Background:Accumulating evidence highlights a strong association between insulin resistance (IR) and inflammation in the context of cardiovascular disease (CVD). However, the combined impact of both factors on the risk of developing CVD remains underexplored. This study aims to investigate how inflammation and insulin resistance interact to influence the risk of incident CVD. Methods:A total of 6,534 adults from the CHARLS were included. The primary endpoint was the occurrence of cardiovascular disease (CVD), defined as a composite of stroke and cardiac events. Participants were categorized according to the median values of two key markers: the triglyceride glucose-body mass index (TyG-BMI index) and high-sensitivity C-reactive protein (hsCRP). Cox proportional hazard models assessed the associations between TyG-BMI index, hsCRP, and the endpoints. To validate the reliability of the results, we clinically enrolled 805 patients who had undergone percutaneous coronary intervention (PCI). Results:In CHARLS, Multivariate Cox regression analysis revealed a significant association between elevated TyG-BMI index and hsCRP levels and an increased risk of CVD. Participants in the high TyG-BMI and high hsCRP group demonstrated a substantially higher risk of CVD (HR: 1.38, 95% CI: 1.18-1.62, P < 0.001) compared to those with low TyG-BMI and low hsCRP. Restricted cubic spline (RCS) analysis indicated a non-linear, positive relationship between both the TyG-BMI index and hsCRP levels with the risk of developing CVD. In the validation cohort, we also observed that the high TyG-BMI group had higher risks of MACCE, stroke, and cardiac events (all P < 0.05), and that the predictive performance of the model was significantly improved after adding TyG-BMI to the baseline model. Conclusion:These results emphasize the importance of simultaneously considering both TyG-BMI index and hsCRP levels in risk stratification for CVD, highlighting their combined potential to enhance early identification of high-risk individuals. Importantly, TyG-BMI also demonstrated significant predictive value for adverse outcomes in patients after PCI.

Ambient temperature has been recognized as an environmental trigger for adverse cardiovascular events. However, its association with ventricular arrhythmias (VAs) in patients with implantable cardioverter-defibrillators (ICDs) remains understudied, particularly in China. We conducted a time-stratified case-crossover study among a cohort of patients with ICDs from 2019 to 2024. Conditional logistic regression models, integrated with restricted cubic splines, distributed lag nonlinear models, and distributed lag linear models, were used to estimate the association between ambient temperature and the occurrence of VAs, adjusting for relative humidity and public holidays. A total of 322 VA events were identified among 1053 patients with ICDs. Only extremely high ambient temperatures were significantly associated with increased probabilities of VA events, which increased by 180% (OR = 2.80, 95% CI: 1.08-7.28) over 1 day and 196% (OR = 2.96, 95% CI: 1.06-8.30) over 2 days compared with the incidence at reference temperatures. Subgroup analyses suggested that females, older patients, and those residing in the monsoon climate zone might be more susceptible to high-temperature risks. This investigation into the role of ambient temperature in VAs in patients with ICDs provides insights into its highly complex relationships and emphasizes the need for additional research and public health interventions.

Background For patients with a high risk of sudden cardiac death, despite the benefits of an implantable cardioverter defibrillator (ICD), some patients are still at high risk of death.Aim The purpose of this study was to develop and validate a nomogram predicting all-cause mortality for patients with an ICD.Methods We retrospectively analysed the data of multicentre ICD registration study from 2010 to 2014 in China. A total of 617 ICD patients formed a development cohort. The physical activity monitored by ICD and clinical data was collected. Univariate and multivariate Cox regression analyses were used to screen mortality predictors and construct the nomogram. The performance of the nomogram was evaluated by the consistency index (C-index) and the calibration curve. Additionally, extensive subgroup and sensitivity analyses were conducted to evaluate the model’s robustness. A total of 196 ICD patients formed a validation cohort.Results In the development cohort, physical activity, diabetes and left ventricular end-diastolic diameter were selected as independent prognostic factors. The nomogram was constructed by these three factors. The C-index of the nomogram was 0.80 (95% CI 0.75 to 0.84). The calibration curve showed that the predicted survival probability of the nomogram was in good agreement with the actual survival probability. In the validation cohort, the C-index of the nomogram was 0.74 (95% CI 0.64 to 0.84), and the calibration curve still maintained good consistency. Crucially, the nomogram maintained stable and excellent discriminative capacity across primary and secondary prevention subgroups, as well as for predicting specific cardiac and sudden cardiac death.Conclusions Our study develops and validates a nomogram predicting all-cause mortality for patients with an ICD by integrating the physical activity monitored by ICD and clinical data. The nomogram performs well and can provide personalised death risk assessment for ICD patients.Trial registration number ChiCTR-ONRC-13003695.

BACKGROUND:Premature atrial contractions (PACs) are independently associated with atrial fibrillation, stroke, and heart failure, yet no pharmacological therapy is approved for PAC suppression. Experimental studies have identified a functional cardiac glutamatergic system in which N-methyl-D-aspartate receptors regulate atrial electrophysiology. Preclinical studies show that pharmacological antagonism of N-methyl-D-aspartate receptors with memantine suppresses atrial arrhythmias. METHODS:We conducted an investigator-initiated, phase 2, multicenter, randomized, double-blind, placebo-controlled trial. Symptomatic adults with frequent PACs (≥1000/24 h) were randomly assigned to receive memantine or placebo for 6 weeks. The primary end point was the percentage change in mean 24-hour PAC count from baseline to the end of treatment. The primary analysis was performed in the intention-to-treat population. Prespecified secondary end points included the responder rate (≥50% PAC reduction), percentage change in nonsustained atrial tachycardia burden, and cumulative incidence of new-onset atrial fibrillation. RESULTS:Among 241 patients included in the efficacy analysis, memantine resulted in a greater reduction in PAC count than placebo (between-group difference, 47.1 percentage points; P=0.0045). The responder rate was higher with memantine than with placebo (52.4% versus 23.1%; P<0.0001). Memantine also reduced nonsustained atrial tachycardia burden (between-group difference, 30.98 percentage points; P=0.0043) and was associated with a lower cumulative incidence of new-onset atrial fibrillation (4.8% versus 23.9%; P<0.0001). No clinically meaningful differences were observed in electrocardiographic intervals or left ventricular function, and no drug-related serious adverse events occurred. CONCLUSIONS:In patients with frequent symptomatic PACs, memantine reduced atrial ectopy and atrial tachyarrhythmia burden and demonstrated a favorable safety profile. These findings provide proof of concept for a novel, non-ion channel-based therapeutic strategy targeting the cardiac glutamatergic system. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT06501638.

Background: The triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-c) has been linked to cardiovascular risk. However, its association with device-detected atrial high-rate episodes (AHRE) remains unclear. This study aimed to explore the relationships of TG/HDL-c with incident AHRE and mortality. Methods: This retrospective cohort study included patients implanted with pacemakers equipped with home-monitoring capability and without previous atrial fibrillation, atrial flutter, or atrial tachycardia. AHRE were defined as episodes with a burden exceeding 15 minutes during follow-up. The primary endpoint was AHRE, and the secondary endpoints were all-cause mortality and cardiovascular mortality. Findings: During a mean follow-up of 75.8±16.8 months, AHRE occurred in 303 of 1,463 patients (21.1%). Restricted cubic spline analysis revealed a significant U-shaped nonlinear association of TG/HDL-c ratio with AHRE, all-cause mortality and cardiovascular mortality (all P<0.001 for overall, all P<0.05 for nonlinearity). Multivariable Cox analysis showed that TG/HDL-c was independently and inversely associated with AHRE (hazard ratio [HR] 0.878, 95% confidence interval [CI] 0.771–0.999, P=0.049). As a category variable, compared with the low TG/HDL-c group, the moderate (HR 0.654, 95% CI 0.486–0.881, P=0.005) and high (HR 0.726, 95% CI 0.542–0.973, P=0.032) groups had significantly lower AHRE risk. Notably, the moderate group exhibited the lowest risk for all-cause and cardiovascular mortality. Interpretation: In pacemaker patients undergoing continuous home monitoring, lower TG/HDL-c was independently associated with a higher long-term risk of incident AHRE, and the association was non-linear. TG/HDL-c may serve as an accessible metabolic marker for AHRE risk stratification in this population. Further prospective studies are required to validate these findings and clarify the observed associations with mortality.

To investigate the relationship between abdominal obesity and long-term prognosis in patients with a pacemaker. In the SUMMIT Study, patients were categorized by baseline waist circumference into obesity, normal, and lean groups. WC was measured at the midpoint between the last rib and hip bone after exhalation. Regular follow-ups were conducted, with all-cause mortality as the primary endpoint and cardiac death as the secondary endpoint. In total, 492 patients were included in the analysis. The average baseline waist circumference was 84.2 ± 12.7 cm, and abdominal obesity was observed in 37.6

The correlation between sarcopenia and diabetes mellitus (DM) holds considerable importance. The prognosis of ventricular arrhythmias in individuals with type 2 diabetes mellitus complicated by sarcopenia remains uncertain. A retrospective analysis was conducted on patients with DM who underwent implantable cardioverter defibrillator (ICD) implantation at Fuwai Hospital. Sarcopenia status was assessed using the biomarker sarcopenia index(SI). Patients were divided into low SI (less than 81.33, n = 74) and high SI (greater than 81.33, n = 158) groups according to the best cut-off value. The primary endpoint was the occurrence of ventricular arrhythmias. Secondary endpoint was appropriate shock therapy. A total of 232 patients who met the inclusion criteria were included. The average follow-up period was 25.85 ± 16.13 months. During the follow-up, a total of 69 cases (29.7 Sarcopenia is a prevalent comorbidity of diabetes mellitus that has a substantial impact on prognosis. Does sarcopenia contribute to an elevated risk of ventricular arrhythmia and sudden cardiac death in patients diagnosed with type 2 diabetes? We found that patients with T2DM and lower sarcopenia index values had a significantly increased risk of ventricular arrhythmia, indicating the index’s strong predictive ability in this population. Patients with type 2 diabetes and low sarcopenia index should be screened for potential risk of sudden cardiac death and considered for implantable cardioverter defibrillators.

Although Ubc9-mediated SUMOylation are recognized to regulate the multiple aspects of hepatic biological processes, its impact on hepatic senescence and metabolic dysfunction-associated steatotic liver disease (MASLD), however, is yet to be fully addressed. Herein noted an age-dependent decrease of hepatic Ubc9 expression is first noted along with an escalated decrease of protein SUMOylation, which is coupled with enhanced senescent marker expressions both in humans and mice. Interestingly, Ubc9 is dispensable for liver development at the embryonic stage. However, Ubc9 deficiency in hepatocytes rendered mice with an exacerbated hepatic aging phenotype and more susceptible to fatty liver disease and steatohepatitis following the challenge of a methionine- and choline-deficient (MCD)-diet. Ii is further demonstrated that nuclear ribosomal protein L3 (RPL3) interacts with DExD/H-box (DDX/DHX) helicases (DHX9), which then recruits RNA polymerase II to the p16 promoter to transcribe its expression, thereby exacerbating the hepatocyte aging process. However, Ubc9-mediated SUMOylation prevents RPL3 nuclear translocation, by which it represses the expression of senescent markers such as p16 to attenuate the hepatic aging process. Together, the study highlights that Ubc9-mediated SUMOylation of RPL3 could be an unappreciated mechanism against hepatic aging in clinical settings.

Background The balance of redox states is crucial for maintaining physiological homeostasis. For decades, the focus has been mainly on the concept of oxidative stress, which is involved in the mechanism of almost all diseases. However, robust evidence has highlighted that reductive stress, the other side of the redox spectrum, plays a pivotal role in the development of various diseases, particularly those related to metabolism and cardiovascular health. Aim of Review In this review, we present an extensive array of evidence for the occurrence of reductive stress and its significant implications mainly in metabolic and cardiovascular diseases. Key Scientific Concepts of Review Reductive stress is defined as a shift in the cellular redox balance towards a more reduced state, characterized by an excess of endogenous reductants (such as NADH, NADPH, and GSH) over their oxidized counterparts (NAD+, NADP+, and GSSG). While oxidative stress has been the predominant mechanism studied in obesity, metabolic disorders, and cardiovascular diseases, growing evidence underscores the critical role of reductive stress. This review discusses how reductive stress contributes to metabolic and cardiovascular pathologies, emphasizing its effects on key cellular processes. For example, excessive NADH accumulation can disrupt mitochondrial function by impairing the electron transport chain, leading to decreased ATP production and increased production of reactive oxygen species. In the endoplasmic reticulum (ER), an excess of reductive equivalents hampers protein folding, triggering ER stress and activating the unfolded protein response, which can lead to insulin resistance and compromised cellular homeostasis. Furthermore, we explore how excessive antioxidant supplementation can exacerbate reductive stress by further shifting the redox balance, potentially undermining the beneficial effects of exercise, impairing cardiovascular health, and aggravating metabolic disorders, particularly in obese individuals. This growing body of evidence calls for a reevaluation of the role of reductive stress in disease pathogenesis and therapeutic interventions.

BACKGROUND:Left bundle branch area pacing (LBBAP) is an alternative to biventricular pacing (BVP) for cardiac resynchronization therapy (CRT). However, despite the presence of left bundle branch block, whether cardiac substrate may influence the effect between the 2 strategies is unclear. OBJECTIVES:This study aims to assess the association of septal scar on reverse remodeling and clinical outcomes of LBBAP compared with BVP. METHODS:We analyzed patients with nonischemic cardiomyopathy who had CRT indications undergoing preprocedure cardiac magnetic resonance examination. Changes in left ventricular ejection fraction (LVEF) and echocardiographic response (ER) (≥5% absolute LVEF increase) were assessed at 6 months. The clinical outcome was the composite of all-cause mortality, heart failure hospitalization, or major ventricular arrhythmia. RESULTS:There were 147 patients included (51 LBBAP and 96 BVP). Among patients with low septal scar burden (below median 5.7%, range: 0% to 5.3%), LVEF improvement was higher in the LBBAP than the BVP group (17.5% ± 10.9% vs 12.3% ± 11.8%; P = 0.037), with more than 3-fold increased odds of ER (OR: 4.35; P = 0.033). In high sepal scar subgroups (≥5.7%, range: 5.7%-65.9%), BVP trended towards higher LVEF improvement (9.2% ± 9.4% vs 6.4% ± 12.4%; P = 0.085). Interaction between septal scar burden and pacing strategy was significant for ER (P = 0.002) and LVEF improvement (P = 0.011) after propensity score adjustment. During median follow-up of 33.7 (Q1-Q3: 19.8-42.1) months, the composite clinical outcome occurred in 34.7% (n = 51) of patients. The high-burden subgroups had worse clinical outcomes independent of CRT method. CONCLUSIONS:Remodeling response to LBBAP and BVP among nonischemic cardiomyopathy patients is modified by septal scar burden. High septal scar burden was associated with poor clinical prognosis independent of CRT methods.

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Background: Atrioventricular block (AVB) is thought to be a rare cardiovascular complication of the coronavirus disease 2019 (COVID-19), though limited data are available beyond case reports. We aim to describe the baseline characteristics, proteomics profile, and outcomes for patients with COVID-19-related AVB. Methods: We prospectively recruited patients diagnosed with COVID-19-related AVB between November 2022 and March, 2023. Inclusion criteria were hospitalization for COVID-19 with the diagnosis of AVB. A total of 24 patients diagnosed with COVID-19 without AVB were recruited for control. We analyzed patient characteristics and outcomes and performed a comparative proteomics analysis on plasma samples of those patients and controls. Results: A total of 17 patients diagnosed with COVID-19-related AVB and 24 individuals diagnosed with COVID-19 infection without AVB were included. Among patients with COVID-19-related AVB, the proportion of concurrent pneumonia was significantly higher than controls (7/17 versus 2/24, p < 0.05). All 17 AVB patients (9 of permanent AVB, 8 of paroxysmal AVB) received permanent pacemaker implantation. No procedural-related complication occurred. In laboratory tests, the level of biomarkers indicating myocardial damage were substantially higher than controls, including high-sensitivity cardiac troponin-I (median 0.005 versus 0.002 ng/mL, p < 0.05), myoglobulin (median 39.0 versus 27.6 ng/mL, p < 0.05), and MB isoenzyme of creatine kinase (median 1.2 versus 0.8 U/L, p < 0.05). The level of N-terminal pro-b-type natriuretic peptide (median 241.0 versus 33.5 pg/mL, p < 0.05), C-reactive protein (median 4.8 versus 2.0 mg/L, p < 0.05), D-dimer (median 1.2 versus 0.2 µg/mL, p < 0.05), left ventricular end-diastolic diameter (median 49.3 versus 45.7 mm, p < 0.05) in patients with COVID-19-related AVB were significantly higher than controls. The level of albumin (median 41.9 versus 44.5 g/L, p < 0.05) was significantly lower than controls. In comparative proteomics analysis, we identified 397 human proteins. Several significantly altered plasma proteins related to inflammatory response (Serum amyloid A protein, C-reactive protein, Protein Adenosine 5’-monophosphate-activated protein kinase (AMPK), Alpha-2-macroglobulin), complement and coagulation cascades (Tetranectin, haptoglobin), and immune response (Neutrophil defensin 3, Fibrinogen beta chain) may contribute to the pathogenesis of COVID-19-related AVB. Conclusions: Patients with COVID-19-related AVB are more prone to have myocardial damage and concurrent pneumonia. Through laboratory tests and comparative proteomics analysis, we identified several differential expressed proteins (Serum amyloid A protein, Tetranectin, Neutrophil defensin 3) releated to the inflammatory response, complement and coagulation cascades, and immune response, which provides evidence of potential biomarkers and sheds light on the pathogenesis of COVID-19-related AVB.

The association between the triglyceride-glucose (TyG) index and ventricular arrhythmias (VAs) is unclear. This study aimed to investigate the relationship between the TyG index, VAs, and major cardiovascular events in patients at high risk of sudden cardiac death (SCD). We enrolled 1046 patients at high risk of SCD with an indication for implantable cardioverter-defibrillator (ICD) implantation at the Chinese National Center for Cardiovascular Diseases. The primary outcome was VAs, defined as sustained ventricular tachycardia and ventricular fibrillation documented by the ICD. The secondary outcomes were cardiac mortality, heart transplantation, and rehospitalization for heart failure. The mean (± SD) age was 59.6 ± 14.0 years old, and 25.7

Background Comprehensive data on patients at high risk of sudden cardiac death (SCD) in emerging countries are lacking. The aim was to deepen our understanding of the SCD phenotype and identify risk factors for death among patients at high risk of SCD in emerging countries. Methods Patients who met the class I indication for implantable cardioverter-defibrillator (ICD) implantation according to guideline recommendations in 17 countries and regions underrepresented in previous trials were enrolled. Countries were stratified by the WHO regional classification. Patients were or were not implanted with an ICD at their discretion. The outcomes were all-cause mortality and SCD. Results We enrolled 4222 patients, and 3889 patients were included in the analysis. The mean follow-up period was 21.6 ± 10.2 months. There were 433 (11.1%) instances of all-cause mortality and 117 (3.0%) cases of SCD. All-cause mortality was highest in primary prevention (PP) patients from Southeast Asia and secondary prevention (SP) patients from the Middle East and Africa. The SCD rates among PP and SP patients were both highest in South Asia. Multivariate Cox regression modelling demonstrated that in addition to the independent predictors identified in previous studies, both geographic region and ICD use were associated with all-cause mortality in patients with high SCD risk. Primary prophylactic ICD implantation was associated with a 36% (HR = 0.64, 95% CI 0.531–0.802, p < 0.0001) lower all-cause mortality risk and an 80% (HR = 0.20, 95% CI = 0.116–0.343, p < 0.0001) lower SCD risk. Conclusions There was significant heterogeneity among patients with high SCD risk in emerging countries. The influences of geographic regions on patient characteristics and outcomes were significant. Improvement in increasing ICD utilization and uptake of guideline-directed medical therapy in emerging countries is urgent. Trial registration ClinicalTrials.gov, NCT02099721.

Background Cardiac resynchronization therapy (CRT) is an established therapy for advanced heart failure with prolonged QRS duration. However, 30% of patients have shown no benefit from the treatment. Objectives This study aimed to examine the value of left atrial (LA) mechanics by cardiac magnetic resonance (CMR), to predict response to CRT and clinical outcomes. Methods A total of 163 CRT recipients with pre-implantation CMR examination were retrospectively recruited. CMR feature-tracking was used to evaluate LA size and function. Endpoints include: 1)improvement of at least 5% in left ventricular ejection fraction combined with a reduction of at least 1 NYHA functional class reduction at 6-month follow-up, 2) any all-cause death or heart failure (HF) hospitalization during follow-up. Results Overall, 82 (50.3%) were CRT responders. CRT non-responders had larger LA, and worse LA reservoir and booster function than responders (all P <0.001). LA structural (maximum volume index <47 ml/m2) and functional (booster strain >8.5%) criteria were incremental to traditional indicators in detecting CRT response (Chi-square: 40.83 vs. 9.98, P <0.001). During follow-up (median: 41 months), survival free from death or HF hospitalization increased with the number of positive LA criteria (log-rank p <0.001). After adjustment for clinical confounders, the absence of the 2 criteria remained associated with a considerably increased risk of death or HF hospitalization (adjusted HR: 6.2 [95% CI: 2.15-17.88]; P =0.001). Conclusions The pre-procedure LA mechanics evaluated by CMR may be useful to predict response to CRT and improve risk stratification in CRT recipients.

Background: Device-detected atrial high-rate episodes (AHREs) were associated with an increased thromboembolic risk. Although limited data regarding the long-term prognosis of patients with AHRE were controversial, this study aimed to identify the association of device-detected AHRE with mortality. Methods: This observational study included patients with implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D) placement and no history of atrial fibrillation (AF), atrial flutter (AFL), or atrial tachycardia (AT). During follow-up, patients with at least 1 day of AHRE duration >= 15 minutes were identified. The primary endpoint was cardiovascular mortality, and the secondary endpoint was all-cause mortality. Results: During a mean follow-up period of 4.2 years, AHREs were detected in 124 of 343 (36.2%) patients. Of these, 44 deaths (35.5%) occurred in 124 patients with AHREs, which was significantly higher than those without AHREs (43 of 219; 19.6%; P = 0.001). The multivariate analysis revealed that patients with AHRE had a significantly higher risk of cardiovascular (hazard ratio [HR], 2.40; 95% confidence interval [CI], 1.23-4.67; P = 0.010), and all-cause mortality (HR, 2.31; 95% CI, 1.49-3.59; P < 0.001). Further analysis indicated that this association remained significant in patients with higher burden (>= 6 hours) but not in patients with lower burden (>= 15 minutes to 6 hours). Notably, even after excluding the patients diagnosed with clinical AF during follow-up, the remaining patients with AHREs still exhibited a higher risk of cardiovascular and all-cause mortality compared with patients without AHREs. Conclusions: AHREs were prevalent in ICD or CRT-D recipients with no history of clinical AF, AFL, or AT and were associated with more than twice the risk of cardiovascular and all-cause mortality.

Abstract There are a large number of arrhythmia patients in China, and the field of interventional therapy for the diagnosis and treatment of arrhythmia has developed rapidly and made remarkable achievements. It is currently in a steady growth trend. In 2021, a total of 99,306 cases of pacemaker, 6547 cases of implantable cardioverter defibrillator, 5333 cases of cardiac resynchronization therapy, and 210,609 cases of catheter ablation were registered in the direct reporting system of arrhythmia interventional therapy information network, all of which increased significantly relative to those in 2020. However, there remains a considerable gap when in comparison with advanced countries. Therefore, there is an urgent need to widely implement and standardize advanced arrhythmia diagnosis and treatment techniques. In the future, it is vital to improve the training and development of arrhythmia physicians and teams, advance graded diagnosis and treatment, and foster international cooperation. In addition, there is a growing demand for increased clinical research to guide practical applications and the promotion of new technologies and devices for arrhythmia diagnosis and treatment.