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BMC Cardiovascular Disorders Jan 2021Although most cases of atrial septal defect (ASD) are sporadic, familial cases have been reported, which may be caused by mutation of transcription factor GATA binding...
BACKGROUND
Although most cases of atrial septal defect (ASD) are sporadic, familial cases have been reported, which may be caused by mutation of transcription factor GATA binding protein 4 (GATA4). Herein we combined whole-exome sequencing and bioinformatics strategies to identify a novel mutation in GATA4 accounting for the etiology in a Chinese family with ASD.
METHODS
We identified kindred spanning 3 generations in which 3 of 12 (25.0%) individuals had ASD. Punctilious records for the subjects included complete physical examination, transthoracic echocardiography, electrocardiograph and surgical confirming. Whole-exome capture and high-throughput sequencing were performed on the proband III.1. Sanger sequencing was used to validate the candidate variants, and segregation analyses were performed in the family members.
RESULTS
Direct sequencing of GATA4 from the genomic DNA of family members identified a T-to-C transition at nucleotide 929 in exon 5 that predicted a methionine to threonine substitution at codon 310 (M310T) in the nuclear localization signal (NLS) region. Two affected members (II.2 and III.3) and the proband (III.1) who was recognized as a carrier exhibited this mutation, whereas the other unaffected family members or control individuals did not. More importantly, the mutation GATA4 (c.T929C: p.M310T) has not been reported previously in either familial or sporadic cases of congenital heart defects (CHD).
CONCLUSIONS
We identified for the first time a novel M310T mutation in the GATA4 gene that is located in the NLS region and leads to family ASD with arrhythmias. However, the mechanism by which this pathogenic mutation contributes to the development of heart defect and tachyarrhythmias remains to be ascertained.
Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Child; Child, Preschool; Computational Biology; DNA Mutational Analysis; Female; GATA4 Transcription Factor; Genetic Predisposition to Disease; Heart Septal Defects, Atrial; Heredity; High-Throughput Nucleotide Sequencing; Humans; Male; Middle Aged; Mutation; Pedigree; Phenotype; Exome Sequencing
PubMed: 33413087
DOI: 10.1186/s12872-020-01822-5 -
Anatolian Journal of Cardiology Nov 2023
Topics: Humans; Pulmonary Veins; Cardiac Catheterization; Heart Septal Defects, Atrial
PubMed: 37731350
DOI: 10.14744/AnatolJCardiol.2023.3302 -
Journal of Cardiology Jan 2015
Topics: Echocardiography; Echocardiography, Transesophageal; Heart Septal Defects, Atrial; Humans; Monitoring, Intraoperative; Septal Occluder Device; Surgery, Computer-Assisted
PubMed: 25048177
DOI: 10.1016/j.jjcc.2014.06.002 -
Clinical Cardiology Oct 2018Most antiarrhythmic interventional therapies for atrial fibrillation (AF) have been provided with special focus on the treatment of left-sided valvular disease and...
BACKGROUND
Most antiarrhythmic interventional therapies for atrial fibrillation (AF) have been provided with special focus on the treatment of left-sided valvular disease and enlarged left atrium but few studies have assessed AF associated with congenital heart disease and dilated right atrium.
HYPOTHESIS
We hypothesized that right atrial (RA) function assessed by two-dimensional (2DSTE) and three-dimensional (3DSTE) speckle-tracking echocardiography in patients with atrial septal defect (ASD) before and after percutaneous trancatheter closure could predict paroxysmal atrial fibrillation (PAF) development.
METHODS
Seventy-three patients with hemodynamically significant secundum ASD were prospectively studied and followed up for 6 months after occluder insertion and compared with a normal age-matched group (n = 73). A subgroup of 17 patients who developed PAF after device implantation was also studied. RA peak global longitudinal strain (PS) was determined using 2DSTE. Standard deviations (SDs) of times to peak strain (TPS) were calculated as indices of dyssynchrony. RA volumes, emptying fraction (EF), and expansion index (EI) were determined using 3DSTE.
RESULTS
RA-PS, EF, and EI (pre-closure values) were reduced in patients with atrial devices compared with controls, and further reductions were observed in patients with PAF. Pre-closure 3D-RA-EI (P = 0.009) and RA-TPS (P = 0.023) were independent predictors of PAF by multivariate analysis after adjustment for age and left atrial dysfunction. The areas under the ROC-curve (AUC) for 3D-RA-EI, RA-PS, RA-TPS (pre-closure values) showed high discriminative values(from 0.76 to 0.85) in predicting PAF. By combining 3D-RA-EI and RA-TPS, the AUC increased to 0.90.
CONCLUSIONS
Two-dimensional and three-dimensional speckle tracking echocardiography was clinically helpful in ASD patients in revealing right atrial dilatation and dysfunction pre-existent to device closure and associated with PAF development. RA parameters had a higher association with PAF compared to both the size of the implanted device and left atrial indices.
Topics: Adolescent; Adult; Atrial Fibrillation; Atrial Function, Right; Echocardiography, Three-Dimensional; Electrocardiography, Ambulatory; Feasibility Studies; Female; Follow-Up Studies; Heart Atria; Heart Septal Defects, Atrial; Humans; Male; Middle Aged; Predictive Value of Tests; Young Adult
PubMed: 30117180
DOI: 10.1002/clc.23051 -
Revista Espanola de Cardiologia Jul 2010In patients with an atrial septal defect and severe pulmonary hypertension, it is important to determine whether the latter is reversible before percutaneous or surgical...
In patients with an atrial septal defect and severe pulmonary hypertension, it is important to determine whether the latter is reversible before percutaneous or surgical closure. In addition to determining pulmonary resistance, one simple technique is to transiently occlude the septal defect using a balloon catheter and to evaluate the hemodynamic response. We defined a positive response as a > or = 25% reduction in mean pulmonary artery pressure during occlusion relative to the basal level, without a fall in systemic pressure or an increase in ventricular end-diastolic pressure. The study included five patients aged over 60 years with an atrial septal defect and severe pulmonary hypertension who were referred for percutaneous closure. In one patient, the test gave a negative result and closure of the atrial septal defect was not performed. In the remaining four, closure was indicated. In three patients, closure was performed percutaneously, while the fourth underwent surgery. The drop in pulmonary pressure observed during the test was maintained over the long term at a mean follow-up time of 22 months.
Topics: Aged; Balloon Occlusion; Echocardiography, Transesophageal; Female; Heart Septal Defects, Atrial; Hemodynamics; Humans; Hypertension, Pulmonary; Middle Aged; Nitric Oxide; Pulmonary Circulation; Vascular Resistance; Vasodilator Agents
PubMed: 20609321
DOI: 10.1016/s1885-5857(10)70172-9 -
Circulation Journal : Official Journal... Feb 2003The purpose of this study was to investigate the incidence and clinical features of atrial septal defect (ASD) in school children in Japan who were diagnosed by heart...
The purpose of this study was to investigate the incidence and clinical features of atrial septal defect (ASD) in school children in Japan who were diagnosed by heart disease screening. From 1989 to 1998, a questionnaire, electrocardiography (ECG) and phonocardiogram were obtained from school children when they entered their first year of elementary school (n=86,142) or junior high school (n=80,632). In this program, 33 asymptomatic ASD patients were newly diagnosed (0.020%). The ECG findings showed incomplete right bundle-branch block (79%), right axis deviation (55%), and right ventricular hypertrophy (9%). An ejection systolic murmur was audible in 30 patients (94%) and mid-diastolic murmur in 10 patients (30%). Thirty patients (90%) showed fixed split of second heart sound. Using echocardiography or catheter observation, 31 patients (94%) were judged to require closure of the ASD. Although the medical care is widely available in Japan, undetected ASD patients were not rare and importantly, most of them required closure of the defect even if they were asymptomatic.
Topics: Adolescent; Bundle-Branch Block; Child; Electrocardiography; Female; Heart Murmurs; Heart Septal Defects, Atrial; Humans; Hypertrophy, Right Ventricular; Incidence; Japan; Male; Mass Screening; Surveys and Questionnaires
PubMed: 12547990
DOI: 10.1253/circj.67.112 -
BMC Pediatrics Jun 2021Hereditary spherocytosis (HS) is a common inherited red blood cell membrane disorder characterized by an abnormal increase of spherocytes in peripheral blood. SPTB gene...
Identification of a novel heterozygous SPTB mutation by whole genome sequencing in a Chinese patient with hereditary spherocytosis and atrial septal defect: a case report.
BACKGROUND
Hereditary spherocytosis (HS) is a common inherited red blood cell membrane disorder characterized by an abnormal increase of spherocytes in peripheral blood. SPTB gene mutation is one of the most common causes of HS; however, few cases of HS resulting from SPTB mutation in the Chinese population have been reported so far.
CASE PRESENTATION
A 3-year-old Chinese girl presented to Qingdao Women and Children's Hospital, Qingdao University, with atrial septal defect (ASD). Meanwhile, she was clinically diagnosed with HS. Whole genome sequencing (WGS) was performed for the proband and her parents for genetic molecular analysis. A novel SPTB mutation (c.1756delG) was detected by WGS and confirmed by Sanger sequencing in the proband. This mutation results in a frameshift with a premature termination codon in exon 12, leading to a nonsense mutation (p.Ala586Profs*7). Her parents had no similar symptoms, and blood routine and serum biochemical tests showed no significant abnormalities. The patient's mother did not know of any relatives with HS-like symptoms. Percutaneous transcatheter closure was successfully performed for treating the ASD.
CONCLUSION
In this study, we identified a novel SPTB frameshift mutation in a Chinese girl with HS. This finding would expand the spectrum of SPTB mutations, provide a valuable insight into the genotyping of HS in the Chinese population, and contribute to the clinical management and genetic counseling in HS.
Topics: Child; Child, Preschool; China; Female; Heart Septal Defects, Atrial; Humans; Mutation; Spherocytosis, Hereditary; Whole Genome Sequencing
PubMed: 34182956
DOI: 10.1186/s12887-021-02771-4 -
Kardiologia Polska 2021
Topics: Heart Septal Defects, Atrial; Humans; Septal Occluder Device
PubMed: 34331309
DOI: 10.33963/KP.a2021.0078 -
The Journal of Invasive Cardiology Nov 2023The data on the use of Gore Cardioform Septal Occluder (GCA; W. L. Gore and Associates, Inc.) for atrial septal defect (ASD) with deficient rims is limited.
BACKGROUND
The data on the use of Gore Cardioform Septal Occluder (GCA; W. L. Gore and Associates, Inc.) for atrial septal defect (ASD) with deficient rims is limited.
METHODS
All patients evaluated by transesophageal echocardiogram (TEE) for ASD occlusion were included. TEE planes at 35°, 0°, and 90° were assessed for anterior-superior (AS) and posterior (P), anterior-inferior (AI) and posterior-superior (PS), as well as superior (S) and inferior (I) rims. ASD size >20 mm, and rims less than 5 mm were defined as large and deficient, respectively. We included patients who had a procedural failure along with the patients in whom the procedure was not attempted after echocardiogram in the unsuccessful group.
RESULTS
In 148 patients, the median weight, age, and ASD size were 36 kg (range, 8-60 kg), 11.8 years (range, 1-60 years), and 14.2 ± 8.28 mm, respectively. One or more deficient rims were noted in 112 of 148 (75.7%): 99 (67%) AS, 36 (24%) P, 17 (11%) AI, 30 (20%) PS, 26 (18%) S, and 33 (22%) I. ASD closure was performed in 115 (78%) patients. The procedure was successful in 111 (96.5%) patients with procedural failure in 4 (3.4%) patients. Multiple deficient rims were associated with reduced procedural success (OR 0.36, 95% CI, 0.25-0.56). On multivariate analysis deficient P, PS, and I rims were associated with an unsuccessful group (P = .001, .046, and .005, respectively). Complications included 1 device embolization, 1 vascular injury, and 5 arrhythmias.
CONCLUSIONS
Transcatheter closure of ASDs with deficient rims is feasible using GCA. Large ASDs with deficient P, PS, and I rims were associated with unsuccessful closure. Risk stratification and comprehensive evaluation of ASD rims is vital for the use of GCA.
Topics: Humans; Cardiac Catheterization; Heart Septal Defects, Atrial; Echocardiography, Transesophageal; Echocardiography; Arrhythmias, Cardiac; Septal Occluder Device; Treatment Outcome
PubMed: 37992333
DOI: 10.25270/jic/23.00119 -
Journal of Interventional Cardiology Apr 2013Although it has been demonstrated that cardiac remodeling and exercise capacity improve after transcatheter closure of atrial septal defect (ASD), little is known about... (Clinical Trial)
Clinical Trial
Long-term effects of transcatheter closure of atrial septal defect on cardiac remodeling and exercise capacity in patients older than 40 years with a reduction in cardiopulmonary function.
BACKGROUND
Although it has been demonstrated that cardiac remodeling and exercise capacity improve after transcatheter closure of atrial septal defect (ASD), little is known about long-term benefits in middle-aged and elderly patients with a reduction in cardiopulmonary function.
OBJECTIVES
To evaluate long-term extent and time course of improvements in cardiac remodeling and exercise capacity in those patients.
METHODS
Twenty ASD patients ≥ 40 years of age with a reduction in cardiopulmonary function (predicted peak oxygen uptake [VO(2)] < 65%) were enrolled. Transthoracic echocardiography and cardiopulmonary exercise testing were performed at baseline and at 1 month, 3 months, 6 months, and >12 months after the procedure.
RESULTS
At 1 month after the procedure, significant decreases in right ventricular (RV) end-diastolic diameter (38.2 ± 4.4 to 31.9 ± 4.4 mm; P < 0.001) and RV/left ventricular end-diastolic diameter ratio (0.95 ± 0.17 to 0.71 ± 0.13; P < 0.001) occurred, and they were maintained during the follow-up period. Normal RV size was achieved in 11 of 18 patients with RV enlargement. Predicted peak VO(2) did not change at 1 month and 3 months, but it improved significantly after 6 months (53.6 ± 6.5 to 62.1 ± 12.6%; P < 0.01). Sixteen of the 20 patients showed improved predicted peak VO(2).
CONCLUSIONS
Cardiac remodeling and exercise capacity could be improved over the long-term period after transcatheter closure of ASD in middle-aged and elderly patients with a reduction in cardiopulmonary function. There were differences in the time course of improvement between cardiac remodeling and exercise capacity in those patients.
Topics: Adult; Aged; Cardiac Catheterization; Echocardiography; Exercise; Exercise Test; Female; Follow-Up Studies; Heart Septal Defects, Atrial; Humans; Male; Middle Aged; Time; Treatment Outcome; Ventricular Remodeling
PubMed: 23163398
DOI: 10.1111/joic.12002