Medium-term outcomes of bovine jugular valved conduits for right ventricular outflow tract reconstruction in children: a retrospective cohort study from China.

Background: Bovine jugular valved conduit (BJVC) has been reported as an optional material for right ventricular outflow tract (RVOT) reconstruction in patients with complex congenital heart disease (CHD). It showed comparable or even better performance than homograft. However, the durability of BJVC is still very poor in infants and children. Herein, we retrospectively analyzed and evaluated the mid-term results of RVOT reconstruction by using bovine jugular vein valved conduits (Balance BJVCs) in CHD patients, with a special focus on the functional status of the conduits. Methods: Pediatric patients undergoing RVOT reconstruction using Balance BJVC in Guangzhou Women and Children's Medical Center from January 2018 to December 2020 were enrolled in this study. The demographic information, cardiac anatomical abnormalities, preoperative hemodynamic characteristics, surgical details, postoperative outcomes, and follow-up data of the patients were reviewed retrospectively. Results: Ninety-four patients were enrolled in this study. The median age at implantation was 22 months (range, 2-168 months), the median weight was 10.8 kg (range, 3.8-40.0 kg); 34 children (36.2%) were younger than 1 year. The most common disease in these children was pulmonary atresia with ventricular septal defect (PA/VSD) (66/94, 70.2%). The patients were followed up for a median of 43.5 months (range, 6-60 months). Late mortality occurred in 4 (4.3%). Cumulatively, conduit dysfunction at different levels occurred in 31 (33%), conduit failure in 9 (9.6%), 6 patients underwent reoperation for conduit replacement, 5 (5.3%) developed infective endocarditis (IE) within 24 months (range, 12-36 months) after the surgery. Five-year survival rate is 95.7%. The free of conduit dysfunction rates at 1, 3, and 5 years was 91.4%, 68.5%, and 50.4%, respectively. In addition, the rates of patients who were free of conduit failure at 1, 3, and 5 years were 100%, 88.9%, and 88.9%, respectively. Conclusions: Despite the high risk of BJVC dysfunction, approximately 90% of children are free from conduit failure at 5 years after conduit implantation through aggressive transcatheter intervention without increasing the incidence of IE. Thus, BJVC remains a useful alternative material for RVOT reconstruction in patients with complex CHD.

Transmembrane BAX inhibitor motif containing 6 suppresses presenilin-2 to preserve mitochondrial integrity after myocardial ischemia-reperfusion injury.

Myocardial ischemia-reperfusion (I/R) damage is characterized by mitochondrial damage in cardiomyocytes. Transmembrane BAX inhibitor motif containing 6 (TMBIM6) and presenilin-2 (PS2) participate in multiple mitochondrial pathways; thus, we investigated the impact of these proteins on mitochondrial homeostasis during an acute reperfusion injury. Myocardial post-ischemic reperfusion stress impaired myocardial function, induced structural abnormalities and promoted cardiomyocyte death by disrupting the mitochondrial integrity in wild-type mice, but not in TMBIM6 transgenic mice. We found that TMBIM6 bound directly to PS2 and promoted its post-transcriptional degradation. Knocking out PS2 in mice reduced I/R injury-induced cardiac dysfunction, inflammatory responses, myocardial swelling and cardiomyocyte death by improving the mitochondrial integrity. These findings demonstrate that sufficient TMBIM6 expression can prevent PS2 accumulation during cardiac I/R injury, thus suppressing reperfusion-induced mitochondrial damage. Therefore, TMBIM6 and PS2 are promising therapeutic targets for the treatment of cardiac reperfusion damage.

Identification of novel rare copy number variants associated with sporadic tetralogy of Fallot and clinical implications.

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Highly penetrant copy number variants (CNVs) and genes related to the etiology of TOF likely exist with differences among populations. We aimed to identify CNV contributions to sporadic TOF cases in Han Chinese. Genomic DNA was extracted from peripheral blood in 605 subjects (303 sporadic TOF and 302 unaffected Han Chinese [Control] from cardiac centers in China) and analyzed by genome-wide association study (GWAS). The GWAS results were compared with existing Database of Genetic Variants. These CNVs were further validated by qPCR. Bioinformatics analyses were performed with protein-protein interaction (PPI) network and KEGG pathway enrichment. Across all chromosomes 119 novel "TOF-specific CNVs" were identified with prevalence of CNVs of 21.5% in chromosomes 1-20 and 37.0% including Chr21/22. In chromosomes 1-20, CNVs on 11q25 (encompasses genes ACAD8, B3GAT1, GLB1L2, GLB1L3, IGSF9B, JAM3, LOC100128239, LOC283177, MIR4697, MIR4697HG, NCAPD3, OPCML, SPATA19, THYN1, and VPS26B) and 14q32.33 (encompasses genes THYN1, OPCML, and NCAPD3) encompass genes most likely to be associated with TOF. Specific CNVs found on the chromosome 21 (6.3%) and 22(11.9%) were also identified in details. PPI network analysis identified the genes covering the specific CNVs related to TOF and the signaling pathways. This study for first time identified novel TOF-specific CNVs in the Han Chinese with higher frequency than in Caucasians and with 11q25 and 14q32.33 not reported in TOF of Caucasians. These novel CNVs identify new candidate genes for TOF and provide new insights into genetic basis of TOF.

Outcomes of treatment for right atrial isomerism with functional single ventricle and extracardiac total anomalous pulmonary venous connection beyond neonatal period: Delayed surgical treatment, improving outcomes.

Objective: Total anomalous pulmonary venous connection (TAPVC) is frequently associated with right atrial isomerism (RAI), which is commonly complicated with an unbalanced atrioventricular canal with contralateral hypoplasia, complex systemic and pulmonary venous anatomy, and conotruncal abnormalities, resulting in increased risk of mortality. This study aimed to review the outcomes of delayed surgical treatment for patients with RAI complicated with functional single ventricle (FSV) and TAPVC at a single center. Methods: In this retrospective study, we reviewed the medical records of 24 consecutive patients with RAI complicated with FSV and TAPVC who underwent initial surgical palliation after 5-month old between September 2008 and June 2019. Demographic data, concomitant anomalies, age at initial palliation, and surgical interventions were extracted and analyzed using the Cox proportional hazard model to assess risk factors for mortality and the Kaplan-Meier method to assess survival. Results: The in-hospital mortality was 12.5% (three out of 24). The causes of death were pulmonary arterial hypertension and low cardiac output syndrome. Average follow-up was 65.2 ± 40.3 months (7-137 months). Another 4 patients died during the follow-up due to low cardiac output syndrome, protein-losing enteropathy and pulmonary arterial hypertension, respectively. Kaplan-Meier estimated survival at 1 and 5 years were 83.1 and 69.4%, respectively. Fontan completion was 45.8% (11/24). The mortality for patients with pulmonary venous obstruction (PVO) was 66.7% (4/6). Cox multivariate regression analysis indicated that preoperative PVO was the only risk factor for mortality (p = 0.032; hazard ratio, 10.000; CI 1.222-81.811). Conclusion: Outcomes of delayed surgical treatment for patients with RAI complicated with FSV and TAPVC have improved significantly. The survival and Fontan completion were higher. However, preoperative PVO was still the risk factor for mortality.

Outcomes of the Surgical Management of Atrial Isomerism and Functional Single Ventricle: A Single-Centered Cohort From China.

Objectives: The management of atrial isomerism with complex congenital heart disease remains challenging. Experience has been largely obtained in advanced countries. The clinical diversity is greater in China. We evaluated the early- and medium-term outcomes of surgical treatment of these patients. Methods: We reviewed 86 patients of atrial isomerism with complex congenital heart disease undergoing varied surgeries in our center in 2008-2020. Cox regression models were used to analyze the risk factors for mortality. Results: There were 75 cases of right and 11 of left atrial isomerism. Eighty-three (96.5%) patients underwent single-ventricle staged palliation approach, with 10 early and 7 late deaths. The overall 1-, 5-, and 10-year survival rates were 84.7, 79.3, and 79.3%, respectively. Thirty-six (43.4%) patients completed the Fontan procedure with median age of 48 months and freedom from death or Fontan failure at 1-, 5-, and 8-years were 94.4, 87.4, and 80.7%, respectively. Concomitant total anomalous pulmonary venous connection [hazard ratio (HR): 5.15 (1.95-12.94), p = 0.008], more than moderate atrioventricular valve regurgitation [HR: 4.82 (2.42-6.79), p = 0.003], and the need for first-stage palliative surgery [HR: 4.58 (1.64-10.76), p = 0.015] were independent risk factors for mortality. Conclusions: Despite even greater clinical diversity, the surgical outcomes of atrial isomerism with complex congenital heart disease are improving in China. The early and intermediate outcomes are comparable to many previous reports. Concomitant total anomalous pulmonary venous connection, moderate or severe atrioventricular valve regurgitation, and the need for a first-stage palliative surgery are still independent risk factors for mortality.

Verifying the Usefulness of Pulmonary Blood Flow Studies in the Correction of Pulmonary Atresia and Ventricular Septal Defect with Major Aortopulmonary Collateral Arteries.

OBJECTIVE: We retrospectively analyzed the surgical results of pulmonary blood flow studies to guide ventricular septal defect (VSD) closure in the correction of pulmonary atresia and ventricular septal defect with major aortopulmonary collateral arteries (PA/VSD/MAPCAs). METHODS: A total of 57 children who were diagnosed with PA/VSD/MAPCAs and who underwent intraoperative pulmonary blood flow studies at our hospital between August 2016 and June 2019 were included. Surgery and cardiopulmonary bypass records were collected. The receiver operating characteristic (ROC) curve was used to verify the accuracy of pulmonary blood flow studies to predict VSD closure. RESULTS: Complete VSD closure was achieved in 39 of 57 children (68.42%), with a median age of 2 years and 5 months (range: 7 months to 15 years and 9 months) and a median weight of 11.0 kg (5.7-36.5 kg). Partial VSD repair was recorded for 21 children (36.84%), including 4 children (19.05%) who underwent VSD closure in the later stages and 13 children (61.90%) who were under follow-up and waiting to undergo complete VSD closure. There was only one child (1.75%) with VSD left. After eliminating the data of four unqualified cases, the ROC curve for predicting VSD closure based on 53 pulmonary blood flow studies was obtained at a p value of <0.001, with an area under the curve of 0.922. The maximum Youden's index was 0.713, which corresponded to an optimal mean pulmonary artery pressure cutoff value of 24.5 mmHg. CONCLUSION: The functional evaluation provided by pulmonary blood flow studies is highly accurate to predict intraoperative VSD repair. We recommend using pulmonary blood flow studies with a mean pulmonary artery pressure of ≤25 mmHg during blood perfusion at 3.0 L/min/m2 as the standard to repair VSD.

Early single-stage surgical revascularization of pulmonary artery in unilateral absence of a pulmonary artery.

BACKGROUND: This research aims to summarize the findings of the early single-stage revascularization of remnant pulmonary artery in unilateral absent intrapericardial pulmonary artery. METHODS: We retrospectively analyzed the medical records of 10 patients with unilateral absent pulmonary artery, in which 7 were right and 3 were left, the median age and mean weight at surgery was 4 months and 5.6 kg, respectively. The patients received operation from January 2009 to June 2020. RESULTS: Ten patients, 1 case associated with atrial septal defect, 2 cases with tetralogy of Fallot, and 1 case with aortopulmonary window. The mean diameter of the affected hilar pulmonary artery remnants was 3.14 ± 1.09 mm (1.6-5 mm), and the Z value was - 3.66 ± 1.86 (range, - 6.7 to - 1.75). All the patients received single-stage revascularization: tube graft interposition in 3 patients, autologous pericardial roll in 4, direct anastomosis in one, and main pulmonary artery flap angioplasty in the rest 3. No hospital deaths occurred. Mean follow-up in this cohort was 3.3 ± 1.9 years One case underwent percutaneous balloon dilatation due to new pulmonary artery stenosis. Nonetheless, the results were encouraging, symptoms have improved in all patients. The median Z value of the latest ipsilateral pulmonary artery diameter was - 1.88 (range, - 4.52 to - 1.35), a significantly improvement when compared to the preoperative value. The Z value of that in patients who using Gore-Tex tube increased relatively small. CONCLUSIONS: Single-stage pulmonary artery revascularization is effective at restoring normal antegrade flow to the affected lung, resulting in improved diameter of the PA, regression of pulmonary hypertension, and patient's symptoms. Revascularization by using the autologous tissue or autologous pericardium may obtain a preferred result. The new pulmonary artery stenosis certainly will need to be addressed in the long-term follow-up.

Ndufs1 Deficiency Aggravates the Mitochondrial Membrane Potential Dysfunction in Pressure Overload-Induced Myocardial Hypertrophy.

Mitochondrial dysfunction has been suggested to be the key factor in the development and progression of cardiac hypertrophy. The onset of mitochondrial dysfunction and the mechanisms underlying the development of cardiac hypertrophy (CH) are incompletely understood. The present study is based on the use of multiple bioinformatics analyses for the organization and analysis of scRNA-seq and microarray datasets from a transverse aortic constriction (TAC) model to examine the potential role of mitochondrial dysfunction in the pathophysiology of CH. The results showed that NADH:ubiquinone oxidoreductase core subunit S1- (Ndufs1-) dependent mitochondrial dysfunction plays a key role in pressure overload-induced CH. Furthermore, in vivo animal studies using a TAC mouse model of CH showed that Ndufs1 expression was significantly downregulated in hypertrophic heart tissue compared to that in normal controls. In an in vitro model of angiotensin II- (Ang II-) induced cardiomyocyte hypertrophy, Ang II treatment significantly downregulated the expression of Ndufs1 in cardiomyocytes. In vitro mechanistic studies showed that Ndufs1 knockdown induced CH; decreased the mitochondrial DNA content, mitochondrial membrane potential (MMP), and mitochondrial mass; and increased the production of mitochondrial reactive oxygen species (ROS) in cardiomyocytes. On the other hand, Ang II treatment upregulated the expression levels of atrial natriuretic peptide, brain natriuretic peptide, and myosin heavy chain beta; decreased the mitochondrial DNA content, MMP, and mitochondrial mass; and increased mitochondrial ROS production in cardiomyocytes. The Ang II-mediated effects were significantly attenuated by overexpression of Ndufs1 in rat cardiomyocytes. In conclusion, our results demonstrate downregulation of Ndufs1 in hypertrophic heart tissue, and the results of mechanistic studies suggest that Ndufs1 deficiency may cause mitochondrial dysfunction in cardiomyocytes, which may be associated with the development and progression of CH.

Comprehensive analysis of differential immunocyte infiltration and the potential ceRNA networks during epicardial adipose tissue development in congenital heart disease.

BACKGROUND: To detect the development, function and therapeutic potential of epicardial adipose tissue (EAT); analyze a related gene expression dataset, including data from neonates, infants, and children with congenital heart disease (CHD); compare the data to identify the codifferentially expressed (DE) mRNAs and lncRNAs and the corresponding miRNAs; generate a potential competitive endogenous RNA (ceRNA) network; and assess the involvement of immunocyte infiltration in the development of the EAT. METHODS: Multiple algorithms for linear models for microarray data algorithms (LIMMA), CIBERSORT, gene-set enrichment analysis (GSEA), and gene set variation analysis (GSVA) were used. The miRcode, miRDB, miRTarBase, and TargetScan database were used to construct the ceRNA network. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DE mRNAs were performed. RESULTS: Thirteen co-DE mRNAs and 47 co-DE lncRNAs were subsequently identified. The related categories included negative regulation of myoblast differentiation, regulation of ion transmembrane transport, and heart development, which were primarily identified for further pathway enrichment analysis. Additionally, the hub ceRNA network in EAT development involving MIR210HG, hsa-miR-449c-5p, and CACNA2D4 was generated and shown to target monocyte infiltration. CONCLUSION: These findings suggest that the pathways of myoblast differentiation and ion transmembrane transport may be potential hub pathways involved in EAT development in CHD patients. In addition, the network includes monocytes, MIR210HG, and CACNA2D4, which were shown to target the RIG-I-like receptor signaling pathway and PPAR signaling pathway, indicating that these factors may be novel regulators and therapeutic targets in EAT development.

Prognostic value of perioperative NT-proBNP after corrective surgery for pediatric congenital heart defects.

BACKGROUND: It is critically important to assess the prognostic value of NT-proBNP in the form of repeated measures among children undergoing surgery for congenital heart defects (CHD). The aim of the present study is to assess the value of repeated perioperative NT-proBNP in evaluating the time dependent and temporal trajectory in prognostics diagnosis during the perioperative period in a large series of children with CHD. METHODS: Repeated measures of NT-proBNP from 329 consecutive children with CHD were obtained before and 1, 12, and 36 h after surgery, respectively. For fully utilizing longitudinal characteristics, we employed parallel cross-sectional logistic regression, a two stage mixed effect model and trajectories over time analysis to mine the predictive value of perioperative NT-proBNP on the binary outcome of prolonged intensive care unit (ICU) stay. RESULTS: The two stage mixed effects model confirmed that both the mean NT-proBNP level (aOR = 1.46, P = 0.001) and the time trends had prognostic value on the prediction of prolonged ICU stay. In the fully adjusted logistic regression analyses based on gaussian distributions, "rapidly rising NT-proBNP" put the subjects at 5.4-times higher risk of prolonged ICU stay compared with "slowly rising" group (aOR = 5.40, P = 0.003). CONCLUSIONS: Comprehensive assessment of the time dependent and temporal trajectory in perioperative NT-proBNP, indicated by repeated measurements, can provide more accurate identification of children with higher risk of prolonged ICU stay after CHD surgery.

DNA methylation profile is a quantitative measure of biological aging in children.

DNA methylation changes within the genome can be used to predict human age. However, the existing biological age prediction models based on DNA methylation are predominantly adult-oriented. We established a methylation-based age prediction model for children (9-212 months old) using data from 716 blood samples in 11 DNA methylation datasets. Our elastic net model includes 111 CpG sites, mostly in genes associated with development and aging. The model performed well and exhibited high precision, yielding a 98% correlation between the DNA methylation age and the chronological age, with an error of only 6.7 months. When we used the model to assess age acceleration in children based on their methylation data, we observed the following: first, the aging rate appears to be fastest in mid-childhood, and this acceleration is more pronounced in autistic children; second, lead exposure early in life increases the aging rate in boys, but not in girls; third, short-term recombinant human growth hormone treatment has little effect on the aging rate of children. Our child-specific methylation-based age prediction model can effectively detect epigenetic changes and health imbalances early in life. This may thus be a useful model for future studies of epigenetic interventions for age-related diseases.

Infant cardiosphere-derived cells exhibit non-durable heart protection in dilated cardiomyopathy rats.

Stem cells provide a new strategy for the treatment of cardiac diseases; however, their effectiveness in dilated cardiomyopathy (DCM) has not been investigated. In this study, cardiosphere-derived cells (CDCs) were isolated from infants (≤ 24 months) and identified by the cell surface markers CD105, CD90, CD117 and CD45, which is consistent with a previous report, although increased CD34 expression was observed. The molecular expression profile of CDCs from infants was determined by RNA sequencing and compared with adult CDCs, showing that infant CDCs have almost completely altered gene expression patterns compared with adult CDCs. The upregulated genes in infant CDCs are mainly related to the biological processes of cell morphogenesis and differentiation. The molecular profile of infant CDCs was characterized by lower expression of inflammatory cytokines and higher expression of stem cell markers and growth factors compared to adult CDCs. After intramyocardial administration of infant CDCs in the heart of DCM rats, we found that infant CDCs remained in the heart of DCM rats for at least 7 days, improved DCM-induced cardiac function impairment and protected the myocardium by elevating the left ventricular ejection fraction and fraction shortening. However, the effectiveness of transplanted CDCs was reversed later, as increased fibrosis formation instead of angiogenesis was observed. We concluded that infant CDCs, with higher expression of stem cell markers and growth factors, exhibit non-durable heart protection due to limited residence time in the heart of DCM animals, suggesting that multiple administrations of the CDCs or post-regulation after transplantation may be the key for cell therapy in the future.

Conduit Route Selection for Total Cavopulmonary Connection in Patients With Apicocaval Juxtaposition.

Apicocaval juxtaposition (ACJ) may complicate the selection of conduit route in patients with single ventricles when total cavopulmonary connection (TCPC) is performed. We reviewed our experience of pathway selection and evaluated the clinical results. Of 128 patients who underwent TCPC at our hospital between January 2009 and April 2016, 31 with ACJ were included in this study. In 24 patients, the conduit was placed between the inferior vena cava (IVC) and the ipsilateral pulmonary artery. To avoid compression of the conduit and pulmonary veins in 5 patients, the conduit was placed between the IVC and the contralateral pulmonary artery. In 2 patients, the tube graft was anastomosed with the IVC orifice within the atrium, then guided through the atrial free wall and anastomosed with the contralateral pulmonary artery outside the heart (intra/extracardiac Fontan). Patient demographics were compared with those of patients without ACJ. The mean age and body weight at surgery were 58.5 ±â€¯32.4 months and 16.2 ±â€¯6.0 kg, respectively. The mean postoperative pulmonary artery pressure was 15 ±â€¯3 mm Hg. The postoperative data did not differ significantly from that of patients without ACJ who underwent extracardiac TCPC. One patient died of overwhelming infection. The mean follow-up was 17.5 ±â€¯15.4 months (range, 1-65 months). There were no conduit-related early or late complications. TCPC in patients with ACJ can be performed with excellent early and midterm results. The route between the IVC and the ipsilateral pulmonary artery is our preference.

Circulating microRNA as a Novel Biomarker for Pulmonary Arterial Hypertension Due to Congenital Heart Disease.

Circulating microRNAs (miRNAs) have recently been indicated as practical and promising biomarkers for various diseases. However, circulating miRNAs have not been found to be biomarkers for pulmonary arterial hypertension (PAH) due to congenital heart disease. PAH is defined by a mean pulmonary arterial pressure (mPAP) >25 mmHg at rest. Blood samples and lung tissues were collected from patients with severe PAH due to ventricular septal defect (VSD) (PAH group, mPAP >45 mmHg, n=14) and patients with VSD but non-PAH (control group, mPAP <25 mmHg, n=16). Total RNA was extracted from the tissues and the plasma collected, and the different expression of miRNAs in tissues was detected by miRNA arrays. Selected miRNAs were also verified using real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Levels of miR-19a were quantified in the plasma of 30 patients. We also conducted receiver-operator characteristic curve analysis to evaluate the diagnostic ability of miR-19a; 78 microRNAs changed more than twofold. The changes in miR-19a, miR-130a, and miR-27b were also confirmed using qRT-PCR. miR-19a was then analyzed in prospectively collected plasma taken from both groups. The levels of miR-19a were significantly increased in the PAH samples. The value of the area under the receiver-operating characteristic curve was 0.781 (95% confidence interval, CI = 0.612-0.950, P < 0.0001) for the miR-19a assay. Circulating miR-19a turned out to be a pronounced marker for PAH. Our observations suggest that miR-19a expression is enhanced in PAH blood. Circulating miR-19a may be a novel biomarker for the diagnosis of PAH.

[Surgical treatment of total anomalous pulmonary venous connection under 6 months of age].

OBJECTIVE: To discuss the experience of surgical treatment of total anomalous pulmonary venous connection (TAPVC) in infants. METHODS: The clinic data of 84 cases with TAPVC under 6 months of age underwent surgical treatment at Department of Cardiac Surgery, Guangzhou Women and Children's Medical Center from January 2012 to October 2015 were analyzed retrospectively. There were 58 male and 26 female patients. The patients were aged 1 days to 6 months with a mean of (2.4±2.2) months at surgery, including 22 newborns. Body weight was 1.8 to 6.8 kg with a mean of (4.3±1.2) kg. There were 24 cases of intracardiac type, 46 cases of supracardiac type, 10 cases of infracardiac type and 4 cases of mixed type. There were 26 cases received emergent operation. There were 14 cases used Sutureless technique in operations and 46 cases used conventional methods in the no-intracardiac type cases, and 2 cases enlarged the anastomsis with autologous pericardium. According to the condition, corrective surgeries of other anomalies were performed in the meantime, including 3 Warden operations (right side), 3 bilateral bidirectional Gleen operation, 2 correction of unroofed coronary sinus syndrome, 1 coarctation of aorta correction with deep hypothermic circulation arrest, and 1 repair of ventricular septal defect. RESULTS: The ratio of newborn was higher in Sutureless technique group than in conventional methods group (7/14 vs. 32.6%, χ(2)=4.927, P=0.043), and mean age was less ((1.8±0.4) months vs. (2.4±2.2) months, F=4.257, P=0.042), but there were no difference in body weight, cardiopulmonary bypass time and aorta clamped time between the two groups. Followed up for 1 to 46 months, 10 cases (11.9%) died overall and the mortality of intracardiac (3/10) and mixed (2/4) type were much higher than in intracardiac (4.2%) and supracardiac (13.0%) type. The mortality were no difference between newborn and infants, or whether emergent operation, or Sutureless technique and conventional methods. The maximal pulmonary venous flow velocity was abnormal speed-up >1.8 m/s at 1 week and 1 to 3 months post-operation mostly. CONCLUSIONS: The mortality of TAPVC was differed by different types. Intrinsic pulmonary vein stenosis maybe the main cause of mortality. The high quality of anastomsis could reduce the operative mortality.

Outcomes of total cavopulmonary connection for single ventricle palliation.

BACKGROUND: The aim of this study was to review the early and mid-term outcomes of the total cavopulmonary connection (TCPC) procedure and evaluate risk factors for prolonged pleural effusions. METHODS: The clinical records of 82 consecutive patients, who underwent a TCPC operation between January 2008 and December 2013, were reviewed for incidence of prolonged pleural effusions, duration of ventilation time and pleural drainage, length of intensive care unit (ICU) stay, and early and mid-term morbidity and mortality. RESULTS: The median age at surgery was 3.0 years. The main single ventricle diagnoses included 18 cases of a double-inlet single ventricle, 17 cases of heterotaxy, 16 cases of tricuspid atresia, 4 cases of mitral atresia, 12 cases of unbalanced complete atrioventricular canal (CAVC), 5 cases of double-outlet right ventricle (DORV) combined with ventricular septal defect (VSD) and pulmonary stenosis (PS), 4 cases of transposition of the great arteries (TGA) combined with VSD and PS, 4 cases of corrected transposition of great arteries (cTGA) combined VSD and PS, and 2 cases of criss-cross heart. Preoperative mean pulmonary artery pressure (mPAP) was 13.66±2.21 mmHg with 23.2% (n=19) higher than 15 mmHg. A total of 61 (74.4%) patients underwent a fenestration. The perioperative mortality was 4.9%. The median duration of pleural effusion was 10 days (range, 3-80 days), and prolonged pleural effusions occurred in 16 (19.5%) patients. Multivariable analysis revealed that mPAP >15 mmHg was independently associated with prolonged pleural effusions (OR, 8.33; 95% CI, 2.33-29.74; P=0.001), and creation of a fenestration was associated with decreased odds of effusion (OR, 0.21; 95% CI, 0.06-0.74; P=0.015). Five-year estimated Kaplan-Meier survival of two-stage TCPC was significantly higher than that of one-stage group(96.7% vs. 79.7%, P=0.023). Patients with heterotaxy or obstructed totally anomalous pulmonary venous connection (TAPVC) had significantly worse mid-term survival. CONCLUSIONS: Staged TCPC improved the early and mid-term survival of patients with a single ventricle. mPAP >15 mmHg was independently associated with prolonged pleural effusions and a fenestration significantly associated with a lower odds of effusion.

Infant's DNA Methylation Age at Birth and Epigenetic Aging Accelerators.

Knowing the biological age of the neonates enables us to evaluate and better understand the health and maturity comprehensively. However, because of dearth of biomarkers, it is difficult to quantify the neonatal biological age. Here we sought to quantify and assess the variability in biological age at birth and to better understand how the aging rates before birth are influenced by exposure in intrauterine period by employing a novel epigenetic biomarker of aging (epigenetic clock). We observed that the methylation age at birth was independent of the infant's sex but was significantly influenced by race. Partial correlation analysis showed a significant negative relationship between maternal socioeconomic status and infants' methylation age (rs = -0.48, Ps = 0.005). A significant association with the risk of fast aging was observed for prenatal exposure to tobacco smoke with OR (95% CI) of 3.17 (1.05-9.56). Both estimated cell abundance measures and lymphocyte subpopulations in cord blood showed that tobacco exposed group exhibit an altered T cell compartment, specifically substantial loss of naive T cells. Present study provides the first evidence that common perinatal exposure (such as maternal smoking and lower socioeconomic status) may be important aging accelerators and substantial loss of naive T cells may play a role in the smoking-related fast aging phenomenon.

Early- and Middle-Term Surgical Outcomes in Patients with Heterotaxy Syndrome.

OBJECTIVES: Heterotaxy syndrome is a recognized risk factor for surgical cardiac interventions. We evaluated the early- and middle-term results of a surgical intervention for patients with heterotaxy syndrome. METHODS: A total of 42 patients with heterotaxy syndrome were enrolled (September 2008 to March 2015). Left and right atrial isomerism were identified in 26% (11 out of 42) and 74% of patients (31 out of 42), respectively. The median age of the patients at the time of surgery was 6.8 months (range: 5 days to 22.3 years). Biventricular repair was completed in 3 patients with left atrial isomerism. Seventeen out of 39 patients who were scheduled for single ventricular repair completed a modified Fontan procedure. RESULTS: The hospital mortality rate was 4.7% (2 out of 42). Another 5 deaths occurred in the remaining survivors following hospital discharge with a follow-up duration of 45.8 ± 23.6 months (range: 13-111 months). The 1-year and 5-year survival rates were 88.1% (37/42) and 83.3% (35/42), respectively. Univariate analysis and multivariate analysis identified pulmonary venous obstruction and atrioventricular valve replacement as additional risk factors for mortality. CONCLUSIONS: Right ventricular bypass surgery remains the preferred palliative procedure for patients with heterotaxy syndrome. Based on the current results, the early- and middle-term outcomes are satisfactory.