Effects of atrial septal defects on the cardiac conduction system

The case report presented in this edition by Mu et al.The report presents a case of atrial septal defect(ASD)associated with electrocardiographic changes,noting that the crochetage sign resolved after Selective His Bundle Pacing(S-HBP)without requiring surgical closure.The mechanisms behind the appearance and resolution of the crochetage sign remain unclear.The authors observed the dis-appearance of the crochetage sign post-S-HBP,suggesting a possible correlation between these specific R waves and the cardiac conduction system.This editorial aims to explore various types of ASD and their relationship with the cardiac con-duction system,highlighting the diagnostic significance of the crochetage sign in ASD.

The Role of Transesophageal Echocardiography for Transcatheter Closure of Atrial Septal Defects with the Amplatzer Septal Occluder

Objective: To evaluate of the role of transesophageal echocardiography (TEE)in percutaneous closure of atrial septal defects (ASD) with the Amplatzer septal occluder. Methods:Sixty- two patients (10 to 55 years of age) were selected for percutaneous closure of ASD bytrans-esophageal echocardiography, which was also used to monitor the procedure, to select theappropriate size of the Amplatzer device, to verify its position, and to access the immediateresults of the procedure. During the follow-up, transthoracic echocardiography (TTE) or TEE was usedto evaluate the presence and magnitude of residual shunt (RS), device position, and right cardiacchamber diameters. Results: The mean ASD diameter by TTE ([19. 1 +- 5. 8] mm) was significantlysmaller (P< 0. 001) than the stretched diameter of the ASD (25. 1 +- 6. 4) mm. There are nosignificant differences between the TEE -measured value (23. 5+_6. 2) mm and the stretched diameterof the ASD (P > 0. 05). Due to proper patient selection all procedures were successful. There wasimmediate and complete closure in 61/62 patients, only one patients had trivial residual shunt.Follow- up was performed using TTE or TEE right after operation, 1 d, 1 month, 3 months, 6 monthsand yearly thereafter. Ail, patients remain asymptomatic without any clinical or technical problems.Conclusion: With the aid of TEE, percutaneous closure of ASD can be performed successfully, safely,and effectively.

Transcatheter to Close the Patent Duetus Arteriosus and Atrial Septal Defects in Children

Objective: To evaluate the therapeutic effect, safety and complications oftranscathetering Amplatzer device in the closure of patent ductus arteriosus (PDA) and atrial septaldefects (ASD) in children. Methods: Patients with PDA (n = 25) and ASD ( n = 16), confirmed byechocardiography, were treated by transcatheterization. Amplatzer occluder device was placed by thetranscatheterization with the image support of X-ray and transthoracic echocardiography ( TTE) . TheTTE, ECG and X-ray examination were engaged to evaluate the therapeutic results on the time pointsof 24 h , 1, 3 , 6, 12 months after the operation, and all these cases were engaged to the follow-upexamination. Results: The cardioangiographic diameter was 13.0-28.0 mm ([19.3+-4.9] mm) in ASD and2.0-7.7 mm ([3.9+-1.5] mm) in PDA . The diameter of the Amplatzer occluder selected were 13.0-30.0mm ( [20.6+-5.1] mm) in ASD and 4.0-12.0 mm ([6.6+-1.9] mm) in PDA , respectively. All the Amplatzeroccluders were placed successfully. There were no complications during and after the operation.Very small residual shunt was still found soon after the operation in 10 cases , and there were noresidual or recanalization after three months of the operation. The pulmonary artery pressure andheart size were significantly decreased in follow-up examination . Conclusion: Transcatheteringclosure with Amplatzer device is an effective, simple and safe technique in the treatment of ASD andPDA in children.

Effectiveness and Safety of Transcatheter Closure of Various Ventricular Septal Defects Using Second-Generation Amplatzer Duct Occluders

Objective:This study was designed to determine the long-term safety and efficacy of using the Amplatzer Duct Occluder II(ADO II)for the closure of various ventricular septal defects(VSDs).Methods:From January 2011 to December 2019,selected VSD patients were treated through transcatheter intervention using ADO II occluders.The closure results and complications from 188 patients,involving 167 perimembranous ventricular septal defects(pmVSDs),9 intracristal VSDs,11 post surgery residual shunts and 1 post closure residual shunt with the mean outlet diameter3.1±0.8 mm under angiography,were enrolled in this study.Results:The success rate was 98.9%for all procedures.During the median 77-month follow-up period,no cases of complete atrioventricular block(cAVB),infective endocarditis or death occurred.One major adverse event(0.5%)was recorded:cerebrovascular accident occurred 1 day after the procedure in one patient who was transferred to the neurology department.The residual shunt rate was 44.6%,which was the most common minor adverse event.The cardiac conduction block rate was 4.3%.Specifically,one pmVSD patient developed intermittent LBBB during the 28-month follow-up.There were 3 patients(1.6%)with new-onset mild tricuspid insufficiency,and the insufficiency degree was stable during follow-up.There was no new-onset aortic insufficiency that occurred.Conclusions:Transcatheter closure of pmVSDs,some intracristal VSDs,some postsurgery or postclosure residual shunts using ADO II occluders were both safe and effective and yielded excellent long-term results in selected patients.

Percutaneous closure of secundum type atrial septal defects:More than 5-year follow-up

AIM: To investigate long-term efficacy of two different devices more than five years after percutaneous atrial septal defect(ASD) closure in adults.METHODS: All patients who underwent percutaneous closure of an ASD in the St. Antonius Hospital, Nieuwegein, The Netherlands, between February 1998 and December 2006 were included. Percutaneous closure took place under general anaesthesia and transesophageal echocardiographic moni toring. Transthoracic echocardiography(TTE) was performed 24 h post-procedure to visualize the device position and to look for residual shunting using color Doppler. All complications were registered. All patients were invited for an outpatient visit and contrast TTE more than 5-years after closure. Efficacy was based on the presence of a residual right-to-left shunt(RLS), graded as minimal, moderate or severe. The presence of a residual left-to-right shunt(LRS) was diagnosed using color Doppler, and was not graded. Descriptive statistics were used for patients' characteristics. Univariate analysis was used to identify predictors for residual shunting.RESULTS: In total, 104 patients(mean age 45.5 ± 17.1 years) underwent percutaneous ASD closure using an Amplatzer device(ASO) in 76 patients and a Cardioseal/Starflex device(CS/SF) in 28 patients. The mean follow-up was 6.4 ± 3.4 years. Device migration occurred in 4 patients of whom two cases occurred during the index hospitalization(1 ASO, 1 CS/SF). The other 2 cases of device migration occurred during the first 6 mo of follow-up(2 CS/SF). The recurrent thrombo-embolic event rate was similar in both groups: 0.4% per follow-up year. More than 12 mo post-ASD closure and latest follow-up, new-onset supraventricular tachyarrhythmia's occurred in 3.9% and 0% for the ASO and CS/SF group, respectively. The RLS rate at latest follow-up was 17.4%(minimal 10.9%, moderate 2.2%, severe 4.3%) and 45.5%(minimal 27.3%, moderate 18.2%, severe 0%) for the ASO- and CS/SF groups, respectively. There was no residual LRS in both groups.CONCLUSION: Percutaneous ASD closure has good long-term safety and efficacy profiles. The residual RLS rate seems to be high more than 5 years after closure, especially in the CS/SF. Residual LRS was not observed.

Clinical Value of Stereoscopic Three-dimensional Echocardiography in Assessment of Atrial Septal Defects: Feasibility and Efficiency

Stereoscopic three-dimensional echocardiography（S-3DE） is a novel displaying technol-ogy based on real-time 3-dimensional echocardiography （RT-3DE）. Our study was to evaluate the feasibility and efficiency of S-3DE in the diagnosis of atrial septal defect （ASD） and its use in the guidance for transcatheter ASD occlusion. Twelve patients with secundum ASD underwent RT-3DE examination and 9 of the 12 were subjected to transcatheter closure of ASD. Stereoscopic vision was generated with a high-performance volume renderer with red-green stereoscopic glasses. S-3DE was compared with standard RT-3D display for the assessment of the shape, size, and the surrounding tis-sues of ASD and for the guidance of ASD occlusion. The appearance rate of coronary sinus and the mean formation time of the IVC, SVC were compared. Our results showed that S-3DE could measure the diameter of ASD accurately and there was no significant difference in the measurements between S-3DE and standard 3D display （2.89±0.73 cm vs 2.85±0.72 cm, P〉0.05; r=0.96, P〈0.05）. The appearance of coronary sinus for S-3DE was higher as compared with the standard 3D display （93.3% vs 100%）. The mean time of the IVC, SVC for S-3DE monitor was slightly shorter than that of the standard 3D display （11.0±3.8 s vs 10.3±3.6 s, P〉0.05）. The mean completion time of interven-tional procedure was shortened with S-3DE display as compared with standard 3D display （17.3±3.1 min vs 23.0±3.9 min, P〈0.05）. Stereoscopic three-dimensional echocardiography could improve the visualization of three-dimensional echocardiography, facilitate the identification of the adjacent structures, decrease the time required for interventional manipulation. It may be a feasible, safe, and efficient tool for guiding transcatheter septal occlusion or the surgical interventions.

Genetic Analysis of Variants of the MYH6 Gene Promoter in Congenital Atrial Septal Defects

Background:Atrial septal defect(ASD)is one of the common congenital heart diseases.The MYH6 gene has a critical role in cardiac development but the role of MYH6 promoter variants in patients with ASD has not been explored.Methods:In 613 subjects including 320 ASD patients,we investigated the MYH6 gene promoter variants and verified the effect on gene expression by using cellular functional experiments and bioinformatics analysis.Results:Eleven variants were identified in the MYH6 gene promoter,of which four variants were found only in ASD patients,and two variants(g.3434G>C and g.4524C>T)were identified for the first time.Cellular functional experiments indicated that all four variants reduced the transcriptional activity of the MYH6 gene promoter(p<0.05).Subsequent analysis through the JASPAR(A database of transcription factor binding profiles)suggests that these variants may alter transcription factor binding sites,which may in turn lead to changes in myocardin subunit expression and ASD formation.Conclusions:Our study for the first time focuses on variants in the promoter region of the MYH6 gene in Chinese patients with ASD and the discovered variants have functional significance.The study provides new insights in the role of the MYH6 gene promoter region to better understand the genetic basis of ASD formation and facilitates clinical diagnosis.

Missense mutations in CSX/NKX_(2.5)are associated with atrial septal defects

Objective ：To study the gene mutations of homeobox transcription factor （CSX/NKX2.5） associated with a Chinese family with secundum atrial septal defect （ASD）. Methods ：Polymerase chain reaction and DNA sequencing were used to check all the members in the family with ASD, and single strand conformation polymorphism analysis （SSCP） was used to check 126 normal control people for detecting the mutations of CSX/NKX2.5 gene. Results： Three mutations, G270A（Glu32Lys ）, G378A （Glu68Lys）andG390A （Glu72Lys）were identified in CSX/NKX2.5 gene of ASD patients. However, the other members in the family with ASD and the control did not have such gene mutations. Conclusion：These mutations of CSX/NKX2.5 gene, which were identified in a Chinese family, may be one of the secundum ASD etiologic causes .

Diagnostic chest X-ray in atrial septal defects

A 66-year-old woman with lower limb edema and exertional dyspnea presented to the emergency department.Posteroanterior chest X-ray revealed a Fleischner’s sign in both lungs(Figure 1A)suggesting a pulmonary hypertension.A subsequent transthoracic echocardiogram revealed a 24 mm diameter secundum atrial septal defect(ASD)(Figure 1B)with a dilated right heart and a mean pulmonary pressure of 68 mmHg.Fleischner’s sign refers to a prominent central pulmonary artery that can be commonly caused either by pulmonary hypertension or acute pulmonary embolism.This radiological finding is very rare in patients with secundum ASD unless the defect remains undiagnosed till the elderly.Chest X-ray remains fundamental in making diagnosis of cardiovascular disease.

To What Extent Can Transcatheter Devices Replace Open-Heart Surgery in the Treatment of Cardiac Septal Defects?

Transcatheter treatments are widespread, having the advantages of being less invasive than surgery with quicker recovery times and reduced physical and psychological consequences. However correct patient selection is vital to optimise outcomes. In the case of an isolated atrial septal defect (ASD), transcatheter closure is preferred. Whilst multiple or large ASDs or ventricular septal defects (VSDs) are best treated through the transthoracic approach. Furthermore, the development of the transcatheter approach has yielded devices that can be used in the transthoracic approach resulting in hybrid techniques. This article aims to evaluate both transcatheter devices and open-heart surgery in the treatment of cardiac septal defects. A brief discussion follows on from the causes and history of cardiac defect treatments.

TRANSCATHETER CLOSURE OF LARGE SECUNDUM ATRIAL SEPTAL DEFECTS WITH AMPLATZER~ SEPTAL OCCLUDER

Objective To evaluate the safety and feasibility of transcatheter closure of large secundum atrial septal defects(ASDs)with Amplatzer~ septal occluder(ASO).Methods A total of 26 patients(age 16 to 67 years,median 43 years;body weight 52 to 102 kg,median 67 kg)with large ASDs underwent an attempted transcatheter closure using ASO.Large ASD was defined as those with a balloon-stretched diameter of ≥30 mm.Another 81 patients with small-to-moderate ASD during same period who underwent closure served as controls.Results In patients with large ASDs,the ASD dimension means were(22.1±3.2)mm(range from 16 to 30 mm)and(23.8±2.6)mm(range from 18 to 31mm)assessed by transesophageal echocardiography(TEE)and transthoracic echocardiography(TTE),respectively.The mean balloon-stretched diameter of the ASD was(31.9±2.1)mm(range from 30 to 37mm).The size of device was(32.0±1.9)mm(range from 30 to 36mm).The transcatheter procedure was successful in all patients(100%).Seventeen deployments were performed using the conventional left atrium approach,and remaining 9 patients required the right upper pulmonary vein approach.Immediately after deployment,TEE revealed that complete closure rate was 73%.Procedure-related complications were recorded in 3 patients(12%),including device embolization in one patient,pericardial effusion in one patient,and large hematoma at puncture site in one patient.During follow-up,the complete closure rate increased to 88% at 24h after procedure and 100% at 6 months.The procedural success rates,immediate TEE results and TTE results at 24h and 6 months after procedure,were not significantly different between patients with large ASDs and those with small-to-moderate ASDs.Conclusion Transcatheter closure of large ASDs using ASO is technical feasible and relatively safe.Proper care selection and specific technique modification such as the right upper pulmonary vein approach is vital for the implantation success.

Transcatheter closure of secundum atrial septal defects using Amplatzer device

To evaluate the feasibility and short term results of transcatheter closure of secundum atrial septal defects (TCSASDs) using Amplatzer occluder device A new self centering device, the Amplatzer atrial septal occluder, has recently been evaluated in an animal model with excellent results This paper reports our clinical research with this device Methods 30 patients underwent an attempt at TCSASDs at an average age of 35 6±15 9?y (range, 5-62?y) and average weight of 63 6±14 5?kg (range, 17-78?kg) using the Amplatzer atrial septal occluder The average ASD diameter measured by transesophageal echocardiography (TEE) was 23 6±4 0?mm (range, 16-31?mm), and the average atrial septal defects (ASD) balloon stretched diameter was 25 2±5 8?mm (range, 9-34?mm) All patients had right atrial and ventricular volume overload with a Qp/Qs of 3 4±1 2 (1 4-5 2) A F8 12 catheter was used for delivery of the device in all patients Results The device was placed correctly in all patients There was immediate and complete closure in 30 patients The average device waist size used to close the defect was 25 6±5 9?mm (range, 9-34?mm) There was no episode of device embolization or any other complication Follow up was performed using transthoracic echocardiography (TTE) 1 day, 1 month, 3 months, 6 months and 1 year after the procedure The first day after operation; there was complete closure of the ASD in all patients; there have been no episodes of endocarditis, thromboembolism, or wire fracture Conclusion TCSASDs using the Amplatzer occluder device was an efficient nonsurgical method which had a very high technical success rate and satisfactoy short term and follow up results

Surgical closure of apical multiple muscular septal defects via right ventriculotomy using a single patch with intermediate fixings

Background Multiple apical muscular ventricular septal defects （VSDs） remain a challenge for surgeons because of their anatomical features. We used single patch with intermediate fixations to repair multiple apical muscular VSDs through right ventricuiotomy. Methods We analysed the data of 16 children （median age 8 months, range 2 months to 144 months） with multiple apical muscular VSDs who underwent a single patch technique via apical right ventdcu^otomy. Perioperative data were collected and analysed, and the patients were followed up for three months to 66 months （median, 46 months） to investigate the outcomes. Results All patients recovered from cardiopulmonary bypass easily with median of cardiopulmonary bypass time 87 minutes and of aortic crossclamp time 53 minutes. No surgically related death occurred and no patient required reoperation. One patient died of pseudomonas pyocyanea infection on day 11 postoperatively. Residual shunt happened in one patient with a diameter of 2 mm and spontaneously closed in 12 months after operation. Two patients presented slightly reduced right ventricular volume and apical hypokinesia postoperatively and recovered 24 and 36 months later respectively. No other complication was found during the three months to 66 months follow-up. Conclusion Our experiences using a single patch technique with intermediate fixations via right ventriculotomy in the management of multiple muscular VSDs had favourable outcomes.

2D/3D echocardiography evaluation of efficacy of transcatheter closure ventricular septal defects with double-umbrella nitinol prosthesis

Background A study group of 268 patients with VSD diagnosed by Echocardiography and left ventriculography underwent transcatheter procedure. We observed that double-umbrella devices were successfully deployed in 262 patients. Methods The concentric devices were deployed in 184 patients, eccentric in 78 patients. After deployment of concentric devices in 3 cases with sac VSD, there was evident residual shunt, and then replaced of eccentric devices, there was no residual shunt. Trivial residual shunt occurred in 12 patients disappeared in 10 after 24 hours follow up. There was no complication occurred in 2 patients with trivial residual one month later after procedure. Results Transcatheter occlusion failed in 6 patients： 3 patients gave up finally because occluders replacement caused aortic regurgitation （AR） during procedure. One occluder in VSD dislocated minutely 2 days after procedure, then removed by operation. One occluder was retrieved by snare 5 days after placement because of residual shunt causing hemolysis. One patient developed serve tricuspid regurgitation （TR） after procedure, and accepted operation 3 days later. Conclusions Transcatheter closure of VSD with double-umbrella nitinol occluder is safe and effective. The best indication must be chosen by echocardiography to ensure VSD occlusion successfully and the better prognostic efficacy.

Clinical analysis of transcatheter closure of perimembranous ventricular septal defects with occluders made in China

Background Results of perimembranous ventricular septal defects （pmVSD） transcatheter closure have been reported in the literature mostly using a Amplatzer VSD device. However, the data of percutaneous closure of pmVSD with VSD occluder （VSD-O） made in China are still limited. We sought to analyze safety, efficacy, and follow-up results of percutaneous closure of pmVSD with VSD-O made in China.Methods Between February 2005 and June 2009, 78 patients underwent percutaneous closure of pmVSD at our institution. A VSD device made in China was used for all subjects. The safety and the efficacy of the VSD-O were investigated.Results The average age at closure was 11 years （range 2.5 to 44 years）. The attempt to place device was successful in 74 patients （94.9%）. The average device size used was 8 mm （range 5 to 16 mm）. No deaths occurred. Total occlusion rate was 62.8% at completion of the procedure, rising up to 87.2% at discharge and 99.0% during follow-up. A total of eight early complications occurred （10.3%）, but in all subjects these were transient. The average follow-up period was 40.5 months. The most significant complication was complete atrioventricular block （cAVB） in the early phase （five subjects, 6.4%） and during the follow-up （1 subject, 1.3%）, which saw no need for pacemaker implantation in six subjects.Cox proportional hazards regression analysis showed that the age was only the variable significantly associated with the occurrence of this complication during the procedure （P=0.025; relative risk 0.22）. The subjects who experienced this complication were less than five years old.Conclusions Percutaneous pmVSD closure used VSD-O made in China is associated with excellent success and closure rates, no mortality, and low morbidity. Longer follow-up data and improvements in device characteristics are needed to reduce the risk of cAVB.

Reliability of transthoracic echocardiography in estimating the size of Amplatzer septal occluder and guiding percutaneous closure of atrial septal defects

Background In China, transthoracic echocardiography （TTE） is popularly used for pre-intervention examination for atrial septal defect （ASD） and for guiding ASD closure. However, the ability to determine ASD size and the safety and efficacy of l-rE for guiding ASD closure still has not been widely accepted. This study aimed to evaluate the efficacy and safety of l-rE used before, during and after transcatheter ASD closure with Amplatzer septal occluders （ASO）. Methods Sixty-eight subjects （15 men and 53 women; mean age （33.7±17.3） years） were enrolled. TTE was used to measure the diameters and guide transcatheter closure of ASD. The ASD was examined by long-axis view, basal short-axis view, apical four-chamber view and the subcostal view to observe position, diameter and relation with neighbouring structures. The largest diameter was selected as the reference diameter. Patients were divided into 3 groups according to the ASD reference diameter： 22 subjects with ASD diameter 4-14 mm （group A）; 21 subjects with ASD diameter 15-20 mm （group B）; and 25 subjects with ASD diameter 21-33 mm （group C）. Results ASD was occluded successfully in groups A and B. In group C, occlusion failed in 2 cases; 1 case remained with a 3-mm residual shunt sustained until 6-month follow-up. However, at 6-month follow-up, no case of thromboembolism, ASO dislocation or death occurred in the three groups. The diameter of ASD measured by l-rE could accurately predict the ASO size that could successfully occlude the ASD, especially in patients with ASD 〈20 mm. The ASD diameter measured by l-rE correlated well with ASO size （r= 0.925, P〈0.001 ; r=0.976, P〈0.001 ; r=0.929, P〈0.001 respectively）. Conclusions ASD diameter measured by l-rE can accurately estimate the size of the ASO needed for successful closure of ASD. The larger the ASD, the much larger the ASO needed. l-rE is a satisfactory guiding imaging tool for ASD closure.

Transcatheter Closure of Multiple Membranous Ventricular Septal Defects with Giant Aneurysms Using Double Occluders in Four Patients

The transcatheter closure of perimembranous ventricular septal defect （pmVSD） has become a promising treatment modality. However, transcatheter closure of multiple pmVSDs with giant aneurysm is still very challenging. We present our preliminary experiences.

Transcatheter closure of perimembranous ventricular septal defects by a new Amplatzer membranous ventricular septal defect occluder： a single center study in Beijing

Transcatheter closure of congenital perimembranous ventricular septal defect （VSD） has always been a problem for cardiologists in the past decade because of the risks for interference with the valves and conduction system. Some devices designed for other lesions have been used for closure of perimembranous VSD,^1-3 but the result is unsatisfactory because they are difficult to use and have a high incidence of complications. Until 2002,

Interventricular Septal Hematoma after Congenital Cardiac Defects Repair at a Single Institution

Background: Interventricular septal hematoma is a rare complication after congenital cardiac repair. The managementvaries according to the literature. We present our experience with this rare complication. Methods:Echocardiography database were reviewed with the term ‘‘hematoma’’ or “hypoechoic mass” for patients whounderwent congenital heart surgery from January 2018 to December 2021 at our institution to identify potentialinterventricular septal hematoma cases. Relevant data of the patients identified were collected. Focus was put onthe presentation, management, outcomes according to patent medical charts and serial echocardiographic reportdata. Results: In total, there were 5 patients included. The mean age and weight at surgery were 5.5 ± 3.6 monthsand 5.5 ± 1.4 kg, respectively. Four patients were diagnosed with ventricular septal defect and the other one beingdouble outlet of the right ventricle. While all patients had intraoperative transesophageal echocardiography, 80%(4 of 5) of Interventricular septal hematoma were revealed intraoperatively. Only one patient received hematomadrainage intraoperatively while the other 3 identified in the operating room were only closely observed. One afterventricular septal defect repair presented continuous dysfunction of the left ventricle at the last follow-up, whilethe others were doing well. All hematomas resolved completely with a mean time to interventricular septal hematomaresolution of 35.8 ± 16.9 days. Conclusion: Infants seem to be at a higher risk for Interventricular septalhematoma following congenital heart surgery. While the majority of interventricular septal hematoma has abenign postoperative course, some may result in ventricular dysfunction. Management strategies may be chosenon a case-by-case basis.

Novel and functional DNA sequence variants within the GATA5 gene promoter in ventricular septal defects

Background:Congenital heart disease(CHD)is the most common human birth defect.Genetic causes for CHD remain largely unknown.GATA transcription factor 5(GATA 5)is an essential regulator for the heart development.Mutations in the GATA5 gene have been reported in patients with a variety of CHD.Since misregulation of gene expression have been associated with human diseases,we speculated that changed levels of cardiac transcription factors,GATA5,may mediate the development of CHD.Methods:In this study,GATA5 gene promoter was genetically and functionally analyzed in large cohorts of patients with ventricular septal defect(VSD)(n=343)and ethnic-matched healthy controls(n=348).Results:Two novel and heterozygous DNA sequence variants(DSVs),g.61051165A>G and g.61051463delC,were identified in three VSD patients,but not in the controls.In cultured cardiomyocytes,GATA5 gene promoter activities were significantly decreased by DSV g.61051165A>G and increased by DSV g.61051463delC.Moreover,fathers of the VSD patients carrying the same DSVs had reduced diastolic function of left ventricles.Three SNPs,g.61051279C>T(rs77067995),g.61051327A>C(rs145936691)and g.61051373G>A(rs80197101),and one novel heterozygous DSV,g.61051227C>T,were found in both VSD patients and controls with similar frequencies.Conclusion:Our data suggested that the DSVs in the GATA5 gene promoter may increase the susceptibility to the development of VSD as a risk factor.