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.

Background Double outlet right ventricle (DORV) is a complex congenital heart disease with significant anatomical variations. Patients with atrioventricular discordance have traditionally been managed with univentricular palliation strategies. However, advances in surgical concepts and techniques have enabled biventricular or one-and-a-half ventricle repair in selected patients, even after prior palliation. Case presentation We report a case of a 32-year-old woman with DORV and atrioventricular discordance who successfully underwent conversion to a one-and-a-half ventricle circulation using a combined Hemi-Mustard/Rastelli procedure with preservation of a pre-existing bidirectional Glenn shunt, performed 18 years after initial palliation. Conclusion This case provides insight into the surgical decision-making and technical considerations for managing similarly complex congenital anomalies.

Cardiac fibrosis is a critical pathological feature in nearly all forms of heart disease and contributes to heart failure. However, existing diagnostic and therapeutic approaches are insufficient for detecting fibrosis or targeting conventional pathways. Further molecular investigations are urgently needed to develop effective treatments. Circular RNAs (circRNAs), distinguished by their stability and regulatory roles, show significant potential. CircRNA_006640 was substantially upregulated in left ventricular tissues of male mice subjected to transverse aortic constriction, as well as in blood samples. Gain- and loss-of-function studies confirmed that circRNA_006640 promoted proliferation and phenotypic transformation in mouse cardiac fibroblasts. Real-time quantitative reverse transcription polymerase chain reaction and Western blotting demonstrated that circRNA_006640 suppressed miR-7648-3p and miR-185-3p, which in turn inhibited connective tissue growth factor (CTGF). Furthermore, there was a synergistic effect between miR-7648-3p and miR-185-3p to enhance the suppression of CTGF. In vivo, circRNA_006640 markedly exacerbated cardiac fibrosis. Knockdown of circRNA_006640 using small interfering RNA effectively mitigated cardiac fibrosis and preserved cardiac function, indicating therapeutic potential for antifibrotic strategies. CircRNA_006640 acts as a novel upstream regulator of CTGF, exacerbating cardiac fibrosis by sponging miR-7648-3p and miR-185-3p. The synergistic interaction between miR-7648-3p and miR-185-3p strengthens the profibrotic effect. Targeting CircRNA_006640 may hold promising therapeutic potential for cardiac fibrosis.

Background Left ventricular (LV) reverse remodeling has been linked to long‐term prognosis and life quality of pediatric patients with LV outflow tract obstruction. However, a lack of suitable animal model limits further study of LV reverse remodeling in young hearts. This study reports on the development and mechanism exploration of an animal model mimicking pediatric LV reverse remodeling. Methods A reversible neonatal ascending aorta constriction mice model using absorbable suture was established to simulate pediatric LV reverse remodeling. Cardiac hypertrophy, myocardial fibrosis, angiogenesis, exercise tolerance, and myocardial reserve throughout the reverse remodeling process were evaluated. Multiple‐time points RNA sequencing identified key genes and pathways involved. Cardiomyocyte‐specific stimulator of interferon genes (STING) knockout mice were generated for mechanism study. Results In the reversible neonatal ascending aorta constriction model, hydrolysis of the absorbable suture reduced cardiac afterload after ventricular remodeling, initiating reverse remodeling at 4 weeks postsurgery. Reverse remodeling young hearts displayed improved function, resolution of fibrosis, but persistent hypertrophy, reduced exercise capacity, and myocardial reserve. Multiple‐time points RNA sequencing and in vivo experiments revealed a gradual upregulation of mitophagy during reverse remodeling, along with suppression of the mitochondrial DNA (mtDNA)‐cyclic GMP‐AMP synthase (cGAS) in which the STING gene is flanked by loxP sites‐STING pathway. Cardiomyocyte‐specific STING knockout enhanced early reverse remodeling. The early application of urolithin A promoted mitophagy and suppressed the mtDNA‐cGAS‐STING pathway, accelerating reverse remodeling. Conclusions This study introduces a novel model of pediatric LV reverse remodeling in male mice, delineating the trajectory and transcriptional footprints during the reverse remodeling process. The Mitophagy‐mtDNA‐cGAS‐STING axis plays a vital role and holds therapeutic potential to promote young heart recovery.

The optimal reoperation strategy and long-term outcomes of pediatric patients with congenital aortic stenosis (AS) have not been well elucidated. This study aimed to evaluate the reintervention outcomes and long-term prognosis in patients with isolated AS following their initial aortic valve (AoV) repair. A retrospective analysis was conducted on the clinical data of all patients with isolated AS who underwent initial AoV repair between 2013 and 2024. The primary outcome was the rate of freedom from reoperation after the initial procedure and secondary surgeries. A total of 203 patients who underwent initial AoV repair were included. The median age at initial surgery was 2.4 (0.6, 4.7) years. The 30-day mortality rate was 0.5

Heart failure caused by pressure-overloaded left-heart (poLV) diseases is especially difficult to manage in children. Long-term surveillance and early recognition of poLV remodeling are crucial, while current biomarkers remain inadequate for predicting remodeling in the pediatric population. This study aimed to investigate whether gut dysbiosis is associated with alterations in circulatory extracellular vesicles and their miRNA cargo, and to identify an exploratory combined microbial/miRNA signature associated with pediatric cardiac remodeling. For the animal experiments, a fecal microbiota transplantation strategy using germ-free (GF) mice was adopted. Circulatory extracellular vesicles (cEVs) were isolated and studied in primary mouse cardiomyocytes in vitro and in neonatal ascending aorta constriction (nAAC) mice in vivo. Metagenomics and miRNA sequencing were adopted to identify the characterized gut microbes in fecal samples and cEVs-miRNAs in mice. Next, we performed a clinical cohort study (poLV n = 52 vs. healthy controls n = 60). Fecal microbiota species and cEVs-miRNAs were further validated. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to derive an exploratory combined panel in the clinical cohort. For experimental studies in vivo and in vitro, cEVs isolated from GF mice after transplantation of nAAC fecal microbiota (nAAC FMT-cEVs) significantly increased the cell surface area of primary mouse cardiomyocytes, compared with sham FMT-cEVs treatment. Supplementing nAAC FMT-cEVs to nAAC mice aggravated hypertrophy and fibrosis with worsened cardiac function. Metagenomic sequencing identified gut microbes that characterized nAAC and sham mice. miRNA sequencing identified the top differential miRNAs in FMT-cEVs. In the clinical cohort, four miRNAs and six gut microbes were validated as significant. LASSO analysis derived a four-feature exploratory combined panel including two cEV-miRNAs and two gut microbes, which showed good discriminative performance in the derivation cohort (AUC = 0.898). The panel value showed significant correlation to cardiac remodeling parameters and systolic function measured by echocardiography and computed tomography (CT). Gut dysbiosis was associated with altered cEV-associated miRNA composition and with functional effects on poLV remodeling in vitro and in vivo, offering an additional perspective on gut microbiota–cardiovascular interactions. In the clinical cohort, an exploratory combined panel integrating specific gut microbes and cEV-associated miRNAs showed good discriminative performance in the derivation cohort and was associated with cardiac remodeling parameters. These human findings should be interpreted as exploratory and require validation in independent pediatric cohorts.

Chronic heart failure (HF) remains a global health challenge due to the lack of therapies that effectively disrupt the pathological fibro-inflammatory networks driving disease progression. While current nanomedicine strategies often target intracellular pathways in isolated cell types, they overlook the multicellular crosstalk central to HF. Here, we develop scalably synthesized Prussian blue (PB) nanoparticles that selectively intercept the CCL2-CCR2 chemokine axis, a key pathway in fibroblast-macrophage communication. Single-nucleus RNA sequencing of murine and human failing hearts identifies a conserved pro-fibroinflammatory cardiac fibroblast subpopulation (POSTNhi CCL2hi) that recruits CCR2+ macrophages via CCL2 secretion. PB nanoparticles exhibit ultrahigh affinity (KD = 1.11 × 10-10 m) for free CCL2, inducing conformational distortion in its N-terminal domain via specific C≡N interface interactions with CRS1 residues, thereby blocking CCR2 engagement, a mechanism distinct from conventional nanomaterials. Although ineffective in monocultures, PB nanoparticles robustly improve cardiac function and remodeling in murine and translational porcine pressure-overload HF models, reducing left ventricular end-diastolic volume by 56.2% and fibrosis by 40.5%, while selectively depleting CCR2+ macrophages without systemic immunosuppression. Supported by scalable production (> 100 g/batch), long-term stability, and biosafety, this work establishes a cell communication-targeting nanomedicine strategy for network-driven diseases like HF.

Mechanical sensation has become a recent focus and key pathological driver of cardiac fibrosis. However, the crosstalk between major mechanosensitive cell and fibroblasts remains to be elucidated. In this study, single-cell temporal atlas of mechanosensitive ion channels is depicted in transverse aortic constriction male mouse heart. Piezo1 is the most abundant mechanosensitive ion channel and exhibits the highest expression in epicardial cells. Epicardial-specific Piezo1 knockout mice exhibit decreased fibrosis and cardiac dysfunction. Piezo1 mediates epithelial-mesenchymal transition only contributes to subepicardial fibrosis. Further functional experiments and human samples validation reveal that Piezo1 facilitates intraventricular fibroblast activation via the Chemerin-Cmklr1 paracrine signaling pathway. The activation of cardiac fibroblasts is mediated by Pi3k-Akt1-Pou3f1 pathway. The Cmklr1 inhibitor α-NETA effectively mitigates myocardial fibrosis and dysfunction, holding therapeutical potential. Collectively, this study untangles the global landscape of mechanosensitive channels and the spatiotemporal mechanism of epicardial cells to activate fibroblast via the Chemerin-Cmklr1 paracrine signaling pathway.

Background Right ventricle (RV) decompression for pulmonary atresia with intact ventricular septum (PA/IVS) could be achieved surgically or percutaneously, yet transcatheter valvotomy is not widely accessible in remote regions and classic on-pump pulmonary valvotomy procedure carries risks of by pass in neonatal patients. We aim to summarize our 15-year's surgical experience treating PA/IVS with on-pump valvulotomy, off-pump valvulotomy and hybrid techniques. Methods From January 2010 to March 2025, 104 PA/IVS children who underwent off-pump, on-pump pulmonary valvulotomy or hybrid therapy in our hospital were retrospectively reviewed, including off-pump group (n = 56), on-pump group (n = 34) and hybrid group (n = 14). The postoperative mortality, operation time, early and mid-term follow-up of the three groups were analyzed. Results Both the off-pump and hybrid groups exhibited significantly shorter operative times, reduced vasoactive drug support, shorter intubation times, and shorter intensive care unit (ICU) and postoperative hospital stays compared to the on-pump group (P < 0.001). Cerebral, intestinal and renal oxygen monitor suggested that no obvious hypoxia was caused by clamping in off-pump procedure (P > 0.05). At final follow-up, RV hypoplasia, tricuspid Z score and pulmonary regurgitation were not significant among groups (P > 0.05). However, the hybrid group demonstrated a significantly higher rate of restenosis. Conclusions The off-pump pulmonary valvotomy is an effective, safe and technical-friendly operation. It provides superior early outcomes compared to on-pump surgery and a lower restenosis rate relative to hybrid techniques, highlighting its value for broader adoption across medical centers.

INTRODUCTION:Cartilage defects (CDs) are orthopedic conditions with limited regenerative potential. This study aimed to identify endoplasmic reticulum (ER) stress-related biomarkers and construct a diagnostic model to enhance the early detection of CD. METHODS:This study analyzed the transcriptomic dataset GSE129147 to identify ER stressrelated differentially expressed genes (ERSRDEGs) between CD and control tissues using the limma package (version 3.58.1). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were employed for functional enrichment. Immune infiltration was assessed using cell-type identification, which involved estimating the relative subsets of RNA transcripts and single-sample gene set enrichment analysis. Diagnostic models were constructed using logistic regression, support vector machine, and least absolute shrinkage and selection operator regression. RESULTS:Twenty ERSRDEGs were identified, with CYBB, ATP6V1A, and TNFRSF12A significantly upregulated in CD samples. GO and KEGG analyses highlighted oxidative stress response and extracellular matrix remodeling as key mechanisms in CD pathogenesis. Immune analysis revealed an increase in regulatory T cells and a reduction in CD8⁺ T cells. TNFRSF12A showed strong immune associations and, together with TWIST1 and ATP6V1A, formed the final preliminary diagnostic model. The preliminary LASSO model achieved satisfactory predictive accuracy (AUC: 0.7-0.9). DISCUSSION:These findings suggest that ER stress and immune imbalance jointly contribute to cartilage degeneration. The identified genes, particularly TNFRSF12A, TWIST1, and ATP6V1A, not only serve as potential biomarkers but also provide preliminary evidence for new mechanistic insights into stress-immune crosstalk in CD. CONCLUSION:This study reveals the key roles of ER stress and immune dysregulation in CDs. Moreover, the ERSRDEG-based diagnostic model provides preliminary bioinformatics evidence and potential molecular indicators for targeted diagnostics and therapies.

An anomalous aortic origin of the coronary artery (AAOCA) is a rare congenital heart disease. Some high-risk anatomical structures are at risk of inducing cardiogenic shock or even sudden death. This article summarizes our surgical experience with AAOCA in paediatric patients. We retrospectively analysed the clinical data of 27 paediatric AAOCA patients admitted to the Department of Cardiothoracic Surgery in our hospital from July 2015 to June 2023 and summarized the surgical treatment experience and follow-up results. A total of 27 patients were included in this study, including 14 patients with an anomalous left coronary artery (ALCA) and 13 patients with an anomalous right coronary artery (ARCA). A comparison of clinical data between ALCA and ARCA patients revealed that the preoperative left ventricular ejection fraction (LVEF) in ALCA patients was significantly lower than that in ARCA patients (p < 0.05). There were significantly more patients with preoperative complications, such as major adverse cardiovascular events (MACEs) and mitral regurgitation (MR), in the ALCA group than in the ARCA group (p < 0.05). No postoperative adverse events such as severe bleeding, mediastinitis, central nervous system complications, the need for reoperation, pacemaker implantation, pleural effusion complications occurred after operation.The duration of follow-up was 58.5 (31.5, 77.3) months. During the follow-up period, none of the patients presented symptoms such as chest tightness or chest pain, and cardiac CTA revealed unobstructed coronary arteries. Compared with the preoperative LVEF, the LVEF significantly improved at the last follow-up (p < 0.05). Patients with an AAOCA should be taken seriously, and surgical treatment should be considered for these patients. Surgery should be considered for patients with ALCA as well as patients with ARCA with symptoms of myocardial ischaemia or a positive diagnosis of myocardial ischaemia or ventricular arrhythmia. For patients with other congenital heart defects that require surgical treatment, if the AAOCA is a high-risk anatomical structure, simultaneous surgery should be considered. The surgical method should be tailored to the coronary artery anatomy of the individual patient.

Tracheal replacement is a promising approach for treating tracheal defects that are caused by conditions such as stenosis, trauma, or tumors. However, slow postoperative epithelial regeneration often leads to complications, such as infection and granulation tissue formation. Ferroptosis, which is an iron-dependent form of regulated cell death, limits the proliferation of tracheal basal cells (TBCs), which are essential for the epithelialization of tissue-engineered tracheas (TETs). This study explored the potential of ferrostatin-1 (FER-1), which is a ferroptosis inhibitor, to increase TBC proliferation and accelerate the epithelialization of 3D-printed TETs. TBCs were isolated from rabbit bronchial mucosal tissues and cultured in vitro. Ferroptosis was induced in TBCs at passage 2, as shown by increased reactive oxygen species (ROS) levels, Fe2⁺ accumulation, decreased ATP contents, and mitochondrial damage. TBCs were treated with FER-1 (1 μM) for 48 h to inhibit ferroptosis. The effects on ROS levels, Fe2⁺ levels, ATP contents, and mitochondrial morphology were measured. For in vivo experiments, FER-1-treated TBCs were seeded onto 3D-printed polycaprolactone (PCL) scaffolds, which were implanted into rabbits with tracheal injury. Epithelial regeneration and granulation tissue formation were evaluated 6 months after surgery. FER-1 treatment significantly reduced ferroptosis marker levels in vitro; that is, FER-1 treatment decreased ROS and Fe2⁺ accumulation, ameliorated mitochondrial structures, and increased ATP levels. TBC proliferation and viability were increased after ferroptosis inhibition. In vivo, the group that received 3D-printed scaffolds seeded with TBCs exhibited accelerated TET epithelialization and reduced granulation tissue formation compared with the control groups. These results suggest that inhibiting ferroptosis with FER-1 improves TBC function, leading to more efficient tracheal repair. Ferrostatin-1 effectively inhibits ferroptosis in tracheal basal cells, promoting their viability and proliferation. This results in faster epithelialization of tissue-engineered tracheas, offering a promising strategy for improving tracheal reconstruction outcomes and reducing complications such as infection and granulation tissue formation. Future studies are needed to further investigate the molecular mechanisms underlying ferroptosis in TBCs and its potential clinical applications.

Pressure-overloaded left ventricular remodeling in young population is progressive and readily degenerate into heart failure. The aims of this study were to identify a plasma metabolite that predicts and is mechanistically linked to the disease. Untargeted metabolomics determined elevated plasma kynurenine (Kyn) in both the patient cohorts and the mice model, which was correlated with remodeling parameters. In vitro and in vivo evidence, combined with single-nucleus RNA sequencing (snRNA-seq), demonstrated that Kyn affected both cardiomyocytes and cardiac fibroblasts by activating aryl hydrocarbon receptors (AHR) to up-regulate hypertrophy- and fibrosis-related genes. Shotgun metagenomics and fecal microbiota transplantation revealed the existence of the altered gut microbiota-Kyn relationship. Supplementation of selected microbes reconstructed the gut microbiota, reduced plasma Kyn, and alleviated ventricular remodeling. Our data collectively discovered a gut microbiota–derived metabolite to activate AHR and its gene targets in remodeling young heart, a process that could be prevented by specific gut microbiota modulation.

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.

The gut microbiome is known as the tenth system of the human body that plays a vital role in the intersection between health and disease. The considerable inter-individual variability in gut microbiota poses both challenges and great prospects in promoting precision medicine in cardiovascular diseases (CVDs). In this review, based on the development, evolution, and influencing factors of gut microbiota in a full life circle, we summarized the recent advances on the characteristic alteration in gut microbiota in CVDs throughout different life stages, and depicted their pathological links in mechanism, as well as the highlight achievements of targeting gut microbiota in CVDs prevention, diagnosis and treatment. Personalized strategies could be tailored according to gut microbiota characteristics in different life stages, including gut microbiota-blood metabolites combined prediction and diagnosis, dietary interventions, lifestyle improvements, probiotic or prebiotic supplements. However, to fulfill the promise of a lifelong cardiovascular health, more mechanism studies should progress from correlation to causality and decipher novel mechanisms linking specific microbes and CVDs. It is also promising to use the burgeoning artificial intelligence and machine learning to target gut microbiota for developing diagnosis system and screening for new therapeutic interventions.

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.

ObjectiveThis study aims to assess the early to mid-term clinical efficacy of expanded polytetrafluoroethylene (ePTFE) trileaflet valved conduits in pediatric right ventricular outflow tract reconstruction for congenital heart disease.MethodsWe conducted a retrospective analysis of pediatric patients who underwent right ventricular outflow tract (RVOT) reconstruction using ePTFE trileaflet valved conduits at two cardiac centers in China, between January 2017 and June 2023. The main assessment criterion was the functionality of the prosthetic pulmonary valve conduit.ResultsA total of 162 pediatric patients were included, with follow-up periods ranging from 0.1 to 5 years post-discharge, and a median follow-up duration of 1 year (interquartile range: 1, 2). Three patients (1.9%) required re-operation due to conduit obstruction. During follow-up, pulmonary valve flow velocities were recorded as <3 m/s in 134 patients (82.7%), between 3 and 4 m/s in 24 patients (14.8%), and >4 m/s in 4 patient (2.5%). Mild pulmonary valve regurgitation was noted in 148 patients (91.4%), and moderate pulmonary valve regurgitation was noted in 14 patients (8.6%), with no instances of more than moderate pulmonary valve regurgitation.ConclusionThe ePTFE trileaflet valved conduit, known for its accessibility and simplicity in manufacturing, demonstrates favorable early to mid-term clinical outcomes in pediatric RVOT reconstruction.