Treatment Of Atrial Septal Defect Research Articles

Transcatheter versus surgical closure of atrial septal defect: comparison of early result and complication

Background. Surgical therapy for closure of atrial septal defect with cardiopulmonary bypass is the gold standard. Transcatheter closure has become an alternative for the treatment of atrial septal defect because 80-90% of atrial septal defects can be resolved without surgery. The success of transcatheter closure of atrial septal defect is almost 80% of all patients with atrial septal defect. Objective. To analyze the differences in the results of transcatheter and surgical closure of atrial septal defects. Method. The type of research is observational analytic with a cross-sectional design. The sample is medical record data from pediatric patients with atrial septal defect who underwent transcatheter and surgical closure of the atrial septal defect between January 1, 2019 and June 30, 2023 at Dr. Soetomo Surabaya. All subjects with incomplete data will be excluded. Results. The total research subjects were 81 subjects, divided into 2 groups: transcatheter 41/81 (50.6%) and surgical 40/81 (49.6%). Transcatheter and surgical procedures had similar success rates (100% vs 92.5%, p=1.116). Transcatheter procedures had a longer ICU stay (0.07 day vs 3 days, p<0.001) and longer hospital stay (4,8 days vs 7,3 days, p<0.001) than surgical procedures. The total procedure cost of transcatheter procedures was also cheaper than surgical procedures (61 million vs 91 million, p<0.001). Complications of transcatheter procedures were also lower than surgical procedures (12.2% vs 52.5%, p<0.001). Conclusion. Transcatheter closure of atrial septal defects showed excellent result, shorter ICU and hospital stay, lower costs, and fewer complications.

Transcatheter Closure of Secundum Atrial Septal Defects in Pediatric Patients: A 15-Year Single-Center Experience.

Transcatheter closure is the first-line treatment option for hemodynamically significant secundum atrial septal defects (ASDs). This study examines our center's experience with this procedure over the last 15 years. Pediatric patients aged 0-18 years with secundum ASDs who were planned for transcatheter closure in our clinic between January 2007 and January 2023 were retrospectively evaluated. Transcatheter secundum ASD closure was planned for a total of 334 patients during the study period: 191 girls (57.2%) and 143 boys (42.8%). Their mean age was 8.08±3.9 years, and their mean weight was 30±15.6 kg. Defect diameter measured transesophageally ranged from 5 to 35 mm, with a mean of 12.56±4.02 mm. Transesophageal echocardiographic examination revealed a single secundum ASD in 319 patients (95.5%) and multiple secundum ASDs in 15 patients (4.5%). In 11 patients (3.3%), the procedure was terminated before initiating transcatheter ASD closure because of insufficient vena cava rims or a very large ormulti-fenestrated defect. The 323 patients (96.7%) who underwent transcatheter ASD closure had a mean pulmonary artery pressure of 15.1±4.0 mmHg and a mean Qp/Qs ratio of 1.97±0.56. The procedure failed in four patients (1.3%) because of device embolization (n=2) or the inability to properly position the device (n=2). Major complications other than device embolization observed during or after transcatheter closure included anesthetic-induced respiratory depression (n=1) and total atelectasis of the lung (n=1). No new major complications were detected during the patients' long-term follow-up. With appropriate patient and device selection, transcatheter closure is a safe and effective treatment for secundum ASD and should be the first treatment of choice.

An overview of treatment for atrial septal defect with pulmonary hypertension

Background: Atrial Septal Defect (ASD) is a congenital heart defect which can be the cause of comorbidities in the form of Pulmonary Arterial Hypertension (PAH) and therapy cannot be done simply by correcting the ASD but requires further study and evaluation.Purpose: Describe the treatment given to patients with ASD and PAH and the correlation between the administration of interventional therapy and the patient's probability of PH.Method: This study is a descriptive quantitative using a cross-sectional research design. The sampling technique was total sampling method. The samples were 41 ASD patients with PAH at Prof. Ngoerah General Hospital in Denpasar in 2022. Patients under 18 years of age and those with other congenital heart disease will be excluded. The demographic characteristics assessed were the patient's age and gender. The therapy data included information on medical therapy and intervention therapy.Results: Focus of medical therapy was supportive therapy rather than specific PAH therapy. Percutaneous ASD closure was the most widely-used intervention therapy compared to surgical ASD closure. Based on statistical analysis, the p value > 0.05 is 0.284, so there is no significant correlation between the probability of the patient's pH and the provision of intervention therapy.Conclusion: At Prof Ngoerah General Hospital Denpasar, the majority of ASD patients with complications of pulmonary hypertension were females aged between 21 to 30 years. The medical therapy given is adjusted based on the severity of PH as assessed through echocardiography examination. Majority of patients received supportive therapy compared to specific therapy for PAH. Medical therapy is prioritized for patients who have contraindication criteria for interventional therapy. Percutaneous ASD Closure was found to be the largest percentage in interventional therapy regardless of the severity, except for patients who were indicated to undergo surgical ASD closure. There is no significant relationship between the patient's PH probability level and the choice of intervention therapy.

Case Report: Removal of septal occluder device and closure of atrial septal defect with pulmonary vein flow redirection

BACKGROUND: Atrial septal defect represents 10 to 15% of congenital heart disease and is more frequent in women with a 2:1 ratio. Sinus venosus atrial septal defect is usually associated with partial anomalous pulmonary venous drainage from the right superior pulmonary vein to the right atrium directly or indirectly through the superior vena cava. Rarer still, is the inferior sinus venosus, which may be associated with partial anomalous venous drainage from the right inferior pulmonary vein. CASE REPORT: 13-year-old patient with a history of intervention for interatrial defect closure with Amplatzer occluder at the age of six. He was brought to receive medical attention for fatigue and dyspnea that had been progressing for 2 years. Cardiac CT reported partial anomalous connection of pulmonary veins and echocardiogram reported a residual atrial septal defect of 10 mm and mild to moderate pulmonary hypertension. Based on the findings, surgical treatment was decided. EVOLUTION: In correction surgery, we observed Amplatzer occluder incorrectly positioned, the device was removed and flow was redirected from right pulmonary veins to left atrium with bovine pericardium patch. After the surgical intervention, the patient had a favorable evolution without no post-surgical complications. At follow-up, 15 days after medical discharge, the patient was asymptomatic, and a cardiac CT scan showed the corrected interatrial defect. CONCLUSION: The treatment of atrial septal defect should be individualized, since it will depend on the size of the defect, the age at the time of diagnosis, the magnitude of the shunt, the severity of the symptoms and the presence of other conditions. If the defect requires repair, it is important to weigh the benefits of choosing percutaneous closure vs. surgical intervention to avoid the need for reintervention, as in the present case. Closure and redirection of pulmonary vein flow with bovine patch is a safe and effective option.

Minimally Invasive Surgery for Septal Defects Inchild: Literature Review

Nowadays a minimally invasive approach is a rapidly evolving strategy in particular in the field of congenital heart surgery. The main advantage of minimally invasive approaches is less trauma to a patient which positively effects early postoperative period and recovery after surgery. Own to continuous technological progress and growing experience minimally invasive approaches become widely used in cardiac surgery as well as in treatments of congenital heart defects. This review highlights the main problems and their potential solutions in using minimally invasive approaches in surgical treatment of atrial septal defect, ventricular septal defect, partial atrioventricular canal, partial anomalous pulmonary venous drainage. We describe specific considerations of cardiopulmonary bypass, operative techniques and results of minimally invasive approanes.

Percutaneous Treatment of Pulmonary Valvular Stenosis and Secundum Type Atrial Septal Defect in a Young Adult

Pulmonary valve stenosis (PS) and secundum type atrial septal defect (ASD) are common forms of congenital heart disease. While traditional treatment for PS and ASD is open surgery, percutaneous treatment of both diseases are widely used with high rates of success and lower complication. However, the combination of PS with ASD in the same patient is relatively rare, and the optimal strategy is debated. We performed consecutive percutaneous balloon pulmonary valvuloplasty and ASD occlusion in a young adult patient with severe congenital PS associated with a secundum ASD.

Evaluation of Arrhythmia Prevalence, Management, and Risk Factors in Patients with Transcatheter and Surgically Closed Secundum Atrial Septal Defects.

Atrial septal defect (ASD) accounts for 6-10% of all congenital heart disorders. Secundum ASD closure can be performed surgically or percutaneously. We aimed to identify the various arrhythmias that occur before, during, and after the procedure and evaluate their management. The study included a total of 427 patients aged 0-18 years who underwent transcatheter or surgical closure of isolated secundum ASD between January 2008 and January 2020. Postoperative electrocardiogram (ECG) traces, intraoperative arrhythmias, and treatments were recorded for both groups. Echocardiography and ECG were evaluated at postoperative 1 week, 1, 3, and 6 months, and annually thereafter. After transcatheter closure, follow-up basal ECG showed incomplete right bundle branch block pattern in 21 patients and sinus rhythm in 229 patients. After surgical closure, incomplete right bundle branch block pattern was detected in 23 patients, complete right bundle branch block in 3 patients, and complete AV-block (Atrioventricular Block) pattern in 1 patient. The other 150 patients showed sinus rhythm. At least one postoperative follow-up Holter ECG record could be obtained for 104 patients in the transcatheter group and 96 patients in the surgical group. Of 104 patients who underwent transcatheter closure, 97 (93.3%) had normal Holter ECG findings and 7 (6.7%) had arrhythmia. Of the 96 patients who underwent surgical closure, 85 (88.5%) had normal Holter ECG traces and 11 (11.5%) had arrhythmia. There was no statistically significant difference in the frequency of arrhythmia (P = 0.164). The higher frequency of arrhythmia in adult studies compared to the pediatric age group once again demonstrates the importance of early diagnosis and treatment of ASD in childhood. The similar incidence of arrhythmia in both groups supports the safety and effectiveness of both closure methods in eligible patients.

Follow up and outcome of transcatheter device closure in pediatric patients in a tertiary cardiac centre of Nepal

BackgroundCongenital heart diseases have significant effect on the growth and development of a child. Timely intervention helps a child to grow and develop to full potential. Cardiac interventionists have not long ago developed methods to cure conditions via transcatheter methods like device closures for shunt lesions. These interventions have been hugely accepted and applied all over the world. ObjectivesThe aim of this study was to determine the outcome of Transcatheter device closure in Atrial Septal Defect (ASD), Ventricular Septal Defect (VSD) and Patent Ductus Arteriosus (PDA) in terms of improvement in echocardiographic parameters and nutritional well-being. It also outlined the immediate and long term complications of Transcatheter device closure of the shunt lesions. MethodologyA prospective study was carried out among 129 pediatric patients who underwent Transcatheter device closure of shunt lesions at Shahid Gangalal National Heart Centre from March 2019 to March 2021. Simple convenient, consecutive non-probability sampling method was used for the study.Independent sample t-test was applied to see the correlation and significance of continuous variables and Linear regression was used to find out relation between weight gain and device closure. ResultsAmong 129 pediatric patients having either ASD, PDA or VSD without other comorbidities who underwent transcatheter device closure at Shahid Gangalal National Heart Centre, there was 1 mortality (0.7 %), 3 device embolization (2.3 %), 11 (8.5 %) tiny residual leaks, 6 (4.6 %) femoral artery thrombosis, 19 (14.7 %) Left ventricular systolic dysfunction, 4 (3.1 %) new onset arrhythmia, 13(10.0 %) new onset trivial AR and 2 (1.5 %) mild obstruction to surrounding structures. There were no long term complications observed during the study period. Pulmonary artery pressures improved in most along with normalization of chamber dilatation. There was significant improvement in weight of children at the end of one year follow up (P < 0.001), however among individual shunt lesion, only patients undergoing PDA device closure demonstrated significant weight gain. ConclusionTranscatheter device closure is a promising, safe and effective means of treatment for ASD, PDA and VSD. It has significant bearing in weight gain as well as general well-being of children. Judicious selection of cases, proficient expertise and availability of suitable infrastructures are paramount for successful outcome.

Health-related quality of life in children with congenital heart disease following interventional closure versus minimally invasive closure.

IntroductionThe presence of atrial septal defect (ASD) or ventricular septal defect (VSD) significantly affects children’s quality of life and, if not treated adequately, can contribute to increased mortality. In this study, we evaluated and compared the health-related quality of life (HRQL) of children who underwent treatment using either minimally invasive closure (MIC) or interventional closure (IC).Materials and methodsIn this observational and comparative study 199 children (2 to 4.5 years of age) underwent closure treatment for simple ASD or VSD at the Children’s Hospital of Chongqing Medical University between February 2021 and September 2021. Of these, 116 were treated with IC and 83 with MIC. Both preoperative and postoperative HRQL scores were assessed using the PedsQLTM3.0 Cardiac Module and the children were followed up at 3 and 6 months after surgery.ResultsThe two groups did not differ significantly in terms of demographics, baseline clinical characteristics, or pre-operative data. The duration of anesthesia (45 mins vs. 109 mins), procedures (25 mins vs. 48 mins), and length of postoperative hospital stay (4.32 days vs. 6.87 days) in the IC group were significantly less than in the MIC group (P < 0.001). The incidence of postoperative pneumonia in the VSD patients who underwent MIC was significantly higher than in those who underwent IC treatment (28.9% vs. 0 percent, P < 0.001). The HRQL scores increased significantly in both groups following treatment and follow-up evaluations (P < 0.001). The mean HRQL score of the IC group 3 months after treatment was significantly higher than that of the MIC group (88.9 vs. 85.7, P < 0.001), indicating a significant increase from the baseline score compared with the MIC group (5.4 vs. 2.6, P < 0.001). The IC group also showed higher scores than the MIC group (P < 0.05) in the dimensions of “Heart Problems and Treatment,” “Treatment Anxiety,” and “Cognitive Problems,” with higher scores indicating fewer problems.ConclusionThe health-related quality of life in children with ASD and VSD improved continuously regardless of IC or MIC intervention. However, IC led to better HRQL in the early postoperative stage.

Summary of the Experiences and Results of Transesophageal Ultrasound-Guided Ventricular Septal Defect and Atrial Septal Defect Closure Operation.

Ventricular septal defect (VSD) and atrial septal defect (ASD) are congenital heart diseases. The techniques of transthoracic closure (TC) and percutaneous closure (PC) for the treatment of VSD and ASD have continuously improved and matured. This study aimed to retrospectively analyze the therapeutic effects of TC and PC on VSD and ASD patients. We retrospectively reviewed 928 patients (552 VSD and 376 ASD) who had undergone TC or PC guided by transesophageal ultrasound at the Department of Cardiac Macrovascular Surgery of the First Affiliated Hospital of Nanchang University between August 2010 and August 2020. We collected and evaluated the clinical data of the patients, including age, gender, weight, inlet and outlet diameters of defect, and the operation results of TC and PC. Descriptive statistics were used to analyze means and standard deviations (SD), and the Chi-square test was used to evaluate the difference between groups. Among the 928 patients who were treated with the closure operation, there were no casualties, with 907 patients (97.7%) showing successful closure. Among the 552 VSD patients who were treated with TC, 540 showed successful close, while 12 cases required extracorporeal circulation after the failure of TC. Among the 376 patients with ASD, 256 patients were treated with TC, of which 251 were successful, and five were failures, including three shedding cases. In addition, among the 120 patients who were treated with PC, 116 were successful, and four were failures, including two shedding cases. Postoperative follow up for patients with successful closure operations demonstrated that the complications of aortic and tricuspid regurgitation, hydro-pericardium, III° atrioventricular block, shedding of closure umbrella, hemolysis, and thrombosis had not occurred. Closure operation of VSD and ASD by esophageal ultrasound has the advantages of lower trauma and blood loss, shorter hospital stay, simple operation, fewer postoperative complications, and significant therapeutic efficacy.

The Treatment Strategy for the Atrial Septal Defect in the Presence of Severe Pulmonary Hypertension

Atrial septal defect is one of the most common congenital heart diseases in adults. The defect often leads to volume overload in the right heart coupled with the potential risk of right heart failure and pulmonary arterial hypertension. These conditions lead to worsening in quality of life, decrease in physical capacity, and even to fatal outcomes. The main strategy for treatment of atrial septal defect is a transcatheter or surgical closure of the defect, but in patients with severe pulmonary arterial hypertension, it is recommended to manage pulmonary arterial hypertension and after that treat the defect invasively. This strategy is called “treat and repair” strategy. We present an illustrative case report of management and treatment of atrial septal defect, complicated with severe pulmonary arterial hypertension. In this case, surgical closure of the defect was contraindicated because of the high pulmonary vascular resistance. Therefore, the “treat and repair” strategy was approached. After specific medical treatment of pulmonary arterial hypertension, surgical closure of the defect was chosen and proven successful.

Simultaneous Percutaneous Interventional Treatment of Atrial Septal Defects and Pulmonary Valve Stenosis in Children Under the Guidance of Transoesophageal Echocardiography Alone: Preliminary Experiences.

ObjectiveTo investigate the efficacy and safety of simultaneous percutaneous interventional treatment of atrial septal defects (ASDs) and pulmonary valve stenosis (PS) in children under the guidance of transoesophageal echocardiography (TEE) alone.MethodsEleven children with ASD combined with PS who were treated at our hospital between March 2015 and March 2019 were recruited, including 4 males and 7 females. Preoperative transthoracic echocardiography showed that all patients had type II ASDs of the foramen ovale subtype, with a maximum diameter of 12.9 ± 2.7 mm (9.0–18.0 mm). The guiding principle of septal occluder selection is that the diameter of the occluder should be 2–4 mm larger than the maximum diameter of the ASD. The pressure gradient across the pulmonary valve in patients with PS was 54.7 ± 5.8 mmHg (47.0–64.0 mmHg), and a balloon with a diameter 1.2–1.4 times the diameter of the pulmonary valve annulus was used for dilatation. Effective dilatation was repeated 2–3 times. All children underwent ASD occlusion and PS balloon dilatation through the femoral vein under TEE guidance without radiation or contrast agents. The patients underwent PS balloon dilatation first, followed by ASD occlusion. The treatment effect was evaluated by TEE immediately after the procedure, and the patients were followed up regularly.ResultsAll patients underwent successful simultaneous ASD occlusion and PS balloon dilatation through the femoral vein under the guidance of TEE alone. The pressure gradient across the pulmonary valve immediately after the procedure was 21.3 ± 1.8 mmHg (19.0–25.0 mmHg) (P < 0.01). No shunt was detected at the atrial septum level. The patients were followed for 3.0 ± 1.4 years (1.0–5.0 years) after the procedure. The atrial septal occluders were in the normal position in all of the patients, and there was no arrhythmia, hemolysis, or residual shunting. The pressure gradient across the pulmonary valve at 1 month after the procedure was 18.5 ± 3.3 mmHg (P < 0.01).ConclusionSimultaneous percutaneous interventional treatment of ASD and PS in children under the guidance of TEE alone is not only safe and effective but also prevents trauma caused by extracorporeal circulation and surgical incision and damage caused by X-ray and contrast agents. The surgical sequence included first performing PS balloon dilatation, followed by ASD occlusion.

Atrial septal defects: the role in the development of cerebral circulation disorders caused by paradoxical embolism

The article presents a case report of a patient with cardioembolic ischemic stroke (IS), which was the first clinical manifestation of congenital atrial septal defect (ASD), asymptomatic until adulthood. The issues of anatomical classification, restructuring of intracardiac hemodynamics depending on the size and localization of ASD, its role in the development of IS are discussed. The diagnostic algorithm in patients with IS caused by paradoxical embolism is described, the current possibilities of ASD treatment and prevention of related disorders of cerebral circulation are discussed.

Transcatheter Closure of Atrial Septal Defect

Background: Over the past decade, percutaneous atrial septal defect (ASD) closure has been the preferred treatment option in many clinical programs for ASD. Percutaneous ASD closures with advanced device architecture and distribution have established user experience and process security. The ability to diagnose has also improved. The devices have evolved from the larger fixtures to the reset zone, being easily eliminated with little residual mesh material and comfortable fitting with the surrounding structures. Biodegradable technology has been introduced and will be considered as a future option. The emergence of the use of the ASD closure device over the last forty years includes improvements that reduce the incidence of adverse effects reported over the years. Issues reported in the literature include thrombus formation, air tightness, device insertion, abrasion, residual shunts and nickel hypersensitivity. Modern tools hold medium and long-term data with excellent results. Multi-sized devices securely close simple and complex ASDs that can re-scan, reset, and detect percutaneous advanced delivery procedures. In this review, the most widely used tools and distribution processes are discussed and the tools that show promise for the future.&#x0D; Conclusion: As the field of transcatheter treatment of atrial septal defects (TC-ASD) and congenital interventional cardiology develops, real-world design studies provide valuable developmental information on aspects of care where there is disagreement about best practices and more research is needed.

Anterolateral minithoracotomy versus median sternotomy for the surgical treatment of atrial septal defects: a meta-analysis and systematic review

BackgroundTo compare the short-term safety and efficacy of right anterolateral minithoracotomy (ALMT) and median sternotomy (MS) for the surgical treatment of atrial septal defects (ASDs).MethodsThe PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched for comparative studies focusing on surgical repair of ASDs via ALMT or MS published up to the end of April 27, 2020. We used random-effect or fixed-effect models to obtain pooled estimates.ResultsA total of 7 publications, including 665 patients (ALMT 296 and MS 369), were included. Age (WMD: 1.80 years, 95% CI 0.31–3.29), weight (WMD: − 0.91 kg, 95% CI − 5.57 to 3.75), sex distribution (OR: 1.00, 95% CI 0.74–1.35) and surgical type (patch or direct closure) (OR: 1.00, 95% CI 0.67–1.49) were comparable in the ALMT group and MS group. No significant differences in the success rate (OR 0.23; 95% CI 0.05–1.07) or severe complication rate (OR 1.46; 95% CI 0.41–5.22) were found between the ALMT group and the MS group. In addition, the differences in the cardiopulmonary bypass (CPB) time (WMD 6.33; 95% CI − 1.92 to 14.58 min, p = 0.13) and the operation time (WMD 5.23; 95% CI − 12.49 to 22.96 min, p = 0.56) between the ALMT group and the MS group were not statistically significant. However, the ALMT group had a significantly longer aortic cross-clamp time (2.37 min more, 95% CI 1.07–3.67 min, p = 0.0003). The intubation time was 1.82 h shorter (95% CI − 3.10 to − 0.55 h; p = 0.005), the intensive care unit (ICU) stay was 0.24 days shorter (95% CI − 0.44 to − 0.04 days; p = 0.02), and the postoperative hospital stay was 2.45 days shorter (95% CI − 3.01 to − 1.88 days; p < 0.00001) in the ALMT group than in the MS group. Furthermore, the incision length was significantly shortened by 8.97 cm in the ALMT group compared with the MS group (95% CI − 9.36 to − 8.58 cm; p < 0.00001).ConclusionsIn the surgical treatment of ASD, ALMT and MS are equally safe and effective in terms of success rates and severe complication rates. The surgical procedures are equally difficult, but ALMT is associated with a faster functional recovery and better cosmetic results. Compared to MS, ALMT is the better choice for select ASD patients.

Single‐cell RNA sequencing analysis to characterize cells and gene expression landscapes in atrial septal defect

This study aimed to characterize the cells and gene expression landscape in atrial septal defect (ASD). We performed single‐cell RNA sequencing of cells derived from cardiac tissue of an ASD patient. Unsupervised clustering analysis was performed to identify different cell populations, followed by the investigation of the cellular crosstalk by analysing ligand‐receptor interactions across cell types. Finally, differences between ASD and normal samples for all cell types were further investigated. An expression matrix of 18,411 genes in 6487 cells was obtained and used in this analysis. Five cell types, including cardiomyocytes, endothelial cells, smooth muscle cells, fibroblasts and macrophages were identified. ASD showed a decreased proportion of cardiomyocytes and an increased proportion of fibroblasts. There was more cellular crosstalk among cardiomyocytes, fibroblasts and macrophages, especially between fibroblast and macrophage. For all cell types, the majority of the DEGs were downregulated in ASD samples. For cardiomyocytes, there were 199 DEGs (42 upregulated and 157 downregulated) between ASD and normal samples. PPI analysis showed that cardiomyocyte marker gene FABP4 interacted with FOS, while FOS showed interaction with NPPA. Cell trajectory analysis showed that FABP4, FOS, and NPPA showed different expression changes along the pseudotime trajectory. Our results showed that single‐cell RNA sequencing provides a powerful tool to study DEG profiles in the cell subpopulations of interest at the single‐cell level. These findings enhance the understanding of the underlying mechanisms of ASD at both the cellular and molecular level and highlight potential targets for the treatment of ASD.

Abstract P305: Patient-specific Ipsc-derived Cardiomyocytes Reveal Abnormal Regulation Of Fgf16 In A Familial Atrial Septal Defect

Aims: Congenital heart disease (CHD) frequently occurs in newborns due to abnormal formation of the heart or major blood vessels. Mutations in the GATA4 gene, which encodes GATA binding protein 4, are responsible for atrial septal defect (ASD), a common CHD. This study aims to gain insights into the molecular mechanisms of CHD using human induced pluripotent stem cells (iPSCs) from a family cohort with ASD. Methods and Results: Patient-specific iPSCs possess the same genetic information as the donor and can differentiate into various cell types from all three germ layers in vitro , thus presenting a promising approach for disease modeling and molecular mechanism research. Here, we generated a patient-specific iPSC line (iPSC-G4 T280M ) from a family cohort carrying a hereditary ASD mutation in GATA4 gene (T280M), as well as a human embryonic stem cell line (ESC-G4 T280M ) carrying the isogenic T280M mutation using the CRISPR/Cas9 genome editing method. The GATA4-mutant iPSCs and ESCs were then differentiated into cardiomyocytes (CMs) to model GATA4 mutation-associated ASD. We observed an obvious defect in cell proliferation in cardiomyocytes derived from both GATA4 T280M -mutant iPSCs (iPSC-G4 T280M -CMs) and ESCs (ESC-G4 T280M -CMs), while the impaired proliferation ability of iPSC-G4 T280M -CMs could be restored by gene correction. Integrated analysis of RNA-Seq and ChIP-Seq data indicated that FGF16 is a direct target of wild-type GATA4. However, the T280M mutation obstructed GATA4 occupancy at the FGF16 promoter region, leading to impaired activation of FGF16 transcription. Overexpression of FGF16 in GATA4-mutant cardiomyocytes rescued the cell proliferation defect. The direct relationship between GATA4 T280M and ASD was demonstrated in a human iPSC model for the first time. Conclusions: In summary, our study revealed the molecular mechanism of the GATA4 T280M mutation in ASD. Understanding the roles of the GATA4-FGF16 axis in iPSC-CMs will shed light on heart development and provide novel insights for the treatment of ASD and other CHD disorders.

Evaluation of Surgical Effect of Atrial Septal Defect with Tricuspid Regurgitation by Transesophageal 3D Echocardiography Based on MC Image Reconstruction Algorithm

This study was to explore the application and effect of three-dimensional (3D) images of the esophagus in the treatment of atrial septal defect (ASD) combined with tricuspid regurgitation (TR) surgery under the processing of marching cubes (MC) image reconstruction algorithm. The MC image reconstruction algorithm was improved as the optimized MC image reconstruction algorithm. 100 patients who had successfully undergone the ASD combined with TR surgery in the hospital from January 2017 to December 2019 were selected as the research objects and grouped based on size of the defect. The preoperative and postoperative conditions of the patients were analyzed with the MC image reconstruction algorithm. Compared with the traditional MC image algorithm, the optimized MC was advanced with less running time and fewer fixed points ( P &lt; 0.05 ). There were significant differences in TR of all ASD patients after the surgery ( P &lt; 0.05 ), and the TR of all patients showed obvious declines from the 1st day to 30th day after surgery and gradually stabilized from the 3rd month to the 6th month after surgery. Compared with patients with normal pulmonary artery pressure, the amount of TR in patients with elevated pulmonary artery pressure increased significantly, and the difference was statistically significant ( P &lt; 0.05 ). In addition, the improvement of TR after occlusion was correlated with the preoperative ASD of the patient. The optimized MC algorithm had been improved greatly in the number of fixed points and running time. The analysis using the optimized MC algorithm showed that ASD patients generally suffered different degrees of TR, TR increased with the increase of the defect, and good effect could be achieved in surgery of all kinds of ASD patients.

Patient-specific iPSC-derived cardiomyocytes reveal abnormal regulation of FGF16 in a familial atrial septal defect.

Congenital heart disease (CHD) frequently occurs in newborns due to abnormal formation of the heart or major blood vessels. Mutations in the GATA4 gene, which encodes GATA binding protein 4, are responsible for atrial septal defect (ASD), a common CHD. This study aims to gain insights into the molecular mechanisms of CHD using human-induced pluripotent stem cells (iPSCs) from a family cohort with ASD. Patient-specific iPSCs possess the same genetic information as the donor and can differentiate into various cell types from all three germ layers in vitro, thus presenting a promising approach for disease modelling and molecular mechanism research. Here, we generated a patient-specific iPSC line (iPSC-G4T280M) from a family cohort carrying a hereditary ASD mutation in GATA4 gene (T280M), as well as a human embryonic stem cell line (ESC-G4T280M) carrying the isogenic T280M mutation using the CRISPR/Cas9 genome editing method. The GATA4-mutant iPSCs and ESCs were then differentiated into cardiomyocytes (CMs) to model GATA4 mutation-associated ASD. We observed an obvious defect in cell proliferation in cardiomyocytes derived from both GATA4T280M-mutant iPSCs (iPSC-G4T280M-CMs) and ESCs (ESC-G4T280M-CMs), while the impaired proliferation ability of iPSC-G4T280M-CMs could be restored by gene correction. Integrated analysis of RNA-Seq and ChIP-Seq data indicated that FGF16 is a direct target of wild-type GATA4. However, the T280M mutation obstructed GATA4 occupancy at the FGF16 promoter region, leading to impaired activation of FGF16 transcription. Overexpression of FGF16 in GATA4-mutant cardiomyocytes rescued the cell proliferation defect. The direct relationship between GATA4T280M and ASD was demonstrated in a human iPSC model for the first time. In summary, our study revealed the molecular mechanism of the GATA4T280M mutation in ASD. Understanding the roles of the GATA4-FGF16 axis in iPSC-CMs will shed light on heart development and provide novel insights for the treatment of ASD and other CHD disorders.

Cardiac Erosions with the Amplatzer Septal Occluder: Adverse Events in the Manufacturer and User Facility Device Experience (MAUDE) Database since the 2012 FDA Review

ABSTRACT Background: Transcatheter closure is the preferred treatment for atrial septal defects. The available devices are effective and safe though concerns persist over cardiac erosion risk. A review of the FDA Manufacturer and User Facility Device Experience (MAUDE) database has not been performed since early reports covering the first decade of device experience. Methods: The FDA MAUDE database was queried for adverse event (AE) reports from 2012 through 2018 involving the Amplatzer Septal Occluder (ASO), Cribriform Occluder (ACO) and PFO Occluder (PFO) devices (Abbott Vascular, Santa Clara, California). Device and event descriptions were analyzed based on report classification, device type and event description. The incidence of AEs was analyzed over time for all event types and devices. Results: There were 732 MAUDE reports describing 764 AEs. The majority of AEs involved the ASO, and the most common AE was device embolization (n = 347). Ninety erosion events were reported (ASO 83, ACO 6, and PFO 1) and 4 erosions were associated with death. The annual number of AE and erosion reports declined from 2012 to 2015 but increased in 2018. Five ASO sizes accounted for 60% of erosions with the 26 mm ASO device being most common. Conclusions: The overall frequency of erosion events in the MAUDE dataset remains low and consistent with prior studies. Adverse events and erosions declined from 2012 to 2015 but have increased in recent years, necessitating future review of this database to ensure that real-world device performance remains consistent with the safety profile demonstrated elsewhere.