Key Regulatory Differentially Expressed Genes in the Blood of Atrial Septal Defect Children Treated With Occlusion Devices.

Atrial septal defects (ASDs) are the most common types of cardiac septal defects in congenital heart defects. In addition to traditional therapy, interventional closure has become the main treatment method. However, the molecular events and mechanisms underlying the repair progress by occlusion device remain unknown. In this study, we aimed to characterize differentially expressed genes (DEGs) in the blood of patients treated with occlusion devices (metal or poly-L-lactic acid devices) using RNA-sequencing, and further validated them by qRT-PCR analysis to finally determine the expression of key mediating genes after closure of ASD treatment. The result showed that total 1,045 genes and 1,523 genes were expressed differently with significance in metal and poly-L-lactic acid devices treatment, respectively. The 115 overlap genes from the different sub-analyses are illustrated. The similarities and differences in gene expression reflect that the body response process involved after interventional therapy for ASDs has both different parts that do not overlap and the same part that crosses. The same portion of body response regulatory genes are key regulatory genes expressed in the blood of patients with ASDs treated with closure devices. The gene ontology enrichment analysis showed that biological processes affected in metal device therapy are immune response with CXCR4 genes and poly-L-lactic acid device treatment, and the key pathways are nuclear-transcribed mRNA catabolic process and proteins targeting endoplasmic reticulum process with ribosomal proteins (such as RPS26). We confirmed that CXCR4, TOB1, and DDIT4 gene expression are significantly downregulated toward the pre-therapy level after the post-treatment in both therapy groups by qRT-PCR. Our study suggests that the potential role of CXCR4, DDIT4, and TOB1 may be key regulatory genes in the process of endothelialization in the repair progress of ASDs, providing molecular insights into this progress for future studies.

Genetic syndromes screening by facial recognition technology: VGG-16 screening model construction and evaluation.

BACKGROUND: Many genetic syndromes (GSs) have distinct facial dysmorphism, and facial gestalts can be used as a diagnostic tool for recognizing a syndrome. Facial recognition technology has advanced in recent years, and the screening of GSs by facial recognition technology has become feasible. This study constructed an automatic facial recognition model for the identification of children with GSs. RESULTS: A total of 456 frontal facial photos were collected from 228 children with GSs and 228 healthy children in Guangdong Provincial People's Hospital from Jun 2016 to Jan 2021. Only one frontal facial image was selected for each participant. The VGG-16 network (named after its proposal lab, Visual Geometry Group from Oxford University) was pretrained by transfer learning methods, and a facial recognition model based on the VGG-16 architecture was constructed. The performance of the VGG-16 model was evaluated by five-fold cross-validation. Comparison of VGG-16 model to five physicians were also performed. The VGG-16 model achieved the highest accuracy of 0.8860 ± 0.0211, specificity of 0.9124 ± 0.0308, recall of 0.8597 ± 0.0190, F1-score of 0.8829 ± 0.0215 and an area under the receiver operating characteristic curve of 0.9443 ± 0.0276 (95% confidence interval: 0.9210-0.9620) for GS screening, which was significantly higher than that achieved by human experts. CONCLUSIONS: This study highlighted the feasibility of facial recognition technology for GSs identification. The VGG-16 recognition model can play a prominent role in GSs screening in clinical practice.

Predictors of operability in children with severe pulmonary hypertension associated with congenital heart disease.

BACKGROUND: Pulmonary artery hypertension associated with congenital heart disease (PAH-CHD) occurs predominantly among patients with uncorrected CHD. Treatment of severe pediatric PAH-CHD remains a major intractability. This study evaluated the predictors and prognoses of children with PAH-CHD who underwent surgical correction. METHODS: The data for 59 children with severe PAH-CHD who underwent surgical correction, with or without postoperative medication, between May 2011 and June 2015 at the Guangdong Provincial People's Hospital were analyzed retrospectively. A regression analysis, receiver-operating characteristic (ROC) curves, and Kaplan-Meier curves were used for survival analysis. RESULTS: Fifty-nine children with severe PAH-CHD underwent heart catheterization and correction, with or without specific anti-PAH drugs postoperatively, were included in this study. The pulmonary pressure, heart function, and ending events were observed and median observation period was 49 ±â€Š20 months. Twenty-eight patients (50%) received at least one additional anti-PAH drug after correction. The survival rate after 2 years was 91.5% (54/59); two patients were in a critical condition, and three were lost to follow-up. Twelve patients (29%) still received over one additional PAH-specific therapy at follow-up, whereas 42 (75%) had successfully stopped drug treatment. Two patients (3.5%) died and one underwent a second thoracotomy to remove the ventricular septal defect patch. Acute vasoreactivity test (AVT) criteria had limited efficacy in predicting pediatric PAH-CHD, whereas pulmonary vascular resistance (PVR) ≤ 6.65 Wood units (WU)/m or PVR/systemic vascular resistance (SVR) ≤ 0.39 during AVT indicated a good prognosis after surgical correction with an AUC of 98.3% (95% confidence interval [CI]: 96.0-100%), 98.4% (95% CI: 96.0-100%) sensitivity of 100%, 100% and specificity of 82.1%, 92.9%, respectively. CONCLUSIONS: Although the criteria for positive AVT currently used are unsuitable for pediatric patients with PAH-CHD, PVR and PVR/SVR during AVT are excellent predictors of outcome in pediatric PAH-CHD. Surgery aided by anti-PAH drugs is an effective strategy and should be recommended for severe pediatric PAH-CHD with PVR ≤ 6.65 WU/m and PVR/SVR ≤ 0.39 after iloprost aerosol inhalation.

Immediate Therapeutic Outcomes and Medium-term Follow-up of Percutaneous Balloon Pulmonary Valvuloplasty in Infants with Pulmonary Valve Stenosis: A Single-center Retrospective Study.

BACKGROUND: Percutaneous balloon pulmonary valvuloplasty (PBPV) is the preferred therapy for pulmonary valve stenosis (PVS). This study retrospectively reviewed recent PBPV outcomes in infants with PVS. The aim of this study was to evaluate factors associated with immediate therapeutic outcomes and restenosis during medium-term follow-up. METHODS: The study included 158 infants with PVS who underwent PBPV from January 2009 to July 2015. Demographic characteristics and patient records were reviewed, including detailed hospitalization parameters, hemodynamic data before and immediately after balloon dilation, cineangiograms, and echocardiograms before PBPV and at each follow-up. All procedures were performed by more than two experienced operators. RESULTS: Immediately after balloon dilation, the pressure gradient across the pulmonary valve decreased from 73.09 ± 21.89 mmHg (range: 43-151 mmHg) to 24.49 ± 17.00 mmHg (range: 3-92 mmHg; P < 0.001) and the right ventricular systolic pressure decreased from 95.34 ± 23.44 mmHg (range: 60-174 mmHg) to 52.07 ± 18.89 mmHg (range: 22-134 mmHg; P < 0.001). Residual transvalvular pressure gradients of 67.31 ± 15.19 mmHg (range: 50-92 mmHg) were found in 8.2% of patients, indicating poor therapeutic effects; 6.4% of patients had variable-staged restenosis at follow-up and 3.8% underwent reintervention by balloon dilation or surgical repairs. Further analysis demonstrated that the balloon/annulus ratio showed statistically significant differences (P < 0.05) among groups with different therapeutic effects and between the restenosis and no-stenosis groups. Binary logistic regression analysis further revealed that higher balloon/annulus ratio (odds ratio: 0.005, 95% confidence interval: 0-0.39) was an independent protective factor for restenosis. The rate of severe complications was 1.9%. CONCLUSIONS: PBPV is a definitive therapy for infants with PVS based on its effectiveness, feasibility, and safety. Restenosis upon medium-term follow-up is relatively rare.

Transcatheter closure of coronary arterial fistula in children and adolescents.

BACKGROUND: Transcatheter closure of coronary arterial fistula (CAF) is being utilized increasingly as an alternative to surgical closure, but most of the literature on transcatheter closure of CAF in children and adolescents consists of case reports and reports of small series. The aim of this study was therefore to describe our experience of percutaneous closure of CAF in children and adolescents. METHODS: Between April 1998 and December 2012, 37 children and adolescents with congenital CAF underwent percutaneous transcatheter closure. After aortic root angiography and selective coronary angiography, a guidewire was positioned to the fistula. In some cases, an arteriovenous wire loop (AV loop) was created. The sheath passed along the wire to the site of the desired occlusion of the fistula. One or more occlusion devices were selected to embolize the fistula. RESULTS: Occlusion devices were placed in 33 procedures (32 patients). Occlusion was unsuccessful in five patients. Duct occluders were placed in 12 procedures, coils in 11 (10 patients), muscular ventricular septal occluders in six, and vascular plugs in four procedures. The tricuspid valve was injured in two patients. One patient with a giant CAF aneurysm had a thrombosis within the aneurysm after transcatheter closure. There were no deaths, fistula dissection or myocardial infarction. CONCLUSION: Transcatheter closure of CAF is feasible in anatomically suitable cases, but injury to the tricuspid valve involved with AV loop methods can occur in closure procedures, and thrombus formation is possible in the blind pouch of the residual fistula after closure. Long-term follow up after fistula closure is necessary.

[Transcatheter interventional therapy of congenital heart disease: the results of Chinese TIT registry].

OBJECTIVE: To report the results of transcatheter interventional therapy (TIT) of congenital heart disease (CHD) register from 23 medical centers in China. METHOD: In this retrospective multicenter registry study, clinical data from 5808 patients who underwent TIT between January 2008 to December 2010 in 23 Chinese medical centers in 14 cities were analyzed. RESULTS: Procedure was successful in 5720 cases (98.5%), success rate was 99.5% for PDA, 98.8% for ASD, 97.4% for VSD and 98.5% for pulmonary stenosis (PS). Multivariate regression analysis showed that PDA size and procedure time, age and procedure time, distance from VSD to AV were significantly associated with the procedure success rate of PDA, ASD and VSD closure, respectively. Early complications occurred in 306 cases (5.3%), 36 cases (0.6%) experienced major complications including device embolization in 7 cases, serious aorta regurgitation in 5 cases, serious tricuspid regurgitation in 4 cases, tricuspid stenosis in 2 cases, heart block (HB) in 13 cases (2 in ASD and 11 in VSD), cardiac tamponade in 2 cases (1 ASD and 1 PS) and hemolysis in 3 cases. Procedure time and PDA size, ASD size, device size, age and PS degree were risk factors related to the occurrence of the early complications for PDA, ASD and VSD closure and PBPV respectively. The median follow-up time was 15 months (range 1-36 months). The complete closure rate during follow up was 100% for ASD, PDA and VSD and the pressure gradient in PS decreased to normal range in all PS patients. Late complications occurred in 15 cases (0.2%), of which 3 cases needed surgery intervention and permanent pacemaker was implanted in 1 patient. There was no death during procedure and at follow-up period. CONCLUSIONS: TIT of CHD offers encouraging results in China. Follow up is warranted to monitor the occurrence of serious complications, especially late complications.

[Non-drug treatment for hypertrophic obstructive cardiomyopathy in children].

OBJECTIVE: To retrospectively summarize the effect of non-medical therapies for pediatric patients with hypertrophic obstructive cardiomyopathy (HOCM). METHODS: From Nov. 2008 to Jun. 2010, 4 children with drug-refractory HOCM were admitted to our hospital. Their ages were 14, 7, 9 and 6 years old, respectively. Their body weights were 38, 17, 21.5 and 17 kg, respectively. Before operation, the pressure gradients over left ventricular outflow tract (LVOTG) were 60, 147, 58 and 114 mm Hg (1 mm Hg = 0.133 kPa), respectively. And mitral regurgitation (MR) areas were 2.2, 7.3 cm(2) and 2.9 cm(2), respectively, except that it was trivial in one case. Percutaneous transluminal septal myocardial ablation (PTSMA) was performed in case 1 and 2. Septal myectomy (SM) was performed in case 3 and 4. Follow-up was first performed right after operation or before discharge, then 1 month, 3 months, 6 months, and 12 months after operation, and then once a year. The follow-up period was 1 - 18 (9.3 ± 8.1) months. RESULTS: All patients experienced relieved symptoms. Three of them had their NYHA functional class improved except case 2. Echocardiography revealed that LVOTGs right after operations were 38, 79, 20 and 0 mm Hg, respectively, suggesting significant improvement of left ventricular outflow tract obstruction (LVOTO) in all patients. During follow-up, case 2 suffered from recurrence of LVOTO, while the other 3 cases showed sustained relief. In the last follow-up, the LVOTGs of the four patients were 19, 168, 16 and 0 mm Hg, respectively. Echocardiography also revealed that MRs of all patients were significantly reduced, even in case 2 whose LVOTG rebounded, with no recurrence during follow-up. Severe complications were absent, such as ventricular septum perforation, cardiac tamponade, ventricular tachycardia or ventricular fibrillation. No one suffered from complete heart block. Transient complete right bundle branch block (CRBBB) was observed in case 1 after PTSMA and converted to intraventricular block after 1 month. Complete left bundle branch block (CLBBB) was present in both case 3 and 4, who received SM. In case 4, it converted to intraventricular block after 1 month while in case 3 CLBBB persisted. CONCLUSIONS: The initial experience showed that PTSMA and SM were safe and effective for drug-refractory symptomatic HOCM children, with satisfactory short-term results. Further studies are needed to evaluate the long-term results and complications.

[Interventional catheterization management for patients with postoperative residual cardiovascular malformations].

OBJECTIVE: To evaluate the efficacy of interventional therapy for complex congenital heart defects patients with un-repaired or postoperative residual lesions. METHODS: Between March 1998 and April 2009, 42 patients (12 females), mean age 6 years (5 months to 30 years) received interventional therapy, 17 cases underwent occlusion of major aorto-pulmonary collateral arteries (MAPCAs), 15 underwent device closure of residual ventricular or atrial septal shunting, 12 underwent balloon angioplasty (n = 10) and stenting (n = 2) for stenosis of the anastomosis of vessels or branched pulmonary arteries. RESULTS: Twenty-three MAPCAs were performed in 17 patients without residual shunting. One patient died of multiple organ failure after intervention therapy and the remaining patients discharged without complication, successful device closure was performed in 15 patients and there was minimal residual shunting in 1 patient. There were no severe arrhythmias such as complete atrio-ventricular block during and post procedure. Exercise capacities were significantly improved in 12 patients underwent balloon angioplasty or stenting. Pressure gradients were significantly decreased and there was no aneurysmal or thromboembolic formation post procedure. CONCLUSIONS: Interventional therapy is a safe and effective therapy option for treating complex congenital heart defects patients with un-repaired or postoperative residual lesions.

[Diagnosis and treatment of arrhythmogenic right ventricular cardiomyopathy in children].

OBJECTIVE: To summarize the experience in diagnosis and treatment of arrhythmogenic right ventricular cardiomyopathy (ARVC) in children. METHODS: A total of 14 children (7 females and 7 males) with ARVC were involved. The cases underwent electrocardiography, echocardiography, cardiac CT or MRI examinations. All cases were treated with sotalol or amiodarone in combination with propranolol. In 2 cases with drug-refractory ventricular extrasystoles, catheter ablation treatment was performed. In 6 cases with obvious impaired ventricular function, additional pharmacological therapy including vasodilators, diuretics, and digitalis were given. RESULTS: Ventricular extrasystoles occurred in all 14 cases and ventricular tachycardia in 8 cases. Ten cases showed Epsilon wave on electrocardiography. All 14 cases had enlarged right ventricle and reduced right ventricular ejection fraction. CT or MRI examination showed right ventricular dilatation and a thinned wall of right ventricle in 10 cases. Ventricular extrasystoles or tachycardia disappeared in 7 cases and was reduced in 4 cases after treatment. The two children receiving catheter ablation treatment did not present ventricular extrasystoles or tachycardia in a 3-month follow-up. The heart function was improved in the 6 children with obvious impaired ventricular function after pharmacological therapy. CONCLUSIONS: The clinical manifestations are diverse in children with ARVC. A definite diagnosis of ARVC should be based on a combination of electrocardiography and echocardiography examinations. Pharmacological therapy is effective partially. Catheter ablation treatment appears to be a promising option in patients with drug-refractory ventricular extrasystoles.

[Early complications following transcatheter occlusion of perimembranous ventricular septal defects in children].

OBJECTIVE: To evaluate the early complications during and after transcatheter closure of perimembranous ventricular septal defects (PMVSDs) in children. METHODS: A total of 223 patients received transcatheter closure of PMVSDs from March 2002 to December 2005 in our hospital were included in this retrospective study. RESULTS: The overall complications rate was 26.9% (60/223). Major complications occurred in 9 patients (4.0%) including III degrees atrioventricular block (AVB) in 2 (0.9%), hemolysis in 3 (1.3%) and surgical interventions in 4 patients (1.8%) because of device malposition (1), mild aortic regurgitation (2) and device embolization (1) and all 4 patients recovered without further complications. The 2 patients with III degrees AVB were completely recovered to normal sinus rhythm after 7 days treatment with temporary pacemaker and corticosteroid. Hemolysis in 3 patients disappeared after corticosteroid treatment. Minor complications occurred in 51 patients (22.8%) including bundle branch block (BBB) in 37 (16.6%), first-degree AVB in 2 (0.9%), second-degree AVB in 1 (0.4%), new-onset mild aortic regurgitation in 5 (2.2%) and new-onset mild to moderate tricuspid regurgitation in 6 patients (2.6%). Except for right bundle branch blocks, other BBBs were treated with albumin and corticosteroid and completely recovered. No treatment was applied for new-onset valve regurgitations. There was no death in all 223 patients. CONCLUSIONS: Early complications post PMVSDs in children are mostly minor with good prognosis and the prognosis for major complications post PMVSDs is good after proper treatment.

[A follow-up study on transcatheter closure of patent ductus arteriosus with Amplatzer duct occluder in children].

OBJECTIVE: To document the five-year follow-up results of transcatheter Amplatzer duct occluder (ADO) occlusion of patent ductus arteriosus (PDA) in children and to assess the safety and effectiveness of this method for PDA closure. METHODS: A retrospective cohort study was completed in patients with PDA underwent transcatheter closure by the ADO in Guangdong Cardiovascular Institute from April 1998 to December 2003. RESULTS: Transcatheter closure of PDA with ADO was attempted in 250 children patients. The median age was 5.3 years and median weight was 15.1 kg. The PDAs were from 1.8 mm to 11.0 mm (median 4.2 mm) in the narrowest diameter, of which 52 were larger than 5 mm (20.0%). All PDAs were occluded with 4 approximately 14 mm ADO through 6F (n = 205) or 7F (n = 45) sheaths. Devices were successfully implanted in 245 patients (98.0%). The Qp/Qs decreased from 1.90 +/- 0.60 to 1.03 +/- 0.21 (P < 0.05). All shapes of the PDA could be closed. Late complication occurred in five patients, including hemolysis in three patients and the los of the pulse of femoral artery in two patients. Follow-up after device implantation was accomplished in 205 patients (82.0%). The incidence of residual shunt at follow-up periods of 1 d, 1 m, 6 m, 12 m, 24 m, 36 m, 48m and 60 m after device occlusion was 9.2%, 2.8%, 1.2%, 0.8%, 0, 0, 0 and 0, respectively. Five patients (2.0%) required re-intervention to treat residual shunt with or without hemolysis. Event-free rates were 98.0% at one year and five years. CONCLUSION: This long-term follow-up result confirmed the safety and effectiveness of ADO closure of PDAs in children.

[Applying interventional treatment for the atrial septal defect in 165 children under five years of age].

OBJECTIVE: To study the clinical technology of transcatheter closure of secundum atrial septal defects (ASD) with Amplatzer device in younger and lower body weight children. METHODS: The transcatheter closure of ASD using Amplatzer septal occluder (ASO) was performed in 165 children under 5 years of age (75 boys and 90 girls) with secundum ASD from Aug 1998 to May 2004. The age of the cases ranged from 2 to 5 (mean 3.7 +/- 1.1) years. The body weight ranged from 9 to 18 (mean 12.6 +/- 2.3) kg. The ratio of pulmonary circulation quantity to the systemic circulation quantity (Qp/Qs) was 3.2 +/- 1.9. All the patients underwent clinical examination, X-ray, electrocardiography (ECG) and echocardiography (Echo) for diagnosis of secundum ASD. The transthoracic echocardiography (TTE) was used to detect and measure the defect of the patients and even trans-esophageal echocardiography (TEE) had to be used when it was necessary. With Echo and X-ray guidance, the measuring balloon was used in the body and outside the body to determine the balloon-stretch diameters of ASD, and proper occluders were selected accordingly for the patients for interventional treatment of ASD. RESULTS: The devices were implanted successfully in 163 (98.8%) cases. One failure occurred in a case in whom the device moved into the left atrium after release, and the other failure was that the position of the device was uncertain because of temporary unavailability of a special transducer for TEE. Surgical operations were performed for these two cases. The stretch diameter of ASD was from (8 - 30) mm, (mean 18.3 +/- 5.1) mm. The size of device was selected according to the stretch diameter of ASD. The diameter of the occluders selected was from (8 - 30), (mean 18.6 +/- 5) mm in this series. The occlusion procedure was monitored by fluoroscopy and TTE and in 5 cases (3%) by TEE. The diameter of right ventricle was improved within 2 days after occlusion from (mean 16.4 +/- 4.9) mm to (mean 12.6 +/- 3.8) mm, (p < 0.01). One hundred and forty seven cases belonged to the simple secundum ASD(89%). Thirteen cases who were complicated with other cardiac deformity were treated successfully with different interventional procedure. Six cases had multiple openings and three of these cases had tumour-like changes of the atrial septum which were closed completely just by one occluder. In only one case small quantity of residual shunt remains. No other severe complication was found in this group. About 100 cases (60%) had large ASD, so the procedure was more difficult in those cases. CONCLUSION: The clinical effectiveness of treatment of ASD in children under 5 years of age with Amplatzer occluders was satisfactory and therefore this therapeutic procedure is feasible for this age group of patients. Nevertheless, we do not recommend to use the technique for infants and children under 2 years of age. Strict selection of indications and proper size of occluder and good cardiologic and surgical settings are among the basic factors for successful interventional occlusion of ASD in young children.

[Management of the arrhythmia around the procedure of transcatheter closure of ventricular septal defects in pediatric patients].

OBJECTIVE: To discuss the treatment of arrhythmia occurs in the process of transcatheter closure of perimembranous ventricular septal defects (VSD) in pediatric patients. METHODS: 182 cases (mean age: 6.2 +/- 3.3 years) with membranous VSD underwent transcatheter occlusion procedure. Two different devices were used: the Amplatzer membranous VSD occluder in 81 patients and the domestic-made device in 101 patients. Electrocardiogram of all patients was recorded before and during closure and at one day after the procedure, and Holter monitoring was performed one week after the procedure. RESULTS: Perioperation arrhythmia occurred in thirty-one patients (17%). Second- or third-degree atrioventricular bundle (AVB) was noted during the procedure in four patients. Normal AV conduction recovered spontaneously before the catheters were withdrawn in three cases and another patient underwent surgical repair. In the other twenty-seven patients, arrhythmia was first documented between one day and one week after the procedure. Third-degree AVB was found in three (1.6%) children after the procedure and underwent the temporary pacemaker (TPM) was implanted, two of them recovered to normal sinus rhythm within one week, another patient underwent elective surgery to remove the occluder and repair the defect. Other arrhythmias were: left bundle-branch block (n = 3), right bundle-branch block (n = 12), second-degree AVB (n = 2), sinus tachycardia (n = 6). CONCLUSIONS: In properly selected cases of perimembranous VSD, the transcatheter closure is safe and effective by using appropriate devices. During and after the procedure, closure of VSD can be associated with some kinds of arrhythmia, such as A-V block, more intensive observation and follow-up were therefore needed.