends. Instantaneous (in-silico) occlusion models provided mechanistic insights into the dynamic vessel adaptation process, predicting pressure-area trends for a number of experimental occlusion arches. We follow the propagation of small defects in a single embryo Hamburger Hamilton (HH) Stage 18 embryo to a more serious defect in an HH29 embryo. Results demonstrate that hemodynamic perturbation of the presumptive aortic arch, through varying degrees of vessel occlusion, overrides natural growth mechanisms and prevents it from becoming the dominant arch of the aorta.
Topics: Animals; Aorta, Thoracic; Blood Flow Velocity; Chick Embryo; Hemodynamics; Imaging, Three-Dimensional; Models, Cardiovascular; Morphogenesis; Pharynx; Pulsatile Flow; Tomography, X-Ray Computed; Ultrasonography, Doppler
PubMed: 34117583
DOI: 10.1007/s10439-021-02802-2 -
European Journal of Cardio-thoracic... Jul 2019Tetralogy of Fallot is characterized by anterocephalad deviation of the outlet septum, along with abnormal septoparietal trabeculations, which lead to subpulmonary...
OBJECTIVES
Tetralogy of Fallot is characterized by anterocephalad deviation of the outlet septum, along with abnormal septoparietal trabeculations, which lead to subpulmonary infundibular stenosis. Archives of retained hearts are an important resource for improving our understanding of congenital heart defects and their morphological variability. This study aims to define variations in aortic override, coronary arterial patterns and ventricular septal defects in tetralogy of Fallot as observed in a morphological archive, highlighting implications for surgical management.
METHODS
The Birmingham Children's Hospital archive contains 211 hearts with tetralogy of Fallot, of which 164 were analysed [69 (42.1%) unrepaired and 95 (57.9%) operated specimens]. A detailed morphological and geometric analysis was performed using a rigorous 5-layer review process.
RESULTS
Anomalies were observed in the orifices, origins and course of the coronary arteries: 20 hearts (13.0%) had more than 2 orifices and 3 hearts (1.9%) had a single orifice. In 7 hearts (4.3%), a coronary artery crossed the right ventricular outflow tract. The extent of aortic override ranged from 31.0% to 100% (median of 59.5%). The ventricular septal defect was most often perimembranous (139, 84.8%), but we also found muscular (14, 8.5%), atrioventricular (7, 4.3%) and doubly committed juxta-arterial (2, 1.2%) variants.
CONCLUSIONS
Anatomical variations are common and can impact surgical management. Anomalous coronary arteries may require a conduit rather than a transannular patch. Variability in aortic override determines the size of patch used to baffle blood to the aorta. The type of ventricular septal defect affects patch closure and the risk of postoperative conduction defects.
Topics: Adolescent; Child; Child, Preschool; Cohort Studies; Coronary Vessel Anomalies; Coronary Vessels; Female; Humans; Infant; Infant, Newborn; Male; Tetralogy of Fallot
PubMed: 30657877
DOI: 10.1093/ejcts/ezy474 -
Journal of Investigative Medicine High... 2020Tetralogy of Fallot is the most common cyanotic congenital heart defect consisting of an overriding aorta, right ventricular outflow obstruction, ventricular septal...
Tetralogy of Fallot is the most common cyanotic congenital heart defect consisting of an overriding aorta, right ventricular outflow obstruction, ventricular septal defect, and right ventricular hypertrophy. Without surgical management, approximately only 3% of patients survive past the age of 40 years. Cases of unoperated patients reaching adulthood have been reported; however, few studies describe treatment guidelines for surgical or therapeutic management. In this article, we report the case of a 59-year-old Hispanic male with unoperated tetralogy of Fallot presenting to our cardiology clinic for initial workup and management.
Topics: Anticoagulants; Atrial Fibrillation; Cardiac Catheterization; Disease Management; Eisenmenger Complex; Electrocardiography; Humans; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Male; Middle Aged; Radiography, Thoracic; Survivors; Tetralogy of Fallot
PubMed: 32462941
DOI: 10.1177/2324709620926908 -
Journal of Cardiovascular Development... Mar 2021Left ventricular noncompaction (LVNC) is a cardiomyopathy that can lead to arrhythmias, embolic events and heart failure. Despite our current knowledge of cardiac...
BACKGROUND
Left ventricular noncompaction (LVNC) is a cardiomyopathy that can lead to arrhythmias, embolic events and heart failure. Despite our current knowledge of cardiac development, the mechanisms underlying noncompaction of the ventricular myocardium are still poorly understood. The small GTPase acts as a crucial regulator of numerous developmental events. The present study aimed to investigate the cardiomyocyte specific role of in embryonic heart development.
METHODS AND RESULTS
The transgenic mice were crossed with mice to generate mice with a cardiomyocyte specific deletion of () during heart development. Embryonic hearts at E12.5-E18.5 were collected for histological analysis. Overall, hearts displayed a bifid apex, along with hypertrabeculation and a thin compact myocardium. hearts also exhibited ventricular septal defects (VSDs) and double outlet right ventricle (DORV) or overriding aorta. Cardiomyocytes had a rounded morphology and were highly disorganized, and the myocardial expression of Scrib, a planar cell polarity protein, was reduced in hearts. In addition, cell proliferation rate was significantly decreased in the ventricular myocardium at E9.5.
CONCLUSIONS
deficiency in the myocardium impairs cardiomyocyte elongation and organization, and proliferative growth of the heart. A spectrum of CHDs arises in hearts, implicating signaling in the ventricular myocardium as a crucial regulator of OFT alignment, along with compact myocardium growth and development.
PubMed: 33804107
DOI: 10.3390/jcdd8030029 -
Taiwanese Journal of Obstetrics &... Sep 2021We present rapid diagnosis of trisomy 13 of maternal origin by quantitative fluorescent polymerase chain reaction (QF-PCR) in a pregnancy with multiple fetal...
Rapid diagnosis of trisomy 13 of maternal origin by quantitative fluorescent polymerase chain reaction analysis in a pregnancy with fetal holoprosencephaly, premaxillary agenesis, postaxial polydactyly of left hand and overriding aorta.
OBJECTIVE
We present rapid diagnosis of trisomy 13 of maternal origin by quantitative fluorescent polymerase chain reaction (QF-PCR) in a pregnancy with multiple fetal abnormalities.
CASE REPORT
A 35-year-old, primigravid woman was referred for amniocentesis at 24 weeks of gestation because of multiple congenital anomalies in the fetus. Prenatal ultrasound at 23 weeks of gestation revealed holoprosencephaly, premaxillary agenesis, postaxial polydactyly of the left hand and overriding aorta. Amniocentesis was performed subsequently, and QF-PCR analysis using the polymorphic DNA markers of D13S789 (13q22.3), D13S790 (13q31.1) and D13S767 (13q31.3) on the DNA extracted from uncultured amniocytes and parental bloods showed trisomy 13 of maternal origin. Conventional cytogenetic analysis on the cultured amniocytes confirmed trisomy 13. The pregnancy was subsequently terminated, and a malformed fetus was delivered with multiple anomalies consistent with the prenatal diagnosis.
CONCLUSION
QF-PCR analysis is useful for rapid confirmation of trisomy 13 and the parental origin when prenatal ultrasound findings are suspicious of fetal trisomy 13.
Topics: Abnormalities, Multiple; Adult; Amniocentesis; Comparative Genomic Hybridization; Female; Fetus; Fingers; Heart Defects, Congenital; Holoprosencephaly; Humans; In Situ Hybridization, Fluorescence; Polydactyly; Polymerase Chain Reaction; Pregnancy; Quantitative Light-Induced Fluorescence; Toes; Trisomy 13 Syndrome
PubMed: 34507670
DOI: 10.1016/j.tjog.2021.07.020 -
Romanian Journal of Morphology and... 2020The latest decades are characterized by an enormous progression in the field of human genetics. In consequences, for various phenotypic manifestations, genetic testing...
The latest decades are characterized by an enormous progression in the field of human genetics. In consequences, for various phenotypic manifestations, genetic testing could identify a specific underlying cause. An estimated incidence for all types of 18q deletions is one in 55 000 births predominant on females. About 94% of cases with 18q deletion syndrome appearance are de novo, and the remaining 6% are the inherited from a parent carrying a balanced chromosomal translocation. We present the case of a 35-year-old female who was admitted in our Unit for a second ultrasound opinion after being diagnosed at the second trimester scan at gestational age of 21 weeks of pregnancy with multiple brain and heart malformations, having the recommendation for fetal magnetic resonance imaging (MRI). Further investigations included genetic analysis and pathological examination. Major malformations diagnosed and confirmed were agenesis of the corpus callosum, ventriculomegaly with dilated fourth ventricle, partial agenesis of vermis, bilateral anophthalmia with wide nasal base and left cleft lip. Additional, cardiac malformation, with an important ventricular septal defect and overriding aorta were noted. The results of the microarray analysis showed an abnormal fetal karyotype with a loss of 30.5 basis identified in the long arm of chromosome 18. Although most of the cases of 18q deletion are sporadically or de novo, could be cases where the possible existing syndromes can be inherited from a healthy or mild affected parent. Therefore, in order to establish the recurrence risk, parental karyotypes are recommended.
Topics: Adult; Chromosome Deletion; Chromosome Disorders; Chromosomes, Human, Pair 18; Female; Fetus; Humans; Infant; Phenotype; Pregnancy
PubMed: 33817732
DOI: 10.47162/RJME.61.3.29