Congenital heart disease (CHD) is a common birth defect in children, and surgical intervention is the primary treatment. The traditional standard median sternotomy (MS) has drawbacks such as significant trauma and obvious scarring. The right axillary incision (RAI) has gradually become a conventional approach due to its advantages of preserving thoracic cage integrity, small incision size, rapid recovery, and hidden scarring. However, there is currently a lack of relevant guidelines and consensus for its application. This consensus adopts the international Delphi process, systematically searching domestic and foreign literature on CHD from 1982 to 2024. It uses the GRADE system for evidence grading and, through multidisciplinary expert discussions, clarifies the applicable CHD types, surgical techniques, establishment of extracorporeal circulation, organ protection strategies, management of special disease types, and approaches to common complications of RAI. Results show that RAI is strongly recommended for most simple congenital heart diseases (CHDs) (e.g., simple ventricular septal defect, atrial septal defect), weakly recommended for some complex CHDs (e.g., mild tetralogy of Fallot), and not recommended for complex CHDs such as transposition of the great arteries or in children with severe right thoracic deformity. Additionally, it standardizes key operational parameters: weight (5-30 kg as optimal), age (6 months-6 years as preferred), incision location, extracorporeal circulation cannulation, and organ protection measures. This consensus provides an evidence-based basis for standardizing the clinical application of RAI in open-heart surgery for CHD, ensuring surgical safety and efficacy.

To develop a predictive model for optimal anastomosis sizing in TAPVC surgery, focusing on the role of pulmonary venous confluence (PVC) size. A patient-specific fluid-structure interaction (FSI) model simulated blood flow through various anastomosis sizes. Key variables included body weight, anastomosis length, and PVC size. The model's predictions were validated against postoperative echocardiographic measurements from nine TAPVC cases. A strong positive correlation was found between flow velocity and the ratio of body weight to anastomosis length and PVC circumference. Including PVC size significantly improved predictive accuracy. No significant difference was observed between predicted and measured velocities. PVC size is a critical factor for planning TAPVC surgery. Incorporating it into computational models enhances the prediction of flow dynamics and supports personalized surgical decision-making.

Pediatric heart transplantation is limited by donor avail-ability with those needing transplantation often requiring prolonged mechanical circulatory support.

BACKGROUND:The THOC6 protein is an essential part of the THO complex. Biallelic loss-of-function variants in the THOC6 gene are linked to Beaulieu-Boycott-Innes syndrome (BBIS; OMIM #613680). Although research predominantly focuses on THOC6's involvement in neurodevelopmental disorders, approximately 80% of BBIS patients present with cardiac anomalies, including structural heart disease, cardiomyopathy, and arrhythmia. Despite this, the connection between THOC6 expression and cardiac development remains underexplored. This study firstly investigates THOC6's role in heart development. METHODS AND RESULTS:This study we firstly utilized CRISPR/Cas9 to knock out THOC6 in H9C2 cardiomyocytes, revealing a reduction in cell proliferation and an increase in apoptosis. With RNA sequencing (RNA-seq) analysis we found abundant gene changes after THOC6 knockout (KO) in H9C2, which associated with hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and dilated cardiomyopathy. Protein-protein interaction analysis and experimental validation indicated that THOC6 regulates the expression of type I collagen (COL1A1, COL1A2) and cytoskeletal protein (Cardiac α actin 1) in cardiomyocytes. Subsequently, we generated a THOC6 knockout cell lines in human induced pluripotent stem cells (hiPSCs) derived from a healthy individual using CRISPR/Cas9 technology. THOC6 knockout (KO) in hiPSCs-derived cardiomyocytes (hiPSC-CMs) led to the early manifestation of hypertrophic cardiomyopathy and dilated cardiomyopathy phenotypic characteristics, including disrupted sarcomeric organization. Notably, THOC6 KO hiPSC-CMs demonstrated a significant decreased in COL1A2 and β-tubulin expression levels. CONCLUSION:THOC6 may influence cardiac development by regulating myocardial contractile proteins, primarily type I collagen, cardiac α actin 1 and β-tubulin.

Dilated cardiomyopathy (DCM) represents the most prevalent form of cardiomyopathy. Multiple genetic variants are linked to DCM severity. We have established a human induced pluripotent stem cell (iPSC) line derived from a DCM patient harboring the p.M17164T (c.51491T>C) and p.Y138C (c.413A>G) mutations in the Titin (TTN) gene, as well as the p.Q3_S5del (c.9_17del) deletion in the TAB2 gene. The established iPSCs exhibited a normal karyotype (46, XX) and expressed pluripotency markers, successfully differentiating into cardiomyocytes. This cell line serves as a valuable resource for investigating the pathogenic mechanisms underlying DCM associated with TTN and TAB2 variants.

Objectives: To analyze factors associated with prolonged mechanical ventilation (MV) after patent ductus arteriosus (PDA) ligation in preterm infants and identify high-risk patients. Methods: A retrospective analysis (2021-2025) was conducted on preterm infants (≤32 weeks) who underwent PDA ligation. Demographic, preoperative and postoperative data were analyzed; machine learning and SHAP analysis identified associated factors. Results: A total of 271 infants (152 males, 119 females; median gestational age 27 weeks [23-32 weeks], median birth weight 920 g [470-2220 g]) were included. Based on postoperative MV duration ≤6 days or >6 days, 150 cases were assigned to the short MV group and 121 to the prolonged MV group. Significant differences were found between groups in terms of gestational age, birth weight, weight at surgery, PDA diameter, postoperative slowest heart rate, Respiratory Severity Score (RSS), rate of bidirectional PDA shunting, preoperative high-frequency ventilation use, post-ligation cardiac syndrome incidence, and rate of preoperative pulmonary hemorrhage/atelectasis (p < 0.05). RSS was identified as the most central predictor of prolonged postoperative MV duration. RSS > 4.5 was associated with a markedly elevated risk of MV >6 days (AUC = 0.865, sensitivity = 80.2%, specificity = 82.5%). In contrast, birth weight > 1500 g or post-ligation heart rate >135 bpm was correlated with shorter MV duration. Conclusions: High RSS, low birth weight, and slow postoperative heart rate are associated with prolonged postoperative MV. This may aid in identifying infants requiring closer perioperative monitoring.

IntroductionLeft ventricular assist devices (LVADs) are widely used in advanced heart failure, but require accurate hemodynamic assessment for optimal management. Current invasive methods such as right-heart catheterisation (RHC) are limited in routine use, highlighting the need for non-invasive alternatives.MethodsA non-invasive framework combining a lumped parameter model (LPM) with a hierarchical neural network (CLPM-Net) was developed to estimate patient-specific hemodynamic parameters from echocardiography and blood pressure. Model identifiability analysis was performed to select key parameters. The model was trained on synthetic data and validated with clinical cases.ResultsThe proposed method achieved accurate parameter estimation with errors below 10% (RMSE). Simulated hemodynamic indicators showed strong agreement with ground truth (nMED < 1%). Clinical validation demonstrated close consistency with invasive measurements.DiscussionThis framework enables non-invasive, patient-specific hemodynamic assessment for LVAD management. It shows potential as an alternative to invasive monitoring, though further large-scale clinical validation is required.

Cerebral stroke is a predominant cause of disability and mortality, with restricted therapeutic alternatives beyond the initial period. The transcription factor Creb1 is a pivotal regulator of genes that govern neuronal survival, plasticity, and memory; nevertheless, its endogenous activation frequently proves inadequate after ischemia injury. Forskolin, a direct stimulant of adenylate cyclase, increases intracellular cAMP, which may result in Creb1 activation through Protein Kinase A (PKA). The exact mechanism and therapeutic effectiveness of this route in cerebral stroke are still insufficiently investigated.This work seeks to clarify the mechanism by which forskolin activates Creb1 and to assess its neuroprotective efficacy in an in vivo model of cerebral stroke.We employed a transient middle cerebral artery occlusion (tMCAO) paradigm in adult C57BL/6 mice. Animals were randomly allocated to receive either forskolin or a vehicle control following reperfusion. The infarct volume was evaluated using TTC staining and LSC imaging. Neurological deficiency scores were assessed at 3 and 7 days. The activation of the cAMP/PKA/Creb1 pathway was assessed via Western blotting for Creb1 and p-Creb1 (Ser133). The expression levels of apoptosis and autophagy-related protein genes (Bax, Bcl-2, Beclin1, and LC3B) were assessed via western blotting. Our research indicates that forskolin provides substantial neuroprotection against ischemic stroke through the activation of the Creb1 signaling pathway. These findings establish forskolin as a potential therapeutic agent for enhancing endogenous healing processes and improving outcomes following cerebral stroke.

Background Open-heart surgeries carry significantly greater risks in neonates than in older children.The current study aimed to analyze the short-term outcomes and risk factors for mortality in neonates undergoing cardiac surgeries. Methods This retrospective analysis included neonates who underwent cardiac surgeries with cardiopulmonary bypass(CPB)at our center between 2019 and 2023.Perioperative and operative factors were collected,and in-hospital outcomes and risk factors for mortality were identified. Results We analyzed the medical records of 190 neonates,including 111 males and 79 females.The median age at the time of surgery was 15 days,with a median weight of 3.2 kg.The overall mortality rate was 11.6％.Major postoperative complications included infection(48.9％),low cardiac output(48.4％),hepatic insufficiency(24.9％),acute kidney injury(22.1％),unplanned reintervention(13.1％),intracranial hemorrhage(3.7％),and cerebral infarction(0.5％).Multivariable analysis identified prolonged CPB time(odds ratio(OR)=1.018,p=0.014),Risk Stratification for Congenital Heart Surgery(RASCH-2)categories of ≥4(OR=11.927,p=0.026),extracorporeal membrane oxygenation(ECMO)duration(OR=1.606,p=0.036),and peritoneal hemodialysis(OR=9.252,p=0.014)as significant predictors for mortality. Conclusions Despite advancements in recent decades,continued vigilance is required to further reduce mortality rates among neonates undergoing cardiac surgeries.

Background:Paediatric patients who underwent surgery for mitral regurgitation (MR) have a high risk of recurrence or death; however, no prediction tool has been developed to risk-stratify this challenging subpopulation. Methods:In this multicentre cohort study, paediatric patients undergoing surgery for congenital MR in Shanghai Children's Medical Center in January 1st, 2009-December 31st, 2022 were included for analysis while those had a combination with infective endocarditis, anomalous left coronary artery from the pulmonary artery, rheumatic valvular disease, connective tissue disease, or single ventricle were excluded. A Cox regression model predictive of the primary outcome (a composite of mortality or mitral valve [MV] re-operation) was derived and converted to a point-based risk score. This score was externally validated in a cohort of patients undergoing MR surgeries between January 1st, 2009 and December, 31st, 2022 in eight independent hospitals in China. The Harrell's c index and Hosmer-Lemeshow test was used to quantify the discrimination and calibration of the risk score. Findings:In total, 2640 patients (female: 57% [n = 1505]) with a median age of 0.99 (IQR, 0.47-2.60) years were included. The primary outcome occurred in 262 patients (16.6%) over a median of 5.7-year follow-up in the derivation cohort (n = 1581; median age of 1.03 years [IQR, 0.47-2.67]) and in 130 (12.3%) over a median of 7.1-year follow-up in the validation cohort (n = 1059; median age of 0.93 years [IQR, 0.46-2.51]). The score variables included preoperative variables (age, the presence of primary MR, N-terminal pro-brain natriuretic peptide, left ventricular ejection fraction, and left atrium z score), perioperative changes in z scores of LA and left ventricular end-diastolic dimension, and the procedural variable (use of MV annuloplasty or not). This risk score, ranging from -22 to 10, yielded strong discrimination (Harrell's c index: 0.85, 95% CI, 0.83-0.87) and exhibited good calibration of postoperative 10-year primary outcome (Hosmer-Lemeshow; χ2 = 9.85; P = 0.33) in the derivation cohort, which maintained in the validation cohort (Harrell's c index: 0.86, 95% CI, 0.83-0.89; Hosmer-Lemeshow; χ2 = 23.80; P = 0.64). In addition, a simplified stratification of the score model (low-risk: -22 to -5, intermediate risk: -4 to 0, high risk: >0) showed good performances in predicting the primary outcome in both derivation and validation (Ps < 0.001). Interpretation:The scoring system represents a crucial step towards personalised management care for paediatric MR. However, this model has not been applied in clinical practice and require validation in large and diverse cohorts of patients. Further work should aim to incorporate other novel multi-modality metrics to optimise the PRIMARY score. Funding:Chinese National Natural Science Foundation of China, Science and Technology Commission of Shanghai Municipality, Science and Technology Project of Guizhou Province.

BACKGROUND:There is limited experience of robotic-assisted surgery for patent ductus arteriosus (PDA) treatment in children. In the present study, we update the experience of robotic PDA ligation in a larger number of pediatric populations. METHODS:From August 2020 to March 2025, 425 children with PDA who underwent robot-assisted thoracoscopic surgery were enrolled in Children's Hospital of Zhejiang University School of Medicine. The patients' demographic data together with their perioperative clinical variables were retrospectively analyzed. RESULTS:The average age of the patients was 34.2 ± 26.2 months which ranged from 6 months to 13 years with a median age of 24 months. The average weight was 14.8 ± 7.1 kg (kg) which ranged from 6 kg to 66 kg with a median weight of 13.2 kg. There were 160 (37.6 %) boys and 265 (62.4 %) girls respectively. In addition, the PDA diameter was between 0.2 cm (cm) and 0.8 cm, with a median diameter of 0.3 cm (average was 0.38 ± 0.25 cm). The robot system operation surgery time ranged from 12 min (min) to 90 min, with a median 26 min (average was 45.6 ± 31.9 min). The length of hospital stay ranged from 1 day to 5 days over all. Notably, 263 patients (61.9 % in all patients) underwent day surgery management. CONCLUSIONS:Robotic assisted surgery for PDA ligation in children older than 6 months old is safe and effective procedure with good prospects. As a minimally invasive approach, it should be considered as an option for PDA treatment in children with age older than 6 months.

Objective To develop a model using patient-specific computational fluid dynamics (CFD) to predict the required anastomotic size for total anomalous pulmonary venous connection (TAPVC) surgery and to forecast surgical outcomes.Methods Based on clinical data from patients, a CFD model was used to simulate the anastomosis between pulmonary venous confluence and the left atrium. Blood flow velocity, wall shear stress, power loss, and pressure were calculated using numerical algorithms within the model. Various sizes of anastomosis were applied during the simulation. The energy dissipation at the anastomosis was computed from the results and compared with real-world data.Results As the simulated anastomotic size increased, blood flow velocity, pulmonary venous pressure, and energy loss decreased. However, when the anastomotic size exceeded 18 mm, the efficiency of energy conversion no longer improved. The realistic and simulated velocities matched well for anastomosis sizes ranging from 15 to 20 mm.Conclusion The model can assist surgeons in preoperative planning for determining the anastomotic size in TAPVC surgical treatment.

Background: Although evidence-based medicine proposes personalized care that considers the best evidence, it still fails to address personal treatment in many real clinical scenarios where the complexity of the situation makes none of the available evidence applicable. "Medicine-based evidence" (MBE), in which big data and machine learning techniques are embraced to derive treatment responses from appropriately matched patients in real-world clinical practice, was proposed. However, many challenges remain in translating this conceptual framework into practice. Objective: This study aimed to technically translate the MBE conceptual framework into practice and evaluate its perform-ance in providing general decision support services for outcomes after congenital heart disease (CHD) surgery. Methods: Data from 4774 CHD surgeries were collected. A total of 66 indicators and all diagnoses were extracted from each echocardiographic report using natural language processing technology. Combined with some basic clinical and surgical information, the distances between each patient were measured by a series of calculation formulas. Inspired by structure-mapping theory, the fusion of distances between different dimensions can be modulated by clinical experts. In addition to supporting direct analogical reasoning, a machine learning model can be constructed based on similar patients to provide personalized prediction. A user-operable patient similarity network (PSN) of CHD called CHDmap was proposed and developed to provide general decision support services based on the MBE approach. Results: Using 256 CHD cases, CHDmap was evaluated on 2 different types of postoperative prognostic prediction tasks: a binary classification task to predict postoperative complications and a multiple classification task to predict mechanical ventilation duration. A simple poll of the k-most similar patients provided by the PSN can achieve better prediction results than the average performance of 3 clinicians. Constructing logistic regression models for prediction using similar patients obtained from the PSN can further improve the performance of the 2 tasks (best area under the receiver operating characteristic curve=0.810 and 0.926, respectively). With the support of CHDmap, clinicians substantially improved their predictive capabilities. Conclusions: Without individual optimization, CHDmap demonstrates competitive performance compared to clinical experts. In addition, CHDmap has the advantage of enabling clinicians to use their superior cognitive abilities in conjunction with it to make decisions that are sometimes even superior to those made using artificial intelligence models. The MBE approach can be embraced in clinical practice, and its full potential can be realized.

Interrupted Aortic Arch (IAA) combined with aortic stenosis (AS) is a rare and complex congenital cardiac anomaly that presents significant challenges in clinical management. In this letter, we aim to share our experience in performing hybrid procedures on an infant diagnosed with IAA combined with bicuspid AS. This child exhibited significant recovery during follow-up.

Objective:To summarize the management experiences and follow-up outcomes of persistent fifth aortic arch (PFAA) cases and to explore their anatomical characteristics and surgical approaches for optimal outcomes.Methods:From January 2017 to December 2022, retrospective review was performed for 5 children hospitalized with systemic-systemic type PFAA.There were 2 boys and 3 girls.A definite diagnosis was made by computed tomography angiography (CTA) in neonatal period.There were coarctation of the fifth aortic arch with interruption of the fourth aortic arch (n=4) and double-lumen aortic arch without stenosis (n=1). None had serious intracardiac malformation.Clinical features, imaging studies and surgical approaches were examined.Results:Two cases underwent two different kinds of surgical methods to reconstruct aorta.One case was followed up for over 4 years without stenosis and another case of restenosis at 6 months postoperatively underwent percutaneous balloon dilatation.One girl of chromosomal abnormality died after declining treatments.One case complicated with complex variation of aorta and its branches became lost during follow-ups.The anatomical combination of right PFAA with interruption of right fourth aortic arch, aberrant left subclavian artery and Kommerell diverticulum at the stump of left arch has not been reported in the literature.Conclusions:CTA is the most effective non-invasive diagnostic tool for PFAA.In light of the histological characteristics of PFAA, tissue of fifth arch should be removed as completely as possible to prevent postoperative restenosis.

The second edition of the expert consensus on pediatric nutrition was formed based on a global update of pediatric nutrition guidelines or consensus worldwide, the management of congenital heart disease, and the results of multi-center clinical nutrition research for congenital heart disease following the first Chinese consensus edition of 2016. The consensus was also shaped by the results of three discussion sessions and two questionnaires conducted by the 13-member collaboration group. This process was informed by both clinical guidelines and expert consensus. The quality of literature, both in English and Chinese, and the level of recommendations were evaluated using the Grading of Recommendations Assessment, Development, and Evaluations (GRADE) system.

BACKGROUND:This study aimed to investigate if surgery before pregnancy would result in better maternal and fetal outcomes in patients with congenital heart disease.METHODS:A retrospective study was conducted using data collected from the medical records of pregnant patients with congenital heart disease, who were seen at Beijing Anzhen Hospital between 2010 and 2019. The patients were divided into surgical and non-surgical groups, and the differences in outcomes were compared.RESULTS:A total of 999 patients with congenital heart disease (mean age, 28.7±4.3 years) were enrolled, with 403 (40.0%) and 596 (60.0%) in the surgical and non-surgical groups, respectively. The percentages of almost all adverse events were higher in the non-surgical group than in the surgical group. The adverse events included preterm delivery (9.9 vs. 17.1%), low birth weight (6.5 vs. 11.6%), heart failure (2.7 vs. 6.7%), cesarean section (75.7 vs. 85.9%), pulmonary hypertension (13.6 vs. 36.2%), and death (0.5 vs. 2.3%) (all P < 0.05). A total of 16 (1.6%) patients died, including 14 and two in the non-surgical and surgical groups, respectively. Regardless of the type of congenital heart disease, preterm delivery and low birth weight were more common in the non-surgical group compared with the surgical group, and there were no statistical between group differences in the other remaining events.CONCLUSIONS:In the non-surgical group, the results were similar regardless of the type of congenital heart disease, except for preterm delivery and low birth weight. The overall outcome of the surgical group was better than that of the non-surgical group, and surgery before pregnancy reduced maternal and infant risk.

Background: Acute kidney injury (AKI) is a common complication after pediatric cardiac surgery. And autologous blood transfusion (ABT) is an important predictor of postoperative AKI. Unlike previous studies, which mainly focused on the correlation between ABT and AKI, the current study focuses heavily on the causal relationship between them, thus providing guidance for the treatment of patients during hospitalization to reduce the occurrence of AKI. Methods: A retrospective cohort of 3386 patients extracted from the Pediatric Intensive Care database was used for statistical analysis, multifactorial analysis, and causal inference. Characteristics that were correlated with ABT and AKI were categorized as confounders, instrumental variables, and effect modifiers, and were entered into the DoWhy causal inference model to determine causality. The calculated average treatment effect (ATE) was compared with the results of the multifactorial analysis. Results: The adjusted odds ratio (OR) for ABT volume was obtained by multifactorial analysis as 0.964. The DoWhy model refute test was able to indicate a causal relationship between ABT and AKI. Any ABT reduces AKI about 15.3%–18.8% by different estimation methods. The ATE regarding the amount of ABT was –0.0088, suggesting that every 1 mL/kg of ABT reduced the risk of AKI by 0.88%. Conclusions: Intraoperative transfusion of autologous blood can have a protective effect against postoperative AKI.

The pathogenesis of ischemia–reperfusion acute lung injury (IR-ALI) is not yet fully understood. We previously reported that unwonted increased type 2 immunity plays a key role in the pathogenesis and the pathophysiological process in acute haemorrhagic inducedlung injury. Progressive lung edema after ischemia reperfusion is accompanied by the change of lung cyclical hydrostatic force. The changed lung mechanical force could activate the mechanosensitive Piezo1 channel in alveolar macrophages. Furthermore, our group had elucidated that microenvironmental stiffness exacerbated hindlimb ischemia reperfusion injury by activating Piezo1 in bone marrow-derived macrophages. Considering early findings that IL-33 is a potent driver of pulmonary type 2 immunity, that Piezo1 plays an important role in regulating macrophages biological activity and that alveolar macrophages are involved in orchestrating the early abnormal detrimental type 2 inflammatory response in lung ischemia–reperfusion injury, we herein hypothesize that the change of mechanical force in lung after ischemia–reperfusion might activate Piezo1/IL-33/type 2 immunity axis and aggravate lung ischemic injury. Mechanistically, Piezo1 mediates extracellular Ca2+influx and activates Ca2+-dependent Calcineurin-NFAT signaling in alveolar macrophages, leading to transcriptional activation of IL-33, thereby promoting abnormal type 2 immune response and participating in the occurrence and development of IR-ALI. Future validation of these mechanisms could provide a deeper explanation of the new pathogenesis of IR-ALI and ultimately serve for clinical treatment.