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:Desmoglein 2 (DSG2)-associated cardiomyopathy represents a distinct subset of arrhythmogenic cardiomyopathy. A founder variant, NM_001943.5 (DSG2): c.T1592G (p.Phe531Cys), was identified with high frequency in China. OBJECTIVE:The study aimed to describe clinical features and outcomes of this founder variant. METHODS:Individuals with DSG2 c.T1592G (p.Phe531Cys) variants were recruited from 9 centers across China and categorized as single heterozygous, compound heterozygous (single variant plus rare variants of uncertain significance; abbreviated as compound), and homozygous. Clinical features and risk factors for malignant ventricular arrhythmias (MVAs), end-stage heart failure, and composite events of heart transplantation or cardiac death were analyzed. RESULTS:91 subjects were included: 21 (23.1%) single heterozygous, 21 (23.1%) compound, and 49 (53.8%) homozygous. Most subjects (74.7%) showed right ventricular dilatation, and nearly half (49.5%) had biventricular involvement. In patients with contrast-enhanced magnetic resonance imaging, 75.9% exhibited biventricular involvement. Compared with single heterozygous variant carriers, compound and homozygous variant carriers had a younger age at onset, more T-wave inversion, epsilon waves, and biventricular involvement (all pairwise P < .05). Homozygous variant carriers experienced significantly earlier MVA than compound (P = .013) and single heterozygous variant carriers (P < .001), with a trend toward earlier MVA in compound than single heterozygous variant carriers (P = .089). Compound and homozygous variant carriers exhibited significantly higher incidences of end-stage heart failure and composite events, whereas single heterozygous variant carriers remained event-free (all P < .05). CONCLUSION:DSG2 c.T1592G (p.Phe531Cys) founder variant defines a distinct arrhythmogenic cardiomyopathy subset with a high prevalence of biventricular involvement. Single heterozygous variant carriers held a less severe phenotype and relatively favorable prognosis, whereas compound and homozygous variant carriers held an advanced phenotype and poorer prognosis.

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.

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

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.

Arrhythmogenic cardiomyopathy (ACM) is a genetic myocardial disease characterized by progressive myocyte loss and fibrofatty (fibrous and adipose) tissue replacement to predispose these patients to fatal ventricular arrhythmias and impairment of ventricular systolic function. The relationship of ACM and myocarditis has gained significant attention. This case presented a 28-year-old female who was admitted to the hospital with complaints of recurrent lower limb edema and palpitations for 6 months. Her electrocardiogram revealed a typical manifestation of an advanced form of biventricular arrhythmogenic cardiomyopathy (ACM). Despite systematic medical management, her right ventricle (RV) function deteriorated rapidly, necessitating heart transplantation. Postoperative histopathological examinations confirmed the RV involvement as reflected in the electrocardiogram. Especially, multiple foci of lymphocytic infiltration were observed throughout the heart, with the RV being the most severe. When a rapid progression of ACM occurs, a concomitant myocarditis should be considered. ACM may be an inflammation-mediated transformation from myocardial tissue to fibrofatty tissue, and myocarditis may be a part of the natural history in some ACM cases.

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.

INTRODUCTION:The challenging and restrictive settings have been proposed in the updated indications for endomyocardial biopsy (EMB), but no data shows its performance. This study aimed to evaluate the diagnostic yield and find its clinical predictors. METHODS:All EMB performed between 2018 and 2022 were reviewed. Their clinical scenario and diagnostic yield were categorized retrospectively. Repeated and inadequate biopsies were excluded. Multivariate analysis was used to find the predictors. RESULTS:A total of 681 cases were collected (median age 44.0 years, 65.5% male) and 230 cases (33.8%) yielded specific diagnosis. The higher yield (52.8%) was found in clinically suspected myocarditis while no significant difference between cases with and without acute unstable hemodynamics (66.7% vs 47.1%; P=0.130). There was a much higher yield in unexplained restrictive or hypertrophic cardiomyopathy (RCM/HCM) with suspected infiltrative or storage disorder compared to those without (86.2% vs 10.3%; P<0.001). Dilated cardiomyopathy showed a lower yield, with or without recent-onset moderate-to-severe cardiac dysfunction (13.6% vs 16.3%; P=1.000). The same was true for unexplained atrioventricular block and ventricular arrhythmias (AVB/VA), with or without obvious structural abnormalities (8.2% vs 10.3%; P=0.675). On multivariate analysis, diffuse late gadolinium enhancement (odds ratio [OR] 4.14, 95% confidence interval [CI] 1.86-9.25; P=0.001), time course of disease ≤12 months (OR 3.31, 95% CI 1.75-5.57; P<0.001), elevated（≥1250 pg/ml）NT-proBNP (OR 2.91, 95% CI 1.67-5.06; P<0.001), and elevated (>0.068 ng/ml) hs-cTnI (OR 2.37, 95% CI 1.33-4.22; P=0.004) were independently associated with diagnostic yield. CONCLUSION:Our results partially support the restrictive settings. EMB can achieve higher yield for unexplained RCM/HCM with suspected infiltrative or storage disorder, as well as strictly defined clinically suspected myocarditis, even in hemodynamically stable patients. However, the restrictive settings of unexplained AVB/VA and dilated cardiomyopathy did not show a clear advantage in diagnostic yield. The predictors this study found may help clinicians in selecting adequate candidates.

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.

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 Arrhythmogenic cardiomyopathy (ACM) patients in China exhibit unique genetic and clinical charac-teristics. There is a lack of prognostic models specific to Chinese ACM patients. OBJECTIVES This study aims to establish a large, national ACM patient cohort with uniformly collected, high-quality data for future risk prediction. METHODS This study includes patients with definite or borderline ACM diagnoses, along with their genotype-positive relatives. At baseline, comprehensive data collection includes medical history, electrocardiograms, imaging data, genetic testing, and laboratory evaluations. Outcome data include heart failure events and malignant ventricular arrhythmias. RESULTS As of September 2024, the registry has enrolled 622 participants, including 552 probands (88.7%) and 70 family members (11.3%) carrying ACM-related variants. Preliminary cohort includes 577 patients (92.8%), of whom 495 were diagnosed with definite arrhythmogenic right ventricular cardiomyopathy. The median age of symptom onset was 33.0 years (Q1-Q3: 22.0-45.0 years), with 41.6% experiencing arrhythmia-related symptoms. Abnormal electrocardio-gram findings included T-wave inversion (72.7%) and epsilon waves (24.8%) in leads V1 to V3. Imaging evaluation revealed RV dilatation in 44.6% and left ventricular dilatation in 29.8%, with a mean left ventricular ejection fraction of 53.0% f 14.5%. Regarding outcomes, malignant ventricular arrhythmias occurred in 255 (40.1%) individuals, while 21.9% developed end-stage heart failure, including 35 individuals who died of heart failure and 101 patients who un-derwent heart transplantation. CONCLUSIONS The ChinaCORE ACM (China Multi-Center Cohort Study on Risk Evaluation of Arrhythmogenic Cardiomyopathy) registry is a national, longitudinal, observational cohort study. This study contributes to expanding the understanding of the disease spectrum of Chinese ACM patients and improving prognostic predictions. (JACC Asia. 2025;5:914-923) (c) 2025 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).

Introducción y objetivos Las enfermedades autoinmunitarias (EA) se asocian a un mayor riesgo de nueva aparición de arritmias cardiacas. Sin embargo, el efecto pronóstico de las EA en pacientes con arritmias cardiacas no se ha investigado de forma exhaustiva. El objetivo fue identificar la asociación entre EA y pronóstico en esta población. Métodos Basado en una gran cohorte observacional retrospectiva, este estudio incluyó pacientes con diferentes arritmias cardiacas, incluyendo fibrilación auricular (FA)/flutter auricular, taquicardia/fibrilación ventricular (TV/FV) y bradiarritmias. Las EA se establecieron como factor de exposición. El criterio de valoración fue la mortalidad por cualquier causa. Se realizaron análisis de regresión de riesgos proporcionales de Cox para calcular las hazard ratio (HR) y los intervalos de confianza del 95% (IC95%) para cuantificar las asociaciones. Se utilizó el emparejamiento por puntuación de propensión para mitigar el sesgo potencial de los factores de confusión. Resultados El análisis incluyó a 14.225 pacientes (edad media: 73,9±12,5 años, 59,2% mujeres), de los cuales 4.552 (32,0%) fallecieron en el plazo de un año tras el alta. Tras ajustar diversas covariables, los pacientes con EA mostraron un mayor riesgo de mortalidad en FA/flutter auricular (HR=1,23; IC95%, 1,13-1,33; p<0,001) y TV/FV (HR=1,28; IC95%, 1,02-1,60; p=0,032). Sin embargo, en el caso de las bradiarritmias, aunque se observó una posible asociación, la tendencia no alcanzó la significación estadística (HR=1,20; IC95%, 0,93-1,56; p=0,168). La asociación persistió en múltiples análisis de sensibilidad y se mantuvo constante tras ajustar por una amplia gama de covariables. Conclusiones Las EA se asociaron significativamente con un mayor riesgo de mortalidad por todas las causas en pacientes con arritmias cardiacas, particularmente en aquellos con FA/flutter auricular y TV/FV.

BACKGROUND:Genetic variants in desmosomal cadherins, desmoglein 2 (DSG2) and desmocollin 2 (DSC2), cause a distinct form of arrhythmogenic right ventricular cardiomyopathy (ARVC), which remains poorly reported. In this study, we aimed to provide a comprehensive description of the phenotypic expression, natural history, and clinical outcomes of patients with this ARVC subset. METHODS:Genetic and clinical data of DSG2 and DSC2 variant carriers were collected from 5 countries in Europe and Asia. We assessed the phenotypic profile of these patients and their clinical outcomes, focusing on heart failure and ventricular arrhythmia events. RESULTS:Overall, 271 subjects, 254 with DSG2 variants, were included in this study (median age, 38 years [interquartile range, 25-52]; 62.7% male). Of these, 165 were probands, and 200 were diagnosed with definite ARVC. A total of 181 (66.8%) individuals carried missense variants, mainly distributed in the extracellular domains. Notably, we included 78 (28.8%) individuals with multiple variants. Of the 200 cases with diagnosed ARVC, 41 (20.5%) experienced premature cardiac death before the age of 65. Among the 81 individuals for whom both left ventricular ejection fraction and right ventricular fractional area change data were available at presentation, 29 (35.8%) had isolated right ventricular dysfunction, and 16 (19.8%) had biventricular dysfunction. Single-variant carriers who engaged in intense physical exercise were younger at disease onset compared with those who did not (P=0.001). Compared with single-variant carriers, those with multiple variants were more likely to be diagnosed with ARVC (96.2% versus 64.8%; P<0.001) and exhibited more severe left ventricular dysfunction (44.4% versus 22.1%; P=0.001) and right ventricular dilation (88.9% versus 55.8%, P<0.001). Multiple-variant carriers were significantly younger at ARVC diagnosis compared with single-variant carriers (33 [18-49] years versus 42 [27-54] years; P<0.001]. During follow-up, end-stage heart failure (P<0.001) and malignant ventricular arrhythmias (P=0.004) were significantly more frequent in multiple-variant compared with single-variant carriers. Compared with PKP2 patients, DSG2/DSC2 patients exhibited a significantly higher risk of end-stage heart failure (P<0.001). CONCLUSIONS:ARVC attributable to variants in desmosomal cadherins mostly present with right ventricular or biventricular disease. Multiple variants are common in these patients and are associated with more frequent clinical penetrance, earlier onset of disease, and adverse clinical outcomes.

BACKGROUND:Arrhythmogenic cardiomyopathy (ACM) patients in China exhibit unique genetic and clinical characteristics. There is a lack of prognostic models specific to Chinese ACM patients. OBJECTIVES:This study aims to establish a large, national ACM patient cohort with uniformly collected, high-quality data for future risk prediction. METHODS:This study includes patients with definite or borderline ACM diagnoses, along with their genotype-positive relatives. At baseline, comprehensive data collection includes medical history, electrocardiograms, imaging data, genetic testing, and laboratory evaluations. Outcome data include heart failure events and malignant ventricular arrhythmias. RESULTS:As of September 2024, the registry has enrolled 622 participants, including 552 probands (88.7%) and 70 family members (11.3%) carrying ACM-related variants. Preliminary cohort includes 577 patients (92.8%), of whom 495 were diagnosed with definite arrhythmogenic right ventricular cardiomyopathy. The median age of symptom onset was 33.0 years (Q1-Q3: 22.0-45.0 years), with 41.6% experiencing arrhythmia-related symptoms. Abnormal electrocardiogram findings included T-wave inversion (72.7%) and epsilon waves (24.8%) in leads V1 to V3. Imaging evaluation revealed RV dilatation in 44.6% and left ventricular dilatation in 29.8%, with a mean left ventricular ejection fraction of 53.0% ± 14.5%. Regarding outcomes, malignant ventricular arrhythmias occurred in 255 (40.1%) individuals, while 21.9% developed end-stage heart failure, including 35 individuals who died of heart failure and 101 patients who underwent heart transplantation. CONCLUSIONS:The ChinaCORE ACM (China Multi-Center Cohort Study on Risk Evaluation of Arrhythmogenic Cardiomyopathy) registry is a national, longitudinal, observational cohort study. This study contributes to expanding the understanding of the disease spectrum of Chinese ACM patients and improving prognostic predictions.