JAMA cardiologyPub Date : 2025-10-22DOI: 10.1001/jamacardio.2025.3932
Wenli Ni,Lina Benson,Petter Ljungman,Federica Nobile,Susanne Breitner,Siqi Zhang,Jeroen de Bont,Lars H Lund,Gianluigi Savarese,Alexandra Schneider,Stefan Agewall
{"title":"Short-Term Exposure to Low and High Temperatures and Mortality Among Patients With Heart Failure in Sweden.","authors":"Wenli Ni,Lina Benson,Petter Ljungman,Federica Nobile,Susanne Breitner,Siqi Zhang,Jeroen de Bont,Lars H Lund,Gianluigi Savarese,Alexandra Schneider,Stefan Agewall","doi":"10.1001/jamacardio.2025.3932","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.3932","url":null,"abstract":"ImportancePatients with heart failure may be particularly susceptible to nonoptimal temperature exposure, but the associations between short-term low and high temperature exposure and mortality in this population remain unclear, especially in Sweden-a high-latitude country where no nationwide study has been conducted.ObjectiveTo investigate the associations between short-term exposure to low and high ambient temperatures and all-cause and cardiovascular mortality among Swedish patients with heart failure.Design, Setting, and ParticipantsThis nationwide, time-stratified case-crossover study was conducted in Sweden among 250 640 patients with heart failure who died from any cause from 2006 to 2021, identified from the Swedish National Patient Register and the Cause of Death Register.ExposureDaily mean ambient temperature was assessed at 1 × 1-km spatial resolution. To account for regional adaptation, temperature exposures were defined using municipality-specific percentiles, with low and high temperatures corresponding to the 2.5th and 97.5th percentiles, respectively.Main Outcomes and MeasuresThe primary outcome was all-cause and cardiovascular mortality among patients with heart failure.ResultsThe mean (SD) age at death among patients with heart failure was 84.3 (9.4) years, with 121 061 female patients (48.3%). Short-term exposure to ambient temperature demonstrated a U-shaped association with both all-cause and cardiovascular mortality. For all-cause mortality, odds ratios (ORs) were 1.130 (95% CI, 1.074-1.189) for low temperatures and 1.054 (95% CI, 1.017-1.093) for high temperatures over the entire study period. For cardiovascular mortality, low temperatures were associated with an OR of 1.160 (95% CI, 1.083-1.242) over the entire study period, and high temperatures with an OR of 1.084 (95% CI, 1.014-1.159) during 2014-2021. The mortality risk associated with high temperatures was more pronounced during the 2014-2021 period compared to 2006-2013. Male patients, those with comorbid diabetes, and diuretic users were more susceptible to low temperatures, whereas high temperature was more strongly associated with mortality in patients with comorbid atrial fibrillation or flutter and those exposed to elevated ozone levels.Conclusions and RelevanceThis nationwide Swedish time-stratified case-crossover study indicates that short-term exposure to both low and high temperatures was associated with increased risk of all-cause and cardiovascular mortality in patients with heart failure. The mortality risk associated with high temperatures appears to be increasing over time, emphasizing the need for adaptation, even in high-latitude regions.","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"1 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Adverse Pregnancy Outcomes and Long-Term Risk of Atrial Fibrillation.","authors":"Casey Crump,Jingkai Wei,Jan Sundquist,Kristina Sundquist","doi":"10.1001/jamacardio.2025.3951","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.3951","url":null,"abstract":"ImportanceWomen with adverse pregnancy outcomes have higher subsequent cardiovascular risks, but their long-term risk of atrial fibrillation (AF) and potential causality are unclear. A better understanding of such risks is needed to identify women with high risk early in life and guide interventions to prevent AF and its complications.ObjectiveTo determine long-term risks of AF associated with 6 major adverse pregnancy outcomes in a large population-based cohort and assess for familial confounding using cosibling analyses.Design, Setting, and ParticipantsThis national cohort study included all women with a singleton delivery in Sweden between 1973 and 2015. Analyses were conducted between May 23 and August 18, 2025.ExposuresAdverse pregnancy outcomes (preterm delivery, small for gestational age, large for gestational age, preeclampsia, other hypertensive disorders, and gestational diabetes), identified from nationwide birth records.Main Outcome and MeasuresThe primary outcome was AF identified from nationwide inpatient and outpatient diagnoses through 2018. Cox regression was used to compute hazard ratios (HRs) for AF associated with specific adverse pregnancy outcomes, adjusting for other maternal factors. Cosibling analyses assessed for potential confounding by shared familial (genetic and/or environmental) factors.ResultsAmong 2 201 047 women with 54 million person-years of follow-up, 51 173 (2.3%) were diagnosed with AF (median [IQR] age at diagnosis, 63 [56-69] years). All adverse pregnancy outcomes except small for gestational age were associated with long-term increased risks of AF. Within 10 years following delivery, adjusted HRs for AF were significantly elevated only among women with other hypertensive disorders (HR, 1.69; 95% CI, 1.32-2.15), preterm delivery (HR, 1.46; 95% CI, 1.26-1.70), or large for gestational age (HR, 1.16; 95% CI, 1.01-1.32). However, at 30 to 46 years after delivery, adjusted HRs were increased among women with other hypertensive disorders (HR, 1.44; 95% CI, 1.24-1.66), preeclampsia (HR, 1.38; 95% CI, 1.33-1.50), gestational diabetes (HR, 1.19; 95% CI, 1.03-1.37), large for gestational age (HR, 1.17; 95% CI, 1.14-1.21), or preterm delivery (HR, 1.11; 95% CI, 1.07-1.16). These findings were largely unexplained by shared familial factors. Women with multiple adverse pregnancy outcomes had further increases in risk.ConclusionsIn this large national cohort, all adverse pregnancy outcomes except small for gestational age were associated with increased risk for AF up to 46 years later. Women with adverse pregnancy outcomes need early preventive actions and long-term clinical follow-up for timely detection and treatment of cardiovascular disorders related to the development of AF.","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"78 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JAMA cardiologyPub Date : 2025-10-22DOI: 10.1001/jamacardio.2025.3939
Sanjay Rajagopalan, Robert D Brook, Salil Deo
{"title":"Heart Failure and Nonoptimal Temperatures.","authors":"Sanjay Rajagopalan, Robert D Brook, Salil Deo","doi":"10.1001/jamacardio.2025.3939","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.3939","url":null,"abstract":"","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":" ","pages":""},"PeriodicalIF":14.1,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JAMA cardiologyPub Date : 2025-10-15DOI: 10.1001/jamacardio.2025.3744
Nicholas Chiu,Peter Libby
{"title":"A New Bleeding Signal in Clonal Hematopoiesis-White Cells, Red Flags.","authors":"Nicholas Chiu,Peter Libby","doi":"10.1001/jamacardio.2025.3744","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.3744","url":null,"abstract":"","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"22 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145288384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JAMA cardiologyPub Date : 2025-10-15DOI: 10.1001/jamacardio.2025.3822
Yodying Kaolawanich,David C Wendell,Han W Kim,Enn-Ling Chen,Céleste Chevalier,Piyapat Chunharas,Michele A Parker,Raymond J Kim
{"title":"Prognostic Value of Papillary Muscle Scarring in Patients With Dilated Cardiomyopathy.","authors":"Yodying Kaolawanich,David C Wendell,Han W Kim,Enn-Ling Chen,Céleste Chevalier,Piyapat Chunharas,Michele A Parker,Raymond J Kim","doi":"10.1001/jamacardio.2025.3822","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.3822","url":null,"abstract":"ImportancePapillary muscle scarring (papSCAR) can occur without epicardial coronary artery disease, likely due to microvascular dysfunction. Dilated cardiomyopathy (DCM) has been associated with microvascular dysfunction; the prevalence and prognostic significance of papSCAR in patients with DCM are unclear.ObjectiveTo determine the prevalence of papSCAR in patients with DCM and to evaluate if papSCAR is associated with adverse outcomes.Design, Setting, and ParticipantsThis cohort study was conducted among consecutive patients with known or suspected DCM prospectively enrolled at an academic hospital in North Carolina from January 2011 to December 2020. Patients were referred for cardiovascular magnetic resonance (CMR) imaging, and the study protocol included flow-independent dark blood delayed-enhancement (FIDDLE) imaging, which improves the detection of papSCAR. Data were analyzed from January 2022 to December 2022.Main Outcomes and MeasuresThe primary end point was cardiac mortality. Secondary end points included a composite of heart failure events (heart failure death or cardiac transplant) and a composite of arrhythmia events (sudden cardiac death [SCD] or aborted SCD).ResultsThis cohort study included 470 patients (mean [SD] age, 55.3 [14.3] years; 205 female patients [43.6%]). During up to 8 years of follow-up (2082 patient-years), there were 53 cardiac deaths, 49 heart failure events, and 24 arrhythmia events. PapSCAR was present in 137 patients (29.1%), and mean (SD) left ventricular ejection fraction (LVEF) was similar between those with and without papSCAR (30.7% [11.0%] vs 31.4% [10.3%]; P = .52). Patients with papSCAR had a higher rate of cardiac death than those without (19.0% vs 8.1%; hazard ratio [HR], 2.30; 95% CI, 1.34-3.95; P = .002). After adjustment for prespecified variables known to have prognostic value in DCM (age, systolic blood pressure, heart rate, LVEF, and midwall myocardial scar), papSCAR was independently associated with cardiac death (HR, 1.86; 95% CI, 1.07-3.24; P = .03) and provided incremental prognostic value (incremental χ2, 4.68; P = .03). PapSCAR was also independently associated with heart failure events (HR, 2.05; 95% CI, 1.16-3.61; P = .01) and arrhythmia events (HR, 3.41; 95% CI, 1.46-7.94; P = .005).Conclusions and RelevanceIn this single-center cohort study, papSCAR as detected by dark blood delayed-enhancement CMR was present in approximately one-third of patients with DCM and was independently associated with cardiac death.","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"4 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145288385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JAMA cardiologyPub Date : 2025-10-15DOI: 10.1001/jamacardio.2025.3756
Zoe K McQuilten,Le T P Thao,Alexander G Bick,Sean Byars,Andrew T Chan,Leslie Ford,Anna Leichter,John J McNeil,Anne M Murray,Andrew J Murphy,Suzanne G Orchard,James Phung,Hayley S Ramshaw,Jasmine Singh,Andrew M Tonkin,Asad Umar,Rory Wolfe,Erica M Wood,Robyn L Woods,Paul Lacaze,David J Curtis
{"title":"Clonal Hematopoiesis and Cardiovascular Disease and Bleeding Risk and the Effectiveness of Aspirin.","authors":"Zoe K McQuilten,Le T P Thao,Alexander G Bick,Sean Byars,Andrew T Chan,Leslie Ford,Anna Leichter,John J McNeil,Anne M Murray,Andrew J Murphy,Suzanne G Orchard,James Phung,Hayley S Ramshaw,Jasmine Singh,Andrew M Tonkin,Asad Umar,Rory Wolfe,Erica M Wood,Robyn L Woods,Paul Lacaze,David J Curtis","doi":"10.1001/jamacardio.2025.3756","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.3756","url":null,"abstract":"ImportanceClonal hematopoiesis of indeterminate potential (CHIP) has been associated with increased risk of cardiovascular disease (CVD) events and mortality. However, there are no approved therapies for preventing or treating CHIP.ObjectiveTo investigate whether low-dose aspirin might benefit older adults with CHIP for the primary prevention of CVD.Design, Setting, and ParticipantsThis was a prespecified substudy of the Aspirin in Reducing Events in the Elderly (ASPREE) double-blind, randomized clinical trial of daily low-dose aspirin vs placebo evaluating disability-free survival, which took place at primary and community care facilities in the US and Australia. Enrollment was from March 2010 to December 2014, and the randomized trial ended in June 2017. Community-dwelling Australian adults aged 70 years and older without a diagnosed cardiovascular event, atrial fibrillation, a serious intercurrent illness likely to cause death within the next 5 years, anemia, or a current or recurrent condition with a high risk of bleeding were included in the original study. Of 19 114 in the original trial, 11 402 were included in the substudy, and 9434 were included in the analysis. Follow-up for this substudy went through June 2022, with data analysis in February 2025. In-trial median (IQR) follow-up time was 4.6 (3.5-5.6) years, and posttrial observational follow-up was 8.7 (7.5-10.1) years from randomization.InterventionsParticipants were randomized to aspirin, 100 mg, daily or placebo.Main Outcomes and MeasuresCHIP was measured in blood specimens collected at trial entry. Major adverse cardiovascular events (MACEs), including fatal and nonfatal ischemic stroke, nonfatal myocardial infarction and coronary heart disease death, and clinically significant bleeding were adjudicated by independent expert committees blinded to trial-group assignments.ResultsA total of 9434 participants (median [IQR] age, 73.7 [71.6-77.1] years; 5067 [54%] female) provided a sample at baseline for analysis, 2124 of whom (23%) had CHIP at variant allele fraction (VAF) ≥2%, with 532 (5.6%) at ≥10% VAF. CHIP was not associated with increased risk of MACEs at 2% to 10% VAF (adjusted hazard ratio [aHR], 0.84, 95% CI, 0.68-1.03; P = .09) or ≥10% VAF (aHR, 0.80, 95% CI, 0.57-1.12; P = .19). However, CHIP was associated with increased risk of clinically significant bleeding (2%-10% VAF: aHR, 1.24; 95% CI 1.02-1.51; P = .03; ≥10% VAF: aHR, 1.21; 95% CI, 0.85-1.73; P = .28). There was no evidence of a differential effect of aspirin according to presence of CHIP on MACEs (without CHIP: HR, 0.91; 95% CI, 0.72-1.16; 2%-10% VAF: HR, 1.40; 95% CI, 0.77-2.53; ≥10% VAF: HR, 1.33; 95% CI, 0.52-3.37; heterogeneity P = .35) or clinically significant bleeding (without CHIP: HR, 1.64; 95% CI, 1.22-2.30; 2%-10% VAF: HR, 1.45; 95% CI, 0.82-2.57; ≥10% VAF: HR, 1.41; 95% CI, 0.49-4.07; heterogeneity P = .91).Conclusion and RelevanceIn this secondary analysis of a randomized clinical trial of daily low-do","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"19 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145288431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Intracardiac vs Transesophageal Echocardiography in Atrial Fibrillation Ablation: A Randomized Clinical Trial.","authors":"Xiaofeng Hu,Weifeng Jiang,Xinhua Wang,Ping Ye,Xiangting Li,Ying Wang,Qidong Zheng,Yanzhe Wang,Lihua Leng,Zengtang Zhang,Bing Han,Yu Zhang,Mu Qin,Xu Liu,Xumin Hou, ","doi":"10.1001/jamacardio.2025.3687","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.3687","url":null,"abstract":"ImportanceTransesophageal echocardiography (TEE) is the standard imaging modality for thrombus screening prior to atrial fibrillation (AF) ablation but carries procedural risks. Intracardiac echocardiography (ICE) is an alternative that may offer comparable safety with procedural advantages.ObjectiveTo determine whether ICE is noninferior to TEE in preventing periprocedural thromboembolic events in AF ablation.Design, Setting, and ParticipantsThis multicenter randomized clinical trial was conducted at 10 hospitals in China from August 2022 to July 2023, with a 30-day follow-up, enrolling adults with AF scheduled for catheter ablation who met predefined eligibility criteria. Data analysis was performed from August 2023 to December 2023.InterventionsThrombus screening with ICE or TEE prior to ablation.Main Outcomes and MeasuresThe primary end point was the incidence of periprocedural thromboembolic events (stroke, transient ischemic attack, or systemic embolism). Secondary end points included thrombus detection, procedural safety and efficiency, and patient-reported comfort.ResultsA total of 1810 patients (mean [SD] age, 64.3 [9.4] years; 868 women [48.0%]; 887 patients [49.0%] with paroxysmal AF) were randomized to ICE (n = 906) or TEE (n = 904). Thromboembolic events occurred in 4 of 906 patients undergoing ICE (0.4%) and 5 of 904 patients undergoing TEE (0.6%) (risk difference, -0.11%; Farrington-Manning 95% CI, -0.84% to 0.62%; P for noninferiority = .01). Thrombus was detected in 2.0% vs 1.5% (relative risk [RR], 1.29; 95% CI, 0.64-2.61; P = .48) with ICE vs TEE, respectively, with more non-left atrial appendage thrombi in ICE (0.6% vs 0%; P < .001). Major bleeding related to transseptal puncture was lower with ICE (0.2% vs 1.2%; RR, 0.18; 95% CI, 0.04-0.81; P = .03). ICE reduced mean (SD) fluoroscopy time (4.2 [1.5] vs 9.3 [3.0] minutes; P < .001), preprocedural waiting time (14.4 [8.0] vs 23.6 [10.5] hours; P < .001), and anxiety or depression prevalence (24.6% vs 37.5%; RR, 0.66; 95% CI, 0.56-0.76; P < .001).Conclusions and RelevanceIn this multicenter randomized clinical trial, ICE was noninferior to TEE for preventing thromboembolic complications in AF ablation and offered additional advantages in safety, efficiency, and patient comfort, supporting its use as a viable alternative in clinical practice.Trial RegistrationClinicalTrial.gov Identifier: NCT05466266.","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"29 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JAMA cardiologyPub Date : 2025-10-08DOI: 10.1001/jamacardio.2025.3679
Wilfried Le Goff,Philippe Giral
{"title":"Inquiry Regarding Body Temperature Data in HuMAIN-HFpEF Trial.","authors":"Wilfried Le Goff,Philippe Giral","doi":"10.1001/jamacardio.2025.3679","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.3679","url":null,"abstract":"","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"30 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JAMA cardiologyPub Date : 2025-10-08DOI: 10.1001/jamacardio.2025.3682
Ambarish Pandey,Dalane Kitzman
{"title":"Inquiry Regarding Body Temperature Data in HuMAIN-HFpEF Trial-Reply.","authors":"Ambarish Pandey,Dalane Kitzman","doi":"10.1001/jamacardio.2025.3682","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.3682","url":null,"abstract":"","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"158 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JAMA cardiologyPub Date : 2025-10-08DOI: 10.1001/jamacardio.2025.3664
Rufan Zhang, Min Seo Kim, Wanqing Yin, Shuangqiao Liao, Xinyu Zhu, Xiong Yang, Kang Yu, Yang Sui, Carolina Roselli, Shaan Khurshid, Qiuli Chen, Yunga A, Hongqiang Zhao, Tingfeng Xu, Xiufeng Huang, Jun Pu, Zhaoqi Liu, Pradeep Natarajan, Guangyao Zhai, Patrick T. Ellinor, Minxian Wang, Akl C. Fahed
{"title":"Contributions of Common, Rare, and Somatic Genetic Variants to Incidence of Atrial Fibrillation","authors":"Rufan Zhang, Min Seo Kim, Wanqing Yin, Shuangqiao Liao, Xinyu Zhu, Xiong Yang, Kang Yu, Yang Sui, Carolina Roselli, Shaan Khurshid, Qiuli Chen, Yunga A, Hongqiang Zhao, Tingfeng Xu, Xiufeng Huang, Jun Pu, Zhaoqi Liu, Pradeep Natarajan, Guangyao Zhai, Patrick T. Ellinor, Minxian Wang, Akl C. Fahed","doi":"10.1001/jamacardio.2025.3664","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.3664","url":null,"abstract":"ImportanceAtrial fibrillation (AF) has a complex genetic architecture involving common, rare, and somatic variants. The association between these components requires further investigation.ObjectiveTo examine the individual and combined contributions of polygenic, monogenic, and somatic genetic variants to AF incidence, and develop an integrated genomic model (IGM-AF) for improved risk prediction.Design, Setting, and ParticipantsThis cohort study used whole-genome sequence data from participants of the UK Biobank, with follow-up for AF events through hospital records, death registries, and self-report. The UK Biobank recruited participants aged 40 to 69 years in the UK between 2006 and 2010. Study data were analyzed from August 2022 to November 2024.ExposuresIGM-AF comprising an AF polygenic risk score (PRS), a composite rare variant gene set (AFgeneset), and somatic variants associated with clonal hematopoiesis of indeterminate potential (CHIP). Clinical AF risk was estimated using the Cohorts for Heart and Aging Research in Genomic Epidemiology AF (CHARGE-AF) score.Main Outcomes and MeasuresThe primary outcome was hazard ratios (HRs) for 5-year incident AF attributable to PRS, AFgeneset, CHIP, and their interactions. The predictive performance of IGM-AF and its components was quantified using HRs, C statistics, and reclassification indices.ResultsA total of 416 085 individuals (mean [SD] age, 56.6 [8.0] years; 224 642 female [54.0%]) with 30 797 AF cases were included. The PRS (HR per 1 SD, 1.65; 95% CI, 1.63-1.67; <jats:italic>P</jats:italic> &amp;lt; 1 × 10<jats:sup>−8</jats:sup>), AFgeneset (HR, 1.63; 95% CI, 1.52-1.75; <jats:italic>P</jats:italic> = 1.46 × 10<jats:sup>−42</jats:sup>), and CHIP (HR, 1.26; 95% CI, 1.15-1.38; <jats:italic>P</jats:italic> = 1.41 × 10<jats:sup>−6</jats:sup>) were associated with incident AF. The 5-year cumulative incidence of AF was at least 2-fold among individuals having all 3 genetic drivers (common, rare, and somatic drivers) compared with those with only 1 driver. Integration of IGM-AF with a clinical risk model (CHARGE-AF) showed higher predictive performance (C statistic, 0.80; 95% CI, 0.80-0.80) compared with IGM-AF and CHARGE-AF alone. The classification of the at-risk population for AF was improved when IGM-AF was added to CHARGE-AF (net reclassification index, 0.08; 95% CI, 0.07-0.09).Conclusions and RelevanceResults of this cohort study demonstrated the complementary value of common, rare, and somatic variants in shaping genomic AF risk. Leveraging comprehensive genetic information may enhance screening and preventive interventions for AF.","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"31 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}