BACKGROUND:Cardiovascular diseases (CVDs) account for a large and increasing health burden worldwide, as shown in the Global Burden of Disease Study 2021. However, there has been no comprehensive assessment of CVDs in Asia, which bears the largest population globally. OBJECTIVES:This study sought to evaluate the burden of CVD in Asia from 1990 to 2021. METHODS:Mortality, prevalence, and disability-adjusted life years (DALYs) along with their age-standardized rates (ASRs) per 100,000 population from 1990 to 2021 were used to measure the CVDs burden. Further subanalyses were conducted based on age group and sex. RESULTS:In 2021, CVDs caused an estimated 11.9 million deaths (95% uncertainty interval [UI]: 10.9-12.9 million deaths), 340.4 million prevalent cases (95% UI: 315.1-366.9 million prevalent cases), and 270.4 million DALYs (95% UI: 251.6-290.2 million DALYs). Although the ASR of prevalence slightly increased from 1990 to 2021 with a percentage change of 5.7% (95% UI: 3.9%-8.1%), the ASRs of death and DALYs were significantly decreased, with percentage changes of -28.2% (95% UI: -42.2% to -12.5%) and -37.8% (95% UI: -50.5% to -24.3%), respectively. The Asian burden of CVDs was higher in males and the elderly. The primary contributors to DALYs across Asia were ischemic heart disease, stroke, and hypertensive heart disease. CONCLUSIONS:Burden of CVDs in Asia remains substantial. Certain populations, including males and the elderly, experienced a heavier burden of CVDs.

BACKGROUND AND AIMS:Quantifying the multidimensional risk that subclinical liver disease imposes on cardiovascular health remains a critical unmet need. This study aimed to investigate the independent and synergistic associations of hepatic steatosis, fibrosis, and functional decline with incident cardiovascular disease (CVD). METHODS:In this prospective cohort study of 318 308 participants free of clinical liver and CVD at baseline, this study evaluated the association of three non-invasive liver biomarkers-fatty liver index (FLI) for steatosis, fibrosis-4 index (FIB-4) for fibrosis, and albumin-bilirubin (ALBI) score for functional reserve-with major incident CVD events, including myocardial infarction, heart failure, atrial fibrillation, ischaemic stroke, and cardiovascular death. RESULTS:Over a median follow-up of 14.0 years, 32 637 incident CVD events (10.3%) occurred. Each biomarker independently predicted CVD risk after multivariable adjustment: the highest quartile (Q4) of FLI (adjusted hazard ratio [aHR] 1.46, 95% confidence interval [CI] 1.40-1.52), FIB-4 (aHR 1.66, 95% CI 1.60-1.73), and ALBI (aHR 1.42, 95% CI 1.37-1.47) showed significantly elevated risks compared to Q1. Critically, participants with all three biomarkers in Q4 exhibited a substantially elevated synergistic risk (aHR 2.53, 95% CI 2.38-2.70). Sex-specific analyses revealed FLI was more strongly associated with CVD in women, whereas FIB-4 and ALBI showed greater risk in men. Results were consistent across sensitivity analyses and specific CVD endpoints. CONCLUSIONS:These findings establish subclinical liver disease-through steatosis, fibrosis, and functional impairment-as an independent and synergistic determinant of CVD risk. Incorporation of these non-invasive biomarkers could refine CVD risk stratification and enable targeted prevention strategies.

BACKGROUND:Although tissue contact significantly affects pulsed field ablation (PFA) efficacy, evidence supporting contact force-guided PFA for recurrent left atrial flutter (AFL) remains scarce. In this study we investigated the efficacy and safety of PFA in this difficult-to-treat population compared with radiofrequency ablation (RFA). METHODS:Patients with atypical AFL who had undergone at least 1 previous persistent atrial fibrillation ablation were prospectively enrolled for PFA and compared with a retrospectively analyzed control group treated with conventional RFA at the same period. Coronary artery spasm risk was assessed via coronary angiography. The efficacy end points were recurrence of atrial arrhythmias after a 3-month blanking period. The safety end point included severe procedure-related complications. RESULTS:A total of 253 patients were included in this study (mean age 59 years, 68% male), 119 patients received PFA treatment, 134 patients received RFA. At 12-month follow-up, the RFA group demonstrated a significant higher atrial tachyarrhythmia recurrence rate compared with the PFA group (36% vs 24%; log rank P = 0.027). In the multivariable Cox regression model, PFA was linked to lower risk of the recurrence risk compared with RFA (hazard ratio, 0.56; 95% confidential interval, 0.35-0.90; P = 0.017). Moreover, acute mitral isthmus block rate in the PFA group was significantly higher than in the RFA group (100% vs 64%; P < 0.001). No procedure-related complications were observed, including esophageal fistula, phrenic nerve injury, and coronary artery spasm. CONCLUSIONS:In patients with refractory left AFL post atrial fibrillation ablation, contact force-guided PFA appears promising and demonstrates favourable efficacy compared with conventional RFA.

BACKGROUND:The autonomic effects of pulsed-field ablation (PFA) remain incompletely defined. Previous work has relied on heart rate variability (HRV), which cannot differentiate sympathetic from vagal activity. We used deceleration capacity (DC) and acceleration capacity (AC)-valid vagal/sympathetic activity measures-to evaluate autonomic changes before and after PFA for paroxysmal atrial fibrillation (PAF). OBJECTIVE:The study aimed to characterize peri-PFA changes in DC/AC in patients with PAF. METHODS:This prospective study included 45 consecutive patients with PAF who experienced PFA. DC/AC and HRV were performed at baseline, immediately after ablation, and at 3-month follow-up. The relationship between HRV and DC/AC was assessed using Pearson correlation. Receiver operating characteristic analyses were used to evaluate the predictive value of DC/AC for atrial fibrillation (AF) recurrence. Kaplan-Meier analysis assessed freedom from AF recurrence over 12 months in relation to autonomic indices. RESULTS:Pulmonary vein isolation was successful in all patients; 91.1% exhibited intraprocedural vagal responses. DC and |AC| decreased immediately after PFA and partially recovered at 3 months (overall P < .05 for both). Most HRV parameters had weak correlations with DC/AC (Pearson r = 0.08-0.67). At 12 months, the drug-free atrial tachycardia-free rate was 75.56%. Preablation DC/AC (area under the curve 0.63/0.64) and changes in DC/AC (area under the curve 0.68/0.67) were able to predict AF recurrence. Patients with lower preablation |AC| and smaller ΔDC/ΔAC had significantly higher AF recurrence rates (log-rank P < .05). CONCLUSION:Our evaluation via DC/AC revealed significant alterations in autonomic activity after PFA. Furthermore, DC/AC and their trajectories demonstrated moderate predictive value for AF recurrence, underscoring the need to reconsider the impact of PFA on cardiac autonomic innervation.

BACKGROUND:Atrial fibrillation (AF) independently increases dementia risk, but whether accelerometer-measured physical activity (PA) modifies this association remains unquantified, particularly against self-reported PA limitations. METHODS:Prospective analysis of 91,795 UK Biobank participants with valid accelerometer data (median age 57, 42.9 % male; 2800 with baseline AF). We categorized whether measured activity met the standard recommendation [moderate-to-vigorous physical activity (MVPA) >_150 min/week]. Questionnaire-derived MVPA data from 353,643 UK Biobank participants (median age 57, male: 46.7 %) between 2006 and 2010 were used for validation. The primary outcome was the diagnosis of incident all-cause dementia. We also assessed correlation between accelerometer-derived and self-reported activity. RESULTS:Over 7.6-year median follow-up, AF was significantly associated with a higher dementia risk [Adjusted hazard ratio (aHR): 1.76, 95 % confidential interval (CI): 1.51-2.05]. Guideline-adherent PA was associated with a lower AF-related dementia risk to non-significance (aHR: 1.36, 95 %CI: 0.96-1.91). Moreover, PA may be associated with higher protection effect on dementia risk in AF patients (aHR: 0.55, 95 % CI: 0.33-0.92) than in non-AF (aHR: 0.81, 95 % CI: 0.69-0.96), although without statistical difference (Pinteraction = 0.213). Correlation between accelerometer-derived and selfreported MVPA was weak (Spearman r = 0.155, 95 % CI: 0.148-0.162). Self-reported activity was not associated with a decreased risk of dementia in both AF and non-AF participants. CONCLUSION:Higher accelerometer-measured PA is associated with lower AF-associated dementia risk. Future prospective studies with extended follow-up and serial activity monitoring are needed to confirm these findings.

BACKGROUND AND AIMS:Left bundle branch pacing (LBBP) for cardiac resynchronization therapy is emerging as an alternative pacing strategy to biventricular pacing (BiVP) in dyssynchronous heart failure (DHF). This study aimed to explore the differences in treatment effects between the two pacing modalities using electrocardiographic, echocardiographic, and molecular measurements. METHODS:Adult canines underwent left bundle branch ablation, then either followed by 6 weeks of atrial tachypacing (DHF group, n = 8), or 3 weeks of atrial tachypacing followed by another 3 weeks of BiVP (n = 8) or LBBP (n = 8) tachypacing. Non-intervened canines constituted the control group (n = 7). Electrocardiographic, echocardiographic, and molecular features were compared between BiVP-treated and LBBP-treated DHF canines. RESULTS:BiVP- and LBBP-treated canines achieved equivalent reduction in QRS duration (32 ± 6 ms vs 35 ± 5 ms, P = .276). Both BiVP and LBBP increased left ventricular ejection fraction (9 ± 5% and 10 ± 4%, respectively; P = .390) while LBBP significantly outperformed BiVP in improving left ventricular global longitudinal strain (-3.7 ± 1.2% vs -2.3 ± 1.0%, P = .019). Both BiVP and LBBP reversed biomarkers of heart failure, while LBBP more significantly modulated cytoskeleton proteins, TGF-β signalling pathways and SERCA2a expression. Moreover, LBBP contributed to a more comprehensive improvement in myocardial energy metabolism compared to BiVP. CONCLUSIONS:This study in a DHF animal model indicates that LBBP results in electrocardiographic, echocardiographic, and molecular recovery at least as good as that during BiVP. The superiority of LBBP is especially reflected in more pronounced normalization of cardiac cytoskeleton, calcium handling and energy metabolism.

Whether hepatic steatosis, as indexed by the fatty liver index (FLI), is associated with incident atrial fibrillation (AF) among adults with diabetes beyond shared cardiometabolic risk factors remains uncertain. To investigate the association between fatty liver index and incident atrial fibrillation in adults with diabetes. We analyzed 29,341 UK Biobank participants with baseline diabetes and no history of atrial fibrillation or atrial flutter, and no prior cardiovascular disease. FLI was evaluated both categorically (< 30, 30–59, 60–89, ≥ 90) and continuously using restricted cubic splines. Incident AF was identified through linked health records, with death treated as a competing risk. Cox models were sequentially adjusted for demographics, lifestyle, socioeconomic status, and metabolic factors; Fine–Gray models were also applied. Sensitivity analyses included 1:10 propensity score matching (FLI ≥ 60 vs. < 60). Among participants with FLI ≥ 30, AF risk was further stratified by the number of metabolic abnormalities (hypertension, obesity, dyslipidemia), grouped as 0, 1, 2, or ≥ 3. Over a median follow-up of 14.1 years (13.4–14.7), 2,890 incident AF events occurred. AF incidence rose across FLI categories, from 4.88 (95

Abstract Background Persistent atrial fibrillation (PsAF) ablation faces a dilemma between insufficient pulmonary vein isolation (PVI) leading to high recurrence and excessive ablation increasing complications without clear benefit. Ibutilide may help identify critical ablation targets by modifying the arrhythmia substrate. Methods This retrospective single-center study analyzed 367 PsAF patients undergoing ibutilide-guided ablation. After PVI, patients converting directly to sinus rhythm (SR) (PVI group, n = 86) received no further ablation. Non-responders (PVI+Linear group, n = 281) underwent linear ablation and were categorized by acute termination pattern: Directly to SR (n = 109), AFL to SR (n = 87), DC to SR (n = 75), or Failure (n = 10). Subgroups based on low-voltage areas (LVZs) and AF duration were analyzed. AF recurrence (> 30s post 3-month blanking period) was assessed. Results Over a mean follow-up, AF-free survival rate was non-significantly higher in the PVI group vs. PVI+Linear group ((73.9% vs. 60.7%, P = 0.070). In the PVI+Linear group, success rates differed significantly by acute termination pattern (Direct to SR:67.8%, AFL to SR:72.6%, DC to SR:26.4%, Failure to SR:30.0%, P < 0.001), LVZs presence (Absent:63.8% vs. Present:55.8%, P < 0.001), and AF duration (≤ 1 year:73.9%, 1–5 year:55.3%, ≥ 5 year:44.6%, P < 0.001). Female, larger LA diameter, longer AF duration, and DC/Failure termination patterns independently predicted recurrence. Conclusion The use of ibutilide may help identify “PVI‑sensitive” atrial fibrillation, reducing the extent of ablation without compromising efficacy.Female sex, LA enlargement, prolonged AF duration, and requiring DC/failing to terminate acutely predict recurrence. Graphical Abstract

BACKGROUND:The bidirectional liver-heart axis is increasingly recognized. Although compelling evidence links liver fibrosis to adverse cardiovascular outcomes, its specific link to sudden cardiac arrest (SCA) in the general population remains less well elucidated. OBJECTIVE:We aimed to investigate the association between liver fibrosis and SCA. METHODS:This prospective analysis included 452,454 participants from the United Kingdom Biobank. Liver fibrosis was non-invasively assessed using the Fibrosis-4 (FIB-4) index, with participants categorized into low (<1.30), indeterminate (1.30-2.67), and high (>2.67) risk groups. The primary outcome was incident SCA. Associations were evaluated using Cox proportional hazards models, adjusted for comprehensive cardiovascular risk factors. RESULTS:The analysis included participants with a median age of 58 years, and 45.8% were male. During a median follow-up of 13.8 years, 2889 incident SCA cases were documented. Participants with higher FIB-4 scores exhibited significantly higher cumulative incidence of SCA (log-rank P < .001). Compared with the low-risk group, the adjusted hazard ratios for SCA were 1.26 (95% confidential interval [CI]: 1.15-1.39) in the indeterminate-risk group and 1.69 (95% CI: 1.36-2.12) in the high-risk group. Dose-response analysis revealed a nonlinear yet positive association between continuous FIB-4 index and SCA risk. Each standard deviation increase in FIB-4 was associated with a 20% higher SCA risk (adjusted hazard ratios 1.20, 95% CI: 1.15-1.27). CONCLUSION:Liver fibrosis, as assessed by the FIB-4 index, is an independent and graded predictor of SCA risk in the general population. This readily available biomarker could enhance SCA risk stratification and primary prevention strategies.

BACKGROUND:The value of the triglyceride-glucose (TyG) index for predicting the prognosis in patients with hypertrophic cardiomyopathy (HCM) and heart failure with preserved ejection fraction (HFpEF) remains unexplored. METHODS:Patients from 15 centers were included. The primary outcome was all-cause mortality. The secondary outcomes were cardiovascular mortality and sudden cardiac death (SCD). Restricted cubic spline analyses, multivariate Cox regression analyses, competing risk models, subgroup and mediation analyses were used to assess the relationship between the TyG index and outcomes. RESULTS:A total of 1095 patients with HCM and HFpEF were included. During a median follow-up period of 69 months, 224 all-cause deaths, 142 cardiovascular deaths, and 56 SCDs occurred. Multivariable Cox regression showed that the highest TyG index quartile was associated with a lower incidence of all-cause (hazard ratio (HR) 0.74, 95% CI 0.56-0.99, P = .046) and cardiovascular mortality (HR 0.65, 95% CI 0.44-0.94, P = .024) compared to the lowest quartile. However, no significant association was found between the TyG index and SCD (HR 0.74, 95% CI 0.41-1.31, P = 0.300). The competing risk model confirmed a significant association between the TyG index and reduced cardiovascular mortality (HR, 0.56; 95%CI, 0.40-0.78, P = .001) but no significant association with SCD (HR, 0.69; 95% CI, 0.37-1.27, P = .230). Mediation analyses indicated N-terminal pro-B-type natriuretic peptide mediated the association between TyG index and cardiovascular survival, while serum creatinine had a suppression effect. CONCLUSION:A higher TyG index was associated with lower risks of all-cause and cardiovascular mortality but with no significant influence on SCD risk in patients with HCM and HFpEF.

BACKGROUND:Atrial fibrillation (AF) significantly increases stroke, heart failure, and mortality risk. Elevated lipoprotein(a) (Lp[a]) is implicated in AF pathogenesis, but its relationship with systemic inflammation (assessed by high-sensitivity C-reactive protein [hs-CRP]) remains unclear. OBJECTIVE:We investigated whether the Lp(a)-AF association is independent of baseline inflammatory status. METHODS:In this retrospective cohort study, we analyzed 365,899 United Kingdom (UK) Biobank participants without baseline AF. Lp(a) was modeled as a continuous exposure (per 50 nmol/L increase) and categorically (≥125 nmol/L). Systemic inflammation was defined as hs-CRP ≥2 mg/L. Multivariable Cox proportional hazards models (adjusted for age, sex, cardiovascular risk factors, and comorbidities) and Fine-Gray competing risk analyses estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident AF. RESULTS:Over a median 13.5-year follow-up, 25,048 (6.8%) incident AF cases occurred. Elevated Lp(a) (7.44% vs 6.77%, log-rank P < .001) and hs-CRP (8.49% vs 5.96%, log-rank P < .001) were associated with higher incident AF. Cox proportional hazard model adjusted for covariates, higher Lp(a) (≥125 nmol/L) was associated with increased AF risk regardless of hs-CRP levels for AF (hs-CRP ≥2 mg/L: HR, 1.12; 95% CI, 1.06-1.19; P < .001; hs-CRP <2 mg/L: HR, 1.09; 95% CI, 1.04-1.15; P = .001). Results remained consistent in propensity score matched cohorts and sensitivity analyses. CONCLUSION:Lp(a) is an independent risk factor for AF, irrespective of baseline inflammatory status, as measured by hs-CRP.

BACKGROUND AND AIMS:It remains unknown whether the brain glymphatic system, which is driven by the heartbeat-driven pulsation of arteries and is responsible for cerebral waste clearance, is impaired in atrial fibrillation (AF) and mediates cognitive dysfunction related to AF. The aim of this study was to assess brain glymphatic alterations in AF, their role in cognitive function, and whether catheter ablation can improve glymphatic activity. METHODS:In this case-control and prospective before-and-after study, patients with AF and healthy controls (HCs) were enrolled. Participants underwent brain magnetic resonance imaging and a comprehensive neuropsychological battery. Glymphatic activity was quantified by diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Magnetic resonance imaging was repeated after surgery in patients who underwent ablation. RESULTS:Overall, 87 patients with AF and 44 HCs were enrolled. Compared with HCs, patients with AF had a lower ALPS index (P = .016). Nonparoxysmal AF patients showed lower ALPS index than both HCs (P = .002) and paroxysmal AF patients (P = .044). A lower ALPS index was associated with worse scores of Trail Making Test, Digit Symbol Substitution Test, Digit Span Test, and Stroop Colour and Word Test (all P < .05). Mediation analyses revealed that glymphatic activity was a mediator between AF and cognitive decline. Among the 50 patients who underwent ablation therapy, DTI-ALPS index was improved after surgery (P = .015). CONCLUSIONS:Brain glymphatic function measured by DTI-ALPS index was impaired in patients with AF, mediates the association between AF and cognitive decline, and was improved after ablation therapy.

BACKGROUND:Cardioneuroablation has been proposed to be effective in patients with vasovagal syncope, whereas the preferred ablation strategy is undetermined. OBJECTIVES:This study aimed to determine the preferred ablation strategy of cardioneuroablation between the left atrial (LA) and the bilateral atrial (BiA) approach. METHODS:This study was a prospective randomized clinical trial to compare the efficacy of 2 ablation strategies for patients with vasovagal syncope. The participants were randomly assigned to either the LA or BiA ganglion plexus ablation group in a 1:1 ratio. RESULTS:Eighty participants (37 men [46.2%]; age 38 ±16 years) were enrolled, with 40 participants in each group. The efficacy was 87.5% in the LA group (95% CI: 76.8 to 98.2%) and 90% (95% CI: 80.7 to 99.7%) in the BiA group (P = 0.723; P for noninferiority = 0.001). Compared to the BiA group, LA group reduced the average procedure time by 13 minutes (95% CI: 6-20 minutes), the average x-ray dosage by 5.7 mGy (95% CI: 2.1-9.3 mGy), the average ablation lesions by 4 (95% CI: 2-6), and ablation time by 125 seconds (95% CI: 60-190 seconds). No significant difference was observed in presyncope recurrence rate (15% vs 10%; P = 0.498), quality of life (78.7 ± 13.6 vs 80.9 ± 10.6; P = 0.417), mean heart rate (79 ± 11 vs 77 ± 9; P = 0.391), and response to head-up tilt test (57.1% vs 62.2%; P = 0.664) between groups at 12 months. CONCLUSIONS:The LA approach's efficacy was noninferior to the BiA approach, whereas the LA approach showed the added benefit of reduced procedure time, a smaller ablation lesion, and smaller x-ray dosage. (Different Catheter Ablation Strategy in Vasovagal Syncope; NCT05573178).

Autoimmune myocarditis is a complicated, inflammatory heart disease with high morbidity and mortality. Interferon (IFN)-γ-mediated classical activated macrophage (M1 macrophage) polarization and pyroptosis play a vital role in immune injury in myocarditis. Baricitinib, a selective Janus kinase (JAK) 1 and JAK2 inhibitor, has been used in the treatment of some systemic autoimmune diseases to effectively suppress pro-inflammatory macrophages by blocking the JAK2-signal transducer and activator of transcription 1 (STAT1) signaling pathway. Nevertheless, its application to autoimmune myocarditis was hindered due to the difficulty of delivering and accumulating the drug in heart tissue. To overcome these limitations, we synthesized a hybrid membrane containing CC motif chemokine receptor (CCR) 1 and CXC motif chemokine receptor (CXCR) 3 from activated RAW264.7 and EL4 cell lines to target inflammatory lesions. Furthermore, mesoporous polydopamine (MPDA) was employed due to its synergistic effects, including high drug loading efficiency, reactive oxygen species (ROS) adsorption, and dual responsiveness to glutathione (GSH) and pH, to fabricate RAW-EL4 hybrid membrane-coated Baricitinib-MPDA nanoparticles (BM@[RAW-EL4] NPs) for Baricitinib delivery. Subsequent in vitro and in vivo experiments verified that BM@[RAW-EL4] NPs significantly inhibited inflammatory infiltration and heart tissue injury by precisely suppressing macrophage polarization and pyroptosis. Biotoxicity and biosafety tests also revealed the biocompatibility of BM@[RAW-EL4] NPs, which provided the foundation for further clinical translation. Hence, the biomimetic BM@[RAW-EL4] NPs offer new heart-specific delivery opportunities, representing a versatile platform for targeted therapy in autoimmune myocarditis. STATEMENT OF SIGNIFICANCE: Autoimmune myocarditis is defined as an intense immune injury in the heart tissue, with current treatment far from satisfactory. IFN-γ-mediated M1 macrophage polarization and pyroptosis are crucial to disease progression. In this study, we created RAW-EL4 hybrid membrane-coated Baricitinib-MPDA nanoparticles (BM@[RAW-EL4] NPs) to achieve targeted delivery of an IFN-γ inhibitor to the inflammatory site. RAW-EL4 hybrid membranes endowed the nanomedicine with chemotactic property under the mechanism of activated CCR1-CCL7/8 and CXCR3-CXCL9/10 axis. MPDA exhibited a high drug-loading efficiency of 49.0 % and dual responsiveness to GSH and pH. We also observed its ability to clear ROS in the study. These characteristics of MPDA promoted the release of Baricitinib and macrophage suppression. In vivo experiments revealed the therapeutic effect and biosafety of BM@[RAW-EL4] NPs for the potential application to autoimmune myocarditis.

BACKGROUND:The association between the newly defined metabolic dysfunction-associated steatotic liver disease (MASLD) and sudden cardiac arrest (SCA) remains unclear. OBJECTIVE:This study aimed to investigate the association between MASLD, indicated by the fatty liver index (FLI), and SCA. METHODS:This was a prospective cohort study of UK Biobank participants without baseline cardiovascular disease. MASLD was defined as an FLI of ≥30 plus ≥1 cardiometabolic risk factor. Multivariable Cox models and Fine-Gray competing risk analyses estimated hazard ratios (HRs) for incident SCA. RESULTS:Among 347,925 participants, 1843 incident SCA events occurred over 14.1 years. SCA incidence increased significantly across FLI groups, from 2.15 per 10,000 person-years in the lowest group (FLI <30) to 7.17 per 10,000 person-years in the highest group (FLI ≥90) (P for trend < .001). Notably, for participants with an FLI of ≥30, SCA incidence increased exponentially with each additional cardiometabolic comorbidity. The fully adjusted Cox proportional hazards model showed an increase in SCA risk with higher FLI categories than group 1 (FLI <30), with group 2 (FLI 30-59) having an HR of 1.13 (95% confidence interval [CI] 0.99-1.30), group 3 (FLI 60-89) an HR of 1.21 (95% CI: 1.06-1.39), and group 4 (FLI ≥90) an HR of 1.57 (95% CI: 1.34-1.84). The association persisted in sensitivity analyses and after accounting for competing risks. CONCLUSION:This large prospective study demonstrates that MASLD, indicated by higher FLI, is an independent risk factor for SCA. Findings underscore the importance of incorporating MASLD into cardiovascular risk assessment.

BackgroundThis case report documents the application of the Varipulse™ catheter in linear ablation, offering a successful exploratory experience for the linear ablation of atrial fibrillation.Case presentationThe patient exhibited signs of AF. After successful completion of pulmonary vein potential isolation and mitral isthmus line ablation, atrial fibrillation was converted into atrial flutter. Integrating the atrial flutter's activation sequence with coronary sinus electrode mapping, we localized the reentrant circuit to the tricuspid isthmus and the surgical incision. Targeted ablation was sequentially performed at these identified sites, and subsequently, the patient's rhythm converted to sinus rhythm.DiscussionLinear ablation for AF faces substantial technical challenges in regions with complex anatomy, the Varipulse™ catheter is applicable with proven favorable reliability and safety profiles.

Background:Robotic-assisted procedures are rapidly advancing in interventional cardiology and have shown advantages in performing atrial fibrillation ablation. However, their application in combination with pulsed field ablation (PFA) remains unexplored. Case summary:We report the first in vivo experience of robotic-assisted PFA. The robotic-assisted PFA system comprises of a robotic articulating arm with three sterile, single-use functional modules, a workstation console, and a control computer. Following transseptal puncture and electrical mapping, two experienced operators performed pulmonary vein isolation and superior vena cava isolation in a swine model using the robotic system integrated with a guiding sheath and a PFA catheter. The procedure was conducted under fluoroscopy, while operators controlled the system remotely via the console in a zero-radiation environment. Post-procedural voltage mapping and histological analysis confirmed the feasibility of robotic-assisted PFA. Discussion:The primary advantage of robotic-assisted PFA is the potential to enable remote operation. It may also improve catheter stability and reduce the learning curve for performing PFA. Potential risks of robotic-assisted PFA include violent damage to cardiac tissue and complications associated with PFA. The robotic-assisted PFA system is sensitive and accurate when operated on a swine model, though several challenges exist in translating findings from a swine model to human clinical practice, and further studies are needed to evaluate its safety and efficacy before clinical implementation.

BACKGROUND:Although atrial fibrillation (AF) raises heart failure (HF) risk and inflammation is associated with cardiovascular disease, the role of inflammation in linking AF to HF remains unclear. OBJECTIVE:This study aimed to assess whether systemic inflammation, measured by high-sensitivity C-reactive protein (hs-CRP), elevates HF risk in patients with AF. METHODS:This prospective study included 32,502 AF participants from the UK Biobank without baseline HF, significant mitral valve disease, or inflammatory conditions. Hs-CRP was analyzed both as quartiles and using a clinical cutoff value of ≥2 mg/dL. The association with incident HF was evaluated using Cox models and Fine-Gray regression. Sensitivity analyses included sequential exclusion of comorbidities and early events, as well as propensity score matching. RESULTS:Over a median follow-up of 13.3 years, 6805 incident HF cases were documented. The cumulative incidence of HF increased significantly across hs-CRP quartiles, from 16.5% (1386 of 8419) in quartile 1 to 26.9% (2096 of 7786) in quartile 4 (log-rank P < .001). In fully adjusted models, quartile 4 had 61% higher HF risk than quartile 1 (hazard ratio [HR] 1.61; 95% confidence interval [CI] 1.51-1.73). Elevated hs-CRP (≥2 mg/dL) (HR 1.39; 95% CI 1.33-1.46) and per-standard-deviation increase (HR 1.12; 95% CI 1.10-1.15) were consistently associated with higher HF risk. These findings remained robust across all sensitivity analyses, subgroup comparisons, propensity score matching cohorts, and competing risk models. CONCLUSION:Elevated hs-CRP is an independent predictor of increased HF risk in patients with AF, supporting its potential role in improving HF risk stratification.

BACKGROUND:CD4+ T cells are crucial to the cardiac autoimmunity of myocarditis, with the underlying pathogenesis remaining unclear. Sinomenine hydrochloride, a natural compound from Sinomenium acutum, is reported to protect against some autoimmune diseases. This study aimed to elucidate the role of CD4+ T-helper 1 (Th1) cells in regulating inflammatory cell death and investigate the effect of sinomenine hydrochloride on Th1 cells and myocarditis. METHODS:Male Balb/c mice were immunized with myosin heavy chain-α peptides to establish the experimental autoimmune myocarditis (EAM) model. RNA sequencing was used to investigate the functions of T cell subsets in the EAM and explore the effect of sinomenine hydrochloride. Flow cytometry was used to analyze the inhibitory effect of sinomenine hydrochloride on Th1 cells. RESULTS:We observed a novel function of Th1 cells in promoting macrophage pyroptosis, thereby amplifying the immune response in the EAM. Further investigation revealed that the downstream molecule interferon regulatory factor 1 (IRF1) directly bound to the Casp1 gene and initiated its transcription for pyroptosis induction. To address Th1-induced pyroptosis, we found that sinomenine hydrochloride suppressed Th1 cell activation and differentiation in vitro, as well as Th1-induced pyroptosis, heart injury, and cardiac dysfunction in vivo. Further study indicated that sinomenine hydrochloride targeted at Gatm gene to disturb the arginine metabolism of T cells. CONCLUSIONS:Th1 cell-induced M1 macrophage pyroptosis is an essential pathogenic mechanism of EAM. Sinomenine hydrochloride suppresses Th1 cell arginine metabolism, potentially making it a practical approach to treating myocarditis.