Heart rhythmPub Date : 2025-10-16DOI: 10.1016/j.hrthm.2025.10.025
Nipavan Chiamvimonvat, Yang Zheng, Miao Zhang
{"title":"Potassium Channels as Targets for Antiarrhythmic Therapy.","authors":"Nipavan Chiamvimonvat, Yang Zheng, Miao Zhang","doi":"10.1016/j.hrthm.2025.10.025","DOIUrl":"https://doi.org/10.1016/j.hrthm.2025.10.025","url":null,"abstract":"","PeriodicalId":12886,"journal":{"name":"Heart rhythm","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heart rhythmPub Date : 2025-10-15DOI: 10.1016/j.hrthm.2025.10.023
Wanqian Pan, Yujia Wu, Chenyang Jin, Shi Peng, Lujia Dai, Gary Tse, Shaowen Liu, Shouling Wu, Songwen Chen, Tingbo Jiang, Xintao Li
{"title":"Association between Modifiable Risk Factors and Bradyarrhythmia: A Mendelian Randomization Study.","authors":"Wanqian Pan, Yujia Wu, Chenyang Jin, Shi Peng, Lujia Dai, Gary Tse, Shaowen Liu, Shouling Wu, Songwen Chen, Tingbo Jiang, Xintao Li","doi":"10.1016/j.hrthm.2025.10.023","DOIUrl":"https://doi.org/10.1016/j.hrthm.2025.10.023","url":null,"abstract":"<p><strong>Background: </strong>Bradyarrhythmia is associated with adverse outcomes, yet its primary prevention strategies remain undefined.</p><p><strong>Objective: </strong>To evaluate the causal associations between modifiable risk factors and bradyarrhythmia using Mendelian randomization (MR).</p><p><strong>Methods: </strong>Summary statistical data for modifiable risk factors and bradyarrhythmia were obtained from European-ancestry GWAS. Genetic instruments for each risk factor were derived from two datasets. Univariable, multivariable, and mediation MR analyses were conducted. Associations were considered significant at a Bonferroni-corrected threshold (P<sub>adj</sub><0.0023) and suggestive when 0.0023≤P<sub>adj</sub><0.05.</p><p><strong>Results: </strong>In the discovery datasets, a suggestive positive association was found between genetically determined body mass index (BMI) (OR: 1.19; 95% CI: 1.06-1.34) and the risk of sick sinus syndrome. For conduction disorders (CD), genetic predisposition to higher BMI (OR: 1.27; 95% CI: 1.17-1.39), systolic blood pressure (SBP) (OR: 1.43; 95% CI: 1.26-1.63), diastolic blood pressure (DBP) (OR: 1.23; 95% CI: 1.08-1.40), and lipoprotein a (OR: 1.10; 95% CI: 1.04-1.16) were significantly associated with increased risk. When CD subtypes were used as independent outcomes, BMI and SBP exhibited significant associations with the risk of atrioventricular block, whereas SBP and DBP were associated with left bundle branch block. These results remained directionally consistent in replication analyses. Multivariable MR analysis revealed that BMI, SBP, and Lp(a) were independent risk factors for CD. Mediation analysis showed SBP and DBP explained 17.61% and 17.84% of the effect of BMI on CD.</p><p><strong>Conclusion: </strong>This study identified distinct modifiable metabolic and lifestyle factors that are causally associated with different types of bradyarrhythmia.</p>","PeriodicalId":12886,"journal":{"name":"Heart rhythm","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heart rhythmPub Date : 2025-10-14DOI: 10.1016/j.hrthm.2025.10.022
Marc M Terpstra, Martijn H van der Ree, Jolien Neefs, Nicoline W E van den Berg, Elise L Hulsman, Ilse Meijer, Zhenyu Dong, Nerea Arrarte Terreros, Wim Jan P van Boven, Jonas S S G de Jong, Bart P van Putte, Antoine H G Driessen, Lucas V A Boersma, Joris R de Groot
{"title":"Safety of left atrial appendage amputation in cardiac surgery patients without atrial fibrillation.","authors":"Marc M Terpstra, Martijn H van der Ree, Jolien Neefs, Nicoline W E van den Berg, Elise L Hulsman, Ilse Meijer, Zhenyu Dong, Nerea Arrarte Terreros, Wim Jan P van Boven, Jonas S S G de Jong, Bart P van Putte, Antoine H G Driessen, Lucas V A Boersma, Joris R de Groot","doi":"10.1016/j.hrthm.2025.10.022","DOIUrl":"https://doi.org/10.1016/j.hrthm.2025.10.022","url":null,"abstract":"<p><strong>Background: </strong>Left atrial appendage amputation (LAAA) lowers stroke risk in patients with atrial fibrillation (AF), but its safety and functional implications in non-AF patients are uncertain.</p><p><strong>Objective: </strong>To assess early postoperative safety of LAAA in non-AF patients undergoing cardiac surgery.</p><p><strong>Methods: </strong>This retrospective cohort study included 434 patients without AF (CHA2DS2-VASc≥2) who underwent elective cardiac surgery at two centers (2015-2018). We compared 150 patients who underwent LAAA as part of the PREDICT-AF study, with 284 patients who declined participation and did not undergo LAAA. The primary endpoint was a composite of major complications and supraventricular tachycardias within 30 days. Secondary outcomes included individual complications, arrhythmias and surrogate markers for fluid overload (weight changes, diuretic use, blood pressure and chest x-ray congestion). Repeated measures were compared using linear mixed-effects models. 1:1 Propensity score matching was performed to assess outcomes in balanced groups.</p><p><strong>Results: </strong>The LAAA group had more males (87% vs. 73%;p=0.001) and were heavier (86kg [CI:80-92] vs. 82kg [CI:72-91];p=0.001). No significant differences were observed in the primary endpoint (47% vs. 41%;p=0.321) or postoperative AF (38% vs. 32%;p=0.225). Atrial tachycardias were uncommon but more frequent in the LAAA cohort (4% vs. 0.4%;p=0.014). Procedural times and markers for fluid overload did not differ. PSM confirmed no important differences between cohorts.</p><p><strong>Conclusion: </strong>Concomitant LAAA was not associated with increased surgical complications, postoperative AF, or fluid overload in patients without a history of AF. These findings suggest LAAA may be a safe strategy for stroke prevention in patients undergoing cardiac surgery.</p>","PeriodicalId":12886,"journal":{"name":"Heart rhythm","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heart rhythmPub Date : 2025-10-14DOI: 10.1016/j.hrthm.2025.10.021
James E Ip, Jim W Cheung, Christopher F Liu, George Thomas, Erden Goljo, Bruce B Lerman, Steven M Markowitz
{"title":"Maximizing Battery Longevity of Leadless Pacemaker Systems by Optimizing Individualized Programming.","authors":"James E Ip, Jim W Cheung, Christopher F Liu, George Thomas, Erden Goljo, Bruce B Lerman, Steven M Markowitz","doi":"10.1016/j.hrthm.2025.10.021","DOIUrl":"https://doi.org/10.1016/j.hrthm.2025.10.021","url":null,"abstract":"","PeriodicalId":12886,"journal":{"name":"Heart rhythm","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heart rhythmPub Date : 2025-10-14DOI: 10.1016/j.hrthm.2025.10.024
Boroumand Zeidaabadi, Konstantinos Patlatzoglou, Joseph Barker, Libor Pastika, Gul Rukh Khattak, Mehak Gurnani, Xavier Da Silva Anjos Machado, Nicholas S Peters, Daniel B Kramer, Jonathan W Waks, Fu Siong Ng, Arunashis Sau
{"title":"Image based artificial intelligence-enhanced ECG prediction of incident atrial fibrillation.","authors":"Boroumand Zeidaabadi, Konstantinos Patlatzoglou, Joseph Barker, Libor Pastika, Gul Rukh Khattak, Mehak Gurnani, Xavier Da Silva Anjos Machado, Nicholas S Peters, Daniel B Kramer, Jonathan W Waks, Fu Siong Ng, Arunashis Sau","doi":"10.1016/j.hrthm.2025.10.024","DOIUrl":"https://doi.org/10.1016/j.hrthm.2025.10.024","url":null,"abstract":"<p><strong>Background: </strong>Early prediction of atrial fibrillation (AF) is crucial for reducing adverse outcomes. While artificial intelligence-enhanced ECG (AI-ECG) analysis shows promise in predicting AF, most approaches require digital ECG signals, limiting their application in settings where ECGs are stored as images.</p><p><strong>Objective: </strong>We aimed to develop and validate an image-based AI-ECG approach for predicting incident AF across multiple datasets.</p><p><strong>Methods: </strong>We used 1,163,401 ECGs from 189,539 patients in the Beth Israel Deaconess Medical Center (BIDMC) dataset and 70,655 ECGs from 65,610 participants in the UK Biobank. The AI-ECG model was trained on ECG images processed to 310x868 pixels.</p><p><strong>Results: </strong>The model achieved C-statistics of 0.754 (95% CI: 0.747-0.761) in the BIDMC dataset and 0.723 (95% CI: 0.704-0.741) in the UK Biobank for predicting incident AF. Performance was maintained across key subgroups including outpatients, females, and non-White individuals. Compared to the CHARGE-AF risk score, the AI-ECG model showed superior performance (c-statistic 0.696 vs 0.667, p<0.05) and provided significant additive value when combined (c-statistic 0.711, p<0.0001). The model also performed well on smartphone-photographed ECGs (c-statistic 0.736). Saliency mapping indicated the model primarily focused on P-wave morphology and PR interval regions.</p><p><strong>Conclusion: </strong>This image-based approach enables AI-ECG prediction of AF in settings without digital ECG infrastructure and provides additive value to known clinical risk scores.</p>","PeriodicalId":12886,"journal":{"name":"Heart rhythm","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heart rhythmPub Date : 2025-10-13DOI: 10.1016/j.hrthm.2025.10.011
Jose Carlos Pachon-M, Enrique I Pachon-M, Carlos Thiene C Pachon, Tomas G Santillana-P, Tasso J Lobo, Juan Carlos Pachon-M, Maria Zelia C Pachon, John Clark
{"title":"Impact of Vagal Effect on Atrial and Ventricular Refractoriness and Atrial Fibrillation: A Comparative Analysis Before and After Cardioneuroablation.","authors":"Jose Carlos Pachon-M, Enrique I Pachon-M, Carlos Thiene C Pachon, Tomas G Santillana-P, Tasso J Lobo, Juan Carlos Pachon-M, Maria Zelia C Pachon, John Clark","doi":"10.1016/j.hrthm.2025.10.011","DOIUrl":"https://doi.org/10.1016/j.hrthm.2025.10.011","url":null,"abstract":"<p><strong>Background: </strong>Extracardiac vagal stimulation (ECVS) provides a simple, reproducible method to study human vagal effects. While vagus nerve clearly modulates atrial electrophysiology, its influence on human ventricular refractoriness remains uncertain. Likewise, the impact of cardioneuroablation (CNA) on atrial and ventricular refractoriness has not been evaluated in a paired human study OBJECTIVE: To quantify the impact of ECVS on atrial and ventricular effective refractory periods (AERP/VERP) before and after CNA and to evaluate a practical AF ablation functional endpoint.</p><p><strong>Methods: </strong>89 consecutive patients were enrolled (76 paroxysmal AF undergoing pulmonary vein isolation plus CNA; 13 reflex syncope undergoing CNA alone). AERP and VERP were measured at four stages: baseline, during ECVS, post-CNA, and post-CNA during ECVS. AF inducibility was tested at each stage with a single extra-stimulus (Vagal AF Induction Test, VAFIT).</p><p><strong>Results: </strong>ECVS produced marked AERP shortening (right atrium: 213.8±25 to 100.6±33ms; left atrium: 235.2±32 to 143.3±32ms; both p<0.001). After CNA, AERP returned toward baseline and was no longer modified by ECVS. In contrast, VERP in both ventricles remained unchanged across all stages (p>0.13). AF inducibility rose from 3.4% at baseline to 95.5% during ECVS, then fell to 7.9% during ECVS post-CNA (Cochran's Q p<0.00001; McNemar p<0.00001).</p><p><strong>Conclusions: </strong>Vagal activation is a potent atrial AF trigger, whereas ventricular refractoriness remains unchanged facing ECVS and/or CNA, underscoring chamber-specific autonomic effects and supporting the electrophysiological safety of ECVS and of CNA. ECVS and VAFIT provide objective, reproducible functional endpoints to guide ablation strategy, confirm atrial vagal denervation, and potentially reduce AF recurrence.</p>","PeriodicalId":12886,"journal":{"name":"Heart rhythm","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heart rhythmPub Date : 2025-10-13DOI: 10.1016/j.hrthm.2025.10.020
Marek Jastrzębski, Aleksander Kusiak, Darius Chapman, Marek Rajzer, Pughazendhi Vijayaraman, Agnieszka Bednarek
{"title":"Bifascicular pacing: a novel multipoint left conduction system pacing method for cardiac resynchronization.","authors":"Marek Jastrzębski, Aleksander Kusiak, Darius Chapman, Marek Rajzer, Pughazendhi Vijayaraman, Agnieszka Bednarek","doi":"10.1016/j.hrthm.2025.10.020","DOIUrl":"https://doi.org/10.1016/j.hrthm.2025.10.020","url":null,"abstract":"<p><strong>Background: </strong>Pacing a single fascicle of the left bundle branch leads to a delay of the segments served by the contralateral fascicle. Bifascicular (BiF) pacing may offer better cardiac resynchronization therapy (CRT) than left inferior fascicle (LIF) or left superior fascicle (LSF) pacing alone.</p><p><strong>Objective: </strong>To compare synchrony between BiF and single fascicle pacing and present the procedural, clinical, electrocardiographic and echocardiographic outcomes in CRT candidates who received BiF pacing METHODS: The following parameters were investigated to assess acute differences in electrical and mechanical synchrony: paced QRS duration and QRS area, global R-wave peak time (RWPT) and dV/dt time in lateral leads (I, aVL and V6), global longitudinal strain (GLS), peak strain dispersion (PSD) and global work efficiency (GWE). All measurements were performed during BiF, LIF and LSF pacing.</p><p><strong>Results: </strong>28 CRT candidates (age: 74.6 ±12.2 years; 36% female; LVEF = 37.2% ±10.6%) received BiF pacing. Compared to single fascicle pacing, BiF pacing resulted in significantly shorter QRS duration, lower QRS area, shorter global RWPT, shorter global dV/dt time, higher GLS and GWE, and lower PSD; no differences were observed between LIF and LSF pacing with respect to these parameters. Lead I dV/dt time and lead I RWPT correlated with mechanical dyssynchrony, especially with PSD (r = 0.79 and r = 0.67).</p><p><strong>Conclusion: </strong>BiF pacing is a novel physiological pacing method that more completely recruits the left conduction system. Compared to single fascicle pacing, it improves electrical and mechanical synchrony, potentially translating to superior clinical outcomes.</p>","PeriodicalId":12886,"journal":{"name":"Heart rhythm","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heart rhythmPub Date : 2025-10-10DOI: 10.1016/j.hrthm.2025.10.012
Xiaodong Peng, Qifan Li, Xiaoxia Liu, Liu He, Nian Liu, Cong Yuan, Jiangtao Li, Zixu Zhao, Mingxiao Li, Song Zuo, Xueyuan Guo, Xiaopai Zhao, Ning Zhou, Caihua Sang, Xin Du, Jianzeng Dong, Changsheng Ma
{"title":"Asymptomatic Atrial Fibrillation: Clinical Characteristics, Outcomes, and Prognostic Impact of Rhythm Control.","authors":"Xiaodong Peng, Qifan Li, Xiaoxia Liu, Liu He, Nian Liu, Cong Yuan, Jiangtao Li, Zixu Zhao, Mingxiao Li, Song Zuo, Xueyuan Guo, Xiaopai Zhao, Ning Zhou, Caihua Sang, Xin Du, Jianzeng Dong, Changsheng Ma","doi":"10.1016/j.hrthm.2025.10.012","DOIUrl":"https://doi.org/10.1016/j.hrthm.2025.10.012","url":null,"abstract":"<p><strong>Background: </strong>Current guidelines recommend rhythm control for atrial fibrillation (AF) based primarily on symptom management, though accumulating evidence indicates potential prognostic benefits beyond symptom relief.</p><p><strong>Objective: </strong>This study aimed to compare the clinical profile, outcomes, and rhythm control effects between asymptomatic and symptomatic AF patients.</p><p><strong>Methods: </strong>Of the 15,603 patients enrolled in the China-AF registry, symptom status was classified as asymptomatic or symptomatic according to the European Heart Rhythm Association (EHRA) score. Cox proportional hazards models assessed the associations between symptom status, rhythm control, and composite outcomes (cardiovascular death and stroke). The interaction between symptom status and rhythm control was also examined.</p><p><strong>Results: </strong>Among the patients, 1,345 (8.6%) were asymptomatic, with a higher proportion of males, non-paroxysmal AF, a prolonged AF course, and eccentric hypertrophy. Rhythm control treatment was applied in 48.9% of asymptomatic and 62.9% of symptomatic patients. Over a median follow-up of five years, the incidence of composite outcomes was similar between asymptomatic and symptomatic patients (1.99% vs. 2.12% person-year; adjusted hazard ratio [aHR], 0.96; 95% confidence interval [CI], 0.81-1.14). For asymptomatic patients, rhythm control was associated with a reduced risk of composite outcomes (aHR, 0.37; 95% CI, 0.23-0.60), comparable to that in symptomatic patients (aHR, 0.52; 95% CI, 0.49-0.62) (P for interaction = 0.111).</p><p><strong>Conclusion: </strong>Asymptomatic AF patients had a comparable risk of adverse outcomes as symptomatic patients. Rhythm control was similarly beneficial regardless of symptoms. These findings support expanding rhythm control strategies to asymptomatic patients and may inform future updates to AF management guidelines.</p>","PeriodicalId":12886,"journal":{"name":"Heart rhythm","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heart rhythmPub Date : 2025-10-10DOI: 10.1016/j.hrthm.2025.10.018
Soori Sivakumaran, Harald Becher
{"title":"Cardiac resynchronization therapy without leads crossing the tricuspid valve.","authors":"Soori Sivakumaran, Harald Becher","doi":"10.1016/j.hrthm.2025.10.018","DOIUrl":"https://doi.org/10.1016/j.hrthm.2025.10.018","url":null,"abstract":"","PeriodicalId":12886,"journal":{"name":"Heart rhythm","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heart rhythmPub Date : 2025-10-10DOI: 10.1016/j.hrthm.2025.10.015
Yutong Wang, Yanwen Chen, Xinyang Song, Tao Xu, Chenxi Xia, Junsong Gong, Sixian Weng, Fang Wang
{"title":"Insulin sensitivity, genetic predisposition, and risk of atrial fibrillation: a prospective cohort study.","authors":"Yutong Wang, Yanwen Chen, Xinyang Song, Tao Xu, Chenxi Xia, Junsong Gong, Sixian Weng, Fang Wang","doi":"10.1016/j.hrthm.2025.10.015","DOIUrl":"https://doi.org/10.1016/j.hrthm.2025.10.015","url":null,"abstract":"<p><strong>Background: </strong>The estimated glucose disposal rate (eGDR) is a validated clinical metric of insulin sensitivity that may predict cardiovascular health, however the combined and interaction relationship between eGDR and genetic predisposition in determining atrial fibrillation (AF) risk remains unclear.</p><p><strong>Objective: </strong>To investigate the longitudinal relationship between eGDR and incident AF risk, and to assess the combined and interaction effect of eGDR and genetic predisposition on AF development.</p><p><strong>Methods: </strong>In the UK Biobank, eGDR was calculated using waist circumference, hypertension status, and glycated hemoglobin levels. Genetic predisposition was assessed via a polygenic risk score (PRS) for AF. Associations were examined using Kaplan-Meier (KM) curves, restricted cubic spline (RCS) models, and Cox regression.</p><p><strong>Results: </strong>Among 431572 participants with a median follow-up of 13.53-year, 29464 AF cases were identified. Higher eGDR quartiles demonstrated significantly lower AF incidence (log-rank P < 0.001), with L-shaped non-linear association (P nonlinear < 0.001). Each unit increase in eGDR was associated with a 9% reduction in AF risk (HR: 0.91, 95% CI: 0.91-0.92, P < 0.001), with stepwise risk reduction across quartiles (Q4 vs Q1: HR: 0.67, 95% CI: 0.63-0.70, P < 0.001). Participants with low PRS and high eGDR exhibited 74% lower AF risk (HR:0.26, 95% CI:0.23-0.28, P < 0.001) compared to those with high PRS and low eGDR, indicating improved insulin sensitivity confers protection across all genetic risk categories.</p><p><strong>Conclusion: </strong>EGDR demonstrates dose-dependent protective effects against AF across all genetic risk categories, highlighting insulin resistance as a potential intervention target for AF prevention.</p>","PeriodicalId":12886,"journal":{"name":"Heart rhythm","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}