One of the primary challenges in addressing cardiac injury is the limited cardiac specificity of therapeutic drugs. Lipid nanoparticles (LNPs) are a relatively novel class of delivery vehicles used for administering RNA and various drugs. A major challenge in the treatment of cardiac injury remains the poor cardiac specificity of most therapeutic agents. Despite their promise as a relatively novel delivery platform for RNA and other payloads, LNPs do not adequately overcome this limitation. Nevertheless, these LNPs exhibited preferential accumulation in the liver rather than the heart. To address this off-target biodistribution and enhance delivery efficiency to cardiac tissue, surface functionalization with cardiac-homing peptides (CHP) was performed. In this study, the CHP-functionalized LNP loaded with colchicine (termed as CCP) was developed as a targeted therapeutic platform for myocardial repair. This novel drug delivery system successfully localizes to the ischemic myocardium and precisely releases CCP to hypoxic, mildly acidic cardiomyocytes. In conclusion, CCP presents a promising platform for the sustained and localized delivery of drugs to the heart, thereby enhancing the therapeutic efficacy for cardiovascular diseases.

BACKGROUND:With global warming, extreme summer heat has led to a higher morbidity and mortality of heat stroke (HS). Although heat stress has been linked to arrhythmias and cardiomyocyte injury, the specific molecular mechanisms and effective intervention strategies remain to be clarified. METHOD:We retrospectively collected clinical data from HS patients. A rat HS model was established, and the underlying mechanisms were investigated using biochemical and electrophysiological approaches, combined with proteomics and metabolomics analyses of myocardial tissues and cells. In vivo and in vitro intervention experiments were performed using the mitochondrial reactive oxygen species (ROS) scavenger MitoTEMPO and calcineurin inhibitor (FK506). RESULTS:Heat stress caused severe myocardial injury and electrocardiographic abnormalities in HS patients. HS rats exhibited increased susceptibility to ventricular arrhythmias (VAs), manifested by prolonged action potential duration (APD), increased Ca2+ transient duration (CaTD) and Ca2+ alternans ratio, and slowed conduction velocity (CV), which were linked to disrupted Ca2+ handling. Proteomics and metabolomics revealed that mitochondrial dysfunction was closely associated with heat stress-induced myocardial injury. Mechanistically, HS triggers intracellular Ca2+ overload, activating calcineurin. Calcineurin dephosphorylates DRP1 at Ser637 site and promotes its mitochondrial translocation, leading to DRP1-mediated mitochondrial fission and dysfunction, excessive mitochondrial ROS generation, and cardiomyocyte apoptosis. In addition, MitoTEMPO and FK506 treatment partially reversed HS-induced myocardial injury and VAs susceptibility by scavenging mitochondrial ROS and restoring mitochondrial function. CONCLUSION:Heat stress triggers mitochondrial dysfunction through a Ca2+/calcineurin/p-DRP1(Ser637) axis, resulting in myocardial injury and VAs. The mitochondria-targeted antioxidant MitoTEMPO and FK506 partially alleviate these adverse effects by scavenging mitochondrial ROS and restoring mitochondrial function.

Background: heatstroke (HS) is characterized by a high incidence of cardiac injury and multiple complications, with no specific therapeutic agents available. Curcumin (CUR) has demonstrated cardioprotective effects, but its role in HS-induced myocardial injury and arrhythmias remains poorly understood. Objective: this study aims to examine the protective effects of CUR in HS-induced myocardial injury and ventricular arrhythmias and elucidate its mechanism via the BAX/BCL-2/caspase-3 apoptotic pathway. Materials and methods: a rat model of HS was established, consisting of three groups: control (CT) group, HS group, and CUR intervention (HS + CUR) group. Myocardial injury markers were assessed using enzyme-linked immunosorbent assays (ELISAs). Electrophysiological parameters were evaluated utilizing electrocardiography (ECG), electrophysiological examination, a rechargeable animal telemetry system, and a microelectrode array (MEA). Echocardiography and pressure-volume (PV) loop assessment were performed to evaluate changes in cardiac function. Histological alterations in myocardial tissue were examined through hematoxylin-eosin (HE) and wheat germ agglutinin (WGA) staining. Cardiac ultrastructure was observed via transmission electron microscopy (TEM). Integration of transcriptomics, proteomics, and network pharmacology facilitated the identification of the common targets of HS and CUR, followed by gene set variation analysis (GSVA). Molecular docking and molecular dynamics simulations confirmed the interaction of CUR with BAX, BCL-2, and caspase-3. Apoptosis was examined utilizing cell counting kit-8 (CCK-8) assay, Hoechst and TUNEL staining, flow cytometry, and western blotting (WB) in vivo and in vitro. Results: the HS group showed elevated body temperature, reduced weight, lower survival, increased myocardial injury markers, and ventricular electrical/structural remodeling. CUR treatment ameliorated these effects. Multi-omics identified 18 differential molecules and two common targets (Serpine1 and Hspa8). Molecular docking confirmed the stable binding of CUR to BAX/BCL-2/caspase-3. In vivo/in vitro experiments showed that CUR inhibited HS-induced cell apoptosis. Conclusion: CUR exhibits protective effects against HS-induced myocardial damage and decreases susceptibility to ventricular arrhythmias in HS rats and inhibits HS-induced injury in H9C2 cells. Its mechanism to improve myocardial injury and ventricular arrhythmias may involve inhibition of the BAX/BCL-2/caspase-3 pathway.

Background:Vasovagal syncope (VVS) is the most common type of reflex syncope. Although typically benign in its clinical course, VVS may lead to injury and reduced quality of life. Autonomic nervous system imbalance is considered the core pathophysiological mechanism of VVS. Heart rate variability (HRV), a noninvasive marker of autonomic regulation, may have practical value in identifying VVS and its subtypes; however, its predictive utility has not been fully elucidated. Methods:In this single-center retrospective case-control study, we included 415 patients with syncope symptoms who underwent both 24-hour Holter monitoring and a head-up tilt test (HUTT) between January 2021 and December 2024. Based on HUTT results, patients were classified into a VVS-positive group (n = 279) and a control group (n = 136). HRV parameters extracted from Holter recordings included 24 h average, maximum and minimum heart rates (HRs), standard deviation of NN intervals (SDNN), triangular index (TI), root mean square of successive differences (rMSSD), and the percentage of NN intervals differing by more than 50 ms (pNN50). Associations and predictive performance were assessed using logistic regression and receiver operating characteristic (ROC) analysis. Results:Multivariable logistic regression revealed that 24 h average HRs (OR: 0.935; 95% CI: 0.912-0.959; P < 0.001), 24 h maximum HRs (OR: 0.976; 95% CI: 0.964-0.989; P < 0.001), 24 h minimum HRs (OR: 0.947; 95% CI: 0.915-0.980; P = 0.002), TI (OR: 1.032; 95% CI: 1.009-1.056; P = 0.006), SDNN (OR: 1.029; 95% CI: 1.016-1.043; P < 0.001), rMSSD (OR: 1.023; 95% CI: 1.007-1.038; P = 0.004), and pNN50 (OR: 1.028; 95% CI: 1.006-1.051; P = 0.013) were independently associated with the occurrence of VVS. ROC analysis showed that 24 h average HRs (AUC: 0.688; 95% CI: 0.632-0.744), 24 h maximum HRs (AUC: 0.652; 95% CI: 0.594-0.709), and SDNN (AUC: 0.614; 95% CI: 0.557-0.672) exhibited moderate predictive ability for VVS. Conclusion:HRV parameters are associated with the occurrence of VVS. As a noninvasive and continuous physiological biomarker, HRV may aid in the clinical screening, risk stratification, and phenotypic classification of patients with suspected VVS.

BACKGROUND:No previous studies have examined the relationship between Micra transcatheter pacing system (TPS) curvature and acceptable thresholds during implantation. This study aimed to evaluate the association between Micra TPS curvature and pre-deployment capture thresholds. METHODS:The Micra TPS was successfully implanted with the assistance of right ventriculography in 180 patients. The curvature of the Micra TPS prior to deployment was analyzed using archived right anterior oblique (RAO) images from the first deployment, with the aid of Origin software (OriginLab Corporation, USA), while electrical parameters were recorded from 0 to 30 min at 10-min intervals. RESULTS:Among 159 eligible patients, 126 (79.2%) demonstrated acceptable thresholds with a mean curvature of 0.58 ± 0.18. The high-threshold group (n = 33, 20.8%) exhibited significantly greater curvature (1.36 ± 0.64). Receiver operating characteristic analysis indicated that Micra TPS curvature ≤0.799 predicted acceptable thresholds with 90.9% sensitivity and 91.3% specificity (area under the curve = 0.958, 95% confidence interval: 0.924-0.992), with stable thresholds maintained in the acceptable group. No procedural complications occurred. CONCLUSIONS:A curvature of ≤0.799 in the RAO view of the Micra TPS prior to deployment reliably indicates acceptable capture thresholds. Combining curvature assessment with right ventriculography enhances the procedural safety of Micra implantation.

Purpose This study aimed to develop and validate a machine learning model that integrates radiomic features of epicardial adipose tissue (EAT) from pre-procedural CT angiography with clinical variables to predict atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI).Materials and methods This retrospective study initially included 1,551 AF patients who underwent PVI. After data integrity screening and 1:1 propensity score matching (PSM) to balance confounding factors, the final analysis cohort consisted of 302 patients (151 with recurrence and 151 without recurrence). EAT was segmented from preoperative CT angiography images using a SwinUNETR model, which was pre-trained via transfer learning on manually annotated images. Following segmentation, radiomic features were extracted. Subsequently, six machine learning models were developed and evaluated.Results The SwinUNETR segmentation model achieved a dice similarity coefficient of 0.87. For AF recurrence prediction, the fusion model demonstrated superior and robust performance in internal validation. The random forest-based fusion model achieved the highest area under the curve (AUC) of 0.81 (95% CI: 0.59-0.87). Key predictive features included NT-proBNP and texture heterogeneity features from EAT, which align with known pathophysiological mechanisms involving systemic inflammation, metabolic dysregulation, and local atrial adipose tissue remodeling.Conclusion A fusion model incorporating EAT radiomics and clinical variables effectively predicts AF recurrence after PVI, with ensemble methods showing optimal performance. This study provides a multiscale, interpretable computational tool for individualized postoperative risk stratification, highlighting the complementary role of EAT imaging biomarkers to systemic clinical factors.

Background Evidence regarding the link between imaging modality and stroke prevention outcomes of left atrial appendage occlusion is currently lacking. Methods The RECORD (Registry to Evaluate Chinese Real‐World Clinical Outcomes in Patients With AF Using the WATCHMAN Left Atrial Appendage Closure Technology) trial prospectively enrolled 3096 consecutive patients undergoing left atrial appendage occlusion from 39 Chinese centers between April 1, 2019, and October 31, 2020. In the current analyses, patients were stratified into the echocardiographic guidance (transesophageal echocardiography/intracardiac echocardiography) group and the fluoroscopy‐only group. The primary end point was the composite end point of death, stroke, or systemic embolism at 3 years. Outcomes were estimated using the Kaplan–Meier method. Inverse probability of treatment weighting and 1:1 propensity score matching were performed to calculate hazard ratios (HRs) for each outcome at the time of interest. Results Among 3096 participants, 2603 (84.1%) underwent transesophageal echocardiography/intracardiac echocardiography–guided procedures and 493 (15.9%) underwent fluoroscopy‐only guided procedures. Before discharge, procedural complications occurred in 34 patients (1.4%) in the transesophageal echocardiography/intracardiac echocardiography group and 3 patients (0.6%) in the fluoroscopy‐only group (inverse probability of treatment weighting–adjusted absolute difference, −0.67 [95% CI, −1.39 to 0.05], P =0.066). At 3‐year follow‐up (completed by 2989 patients, 97.0%), the primary end point occurred in 269 (10.5%) patients in the transesophageal echocardiography/intracardiac echocardiography group and 52 (10.6%) patients in the fluoroscopy‐only group (inverse probability of treatment weighting–adjusted HR, 1.13 [95% CI, 0.81–1.57], P =0.469). Ischemic stroke was comparable between groups (3.0% versus 4.1%, inverse probability of treatment weighting–adjusted HR, 1.66 [95% CI, 0.95–2.89], P =0.073). These findings remained consistent across patient risk profiles and operator experience levels. Conclusions Fluoroscopy‐only guidance, without compromising long‐term stroke prevention efficacy, may serve as a streamlined and potentially accessible alternative for left atrial appendage occlusion procedures performed with the first‐generation WATCHMAN 2.5 device, and these findings apply to select patients and experienced centers. Registration URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT03917563.

BackgroundAssessment of mortality risk in hospitalized patients with heart failure (HF) constitutes a core tenet of clinical management. Renal function, as quantified by estimated glomerular filtration rate (eGFR), is a key prognostic factor for adverse outcomes; however, its independent association with in-hospital mortality has not been fully elucidated. We quantify the independent prognostic impact of eGFR on the risk of in-hospital mortality and to characterize its underlying nonlinear relationship.MethodsWe retrospectively enrolled 14,591 patients hospitalized for HF at a tertiary care center (2009–2024). eGFR was calculated via the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and categorized into five categories: ≥90, 60–89, 45–59, 30–44, and <30 mL/min/1.73 m2. The primary end point was all-cause in-hospital mortality. Multivariable logistic regression with stepwise covariate adjustment, subgroup analyses, and restricted cubic spline (RCS) modeling were performed to evaluate the association between eGFR and mortality.ResultsIn-hospital mortality rates increased progressively across eGFR strata: 5.77%, 6.37%, 8.19%, 11.72%, and 10.93%, respectively. After full covariate adjustment (Model 3), compared with eGFR ≥ 90 mL/min/1.73 m2, eGFR 45–59 and 30–44 mL/min/1.73 m2 were independently associated with a higher in-hospital mortality risk (OR 1.27, 95% CI 1.02–1.58, P = 0.036; OR 1.36, 95% CI 1.07–1.75, P = 0.014). Subgroup analysis showed that patients with eGFR < 60 mL/min/1.73 m2 had a 37% higher risk of in-hospital mortality (OR1.37, 95% CI 1.19–1.58, P < 0.001). A significant interaction was observed between eGFR and New York Heart Association (NYHA) functional class (P for interaction <0.001), with the risk of in-hospital mortality being significantly amplified in patients with NYHA class Ⅲ (OR 1.75) and class Ⅳ (OR 2.13). RCS analysis revealed a nonlinear association between eGFR and in-hospital mortality risk (P for nonlinearity <0.001), with a critical inflection point at approximately 60 mL/min/1.73 m2; below this threshold, the risk of in-hospital mortality increased sharply.ConclusionsReduced eGFR is a strong, independent prognostic factor for in-hospital mortality in patients hospitalized for HF, particularly in those with New NYHA class III/IV. The risk of in-hospital mortality rises steeply when eGFR is below 60 mL/min/1.73 m2. These findings support routine eGFR-guided risk stratification and early intensive monitoring in patients with advanced HF.

Background: Oxidative stress is pivotal in pulmonary hypertension. The uric acid-to-albumin ratio (UAR) is a readily available composite biomarker reflecting oxidative stress, inflammation and nutritional status. However, its clinical value for short-term risk stratification in PH remains unclear. Objective: This study aimed to evaluate the association of UAR with in-hospital mortality, clinically recorded PH severity grades, and selected cardiac structural and functional indicators in hospitalized patients with PH. Methods: This single-center retrospective cohort study included 8763 PH patients. Patients were stratified by UAR quartiles. Ordinal logistic regression, multivariable logistic regression, and linear regression were used to assess associations of UAR with clinically recorded PH severity grades, in-hospital mortality, left ventricular ejection fraction (LVEF), and right ventricular internal diameter (RVID). Restricted cubic spline analyses, subgroup analyses, receiver operating characteristic curve analyses, and incremental prediction analyses using C-statistics, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were also performed. Results: In-hospital mortality increased stepwise across UAR quartiles (0.5% vs. 1.0% vs. 1.8% vs. 2.8%, p < 0.001). In the fully adjusted model, each 1-unit increase in UAR was associated with higher odds of a more severe clinically recorded PH grade (OR = 1.11, 95% CI: 1.09–1.13, p < 0.001) and higher odds of in-hospital mortality (OR = 1.09, 95% CI: 1.04–1.14, p < 0.001). Higher UAR was also associated with lower LVEF (β = −0.53, 95% CI: −0.58 to −0.47, p < 0.001) and greater RVID (β = 0.18, 95% CI: 0.15–0.22, p < 0.001). Adding UAR to a model containing routinely available clinical, laboratory, and echocardiographic variables improved the C-statistic from 0.6922 to 0.7230, with significant improvements in NRI and IDI. Conclusions: UAR was independently associated with in-hospital mortality, clinically recorded PH severity, LVEF, and RVID, and provided incremental prognostic information. UAR may serve as a low-cost, routinely available, complementary biomarker for short-term in-hospital risk stratification in patients with PH.

BackgroundVentricular electrical storm (ES) is a malignant arrhythmia that seriously threatens the patients' life. Renal denervation (RDN) has been described as a treatment modality for refractory ventricular arrhythmias. This study aims to explore the potential role in patients with ablation-refractory ES.MethodsThis single-center retrospective cohort study included patients with refractory ES who underwent RDN between 2023 and 2024 with a follow-up period for 2–6 months. Implantable cardioverter defibrillator (ICD) programming results and intraoperative parameters were collected. Patients' clinical examination results were also compiled.ResultsThe study involved 10 patients with a mean age of 57.9 ± 7.4 years, including 4 (40%) ischemic cardiomyopathy, 6 (60%) dilated cardiomyopathy and 6 (60%) hypertension. ICD therapies showed a decreasing trend after multimodal therapy including RDN [pre-RDN 22 [9.3, 41], post-RDN 2.5 [0, 26.3]]. ICD shock therapies exhibited a similar descending tendency [pre-RDN 8.5 [1, 12.8] and post-RDN 0.5 [0, 3.5]]. Echocardiography and plasma results remained unchanged before and after surgery, including ejection fraction, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, and creatinine concentration.ConclusionMultimodal therapy including RDN may has the potential to contribute to decrease ICD therapies for patients with ES. Larger sample investigations may further demonstrate the efficacy and safety of RDN.

This report summarizes the case of a neonate with neonatal lupus erythematosus (NLE) and complete third-degree atrioventricular block who underwent permanent pacemaker implantation via an epicardial approach. It focuses on the etiology, indications for intervention, and surgical procedure, and evaluates the feasibility of using the 3830 lead for epicardial permanent pacing in pediatric patients.

Background The Aveir leadless pacemaker employs an active fixation method, enabling real-time monitoring of electrical parameters during implantation. However, comprehensive studies regarding the electrical parameters during this procedure are rare. Objective This study aims to analyze the electrical characteristics to further guide the implantation strategy and improve device stability and safety. Methods This multi-center retrospective study enrolled 119 patients (mean age 70.18 years; 59.58% female) who received the Aveir VR leadless pacemaker from November 2024 to May 2025 across ten centers in China. Intraprocedural variations in commanded electrogram (CEGM), current of injury (COI), impedance, pacing threshold, and sensing parameters were meticulously documented. Results CEGM mapping demonstrated various morphologies (R, RS, QR, QRS, and QS) aiding localization. During fixation, 58.82% of patients exhibited an increased COI from mapping to 0.5 turns, which was associated with reduced short-term pacing thresholds. From 0.5 to 1 turn, 52.94% showed further COI increases. ROC analysis revealed that an impedance increase has predictive value for short-term pacing thresholds, with an AUC of 0.634 and a cut-off value of 230 Ω (sensitivity 0.622, specificity 0.41). Lead stability showed a moderate correlation with impedance increase (ρ=0.44, P<0.001), while the correlation with COI was weak. Conclusion During Aveir implantation, CEGM variations guide site localization. Initial COI increases (0-0.5 turns) are linked to optimal short-term thresholds. Monitoring impedance increase is vital, as a threshold of 230 Ω serves as a key indicator of device stability and fixation quality. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial Not applicable. ### Funding Statement This research was funded by a grant from the Fundamental Research Funds for the Central Universities (Grant No. #3332024039). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All patients provided written informed consent. The present study was approved by the Ethics Committee of Fuwai hospital I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

Lead is a ubiquitous environmental toxic metal. Lead exposure is closely linked to an increased risk of atrial fibrillation (AF), yet its molecular mechanism remains incompletely understood. Here, we conducted an integrated study using network toxicology, machine learning, molecular docking, and in vivo and in vitro experiments to explore lead-induced AF. The global burden of disease analysis showed a marked rise in lead exposure-related AF/atrial flutter mortality and disability‑adjusted life years from 1990 to 2021, especially in low socio‑demographic index regions. We identified 142 overlapping targets between lead exposure and AF. Protein-protein interaction network and machine learning identified MAPK3 and ALB as core hub genes. Functional enrichment indicated critical roles of the PI3K‑Akt pathway. Molecular docking verified strong binding between Pb²⁺ and key pathway proteins. Lead exposure in mice triggered atrial electrical and structural remodeling and increased AF inducibility. In vitro, lead inhibited PI3K‑Akt phosphorylation, which was prevented by the pathway agonist 740 Y‑P. In conclusion, lead exposure was shown to promote AF by suppressing the PI3K‑Akt pathway, with MAPK3 and ALB as key targets. This study provides mechanistic insight and potential intervention targets for lead exposure-related AF.

Patients with heart failure with mildly reduced ejection fraction (HFmrEF) and hypertension represent a high-risk population with limited prognostic tools. The triglyceride-glucose-body mass index (TyG-BMI), a novel metric of insulin resistance and metabolic dysregulation, may enhance risk stratification but has not been evaluated in this specific cohort. We retrospectively analyzed 2,550 hospitalized hypertensive patients with HFmrEF from a single tertiary center (May 2012 to October 2023). Participants were randomly assigned to training (n = 1,785) and validation (n = 765) cohorts. Using least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression, we developed a nomogram to predict in-hospital mortality. Restricted cubic spline (RCS) analysis was used to characterize the dose-response relation between the TyG-BMI index and mortality risk. Model performance was assessed by area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA). In-hospital mortality occurred in 157 patients (6.16

ObjectiveThe International Diabetes Federation has proposed 1-hour plasma glucose (1-h PG) as a potential indicator for the diagnosis of type 2 diabetes mellitus (T2DM). This study aimed to systematically compare the diagnostic performance of 1-h PG, glycated albumin (GA), fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), and the combined HbA1c-or-FPG strategy for identifying T2DM using a network meta-analysis of diagnostic test accuracy.MethodsWe systematically searched PubMed, Embase, Web of Science, the Cochrane Library, Scopus, and gray literature for studies evaluating the diagnostic accuracy of 1-h PG, GA, FPG ≥126 mg/dL, HbA1c ≥6.5%, and the combined HbA1c-or-FPG strategy for identifying T2DM, with 2-hour plasma glucose (2-h PG) ≥200 mg/dL during the oral glucose tolerance test (OGTT) as the reference standard. Data extraction and quality assessment were performed independently by two reviewers according to predefined criteria. Statistical analyses were conducted using the Stan package in R and Stata 14.0.ResultsA total of 78 studies involving 183,902 participants were included. The network meta-analysis showed that the pooled sensitivity of 1-h PG, GA, FPG, HbA1c, and the combined HbA1c-or-FPG strategy was 0.87 [95% credible interval (CrI), 0.82–0.91], 0.53 (95% CrI, 0.36–0.71), 0.51 (95% CrI, 0.47–0.55), 0.53 (95% CrI, 0.47–0.58), and 0.64 (95% CrI, 0.54–0.73), respectively. The corresponding pooled specificity values were 0.88 (95% CrI, 0.82–0.92), 0.86 (95% CrI, 0.71–0.95), 0.96 (95% CrI, 0.95–0.97), 0.92 (95% CrI, 0.89–0.94), and 0.89 (95% CrI, 0.81–0.95). The pooled positive likelihood ratios (LR+) were 7.68 (95% CrI, 4.97–11.28) for 1-h PG, 4.39 (95% CrI, 1.86–9.30) for GA, 12.63 (95% CrI, 9.33–16.01) for FPG, 6.75 (95% CrI, 4.81–9.05) for HbA1c, and 6.28 (95% CrI, 3.25–11.26) for the combined strategy. The pooled negative likelihood ratios (LR−) were 0.15 (95% CrI, 0.11–0.20), 0.55 (95% CrI, 0.36–0.74), 0.51 (95% CrI, 0.47–0.55), 0.52 (95% CrI, 0.46–0.57), and 0.41 (95% CrI, 0.31–0.53), respectively. The pooled diagnostic odds ratios (DORs) were 52.44 (95% CrI, 30.17–84.00), 8.53 (95% CrI, 2.70–20.94), 24.94 (95% CrI, 17.90–32.30), 13.15 (95% CrI, 8.94–18.51), and 15.83 (95% CrI, 6.62–31.47), respectively. The areas under the summary receiver operating characteristic curves (SROC-AUCs) were 0.757, 0.714, 0.717, 0.706, and 0.726, respectively. Sensitivity analyses restricted to low-risk-of-bias studies and studies using a 1-h PG threshold ≥11.6 mmol/L, as well as subgroup analyses stratified by general and high-risk populations, yielded results and rankings broadly consistent with the primary analysis. Pairwise meta-analysis findings were also generally consistent with those from the network meta-analysis.ConclusionsAmong the evaluated diagnostic measures, 1-h PG appeared to provide the best overall diagnostic performance for T2DM, with the highest sensitivity, lowest LR−, and highest DOR. It performed better overall than GA, FPG, HbA1c, and the combined HbA1c-or-FPG strategy. By contrast, FPG showed the highest specificity and LR +. The consistency of the findings across sensitivity analyses, subgroup analyses, and pairwise meta-analysis supports the robustness of the main results. However, given the residual heterogeneity across included studies in terms of study design, population characteristics, and diagnostic thresholds, these findings should be interpreted with caution and confirmed by further large-scale, high-quality studies.Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420261354518.

Background: Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia worldwide. Catheter ablation is the firstline therapy for symptomatic/refractory AF, yet post-procedural recurrence remains extremely common, driving a high rate of repeat ablation procedures. Repeat ablation is associated with elevated medical costs, incremental procedural risks, and impaired quality of life and clinical outcomes in affected patients. Existing clinical risk scores for predicting repeat AF ablation have limited discriminative ability, poor interpretability, and suboptimal clinical utility. This study aimed to develop and validate an explainable machine learning model, using routine clinical and echocardiographic features, to predict the risk of requiring repeat catheter ablation for AF. Methods: A retrospective cohort of 1073 patients undergoing AF ablation from 2012 to 2023 was analyzed, with data split into training (70%) and testing (30%) sets. Feature selection was performed using LASSO regression and the Boruta algorithm, followed by the construction of eight machine learning models. Model performance was evaluated using area under the receiver operating characteristic curve (AUC), sensitivity, specificity, F1 score, balanced accuracy, Brier score, and clinical utility via decision curve analysis. Interpretability was enhanced using Shapley Additive Explanations (SHAP). Results: Among 1073 patients undergoing AF ablation, 352 (32.8%) required a second procedure. LASSO regression combined with the Boruta algorithm identified nine predictive features: NT-proBNP, age, globulin (GLO), direct bilirubin (DBIL), left ventricular ejection fraction (LVEF), cystatin C (Cys-C), smoking history, creatine kinase (CK), and urea. Among the eight models evaluated, XGBoost demonstrated the best overall performance, achieving an AUC of 0.811 (95% CI: 0.762-0.859) in the testing cohort, with a sensitivity of 0.748, specificity of 0.726, and Brier score of 0.1682. It also outperformed alternative models in terms of F1 score and clinical net benefit. SHAP analysis confirmed NT-proBNP and age as the most influential predictors, alongside non-linear contributions from the remaining variables. Conclusion: The XGBoost model may provide a useful and interpretable tool for predicting repeat AF ablation, providing clinical insights to guide patient management and optimize procedural outcomes.

Background: Cardiovascular-kidney-metabolic (CKM) staging provides a multisystem framework for prevention, but does not explicitly capture frailty or physiological reserve. We assessed whether a pragmatic frailty-enhanced CKM phenotype improved risk stratification for incident cardiovascular disease (CVD) across international ageing cohorts. Methods: We harmonised individual-level data from CHARLS, ELSA, HRS, KLoSA, MHAS, and SHARE. Eligible participants were aged 50 years or older, free of baseline heart disease and stroke, followed prospectively for CVD, and had data to construct pragmatic CKM and frailty-enhancement variables. Modified stages combined early CKM risk, established CKM disease, and frailty enhancement. The primary outcome was newly reported heart disease or stroke. Cox models were stratified by cohort and adjusted for age, sex, education, smoking, and alcohol drinking. Findings: The analytic sample included 99,597 participants and 15,666 incident CVD events over 690,917 person-years. Event rates increased from 11.5 per 1000 person-years in Stage 0 to 43.7 per 1000 person-years in Stage 3. Compared with Stage 0, fully adjusted hazard ratios were 1.58 (95% CI 1.50-1.67) for Stage 1, 1.81 (1.71-1.91) for Stage 2, and 2.88 (2.72-3.05) for Stage 3. Adding frailty to standard pragmatic CKM staging modestly improved optimism-corrected discrimination from 0.692 to 0.702. Interpretation: Frailty-enhanced CKM phenotyping identified older adults with coexisting CKM disease burden and reduced physiological reserve as a consistently high-risk group. The findings support further validation of geriatric risk-enhancement strategies within CKM care, but this survey-based phenotype should not replace biomarker-complete guideline CKM staging.