Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and a leading cause of cardioembolic stroke. In nonvalvular atrial fibrillation (NVAF), thrombus formation occurs predominantly within the left atrial appendage (LAA), making it a key therapeutic target. While oral anticoagulation remains standard for thromboembolic risk reduction, contraindications, elevated bleeding risk, and therapy intolerance drive the need for nonpharmacologic alternatives. This review examines the role of the WATCHMAN left atrial appendage occlusion (LAAO) device in NVAF-related stroke prevention, encompassing pathophysiologic rationale, device design, procedural technique, clinical evidence, post-implantation management, and outstanding evidence gaps. The PROTECT AF and PREVAIL trials established WATCHMAN-based LAAO as noninferior to warfarin for prevention of stroke, systemic embolism, and cardiovascular death, though early procedural complications underscored the importance of operator experience. Subsequent real-world registries confirmed safety and effectiveness in higher-risk, anticoagulation-ineligible populations. Newer-generation platforms including the WATCHMAN FLX and FLX Pro, demonstrate improved sealing performance and procedural safety, while contemporary randomized trials further define LAAO's role relative to DOAC therapy. WATCHMAN-based LAAO represents an important alternative for carefully selected patients, particularly those with high bleeding risk. Optimal patient selection, antithrombotic regimens, and long-term outcomes warrant continued investigation.
Pulmonary artery banding (PAB) remains an important palliative strategy in congenital heart disease (CHD), particularly for temporary modulation of pulmonary blood flow and pressure during staged management. Over the past two decades, catheter-based pulmonary flow restrictors (PFRs) have emerged as less invasive alternatives to surgery, expanding treatment options for fragile infants and selected older patients. This review traces the evolution of transcatheter PFR, from early experimental concepts to off-label use of manually fenestrated Medtronic microvascular plugs (MVPs). It examines device mechanics, fenestration geometry and technique, implantation strategies, pulmonary vascular interaction, complications, antithrombotic management, retrieval, and long-term limitations. Key challenges include non-standardized fenestration, device-vessel mismatch, progressive loss of restriction with growth, anatomy-dependent performance, and increasingly time-dependent retrieval difficulty. The principal strength of the MVP-based approach is its intraprocedural adaptability, allowing fenestration to be tailored to individual anatomy, hemodynamics, and therapeutic goals. Given the dynamic and heterogeneous physiology of CHD, future dedicated platforms should preserve this adaptability rather than impose a fixed design. Technical refinement should therefore remain embedded within a patient-centered strategy that allows ongoing adjustment. Multicenter registries and purpose-built platforms may help define the future of controlled and durable transcatheter pulmonary flow modulation.
Computational modeling has become an increasingly important component of thrombosis and hemostasis research, evolving from mechanistic simulations into multidisciplinary approaches that support diagnosis, risk stratification, and therapeutic decision-making. The fourteen contributions included in this Research Topic illustrate this evolution through complementary methodologies, including mechanistic modeling, computational fluid dynamics, machine learning, quantitative imaging, biomarker integration, real-world data analysis, and evidence synthesis. Collectively, these studies demonstrate how biological understanding, individualized prediction, comprehensive patient characterization, and rigorous validation represent interconnected steps toward clinically meaningful computational tools. Rather than competing methodologies, these approaches address complementary dimensions of thrombosis and hemostasis, contributing to more integrated frameworks for precision medicine. Together, this collection highlights both the progress achieved and the challenges that remain in translating computational innovation into robust clinical decision-support systems.
The development of new cancer therapies with greater efficacy has reduced mortality for many cancers, as well as improving survivorship. However, for some cancer treatments, this has uncovered unintended cardiotoxicity during or after treatment, and cardiovascular disease has emerged as a leading cause of mortality in some cancer survivors. This may occur because many of the same growth factor signaling pathways that lead to tumor growth are also critical for maintaining normal heart function. A class IA phosphoinositide 3-kinase, PI3K(p110α), is a critical regulator of normal heart biology, function and exercise-induced cardiac protection, but is also mutated/increased in some cancer types. In this review, we discuss the dual role of PI3K(p110α) signaling in cancer and the heart. The paradox being, that inhibiting PI3K(p110α) in a setting of some cancer types would be beneficial for halting/slowing tumor progression but could also damage heart muscle cells. Exercise and PI3K(p110α) has beneficial effects on heart function via cardiac excitation and contraction, mitochondrial adaptations, cellular stress responses to promote survival, preventing cell death and cardiac fibrosis. We contrast this to the chemotherapy, doxorubicin, which is crucial for the treatment of many cancers but negatively impacts many of the beneficial effects of exercise and PI3K(p110α). Doxorubicin's clinical efficacy is limited by dose-dependent cardiotoxicity including cardiomyopathy, atrial fibrillation, and heart failure. A summary of reported cardiovascular effects in clinical trials using PI3K inhibitors is also provided. Finally, we discuss some of the current and emerging approaches to mitigate cancer therapy-induced cardiotoxicity including pharmacological interventions, gene therapy and dietary approaches based on preclinical studies. Advances in the field are likely to come from continued refinement of cardiotoxicity models, the investigation of targeting molecular pathways and targets with relevant primary endpoints for both cancer and heart function, and collaborative research with discovery/preclinical scientists and clinicians.
Anomalous left coronary artery from the pulmonary artery (ALCAPA), also known as Bland-White-Garland syndrome, is a rare congenital coronary artery anomaly with an incidence of approximately 1 in 300,000 live births, accounting for 0.25%-0.5% of all congenital heart diseases. Without surgical correction, approximately 90% of affected infants die within the first year of life due to myocardial ischemia and heart failure. However, a small subset of patients with well-developed collateral circulation may survive into adulthood without marked symptoms. We report an incidentally diagnosed case of ALCAPA in a 76-year-old man who was admitted for benign prostatic hyperplasia and urinary retention and underwent cardiovascular evaluation before non-cardiac surgery. Electrocardiography showed sinus bradycardia and complete right bundle branch block, and ambulatory celectrocardiography documented frequent supraventricular premature beats and short supraventricular tachycardia runs without significant ST-T abnormalities. Echocardiography showed a dilated right coronary artery, a suspected coronary fistula, mild chamber enlargement, preserved left ventricular systolic function, and no typical resting segmental wall-motion abnormality. Coronary CT angiography (CTA), performed after cardiology consultation, demonstrated the left main coronary artery arising from the pulmonary trunk, a markedly dilated and tortuous right coronary artery, extensive collateral circulation among the right coronary artery, left coronary system, and bronchial arteries, and a high coronary artery calcium score of 941.74 Agatston units. Cardiac enzymes were not elevated, but formal stress testing and cardiac magnetic resonance imaging were not performed during the index admission. The management decision was therefore framed as individualized conservative follow-up rather than evidence that conservative treatment is generally safe in adult ALCAPA. This case illustrates the diagnostic value of CTA for defining coronary anatomy in late adult ALCAPA, the need for functional ischemia and scar assessment when feasible, and the therapeutic tension between guideline-based surgical recommendations and individualized decision-making in elderly patients with preserved resting ventricular function.
Artificial intelligence (AI) applied to the standard 12-lead electrocardiogram (AI-ECG) is being developed as a scalable approach to screen for left ventricular systolic dysfunction (LVSD) and support triage for confirmatory testing. Supervised models trained on paired ECG-echocardiography data show high discrimination for reduced ejection fraction across thresholds and can identify individuals at higher risk of subsequent LV dysfunction despite a normal baseline echocardiogram. External validation of an FDA-cleared ECG-AI device across four geographically diverse U.S. health systems confirmed strong diagnostic accuracy, though signal-format compatibility and quality gating meaningfully affect real-world yield. Two pragmatic randomized trials demonstrate practice-level impact. In primary care, AI-ECG increased the number of new low-ejection-fraction diagnoses and directed echocardiography preferentially to screen-positive patients. In non-cardiology inpatient wards, AI alerts improved diagnostic yield through increased cardiology consultation rather than increased imaging volume. In emergency-department patients with dyspnea, AI-ECG supports a prioritization role with high negative predictive value, outperforming NT-proBNP, but requires confirmatory imaging given prevalence-dependent positive predictive value. In population cohorts, adding AI-ECG signals to PREVENT-HF improves near-term heart-failure risk discrimination and reclassification, though without demonstrated benefit on clinical outcomes such as heart-failure hospitalization or mortality. Foundation models pretrained on large ECG datasets reduce labeled-data requirements and improve transportability, but prospective echocardiography-anchored validation is required before broader deployment. FDA-cleared software is available for left ventricular ejection fraction ≤40% screening from 12-lead ECGs as clinician decision support. This review summarizes performance across thresholds and care settings, outlines threshold selection and calibration, and defines priorities for outcome-oriented trials, equitable deployment, and implementation governance.
Background:Drug-coated balloons (DCB) represent a novel therapeutic approach for treating native coronary artery disease. However, the clinical outcomes of DCB in patients with left anterior descending (LAD) artery stenosis proximal to a myocardial bridge (MB) remain unclear. This study aims to investigate the effects of DCB in patients with LAD artery stenosis proximal to MB. Method:This retrospective cohort study included consecutive patients with LAD artery stenosis proximal to MB who underwent DCB or drug-eluting stent (DES) procedures between January 2020 and July 2021. The DCB group comprised 30 patients treated with DCB alone, while the DES group included 105 patients treated with DES alone. Major adverse cardiac events (MACEs) during a median follow-up of 507 days (IQR 391.5-622.0 days) were defined as a composite of unstable angina requiring hospitalization, acute myocardial infarction, cardiac death, and target lesion revascularization (TLR). Results:Both groups exhibited generally comparable baseline clinical and lesion characteristics, except for age and MB systolic compression. Over a median follow-up of 507 days (IQR 391.5-622.0 days), Kaplan-Meier survival analysis revealed no statistically significant difference in MACE-free survival rates between the two groups (73.96%, 95% CI 55.8-98.0 vs. 82.49%, 95% CI 73.9-90.8; Log-rank P = 0.678). Cox proportional regression analysis showed no statistically significant difference in MACEs between DCB and DES patients (HR = 1.58, 95% CI = 0.56-4.45, P = 0.383). Conclusion:In this exploratory retrospective study, we did not detect a statistically significant advantage of DCB over DES in treating LAD stenosis proximal to MB. Given the limited sample size, these findings should be considered preliminary and do not support DCB as a reasonable alternative to DES. Larger prospective studies are warranted to validate the potential role of DCB in this specific anatomical setting.
Background:Progressive aortic root dilation represents a life-threatening sequela of uncorrected tetralogy of Fallot (TOF), predisposing patients to aortic regurgitation, dissection, and rupture. Valve-sparing aortic root replacement (VSARR) offers an attractive alternative to mechanical valve replacement by eliminating prosthesis-related complications and lifelong anticoagulation. However, experience with VSARR in unoperated adult TOF patients remains exceptionally limited. Case presentation:We report a 35-year-old male with unrepaired TOF who presented with progressive exertional dyspnea, cyanosis, and atrial fibrillation. Comprehensive imaging revealed severe aortic root dilation (55.4 mm), moderate-to-severe aortic regurgitation, perimembranous ventricular septal defect, infundibular stenosis, and secundum atrial septal defect. We performed single-stage surgical correction comprising ventricular septal defect closure, infundibular resection, pulmonary valvotomy with transannular patch, atrial septal defect closure with fenestration, and Yacoub remodeling VSARR. The patient tolerated the 208-min cardiopulmonary bypass procedure well, with immediate postoperative echocardiography demonstrating trivial aortic regurgitation. He was discharged on postoperative day 7 in sinus rhythm without complications. Conclusions:This case demonstrates the feasibility of combining Yacoub VSARR with primary intracardiac TOF repair in unoperated adults. The procedure successfully preserved native aortic valve function while correcting congenital anatomy, avoiding prosthetic valve-related morbidity. This approach may expand surgical options for adults with TOF-associated aortopathy, though long-term durability data are needed.
Aberrant right subclavian artery (ARSA) represents the most prevalent congenital anatomical malformation of the aortic arch. Most affected patients remain asymptomatic, making ARSA prone to misdiagnosis before procedures, which markedly increases the risk of vascular injury during interventional procedures through the right radial artery. We report a 62-year-old woman with coronary artery disease in whom ARSA was not identified preoperatively. During coronary angiography (CAG) performed via right transradial access, iatrogenic dissection of the aberrant right subclavian artery occurred and extended retrogradely to form a Stanford Type B aortic dissection measuring 70 mm in total length, with a 5.6-mm intimal tear at the proximal segment of the ARSA. The patient received conservative management including strict blood pressure control and analgesia after the procedure, and was discharged in improved condition.
Clopidogrel is a drug that is commonly used to prevent occlusive events after coronary artery interventions. However, the efficacy of clopidogrel varies depending on the CYP2C19 polymorphism, as it is not clopidogrel itself but the H4 metabolite that is responsible for the pharmacological effect. Carriers of the CYP2C19 loss-of-function allele genotype - which can affect up to 50% of patients - exhibited a higher likelihood of experiencing cardiovascular events. Administering the H4 metabolite directly avoids this problem. In the first step, the H4 metabolite was successfully produced in vitro from 2-oxo-clopidogrel using human liver microsomes. Thereafter, human platelet-rich plasma was supplemented with the H4 metabolite and then stimulated with adenosindiphosphate (ADP, 20 µM). The present confirmatory, placebo-controlled, parallel-group ex vivo study showed that the H4 metabolite of clopidogrel metabolized by human liver microsomes significantly and relevantly inhibited ADP-induced platelet aggregation. The study thus showed that the H4 metabolite of clopidogrel produced by human liver microsomes completely overcomes the limitations of clopidogrel, such as high inter-individual variability due to genetic polymorphisms of CYP2C19, a delayed onset of action and inadequate efficacy.
Aims:Non-ECG-gated chest CT frequently identifies coronary artery calcification (CAC) and thoracic aortic calcification (TAC), but age- and sex-specific thresholds remain unclear in Chinese communities. The ACC/AHA guideline recommends statins for those with CAC ≥75th percentile1. In subgroups with CAC positivity rate ≤25%, any detectable CAC corresponds to the ≥75th percentile. We aimed to determine precise sex-specific age thresholds using single-year stratification for opportunistic cardiovascular risk stratification. Methods:A total of 42 363 participants aged 1-105 years (mean age: 56.9 ± 17.3 years; 52.0% male) who underwent non‑ECG‑gated chest CT from 2023 to 2025 were enrolled in this retrospective study. CAC and TAC were visually evaluated as binary (present/absent) variables. Single‑year stratification was applied to calculate key age thresholds corresponding to 25%, 50%, and 75% positivity rates of CAC and TAC. Distributions of isolated CAC, isolated TAC, and combined vascular calcification were compared between men and women. Results:The ages at which CAC positivity reached 25%, 50%, and 75% were 48, 57, and 70 years for men versus 58, 67, and 76 years for women. Corresponding TAC threshold ages were 57, 60, and 71 years in men and 60, 67, and 78 years in women; TAC showed strong age dependence with modest sex‑related differences. The inflection age for CAC positivity exceeding 25% was approximately 58 years in women, around 10 years later than that observed in men. Isolated CAC was more frequent among men, while isolated TAC predominated in women; combined calcification became the dominant phenotype with increasing age. Conclusion:In male aged <48 years and women aged <58 years, CAC detected on non-gated chest CT may warrant statin initiation, providing additional cost-free opportunistic risk stratification beyond current guideline recommendations. Moreover, CAC-negative individuals aged <70 years in men and <76 years in women are likely to have a favorable cardiovascular prognosis.
Background:Heart failure (HF) is a major complication of acute coronary syndrome (ACS) and is associated with poor outcomes. Aims:To develop and internally evaluate a machine learning (ML) model for early identification/risk classification of HF or congestion among patients with ACS using bioelectrical impedance analysis (BIA)-derived body composition parameters. Methods:This single-center retrospective cohort study included 527 patients with ACS. Body composition was assessed within 48 h of admission using multi-frequency direct segmental BIA. The dataset was first randomly partitioned into training and locked test cohorts. Imputation, standardization, feature selection, and model selection were performed using training data only. A total of 120 model pipelines were compared by training-stage cross-validation, and the locked test set was reserved for one final evaluation. Results:HF was identified in 198 patients (37.6%). The final plsRglm + glmBoost model used six BIA/body-composition variables: Protein, Muscle-Right arm, Muscle-Trunk, ECW/TBW ratio-Trunk, ECW/TBW ratio-Left leg, and arm muscle circumference. In the locked test set, the model achieved an area under the receiver operating characteristic curve (AUC) of 0.793 (95% CI 0.719-0.859) and a Brier score of 0.186 (95% CI 0.154-0.221). Calibration assessment showed an intercept of 0.266 (95% CI -0.145 to 0.709) and slope of 0.918 (95% CI 0.645-1.287). SHAP analysis indicated that ECW/TBW ratio-Trunk and ECW/TBW ratio-Left leg were the most influential predictors. Conclusions:A leakage-free ML workflow using bedside BIA-derived body composition parameters showed moderate discrimination for early identification/risk classification of HF/congestion among patients with ACS. Because of the retrospective single-center design, limited timing information, and absence of external validation, the model should not be interpreted as proving prospective prediction of future HF events.
Objective:To quantify the association between circulating trimethylamine N-oxide (TMAO) and atrial fibrillation (AF) risk and determine how this association is modified by clinical background. Methods:We performed a systematic review and meta-analysis by searching PubMed, Web of Science, EMBASE, Scopus, and ProQuest for studies published up to April 2026. Studies reporting quantitative associations between circulating TMAO levels and AF outcomes were included. Meta-analytic pooling of odds ratios (ORs) and hazard ratios (HRs) was conducted using R packages meta under random-effects models. Pre-specified subgroup analyses were performed by clinical setting and AF outcome type. Heterogeneity was quantified using I2 statistics and τ 2, with influence diagnostics and assessment of publication bias using Galbraith plots, Baujat plots, and Egger's test. Result:Of the 15 included studies, 9 were included in the quantitative meta-analysis, comprising 8 odds-ratio and 2 hazard-ratio studies with one overlapping. The random-effects meta-analysis of the eight odds ratio studies demonstrated a significant positive association between TMAO and AF (pooled OR 1. 35, 95% CI 1. 15-1. 59, p = 0. 0003). Substantial heterogeneity was observed (I2 = 68.3%, p = 0Subgroup analysis revealed that only 1 of the 8 studies (12. 5%) reported postoperative AF after cardiac surgery, in which the association was significantly stronger (OR 2. 88, 95% CI 1. 35-6. 15) compared with spontaneous incident AF (pooled OR 1. 31, 95% CI 1. 12-1. 52; between-group p = 0. 045). A trim-and-fill sensitivity analysis adjusting for potential publication bias attenuated the pooled estimate (OR 1.18, 95% CI 0.95-1.47). Analysis of two studies reporting hazard ratios showed extreme heterogeneity (I2 = 92.5%) precluding a reliable pooled estimate. Conclusion:Circulating TMAO is significantly associated with increased AF risk, with the magnitude of risk markedly augmented in the postoperative cardiac surgery setting,positioning TMAO as a context-dependent biomarker that requires interventional evidence before being considered a target for gut microbiota-directed interventions.
Introduction:Pulmonary embolism (PE) is a common condition with negative long-term consequences such as reduced quality of life. However, there is little knowledge regarding fatigue after PE. The aim of this study was to determine prevalence and predictors of fatigue after PE. Methods:The Lungenembolie Augsburg (LEA) study includes patients treated for acute PE at the University Hospital of Augsburg, Germany. Patients were interviewed during hospitalization and received postal questionnaires after 3 and 12 months. Fatigue was assessed using the Fatigue Assessment Scale (FAS). Data from the "Stroke Cohort Augsburg (SCHANA)" study and the "Metabolism, Nutrition and Immune System in Augsburg (MEIA)" study were used to compare fatigue prevalence after PE with that after stroke and in the general population. Multiple linear regression models were built to identify baseline predictors for fatigue 3 and 12 months after PE. Results:Three months after PE, the age-sex-standardized fatigue prevalence was 40.76% [95% confidence interval (CI): 24.81%-56.71%] and 12 months after PE it was 32.36% (95% CI: 20.72%-44.01%), which was significantly higher than in the general population (12.68%; 95% CI: 9.75%-15.61%), but did not significantly differ from the prevalences found in patients with stroke (3 months: 30.97% (95% CI: 22.73%-39.22%); 12 months: 28.02% (95% CI: 17.49%-38.55%). Multiple linear regression models revealed that gender modified the relationship between depression at baseline and fatigue 3 and 12 months after PE. In men, Hospital Anxiety and Depression Scale (HADS) Depression score (β = 1.92, p < 0.0001) as well as school education >9 years (β = -3.72, p = 0.0491) and in women, HADS Depression score (β = 0.80, p = 0.0057), were significantly associated with fatigue 3 months after PE. Twelve months after PE, HADS Depression score (β = 1.69, p < 0.0001) and school education >9 years (β = -5.28, p = 0.0059) were significantly associated with fatigue in men. Discussion:The results show that fatigue is common after PE. Early screening for depression and fatigue in both men and women should be considered. Lower school education level in men was shown to be a predictor of fatigue and should be taken into account when screening patients.
Background:The remnant cholesterol inflammation index (RCII) combines remnant cholesterol (RC) and high-sensitivity C-reactive protein (hs-CRP), two markers that may reflect residual lipid-related and inflammatory vascular burden. We examined whether baseline RCII was associated with incident stroke among hypertensive middle-aged and older adults and whether this association was nonlinear. Methods:We analyzed 3,823 stroke-free hypertensive participants aged 45 years or older from the China Health and Retirement Longitudinal Study (CHARLS). Participants were excluded if they lacked follow-up information, were younger than 45 years, had missing or biologically implausible RCII components, had hs-CRP > 10 mg/L, or had missing covariates. RCII was analyzed per 1-standard deviation (SD) increase and by quartiles. Cox proportional hazards models, restricted cubic splines, an exploratory two-piecewise Cox model, subgroup analyses, and sensitivity analyses were performed. Results:During a median follow-up of 9.08 years (interquartile range, 9.08-9.17), 526 incident strokes occurred (13.8%). In the fully adjusted model, the original-scale linear estimate was positive but not statistically significant (HR per 1-SD increase, 1.06; 95% CI, 0.99-1.14; P = 0.110). Compared with Q1, adjusted HRs were 1.38 (95% CI, 1.06-1.81) for Q2, 1.66 (95% CI, 1.28-2.15) for Q3, and 1.60 (95% CI, 1.23-2.08) for Q4 (P for trend <0.001). Spline and threshold analyses suggested a nonlinear association, with a data-driven inflection point near RCII 3.80 and apparent flattening at higher values. Subgroup findings were broadly consistent, although current drinking status showed an exploratory interaction. Sensitivity analyses supported the robustness of the quartile-based associations. Conclusions:Among hypertensive CHARLS participants, higher RCII categories were associated with incident stroke. The association was better characterized by categorical and nonlinear analyses than by a single original-scale linear estimate. RCII should be interpreted as an association marker, not as a validated predictive or clinical decision tool.
Objective:This study aimed to develop an interpretable machine learning model for predicting extubation failure in mechanically ventilated patients with combined respiratory failure and cardiac dysfunction. Methods:A retrospective cohort of 350 patients receiving invasive mechanical ventilation between January 2022 and January 2024 was analyzed. After rigorous data preprocessing ≤5% missing values were imputed using mean, median, or mode based on distribution type. The dataset was partitioned into training (n = 245) and testing (n = 105) sets at 7:3 ratio. Feature selection and hyperparameter tuning were synchronously optimized using an Improved Snow Geese Algorithm (ISGA)-driven Automated machine learning (AutoML) framework. Six supervised models [Logistic Regression (LR), Support vector machine (SVM), Adaptive Boosting (AdaBoost), eXtreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine (LightGBM), AutoML] were evaluated using six classification metrics [Accuracy, Sensitivity, Specificity, F1-score, Area Under the Receiver Operating Characteristic Curve (ROC-AUC), Area Under the Precision-Recall Curve (PR-AUC)] with five-fold cross-validation. Calibration curves and Brier scores assessed reliability, while SHAP analysis provided interpretability of predictors. Results:The ISGA-optimized AutoML framework (converging to LightGBM as the optimal algorithm) demonstrated superior performance on the independent test set, achieving a ROC-AUC of 0.9289 and a PR-AUC of 0.8892. Decision curve analysis confirmed clinical utility across threshold probabilities of 0.3-0.7, outperforming treat-all and treat-none strategies, and the calibration curve yielded a low Brier score of 0.114. Key predictors identified included brain Natriuretic Peptide (BNP), lactate, left ventricular ejection fraction (LVEF), troponin, and central venous pressure (CVP). Conclusion:The interpretable prediction tool accurately stratifies extubation failure risk using clinically available parameters, offering a prototype tool for personalized ventilation management.
Objectives:Transcatheter closure has become an important treatment modality for perimembranous ventricular septal defects (pmVSDs). However, conventional metallic occluders carry the risk of long-term complications. Fully bioabsorbable occluders offer a potential solution, yet their application in children with moderate-to-large pmVSDs remains under-reported. This study evaluated the feasibility and 1-year outcomes of transthoracic, transesophageal echocardiography (TEE)-guided implantation of a bioabsorbable occluder via a small subxiphoid incision in children with moderate-to-large pmVSDs. Methods:Children aged ≥1 year with moderate-to-large pmVSDs (defined as left ventricular defect diameter exceeding one-third of the aortic root diameter) who underwent TEE-guided transthoracic device closure using a bioabsorbable occluder between July 2024 and January 2025 were prospectively enrolled. Baseline characteristics, procedural data, and follow-up outcomes at 1, 3, 6, and 12 months were collected. The primary endpoints were technical success, valvular function, conduction disturbance, and occluder degradation. Results:Five children (mean age 2.4 ± 1.7 years; mean weight 12.6 ± 4.6 kg; mean defect diameter 8.8 ± 2.6 mm) were included. All implants were successful (technical success 100%). One patient with a multi-fenestrated defect had a 2 mm residual shunt immediately post-procedure, which resolved by 6 months. At 1 year, no patient developed new-onset or worsening aortic regurgitation (AR) or tricuspid regurgitation (TR), and none had complete atrioventricular block (cAVB). Quantitative echocardiographic analysis showed that occluder disc area decreased substantially at 1 year, indicating progressive absorption. Conclusions:TEE-guided transthoracic closure of moderate-to-large pmVSDs using a bioabsorbable occluder appears feasible in selected children. One-year follow-up data suggest favorable preservation of valvular and conduction function, with progressive occluder degradation. This approach may offer a minimally invasive alternative to surgery for this challenging population, although larger studies are warranted.
IntroductionR-loops, RNA-DNA hybrid structures with a displaced single-stranded DNA loop, are key regulators of transcriptional control, chromatin architecture, and genome stability and have emerging roles in inflammatory signaling. However, the relationship between R-loop abundance and strongly modulated inflammatory effector genes in metabolic inflammation and influenza virus infection remains underexplored.MethodsWe performed a locus-centric integrative analysis combining robust differentially expressed genes (DEGs) from multiple inflammatory and infection-related murine and human transcriptomic disease models with experimentally validated multi-cell R-loop annotations from the reference atlas RLoopBase. Our correlation framework evaluated the directional relationship between R-loop abundance and inflammatory gene expression rather than assuming disease-sample-matched R-loop measurements. We further analyzed R-loop regulatory proteins, NRF2-associated R-loop regulators, and overlaps between R-loop regulators and CRISPRi-identified mitochondrial and cellular reactive oxygen species (ROS) regulators.ResultsIn angiotensin II-infused apolipoprotein E-deficient (ApoE−/−) mice, a model of abdominal aortic aneurysm (AAA), genomic regions encoding the top significantly upregulated genes exhibited significantly fewer R-loops than those encoding downregulated genes at days 14 and 28. Similarly, in atherosclerotic ApoE−/− mice fed a high-fat diet for 32 and 78 weeks, upregulated genes were associated with fewer R-loops than downregulated genes. Reduced R-loop abundance was also observed in genomic regions encoding the top significantly upregulated genes in liver tissues from patients with non-alcoholic steatohepatitis (NASH), as well as in monosodium urate (MSU)-stimulated lymphatic endothelial cells (LECs) and influenza virus-infected human umbilical vein endothelial cells (HUVECs). R-loop regulatory proteins upregulated during metabolic inflammation were enriched in immune and inflammatory pathways. NRF2 was identified as a regulator of 27 R-loop regulatory proteins, including 10 positively and 17 negatively regulated proteins. Furthermore, 54 R-loop regulatory proteins overlapped with CRISPRi-identified mitochondrial and cellular ROS regulators, suggesting potential reciprocal regulation between R-loop homeostasis and ROS signaling. Disease-associated changes in pro-ROS and anti-ROS R-loop regulatory proteins further linked R-loop regulation to inflammatory and oxidative stress pathways.DiscussionThese findings identify reduced R-loop abundance at genomic regions encoding strongly upregulated inflammatory genes as a shared feature across multiple models of metabolic inflammation and influenza virus infection. The results further suggest that immune-associated R-loop regulatory proteins and the NRF2–ROS axis may contribute to R-loop remodeling during inflammatory disease. This integrative framework provides new insight into the potential role of R-loops and ROS-sensitive R-loop regulators in inflammatory and metabolic diseases and identifies candidate pathways for future mechanistic investigation and therapeutic targeting.
