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.

Clinical characteristics and genetic analysis of a child with specific type of diabetes mellitus caused by missense mutation of GATA6 gene. / 一例GATA6åŸºå› å˜å¼‚å¼•èµ·å„¿ç«¥ç‰¹æ®Šç±»åž‹ç³–å°¿ç— çš„ä¸´åºŠç‰¹ç‚¹åŠåŸºå› å˜å¼‚åˆ†æž.

A 2-year-old boy was admitted to Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine in Nov 30th, 2018, due to polydipsia, polyphagia, polyuria accompanied with increased glucose levels for more than 2 weeks. He presented with symmetrical short stature [height 81 cm (－2.2 SD), weight 9.8 kg (－2.1 SD), body mass index 14.94 kg/m2 (P10-P15)], and with no special facial or physical features. Laboratory results showed that the glycated hemoglobin A1c was 14%, the fasting C-peptide was 0.3 ng/mL, and the islet autoantibodies were all negative. Oral glucose tolerance test showed significant increases in both fasting and postprandial glucose, but partial islet functions remained (post-load C-peptide increased 1.43 times compared to baseline). A heterozygous variant c.1366C>T (p.R456C) was detected in GATA6 gene, thereby the boy was diagnosed with a specific type of diabetes mellitus. The boy had congenital heart disease and suffered from transient hyperosmolar hyperglycemia after a patent ductus arteriosus surgery at 11 months of age. Insulin replacement therapy was prescribed, but without regular follow-up thereafter. The latest follow-up was about 3.5 years after the diagnosis of diabetes when the child was 5 years and 11 months old, with the fasting blood glucose of 6.0-10.0 mmol/L, and the 2 h postprandial glucose of 17.0-20.0 mmol/L.

Oligodendrocyte lineage cells and depression.

Depression is a common mental illness, affecting more than 300 million people worldwide. Decades of investigation have yielded symptomatic therapies for this disabling condition but have not led to a consensus about its pathogenesis. There are data to support several different theories of causation, including the monoamine hypothesis, hypothalamic-pituitary-adrenal axis changes, inflammation and immune system alterations, abnormalities of neurogenesis and a conducive environmental milieu. Research in these areas and others has greatly advanced the current understanding of depression; however, there are other, less widely known theories of pathogenesis. Oligodendrocyte lineage cells, including oligodendrocyte progenitor cells and mature oligodendrocytes, have numerous important functions, which include forming myelin sheaths that enwrap central nervous system axons, supporting axons metabolically, and mediating certain forms of neuroplasticity. These specialized glial cells have been implicated in psychiatric disorders such as depression. In this review, we summarize recent findings that shed light on how oligodendrocyte lineage cells might participate in the pathogenesis of depression, and we discuss new approaches for targeting these cells as a novel strategy to treat depression.

Kartogenin preconditioning commits mesenchymal stem cells to a precartilaginous stage with enhanced chondrogenic potential by modulating JNK and ß-catenin-related pathways.

Cartilage engineering strategies using mesenchymal stem cells (MSCs) could provide preferable solutions to resolve long-segment tracheal defects. However, the drawbacks of widely used chondrogenic protocols containing TGF-ß3, such as inefficiency and unstable cellular phenotype, are problematic. In our research, to optimize the chondrogenic differentiation of human umbilical cord MSCs (hUCMSCs), kartogenin (KGN) preconditioning was performed prior to TGF-ß3 induction. hUCMSCs were preconditioned with 1 µM of KGN for 3 d, sequentially pelleted, and incubated with TGF-ß3 for 28 d. Then, the expression of chondrogenesis- and ossification-related genes was evaluated by immunohistochemistry and RT-PCR. The underlying mechanism governing the beneficial effects of KGN preconditioning was explored by phosphorylated kinase screening and validated in vitro and in vivo using JNK inhibitor (SP600125) and ß-catenin activator (SKL2001). After KGN preconditioning, expression of fibroblast growth factor receptor 3, a marker of precartilaginous stem cells, was up-regulated in hUCMSCs. Furthermore, the KGN-preconditioned hUCMSCs efficiently differentiated into chondrocytes with elevated chondrogenic gene ( SOX9, aggrecan, and collagen II) expression and reduced expression of ossific genes (collagen X and MMP13) compared with hUCMSCs treated with TGF-ß3 only. Phosphokinase screening indicated that the beneficial effects of KGN preconditioning are directly related to an up-regulation of JNK phosphorylation and a suppression of ß-catenin levels. Blocking and activating tests revealed that the prochondrogenic effects of KGN preconditioning was achieved mainly by activating the JNK/Runt-related transcription factor (RUNX)1 pathway, and antiossific effects were imparted by suppressing the ß-catenin/RUNX2 pathway. Eventually, tracheal patches, based on KGN-preconditioned hUCMSCs and TGF-ß3 encapsulated electrospun poly( l-lactic acid-co-ε-caprolactone)/collagen nanofilms, were successfully used for restoring tracheal defects in rabbit models. In summary, KGN preconditioning likely improves the chondrogenic differentiation of hUCMSCs by committing them to a precartilaginous stage with enhanced JNK phosphorylation and suppressed ß-catenin. This novel protocol consisting of KGN preconditioning and subsequent TGF-ß3 induction might be preferable for cartilage engineering strategies using MSCs.-Jing, H., Zhang, X., Gao, M., Luo, K., Fu, W., Yin, M., Wang, W., Zhu, Z., Zheng, J., He, X. Kartogenin preconditioning commits mesenchymal stem cells to a precartilaginous stage with enhanced chondrogenic potential by modulating JNK and ß-catenin-related pathways.

Integrated model for the prenatal diagnosis and postnatal surgical treatment of total anomalous pulmonary venous connection: A multidisciplinary collaborative experience and preliminary results.

BACKGROUND: This study aimed to evaluate an integrated model for the prenatal diagnosis and postnatal treatment of total anomalous pulmonary venous connection (TAPVC). METHODS: From January 2014 to December 2018, 11 patients were considered as a prenatally diagnosed group, who would accept the integrated model for prenatal diagnosis and postnatal treatment of TAPVC. Besides, 25 patients as postnatally diagnosed group underwent emergency surgery during the corresponding period at the same age. The perioperative status, survival and risk factors for death were compared between the two groups. RESULTS: In a prenatally diagnosed group, three pregnant women chose termination; eight patients followed the integrated model, and their newborns were rapidly transported to a children's hospital within 24 hours after birth. Other than one patient who was prenatally diagnosed with infracardiac type was later confirmed as a mixed type of TAPVC, the prenatal and postnatal diagnoses of the other seven patients were consistent. The 30-day, 1-year, and 5-year survival rates in the prenatally diagnosed group were 100%, 100%, and 100%, while those in the postnatally diagnosed group were 92%, 87.8%, and 87.8%, without significant difference (P > .05). Although Fisher's exact test indicated that an oxygen saturation <70% at admission might be an independent predictor of mortality (P < .01), none of the risk factors for death were significantly different by multivariate Cox regression analysis. CONCLUSION: The integrated model of prenatal diagnosis and postnatal treatment by multidisciplinary collaboration could lead to satisfactory outcomes, and prenatal diagnosis combined with postnatal oxygen saturation evaluation would facilitate early intervention for TAPVC.

Rare Copy Number Variations Might Not be Involved in the Molecular Pathogenesis of PA-IVS in an Unselected Chinese Cohort.

Congenital heart defect (CHD) is one of the most common birth defects in China, while pulmonary atresia with intact ventricular septum (PA-IVS) is the life-threatening form of CHD. Numerous previous studies revealed that rare copy number variants (CNVs) play important roles in CHD, but little is known about the prevalence and role of rare CNVs in PA-IVS. In this study, we conducted a genome-wide scanning of rare CNVs in an unselected cohort consisted of 54 Chinese patients with PA-IVS and 20 patients with pulmonary atresia with ventricular septal defect (PA-VSD). CNVs were identified in 6/20 PA-VSD patients (30%), and three of these CNVs (15%) were considered potentially pathogenic. Two pathogenic CNVs occurred at a known CHD locus (22q11.2) and one likely pathogenic deletion located at 13q12.12. However, no rare CNVs were detected in patients with PA-IVS. Potentially pathogenic CNVs were more enriched in PA-VSD patients than in PA-IVS patients (p = 0.018). No rare CNVs were detected in patients with PA-IVS in our study. PA/IVS might be different from PA/VSD in terms of genetics as well as anatomy.

Total Anomalous Pulmonary Venous Connection: The Current Management Strategies in a Pediatric Cohort of 768 Patients.

BACKGROUND: Total anomalous pulmonary venous connection (TAPVC) is a rare form of congenital heart disease. This study describes current surgical treatment strategies and experiences in a cohort of patients from 2 congenital cardiac centers in Shanghai and Guangdong in China. METHODS: This retrospective study included 768 patients operated on between 2005 and 2014. Although most patients (n=690) underwent conventional repair, a sutureless technique was used in 10% (n=78) of cases. A multilevel mixed-effects parametric survival model and a competing-risk analysis were used to analyze associated risk factors for death and recurrent pulmonary venous obstruction (PVO), respectively. Kaplan-Meier analysis was used to analyze the overall survival. The Nelson-Aalen cumulative risk curve was used to compare distributions of time with recurrent PVO. RESULTS: The mean surgical age and weight were 214.9±39.2 days and 5.4±3.6 kg, respectively. Obstructed TAPVC (PVO) was documented in 192 (25%) of the 768 patients. There were 38 intraoperative deaths and 13 late deaths. A younger age at the time of repair (P=0.001), mixed (P=0.004) and infracardiac (P=0.035) TAPVC, preoperative PVO (P=0.027), prolonged cardiopulmonary bypass time (P<0.001), and longer duration of ventilation (P=0.028) were associated with mortality. The median follow-up was 23.2 months (range; 1-112 months). Among the 717 survivors, recurrent PVO was observed in 111 patients (15%). Associated risk factors for recurrent PVO included preoperative PVO (P<0.001), infracardiac TAPVC (P<0.001), mixed TAPVC (P=0.013), and prolonged cardiopulmonary bypass time (P<0.001). Sutureless technique was associated with a lower restenosis rate compared with conventional repair in patients with preoperative PVO (P=0.038), except in newborn patients (P=0.443). Reintervention for restenosis was performed in 24 patients. The function of most survivors (91%) was classified according to the New York Heart Association as functional class I or II. CONCLUSIONS: Surgical correction in patients with TAPVC with a biventricular anatomy can achieve an acceptable outcome. Risk factors such as a younger age at the time of repair, infracardiac and mixed TAPVC, and preoperative PVO were associated with a poorer prognosis.

Outcomes of Right Ventricular Outflow Tract Reconstruction for Children with Persistent Truncus Arteriosus: A 10-Year Single-Center Experience.

The purpose of this report is to assess the mid- and long-term outcomes of right ventricular outflow tract (RVOT) reconstruction for children with persistent truncus arteriosus. Between September 2006 and 2016, 105 patients with persistent truncus arteriosus (PTA) received surgical treatment at Shanghai Children's Medical Center. Direct right ventricle-pulmonary artery anastomosis (pulmonary artery pull-down) was performed in 51 patients; a left auricle or pericardial conduit was inserted between the RVOT and pulmonary artery as a connection in 17 patients; heterograft (bovine jugular vein or Gore-tex) conduits and homograft conduits were used in 30 and 7 cases, respectively, to connect the distal pulmonary and right ventricle outflow tract; and pulmonary valve reconstruction was performed in 38 patients using a Gore-tex monocusp. There were six in-hospital deaths and one delayed death 5 months after operation. After a mean follow-up of 55.8 ± 16.5 months (6-113 months), 19 patients underwent reoperation (3 with pulmonary patch enlargement, 14 with conduit replacement and 2 with aortic valve replacement) 10-89 months after the first operation, with 1 hospital death. The actuarial survival rates were 94.2, 93.3 and 93.3% at 1, 5 and 10 years, respectively. Freedom from reoperation was 98.0, 87.8 and 82.7% at 1, 5 and 10 years, respectively. The follow-up variables included echocardiography, chest radiography, cardiac CT and cardiac function. At the last examination, most of the patients exhibited an improvement of New York Heart Association functional class from III or IV preoperatively to I or II at follow-up. Surgical treatment for PTA has an acceptable survival rate and satisfactory outcomes. Most patients exhibited an improvement in cardiac function during follow-up. Aortic arch deformity, truncal valvular regurgitation and long cardiopulmonary bypass time were regarded as risk factors for hospital mortality. Autologous tissue has a lower reoperation rate and better growth potential than extracardiac conduits. A monocusp valve effectively reduces pulmonary regurgitation in the early postoperative stage.

Single-Stage Correction for Taussig-Bing Anomaly Associated With Aortic Arch Obstruction.

Taussig-Bing anomaly and aortic arch obstruction are two types of complex congenital cardiac malformations. Almost 50% of patients with Taussig-Bing anomaly have aortic arch obstruction. This report assesses the surgical outcomes of single-stage correction in neonates with both defects. Between November 2006 and November 2015, 39 neonates with Taussig-Bing anomaly and aortic arch obstruction (28 patients with coarctation of the aorta and 11 patients with interrupted aortic arch) underwent a one-stage arterial switch operation and aortic reconstruction. There were three in-hospital deaths and one late death (8 months after the surgery). The short-term survival rate was 92.3% (36/39), and the mid-term survival rate was 89.7% (35/39). Follow-up data were available for all patients who survived the operation (range 6-92 months). Echocardiology showed six cases of recoarctation, three cases of left ventricular outflow tract obstruction, three cases of right ventricular outflow tract obstruction, four cases of pulmonary artery stenosis, five cases of aortic regurgitation, and eight cases of pulmonary regurgitation. Eight patients required a reoperation during the follow-up period with no mortality. All survivors remained in good condition (New York Heart association functional class I or II). Single-stage correction of Taussig-Bing anomaly with aortic arch obstruction in neonates had favorable short- and mid-term outcomes in terms of mobility and reoperation rate. The optimal operative procedure should be chosen according to the position of the coronary arteries and the type of aortic anomaly.

Surgical strategies and outcomes of congenital supravalvular aortic stenosis.

BACKGROUND: Various surgical techniques have been introduced to treat supravalvular aortic stenosis (SVAS). However, there is no consensus upon the optimal approach. This study reviewed our institutional experience in the management of SVAS. METHODS: Ninety patients undergoing surgery for SVAS were identified between 2009 and 2016. Based on surgical techniques, patients were divided into three groups: McGoon repair (n = 63), Doty repair (n = 24), and Brom repair (n = 3). Median follow-up was 38.5 months (range, 4 months-7.5 years). Patient status, cumulative event-free survival rate, and risk factors for adverse clinical outcomes were assessed. RESULTS: The early mortality rate was 3.3%. There was one late death and two reinterventions. No differences were observed among three surgical groups. Event-free survival was 98.4% at 3 years and 96.5% at 5 years. Diffuse-type SVAS and a preoperative gradient greater than 60 mmHg were risk factors for adverse cardiac remodeling within 6 months post-surgery. Residual aortic stenosis was associated with male gender, preoperative aortic valve stenosis, and a preoperative peak gradient greater than 90 mmHg. Eleven patients (out of 30) who underwent concomitant pulmonary artery patching had a residual pulmonary gradient greater than 40 mmHg. CONCLUSIONS: Surgical repair of SVAS can be safely achieved using different techniques, with similar midterm mortality and reintervention rates. Higher preoperative gradient is associated with worse clinical results. Issues regarding surgical timing and concomitant pulmonary artery stenosis need to be further addressed.

Primary complete repair of interrupted aortic arch with associated lesions in infants.

OBJECTIVE: Interrupted aortic arch (IAA) is a complicated congenital heart disease requiring an individualized management strategy. We reported the results for surgical repair of IAA with associated anomalies. METHODS: This was a retrospective review of 119 patients undergoing one-stage biventricular repair of IAA with associated lesions at the median age of 18 days (range, 3 to 90) between 2000 and 2013. End-to-side anastomosis with patch augmentation was adopted in all patients. Left ventricular outflow tract obstruction (LVOTO) procedure was performed in 23 patients. Selective cerebral perfusion was used in 55 patients (46%). RESULTS: IAA types were A in 92 patients (77%) and B in 27 (23%). Associated anomalies were multiple including noncomplex lesions in 91 (76%) and complex lesions in 28 (24%). Mean follow-up was 98.7 ± 74.2 months. Follow-up was 80% completed. There were 19 in-hospital and six late deaths. The overall actuarial survival including early mortality was 84% at 30 day, 81% at five years, and 79% at 10 and 13 years. Cox proportional hazard model was used to determine risk factors for death: presence of complex lesions (p = 0.005), critical aortic valve stenosis (AVS) (p = 0.016), and long cardiopulmonary bypass (CPB) duration (p = 0.036). Eighteen patients required re-intervention, including 16 for subsequent LVOTO and two for arch restenosis. CONCLUSIONS: Single-stage repair using end-to-side anastomosis with patch augmentation is an effective approach for infants with IAA.

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.

Targeting a cardiac abundant and fibroblasts-specific piRNA (CFRPi) to attenuate and reverse cardiac fibrosis in pressure-overloaded heart failure.

Cardiac fibrosis under chronic pressure overload is an end-stage adverse remodeling of heart. However, current heart failure treatments barely focus on anti-fibrosis and the effects are limited. We aimed to seek for a cardiac abundant and cardiac fibrosis specific piRNA, exploring its underlying mechanism and therapeutic potential. Whole transcriptome sequencing and the following verification experiments identified a highly upregulated piRNA (piRNA-000691) in transverse aortic constriction (TAC) mice, TAC pig, and heart failure human samples, which was abundant in heart and specifically expressed in cardiac fibroblasts. CFRPi was gradually increased along with the progression of heart failure, which was illustrated to promote cardiac fibrosis by gain- and loss-of-function experiments in vitro and in vivo. Knockdown of CFRPi in mice alleviated cardiac fibrosis, reversed decline of systolic and diastolic functions from TAC 6 weeks to 8 weeks. Mechanistically, CFRPi inhibited APLN, a protective peptide that increased in early response and became exhausted at late stage. Knockdown of APLN in vitro notably aggravated cardiac fibroblasts activation and proliferation. In vitro and in vivo evidence both indicated Pi3k-AKT-mTOR as the downstream effector pathway of CFRPi-APLN interaction. Collectively, we here identified CFPPi as a heart abundant and cardiac fibrosis specific piRNA. Targeting CFRPi resulted in a sustainable increase of APLN and showed promising therapeutical prospect to alleviate fibrosis, rescue late-stage cardiac dysfunction, and prevent heart failure.

Continuous cerebral and myocardial perfusion during one-stage repair for aortic coarctation with ventricular septal defect.

Controversy still exists concerning the use of deep hypothermic circulatory arrest (DHCA) and selective antegrade cerebral perfusion (SACP) for repair of aortic coarctation (CoA) with ventricular septal defect (VSD). This report therefore describes outcomes of patients undergoing continuous cerebral and myocardial perfusion (CCMP) under mild hypothermia compared with DHCA and SACP. Retrospective analysis was performed for 110 consecutive patients undergoing anatomic reconstruction of CoA with VSD closure between 1999 and 2011. Patients repaired under CCMP with mild hypothermia (32 °C) (group A, n = 60) were compared with those repaired under DHCA (18 °C) and SACP (group B, n = 50). In group A, the single arterial cannula perfusion technique was used for 15 patients (25 %), and the dual arterial cannula perfusion technique was used for 45 patients (75 %). The preoperative data were similar in the two groups. Group A had no hospital mortalities, compared with two mortalities (4 %) in group B. Group A had shorter myocardial ischemic and cardiopulmonary times, fewer delayed sternal closures, a shorter time to extubation, lower postoperative lactate levels, and fewer patients with low cardiac output requiring extracorporeal membrane oxygenation or with multiorgan failure than group B. During the postoperative course, no clinical or electrical neurologic events occurred in either group. The mean follow-up period was 5.2 ± 3.2 years for group A and 7.5 ± 3.1 years for group B (P = 0.048). One late death occurred in group B and no late deaths in group A. The actuarial survival for the two groups was similar (100 % for group A vs 96 % for group B; P = 0.264). The freedom from all types of cardiac reintervention was 96.7 % in group A and 89.6 % in group B (P = 0.688). All the patients were free of neurologic symptoms. The authors' perfusion strategy using CCMP with mild hypothermia for repair of CoA with VSD is feasible, safe, and associated with improved postoperative recovery and should be the method of choice.

Outcome of continuous cerebral and myocardial perfusion under mild hypothermia for aortic coarctation with ventricular septal defect repair.

BACKGROUND: Controversy still exists on the use of the optimal cardiopulmonary bypass (CPB) management in aortic coarctation (CoA) with ventricular septal defect (VSD) repair. We report the outcome of patients undergoing continuous cerebral and myocardial perfusion (CCMP) under mild hypothermia. METHOD: This is a retrospective analysis of 60 consecutive patients undergoing anatomic reconstruction of CoA with VSD closure between 1999 and 2011. Single arterial cannula perfusion technique was used in 15 (25%) patients, and a dual arterial cannula perfusion technique was used in 45 (75%) patients. RESULTS: There were no hospital or late mortalities. Average CPB time was 105 ± 28 minutes, aortic clamp 27 ± 7 minutes, and descending aortic cross-clamp time 24 ± 5 minutes. Average continuous cerebral perfusion flow was 64 ± 8 mL/kg per minute. No patient needed delayed sternal closure. Average duration of ventilation was 38 ± 20 hours, ICU stay 7 ± 3 days, and hospital stay 14 ± 6 days. No patient required revision for bleeding and/or extracorporeal membrane oxygenation support. No neurologic complications were noted. CONCLUSION: A perfusion strategy using CCMP with mild hypothermia for CoA and VSD repair is feasible and safe.

Fontan conversion templates: patient-specific hemodynamic performance of the lateral tunnel versus the intraatrial conduit with fenestration.

Intraatrial-conduit Fontan is considered a modification of both extracardiac and lateral-tunnel Fontan. In this study, the patient-specific hemodynamic performance of intraatrial-conduit and lateral-tunnel Fontan with fenestration, considered as conversion templates, was investigated based on the authors' patient cohort. Pulsatile computational fluid dynamics simulations were performed using patient-specific models of intraatrial-conduit and lateral-tunnel Fontan patients. Real-time "simultaneous" inferior and superior vena cava, pulmonary artery, and fenestration flow waveforms were acquired from ultrasound. Multiple hemodynamic performance indices were investigated, with particular focus on evaluation of the pulsatile flow performance. Power loss inside the lateral-tunnel Fontan appeared to be significantly higher than with the intraatrial-conduit Fontan for patient-specific cardiac output and normalized connection size. Inclusion of the 4-mm fenestration at a 0.24 L/min mean flow resulted in a lower cavopulmonary pressure gradient and less time-averaged power loss for both Fontan connections. Flow structures within the intraatrial conduit were notability more uniform than within the lateral tunnel. Hepatic flow majorly favored the left lung in both surgical connections: conversion from lateral-tunnel to intraatrial-conduit Fontan resulted in better hemodynamics with less power loss, a lower pressure gradient, and fewer stagnant flow zones along the conduit. This patient-specific computational case study demonstrated superior hemodynamics of intraatrial-conduit Fontan over those of lateral-tunnel Fontan with or without fenestration and improved performance after conversion of the lateral tunnel to the intraatrial conduit. The geometry-specific effect of the nonuniform hepatic flow distribution may motivate new rationales for the surgical design.

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.

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.

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.

LncRNA CFRL aggravates cardiac fibrosis by modulating both miR-3113-5p/CTGF and miR-3473d/FN1 axis.

Cardiac fibrosis is a major type of adverse remodeling, predisposing the disease progression to ultimate heart failure. However, the complexity of pathogenesis has hampered the development of therapies. One of the key mechanisms of cardiac diseases has recently been identified as long non-coding RNA (lncRNA) dysregulation. Through in vitro and in vivo studies, we identified an lncRNA NONMMUT067673.2, which is named as a cardiac fibrosis related lncRNA (CFRL). CFRL was significantly increased in both mouse model and cell model of cardiac fibrosis. In vitro, CFRL was proved to promote the proliferation and migration of cardiac fibroblasts by competitively binding miR-3113-5p and miR-3473d and indirectly up-regulating both CTGF and FN1. In vivo, silencing CFRL significantly mitigated cardiac fibrosis and improved left ventricular function. In short, CFRL may exert an essential role in cardiac fibrosis and interfering with CFRL might be considered as a multitarget strategy for cardiac fibrosis and heart failure.