Gut microbiota-derived cholic acid mediates neonatal brain immaturity and white matter injury under chronic hypoxia.

Chronic hypoxia, common in neonates, disrupts gut microbiota balance, which is crucial for brain development. This study utilized cyanotic congenital heart disease (CCHD) patients and a neonatal hypoxic rat model to explore the association. Both hypoxic rats and CCHD infants exhibited brain immaturity, white matter injury (WMI), brain inflammation, and motor/learning deficits. Through 16s rRNA sequencing and metabolomic analysis, a reduction in B. thetaiotaomicron and P. distasonis was identified, leading to cholic acid accumulation. This accumulation triggered M1 microglial activation and inflammation-induced WMI. Administration of these bacteria rescued cholic acid-induced WMI in hypoxic rats. These findings suggest that gut microbiota-derived cholic acid mediates neonatal WMI and brain inflammation, contributing to brain immaturity under chronic hypoxia. Therapeutic targeting of these bacteria provides a non-invasive intervention for chronic hypoxia patients.

Novel dominant-negative FOXJ1 mutation in a family with heterotaxy plus mouse model.

Background: Primary ciliary dyskinesia (PCD) is a clinically heterogeneous group of autosomal or, less frequently, X-chromosomal recessive inheritance syndrome of motile cilia dysfunction characterized by neonatal respiratory distress, oto-sino-pulmonary disease, infertility and situs inversus. Recently, type 43 PCD (CILD43, OMIM#618699) was established by autosomal-dominant loss-of-function mutations identified in Forkhead box J1 (FOXJ1). However, the functional validation of FOXJ1 mutations in humans and mice has not been fully performed. Here we studied a three-generation family with heterotaxy and proband with complex congenital heart disease (CHD). Methods: We performed whole-exome sequencing to investigate the causative variant of this family and generated gene knock-in mice carrying the human equivalent mutation by homologous recombination. Then, microscopy analysis was used to characterize the phenotype and ciliary ultrastructure of the model. Effects of the variant on heart anomaly were preliminarily explored through transcriptome sequencing. Results: A novel heterozygous deletion variant (c.1129delC/p.Leu377Trpfs*76) of FOXJ1 was discovered that exerts a dominant-negative effect (DNE) in vitro. Notably, both homozygous (Foxj1c.1129delT/c.1129delT) and heterozygous (Foxj1+/c.1129delT) mice developed situs inversus, hydrocephalus and showed a disruption of trachea cilia structure, whereas these abnormalities were only observed in previously reported Foxj1-/-, not Foxj1+/- mice. Thus, a more severe phenotype and higher expressivity of our mouse model further indicated the DNE of this mutation. Meanwhile, several cardiomyopathy-related genes were differentially expressed in the homozygous Foxj1 knock-in mouse hearts, pointing to a probable function in cardiac pathology. Conclusions: Overall, our study results showed that c.1129delC mutation in FOXJ1 was regarded as the cause of situs inversus in this family and this mutant showed a capacity of DNE over wild-type FOXJ1, causing more serious consequences than the allelic deletion of Foxj1.

Review of surgical experience in 188 infants and young children with Ebstein anomaly.

OBJECTIVES: This study sought to review our single-institutional surgical experience in paediatric Ebstein anomaly (EA). METHODS: We retrospectively reviewed the paediatric patients with EA undergoing operation between 2004 and 2020. The time-to-event analysis was studied using Kaplan-Meier estimates. Cox regression model was used to identify risk factors for recurrent moderate-severe or greater tricuspid regurgitation (TR). RESULTS: A total of 188 patients at a median age of 3.0 [interquartile range (IQR), 1.6-5.6] years were included, among whom 108 (57.4%) underwent cone reconstruction (CR). Bidirectional cavopulmonary shunt was required in 53 patients (28.2%). There were no in-hospital deaths. The median follow-up time was 5.6 (IQR, 2.9-8.9) years. Twenty-three (12.2%) developed recurrent moderate-severe or greater TR, among whom 9 required reoperation and 1 had late death. There was a lower incidence of recurrent TR (P = 0.006) and reoperation for TR (P = 0.037) in the CR group compared with the non-CR group. There was no difference in the incidence of recurrent TR (P = 0.61), reoperation (P = 0.9) and death (P = 0.48) among patients aged <1, 1-4 and 4-18 years. CONCLUSIONS: Acceptable outcomes can be anticipated in paediatric EA undergoing CR in terms of freedom from TR of > moderate degree at a mid-term follow-up.

Maternal Outcomes Among Pregnant Women With Congenital Heart Disease-Associated Pulmonary Hypertension.

BACKGROUND: Studies focused on pregnant women with congenital heart disease (CHD)-associated pulmonary hypertension (PH) are scarce and limited by small sample sizes and single-center design. This study sought to describe the pregnancy outcomes in women with CHD with and without PH. METHODS: Outcomes for pregnant women with CHD were evaluated retrospectively from 1993 to 2016 and prospectively from 2017 to 2019 from 7 tertiary hospitals. PH was diagnosed on the basis of echocardiogram or catheterization. The incidence of maternal death, cardiac complications, and obstetric and offspring complications was compared for women with CHD and no PH, mild, and moderate-to-severe PH. RESULTS: A total of 2220 pregnant women with CHD had completed pregnancies. PH associated with CHD was identified in 729 women, including 398 with mild PH (right ventricle to right atrium gradient 30-50 mm Hg) and 331 with moderate-to-severe PH (right ventricle to right atrium gradient >50 mm Hg). Maternal mortality occurred in 1 (0.1%), 0, and 19 (5.7%) women with CHD and no, mild, or moderate-to-severe PH, respectively. Of the 729 patients with PH, 619 (85%) had CHD-associated pulmonary arterial hypertension, and 110 (15%) had other forms of PH. Overall, patients with mild PH had better maternal outcomes than those with moderate-to-severe PH, including the incidence of maternal mortality or heart failure (7.8% versus 39.6%; P<0.001), other cardiac complications (9.0% versus 32.3%; P<0.001), and obstetric complications (5.3% versus 15.7%; P<0.001). Brain natriuretic peptide >100 ng/L (odds ratio, 1.9 [95% CI, 1.0-3.4], P=0.04) and New York Heart Association class III to IV (odds ratio, 2.9 [95% CI, 1.6-5.3], P<0.001) were independently associated with adverse maternal cardiac events in pregnancy with PH, whereas follow-up with a multidisciplinary team (odds ratio, 0.4 [95% CI, 0.2-0.6], P<0.001) and strict antenatal supervision (odds ratio, 0.5 [95% CI, 0.3-0.7], P=0.001) were protective. CONCLUSIONS: Women with CHD-associated mild PH appear to have better outcomes compared with women with CHD-associated moderate-to-severe PH, and with event rates similar for most outcomes with women with CHD and no PH. Multimodality risk assessment, including PH severity, brain natriuretic peptide level, and New York Heart Association class, may be useful in risk stratification in pregnancy with PH. Follow-up with a multidisciplinary team and strict antenatal supervision during pregnancy may also help to mitigate the risk of adverse maternal cardiac events.

Cardiac-type total anomalous pulmonary venous return is not benign.

OBJECTIVE: The objective of this study was to investigate the association between morphological variation and postsurgical pulmonary vein (PV) stenosis (PPVS) in patients with cardiac total anomalous pulmonary venous connection (TAPVC). METHODS: This single-center, retrospective study included 168 pediatric patients who underwent surgical repair of cardiac TAPVC from 2013 to 2019 (connection to the coronary sinus [CS], n = 136; connection directly to the right atrium [RA], n = 32). Three-dimensional computed tomography modeling and geometric analysis were performed to investigate the morphological features; their relevance to the PPVS was examined. RESULTS: The connection type had no association with PPVS (CS type: 18% vs right atrial type: 19%; P = .89) but there was a higher incidence of PPVS in patients with a single PV orifice than > 1 orifice (P < .001). Confluence-to-total PV area ratio (hazard ratio, 4.78, 95% CI, 1.86-12.32; P = .001) and length of drainage route (hazard ratio, 1.22; 95% CI, 1.14-1.31; P < .001) had a 4- and 1-fold increase in the risk for PPVS in the CS type after adjustment for age and preoperative pulmonary venous obstruction. In the right atrial type, those with anomalous PV return to the RA roof were more likely to develop PPVS than to the posterior wall of the RA (P < .001). CONCLUSIONS: The number of inter-junction PV orifice correlated with PPVS development in cardiac TAPVC. The confluence-to-total PV ratio, length of drainage route, and anomalous PV return to the RA roof are important predictors for PPVS. Morphological subcategorization in this clinical setting can potentially assist in surgical decision-making.

Anatomical attention-based prediction of postoperative pulmonary venous obstruction via CTA images.

Total anomalous pulmonary venous connection (TAPVC) is a rare congenital heart disease, with which some patients suffer from postoperative pulmonary venous obstruction (PPVO), requiring particular follow-up strategies and treatments. PPVO prediction has important clinical significance, while building a PPVO prediction model is challenging due to limited data and class imbalance distribution. Inspired by the anatomical evidence of PPVO, which is related to the structure of the left atrium (LA) and pulmonary vein (PV), we design an effective multi-task network for PPVO classification. The proposed method incorporates clinical priors and merits of the segmentation-based network into the classification task. The features learned from segmenting LA and PV are concatenated into the PPVO classification branch to constrain the learning of discriminative features. Anatomical-guided attention is applied in the aggregation of these features to restrict them focusing on TAPVC-related regions. To deal with the imbalance classification problem of PPVO, a novel classification loss derived by masked class activation map (MCAM) is designed to improve the classification performance. Computed tomography angiography (CTA) images of 146 patients diagnosed with supracardiac TAPVC in Shanghai Children's Medical Center and Guangdong Provincial People's Hospital were enrolled in this work. The comprehensive experiments demonstrate the effectiveness and generalization of our proposed method. The automatic PPVO prediction model shows the potential application in helping clinicians develop follow-up strategies, thereby improving the survival rate of TAPVC patients.

Surgical repair of neonatal total anomalous pulmonary venous connection: A single institutional experience with 241 cases.

Objective: Challenges persist in surgery for neonatal total anomalous pulmonary venous connection (neoTAPVC), with the high mortality risk not mitigated over time. Methods: A prospectively collected single-center database containing all neonates with TAPVC undergoing biventricular repair in 2012 to 2020 was retrospectively reviewed. The primary outcome was death or postoperative pulmonary venous obstruction (PPVO). Based on the preoperative admission location in our hospital, patients were classified into those being admitted to cardiac intensive care unit versus neonatal intensive care unit or general pediatric intensive care unit. Access to dedicated presurgical care (DPC) was defined as patients who were preoperatively admitted to the cardiac intensive care unit. Results: Overall, 241 patients with a median age at surgery of 14 days (interquartile range [IQR], 9-21 days) were included. Anomalous return was supracardiac in 38.6%, cardiac in 26.1%, infracardiac in 28.6%, and mixed in 6.6%. Patients receiving DPC had better survival (96.3% vs 84.3%; P = .0028) and lower incidence of PPVO (15.2% vs 28.6%; P = .011) compared with those without DPC. Patients in the DPC group were less likely to undergo operation within 24 hours on presentation (27.1% vs 40.3%; P = .041), had improved lactate clearance (1.5 [IQR, 1.0-2.2] vs 2.8 [IQR, 1.8-4.1]; P < .001), and had lower incidence of postoperative pulmonary hypertension crisis (2.8% vs 18.7%; P < .001) compared with those in no-DPC group. After matching, no difference in PPVO could be observed in patients undergoing conventional versus sutureless repair (22.6% vs 12.9%; P = .29). Conclusions: Access to DPC potentially improves outcomes in the neoTAPVC setting; freedom from PPVO were similar using conventional versus sutureless repair.

Inattention and hyperactivity in children and adolescents with repaired D-transposition of the great arteries: Prevalence, perioperative risk factors, and clinical outcomes.

Objective: The present study objectives were to determine the prevalence of attention-deficit/hyperactivity disorder symptoms (ADHD-like symptoms) in children and adolescent with d-transposition of great artery (D-TGA) after arterial switch operation (ASO) and examine associated risk factors and adverse personal, family dysfunctions. Methods: This cohort study included 103 patients with D-TGA who underwent ASO in early infancy at Shanghai Children's Medical Center between 2011 and 2016 and then follow-up. Data analysis was conducted from September 2020 to April 2022. A standardized Swanson, Nolan, and Pelham IV (SNAP-IV) questionnaire is used to evaluate inattention and hyperactivity symptoms. Demographic, preoperative, intraoperative, and postoperative factor were collected. Univariate and multivariable regression analyses were performed with odds ratios (OR) and 95% confidence intervals (CIs). Results: Prevalence of ADHD-like symptoms was 27.18% (28/103). Attention-deficit (18/28, 64.29%) symptom was the predominant subphenotype. After underwent TGA surgery, 39% of patients with ADHD-like symptoms receive remedial special academic services. There is none had repeated grade. Univariate analysis showed that, positive inotropic drug score (P = 0.03) and delayed sternal closure (P = 0.02) were risk factors of ADHD-like symptoms; increased preoperative oxygen saturation (SpO2) (P = 0.01) and surgical height (P = 0.01) and TGA subtype (VSD) (P = 0.02) were protective factor of ADHD-like symptoms. Multivariable analysis showed that delayed sternal closure (DSC) (OR, 1.50; 95% CI, 1.02-2.18) is a risk factor for the occurrence of ADHD-like symptom while increased preoperative oxygen saturation [odds ratio (OR), 0.95; 95% confidence interval (CI), 0.92-0.99] is a protective factor of ADHD-like symptom. Conclusion: The children and adolescents with D-TGA after ASO were at high risk of ADHD-like symptoms. Preoperative hypoxic status and postoperative DSC became predominant risk factors. Modification of the risk factors may be helpful to relieve ADHD-like symptoms for these patients.

COVID-19 in a Child With Transposition of the Great Arteries S/P Fontan Palliation: A Case Report and Literature Review.

Background: Although adult patients with cardiovascular disease are at higher risk of adverse outcomes such as death or severe infection, limited data exist regarding pediatric patients with congenital heart disease. We would like to report our experience with COVID-19 in a pediatric patient with Fontan circulation. Furthermore, we present a review of patients with Fontan palliation and COVID-19 previously reported in the literature to summarize the clinical characteristics of this population. Case Presentation: A 9-year-old boy with dextro-transposition of the great arteries, ventricular septal defect, pulmonary stenosis, patent foramen ovale, and borderline left ventricle post bidirectional Glenn shunt and Fontan palliation presented with paroxysmal cough in the context of COVID-19. The coagulation profile was beyond the normal limits, and the patient began to receive anticoagulant aspirin. On the 5th day, the patient presented with fever, sore throat, and fatigue. The oxygen saturations dropped to 93%, and he received nasal catheter oxygen inhalation. On the 7th day, computed tomography of the chest revealed little emerging flaky exudation in the posterior basal segment of the left lower lobe. Nasal cannula was removed on the 12th day, and the coagulation profile returned to normal on the 16th day. After two consecutively negative SARS-CoV-2 viral RNA tests (on the 18th and 19th days, interval ≥ 24 h), he was discharged from the hospital on the 21st day. Literature review indicated that COVID-19 with Fontan palliation seemed to be more common in male adults. Disease presentation varied from mild upper respiratory tract infection to severe pneumonia. Complications were not uncommon in this population. The treatments varied depending on the specific factors. Fortunately, most patients reported a favorable prognosis. Conclusion: Although patients with COVID-19 and Fontan circulation might have the risk of adverse outcomes due to multiple mechanisms, most patients have a favorable prognosis.

Risk factors for postoperative pulmonary venous obstruction after surgical repair of total anomalous pulmonary venous connection: a systemic review and meta-analysis.

OBJECTIVES: A meta-analysis was performed to investigate the risk factors for postoperative pulmonary venous obstruction (PVO) after surgical repair of total anomalous pulmonary venous connection (TAPVC). METHODS: Data bases including PubMed, Embase, Web of Science and Cochrane Library were searched systematically. The goal was to discuss the risk factors for postoperative PVO after TAPVC. Publications were screened by 2 authors independently for criteria inclusion, methodological quality assessment and data extraction. The Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality checklist were obtained to assess the quality of the studies. Data were pooled by the random effect model or the fixed effect model according to the heterogeneity test. RESULTS: A total of 16 studies (2,385 participants) were included in the meta-analysis. All included studies were retrospective studies. Six potential risk factors were pooled, 5 of which were significantly associated with postoperative PVO. Patients with preoperative PVO were more likely to suffer from postoperative PVO [odds ratio (OR)=5.27, 95% confidence interval (CI) = (2.75, 10.11), P < 0.01]. Compared with a sutureless procedure, the conventional operative procedure was associated with postoperative PVO [OR = 1.80, 95% CI=(1.20, 2.71), P < 0.01]. A mixed type TAPVC plays a critical role in postoperative PVO [OR = 3.78, 95% CI=(1.08, 13.18), P = 0.04]. Inverse variance analysis showed that longer cardiopulmonary bypass time [hazard ratio (HR)=1.01, 95% CI=(1.01, 1.02), P < 0.00001] and aortic cross-clamp time [HR = 1.01, 95% CI=(1.01, 1.02), P < 0.01] were significantly associated with postoperative PVO. Heterotaxy [OR = 1.18, 95% CI = 0.13, 10.45, P = 0.88] was not statistically significant as a risk factor for postoperative PVO. CONCLUSIONS: This meta-analysis may provide a perspective on the risk factors for postoperative PVO after TAPVC, thus leading to more studies predicting postoperative PVO after TAPVC with our findings.

Surgical options for proximal and distal transverse arch hypoplasia in infants with coarctation.

Background: Although various surgical techniques have been reported for aortic arch reconstruction for proximal and distal transverse arch (PDTA) hypoplasia, no consensus has been reached on a surgical option for initial arch reconstruction. This study was undertaken to review various arch reconstruction options for PDTA hypoplasia in Chinese infants. Methods: A retrospective review of 121 infants who underwent initial arch reconstruction of the proximal and distal aortic arches between 2010 and 2020 was performed. Freedom from recoarctation was analyzed using Kaplan-Meier analysis. Univariate and multivariable Cox regression analyses were performed to determine perioperative data associated with an increased risk of recoarctation after surgery. Results: Aortic arch reconstruction was performed by end-to-side anastomosis (ESA) (n=37) or patch repair [autologous pericardial patch (APP), n=53; bovine pericardial patch (BPP), n=20; autologous pulmonary artery patch (APAP), n=11]. The relative diameter of the proximal arch was 0.51±0.07, and the relative diameter of the distal arch was 0.43±0.07. The median follow-up time was 679 (range, 388-1,362) days. Recoarctation was observed in 44 (36.4%) patients. ESA was an independent risk factor for further development of recoarctation after the initial aortic arch reconstruction [hazard ratio (HR) =2.13; P=0.020]. Conclusions: Aortic arch reconstruction via ESA was an independent risk factor for late recoarctation of the proximal and distal aortic arches in patients who underwent the initial surgery in infancy. Trial Registration: Chinese Clinical Trials Registry ChiCTR2100048212.

Building a Risk Prediction Model for Postoperative Pulmonary Vein Obstruction via Quantitative Analysis of CTA Images.

Total anomalous pulmonary venous connection (TAPVC) is a rare but mortal congenital heart disease in children and can be repaired by surgical operations. However, some patients may suffer from pulmonary venous obstruction (PVO) after surgery with insufficient blood supply, necessitating special follow-up strategy and treatment. Therefore, it is a clinically important yet challenging problem to predict such patients before surgery. In this paper, we address this issue and propose a computational framework to determine the risk factors for postoperative PVO (PPVO) from computed tomography angiography (CTA) images and build the PPVO risk prediction model. From clinical experiences, such risk factors are likely from the left atrium (LA) and pulmonary vein (PV) of the patient. Thus, 3D models of LA and PV are first reconstructed from low-dose CTA images. Then, a feature pool is built by computing different morphological features from 3D models of LA and PV, and the coupling spatial features of LA and PV. Finally, four risk factors are identified from the feature pool using the machine learning techniques, followed by a risk prediction model. As a result, not only PPVO patients can be effectively predicted but also qualitative risk factors reported in the literature can now be quantified. Finally, the risk prediction model is evaluated on two independent clinical datasets from two hospitals. The model can achieve the AUC values of 0.88 and 0.87 respectively, demonstrating its effectiveness in risk prediction.

Review of surgical experience in 61 patients with mixed total anomalous pulmonary venous connection.

OBJECTIVES: Prior studies have reported a high mortality and incidence of post-repair pulmonary venous obstruction (PVO) in mixed total anomalous pulmonary venous connection (TAPVC). This study sought to review the surgical outcomes in this entity. METHODS: A review of 61 patients undergoing surgical repair of mixed TAPVC was conducted. Patients with a single ventricle were excluded. Patients were subdivided into 3 groups according to Chowdhury's classification. Predictors for death and postoperative PVO were explored by Cox regression model. RESULTS: This study trended towards an older cohort with a median age of 88 days (interquartile range, 56.5-177). Twelve patients belonged to '2 + 2' type, 40 belonged to '3 + 1' type and the remaining 9 belonged to bizarre type. There were no early death and 7 late deaths. Follow-up was available in 96.7% of the patients after discharge with a median duration of 53 months (range, 1-177). Nineteen patients developed post-repair PVO among whom 2 required reintervention. Patients with preoperative PVO had a 4-fold higher risk (95% confidence interval, 1.36-12.38) of postoperative PVO than those without and were more likely to die (P = 0.009). No statistical difference was observed among the 3 subgroups in terms of mortality (P = 0.058) and postoperative PVO (P = 0.186). CONCLUSIONS: Preoperative PVO was significantly associated with postoperative PVO. There was no statistical difference in terms of death and postoperative PVO among the 3 subtypes of mixed TAPVC. Mid-term results favoured a complete rechanneling of pulmonary veins in '3 + 1' type.

Impact of early Coronavirus Disease 2019 pandemic on pediatric cardiac surgery in China.

OBJECTIVE: This study aimed to provide an insight into the impact of the early outbreak of the novel Coronavirus Disease 2019 on the care management for patients with congenital heart disease. METHODS: This study respectively enrolled a cohort of surgical patients who underwent surgery in 2018 (group I), 2019 (group II), and 2020 (group III) and a cohort of follow-up patients who had follow-up in 2017 (group A), 2018 (group B), and 2019 (group C) in 13 children hospitals. RESULTS: During the Coronavirus Disease 2019 era, there was a significant decrease in total surgical volume and a change in case mix in terms of an increase in the proportion of emergency operations. Decrease in migration scale index was correlated to the decrease in both surgical volume (r = 0.64, P = .02) and outpatient visit volume (r = 0.61, P = .03). There was a significantly higher proportion of patients who had follow-up through the internet or phone in group C (26.4% vs 9.6% in group B and 8.9% in group A; P < .0001). There was no statistical difference in death or rehospitalization among the 3 follow-up groups (P = .49). There was higher parents' anxiety score (P < .0001) and more use of telemedicine (P = .004) in group C compared with groups A and B. CONCLUSIONS: The Coronavirus Disease 2019 pandemic has resulted in a considerable decrease in total surgical volume and a change of case mix, which seems to be related to the strict traffic ban. Follow-up through the online medical service appears to be an effective alternative to the conventional method.

Artificial intelligence-assisted auscultation in detecting congenital heart disease.

Aims: Computer-assisted auscultation has become available to assist clinicians with physical examinations to detect congenital heart disease (CHD). However, its accuracy and effectiveness remain to be evaluated. This study seeks to evaluate the accuracy of auscultations of abnormal heart sounds of an artificial intelligence-assisted auscultation (AI-AA) platform we create. Methods and results: Initially, 1397 patients with CHD were enrolled in the study. The samples of their heart sounds were recorded and uploaded to the platform using a digital stethoscope. By the platform, both remote auscultation by a team of experienced cardiologists from Shanghai Children's Medical Center and automatic auscultation of the heart sound samples were conducted. Samples of 35 patients were deemed unsuitable for the analysis; therefore, the remaining samples from 1362 patients (mean age-2.4 ± 3.1 years and 46% female) were analysed. Sensitivity, specificity, and accuracy were calculated for remote auscultation compared to experts' face-to-face auscultation and for artificial intelligence automatic auscultation compared to experts' face-to-face auscultation. Kappa coefficients were measured. Compared to face-to-face auscultation, remote auscultation detected abnormal heart sound with 98% sensitivity, 91% specificity, 97% accuracy, and kappa coefficient 0.87. AI-AA demonstrated 97% sensitivity, 89% specificity, 96% accuracy, and kappa coefficient 0.84. Conclusions: The remote auscultations and automatic auscultations, using the AI-AA platform, reported high auscultation accuracy in detecting abnormal heart sound and showed excellent concordance to experts' face-to-face auscultation. Hence, the platform may provide a feasible way to screen and detect CHD.

Single-institution outcomes of surgical repair of infracardiac total anomalous pulmonary venous connection.

OBJECTIVE: This contemporary study sought to describe the outcomes of patients undergoing biventricular repair of infracardiac total anomalous pulmonary venous connection. METHODS: A retrospective study was performed on patients with infracardiac total anomalous pulmonary venous connection who underwent sutureless technique or conventional repair between 2006 and 2018. Risk factors for survival and post-repair pulmonary vein stenosis (PVS) were assessed with Cox regression model. Time-to-event analysis was conducted using Kaplan-Meier estimates. RESULTS: This study included 82 consecutive patients with the median age of 21 days (interquartile range, 9-40 days). The median follow-up was 29 months (interquartile range, 12.5-59 months) and was available in 95% of the survivors at the end of the study period in 2019. Overall, 8 deaths (8.5%) occurred in the conventional repair group. There was a trend of higher mortality in the conventional repair group, although it did not reach a statistical difference (P = .2). Postrepair PVS occurred at a median of 2 months (interquartile range, 1.2-3.6 months) postoperatively and all occurred in the conventional repair group. Time-to-event analysis with the event of postrepair PVS showed significantly higher freedom from restenosis in the sutureless technique group (P = .0004). Adjusted hazard ratios from time-dependent Cox model described the association between postrepair PVS and pulmonary venous confluence of antler configuration (hazard ratio, 2.14; 95% confidence interval, 1.03-5.47; P = .002) and the use of sutureless technique (hazard ratio, 0.72; 95% confidence interval, 0.39-0.97; P = .003). CONCLUSIONS: Sutureless technique is associated with a lower risk of postrepair PVS in patients with infracardiac total anomalous pulmonary venous connection. pulmonary venous confluence configuration of antler appearance appears to be associated with restenosis and mortality.

15q11.2 deletion is enriched in patients with total anomalous pulmonary venous connection.

INTRODUCTION: CNV is a vital pathogenic factor of congenital heart disease (CHD). However, few CNVs have been reported for total anomalous pulmonary venous connection (TAPVC), which is a rare form of CHD. Using case-control study, we identified 15q11.2 deletion associated with TAPVC. We then used a TAPVC trio as model to reveal possible molecular basis of 15q11.2 microdeletion. METHODS: CNVplex and Chromosomal Microarray were used to identify and validate CNVs in samples from 231 TAPVC cases and 200 healthy controls from Shanghai Children's Medical Center. In vitro cardiomyocyte differentiation of induced pluripotent stem cells from peripheral blood mononuclear cells for a TAPVC trio with paternal inherited 15q11.2 deletion was performed to characterise the effect of the deletion on cardiomyocyte differentiation and gene expression. RESULTS: The 15q11.2 microdeletion was significantly enriched in patients with TAPVC compared with healthy control (13/231 in patients vs 0/200 in controls, p=5.872×10-2, Bonferroni adjusted) using Fisher's exact test. Induced pluripotent stem cells from the proband could not differentiate into normal cardiomyocyte. Transcriptomic analysis identified a number of differentially expressed genes in the 15q11.2 deletion carriers of the family. TAPVC disease-causing genes such as PITX2, NKX2-5 and ANKRD1 showed significantly higher expression in the proband compared with her healthy mother. Knockdown of TUBGCP5 could lead to abnormal cardiomyocyte differentiation. CONCLUSION: We discovered that the 15q11.2 deletion is significantly associated with TAPVC. Gene expression profile that might arise from 15q11.2 deletion for a TAPVC family was characterised using cell experiments.

The therapeutic impact of human neonatal BMSC in a right ventricular pressure overload model in mice.

OBJECTIVE: To determine the impact of donor age on the therapeutic effect of bone marrow-derived mesenchymal stem cells (BMSCs) in treating adverse remodeling as the result of right ventricle (RV) pressure overload. METHODS: BMSCs were isolated from neonatal (< 1 month), infant (1 month to 1 year), and young children (1 year to 5 years) and were compared in their migration potential, surface marker expression, VEGF secretion, and matrix metalloprotein (MMP) 9 expression. Four-week-old male C57 mice underwent pulmonary artery banding and randomized to treatment and untreated control groups. During the surgery, BMSCs were administered to the mice by intramyocardial injection into the RV free wall. Four weeks later, RV function and tissue were analyzed by echocardiography, histology, and quantitative real-time polymerase chain reaction. RESULTS: Human neonatal BMSCs demonstrated the greatest migration capacity and secretion of vascular endothelial growth factor but no difference in expression of surface markers. Neonate BMSCs administration resulted in increasing expression of VEGF, a significant reduction in RV wall thickness, and internal diameter in mice after PA banding. These beneficial effects were probably associated with paracrine secretion as no cardiomyocyte transdifferentiation was observed. CONCLUSIONS: Human BMSCs from different age groups have different characteristics, and the youngest BMSCs may favorably impact the application of stem cell-based therapy to alleviate adverse RV remodeling induced by pressure overload.