Pub 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
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
{"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}
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.
经食管超声心动图（TEE）是房颤（AF）消融前血栓筛查的标准成像方式，但存在操作风险。心内超声心动图（ICE）是一种替代方法，可以提供相当的安全性和程序优势。目的探讨ICE在预防房颤消融术中围术期血栓栓塞事件方面是否优于TEE。设计、环境和参与者该多中心随机临床试验于2022年8月至2023年7月在中国的10家医院进行，随访30天，纳入符合预定资格标准的房颤患者进行导管消融。数据分析时间为2023年8月至2023年12月。干预措施：消融前用ICE或TEE筛查血栓。主要结局和测量主要终点是围手术期血栓栓塞事件（中风、短暂性脑缺血发作或全身性栓塞）的发生率。次要终点包括血栓检测、手术安全性和效率以及患者报告的舒适度。结果共1810例患者（平均[SD]年龄64.3[9.4]岁，女性868例[48.0%]，阵发性房间隔患者887例[49.0%]）随机分为ICE组（n = 906）和TEE组（n = 904）。906例ICE患者中有4例（0.4%）发生血栓栓塞事件，904例TEE患者中有5例（0.6%）发生血栓栓塞事件（风险差异为-0.11%;Farrington-Manning 95% CI, -0.84%至0.62%；非效性P = 0.01）。血栓的检出率为2.0% vs 1.5%(相对危险度[RR]， 1.29; 95% CI, 0.64-2.61；48) ICE组比TEE组有更多的非左房附件血栓（0.6% vs 0%; P < 0.001）。经间隔穿刺相关大出血在ICE组较低（0.2% vs 1.2%； RR, 0.18; 95% CI, 0.04-0.81; P = 0.03）。ICE减少平均（SD）透视时间(4.2 [1.5]vs 9.3[3.0]分钟；P <。0.001)，手术前等待时间（14.4 [8.0]vs 23.6[10.5]小时；P < 0.001）。焦虑或抑郁患病率（24.6% vs 37.5%； RR, 0.66; 95% CI, 0.56-0.76; P < 0.001）。结论和相关性在这项多中心随机临床试验中，ICE在预防房颤消融血栓栓塞并发症方面不逊色于TEE，并且在安全性、效率和患者舒适度方面具有额外的优势，支持其作为临床实践中可行的替代方案。临床试验注册。gov标识符：NCT05466266。
{"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}
Pub 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}
Pub 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}
Pub 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
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; P &lt; 1 × 10−8), AFgeneset (HR, 1.63; 95% CI, 1.52-1.75; P = 1.46 × 10−42), and CHIP (HR, 1.26; 95% CI, 1.15-1.38; P = 1.41 × 10−6) 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.
{"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}
Pub Date : 2025-10-08DOI: 10.1001/jamacardio.2025.3676
Veena B. Krishnan
This essay describes one physician-daughter’s experience with self-healing and self-forgiveness with end-of-life care decisions that she made for her own mother and how physicians should have discussions regarding end-of-life care with the family members of their patients, without losing focus of what the patient would have wanted in those final moments.
{"title":"Daughter and Physician—Having to Be Both When Your Parent Dies","authors":"Veena B. Krishnan","doi":"10.1001/jamacardio.2025.3676","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.3676","url":null,"abstract":"This essay describes one physician-daughter’s experience with self-healing and self-forgiveness with end-of-life care decisions that she made for her own mother and how physicians should have discussions regarding end-of-life care with the family members of their patients, without losing focus of what the patient would have wanted in those final moments.","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"107 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241366","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}
Pub Date : 2025-10-01DOI: 10.1001/jamacardio.2025.3248
Dimitri J Maamari,Kiran J Biddinger,Sean J Jurgens,Joel T Rämö,Liam Gaziano,Alice Zheng,Saketh P Challa,Dolphurs Hayes,Carlos A Gongora,Seung Hoan Choi,Kyong-Mi Chang,Philip S Tsao,Zoltan Arany,Paaladinesh Thavendiranathan,Jennifer E Huffman,Akl C Fahed,Amy A Sarma,Tomas G Neilan,Amit V Khera,Patrick T Ellinor,Krishna G Aragam
ImportanceRare monogenic variants linked to nonischemic dilated cardiomyopathy (DCM) are enriched among individuals with secondary cardiomyopathies, such as peripartum (PPCM), alcohol-induced (ACM), and cancer therapy-related (CCM) cardiomyopathies. However, it remains unclear whether a polygenic predisposition to DCM also contributes to these conditions.ObjectiveTo assess the association of a DCM polygenic score with PPCM, ACM, and CCM, and to evaluate the contributions of monogenic and polygenic susceptibilities to these secondary cardiomyopathies.Design, Setting, and ParticipantsThis was a retrospective genetic association analysis of data from the Mass General Brigham (MGB) Biobank (n = 42 137, 2008-2025), with replication in the UK Biobank (n = 295 160, 2005-2010), FinnGen (n = 417 950, 2017-2025), and the Veterans Affairs Million Veteran Program (n = 516 066, 2011-2025). In MGB Biobank, medical records were reviewed to ascertain secondary cardiomyopathy cases and antecedent clinical risk factors.ExposuresDCM polygenic risk score and DCM monogenic variants.Main Outcomes and MeasuresThe primary outcomes were the association of the DCM polygenic risk score with PPCM, ACM, and CCM and the prevalence of monogenic variants and a high polygenic score among individuals with cardiomyopathy.ResultsThe mean (SD) age in the MGB Biobank was 55.7 (17.0) years at enrollment, and 24 551 (58.3%) were female. Across the 4 study cohorts, 3414 individuals with secondary cardiomyopathy were identified, including 70 with PPCM, 2281 with ACM, and 1063 with CCM. The DCM polygenic score was associated with PPCM (odds ratio [OR], 1.82 per SD; 95% CI, 1.43-2.30), ACM (OR, 1.56; 95% CI,1.34-1.82), and CCM (OR, 1.64; 95% CI,1.24-2.15) (all with P < .001). Monogenic variants were enriched but present in 7 of 113 individuals with medical record-reviewed cardiomyopathy in MGB, while 66 had a high polygenic score, which conferred an approximately 3-fold increased odds of cardiomyopathy. Most individuals with cardiomyopathy lacked antecedent clinical risk factors.Conclusions and RelevanceIn this cohort study, individuals with PPCM, ACM, and CCM were enriched for monogenic DCM variants and a high DCM polygenic score, suggesting a shared genetic susceptibility influenced by distinct environmental precipitants. These findings support a shared genetic architecture between secondary cardiomyopathies and DCM, although additional work with larger numbers of individuals with cardiomyopathy is needed to confirm these findings.
{"title":"Polygenic Susceptibility in Peripartum, Alcohol-Induced, and Cancer Therapy-Related Cardiomyopathies.","authors":"Dimitri J Maamari,Kiran J Biddinger,Sean J Jurgens,Joel T Rämö,Liam Gaziano,Alice Zheng,Saketh P Challa,Dolphurs Hayes,Carlos A Gongora,Seung Hoan Choi,Kyong-Mi Chang,Philip S Tsao,Zoltan Arany,Paaladinesh Thavendiranathan,Jennifer E Huffman,Akl C Fahed,Amy A Sarma,Tomas G Neilan,Amit V Khera,Patrick T Ellinor,Krishna G Aragam","doi":"10.1001/jamacardio.2025.3248","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.3248","url":null,"abstract":"ImportanceRare monogenic variants linked to nonischemic dilated cardiomyopathy (DCM) are enriched among individuals with secondary cardiomyopathies, such as peripartum (PPCM), alcohol-induced (ACM), and cancer therapy-related (CCM) cardiomyopathies. However, it remains unclear whether a polygenic predisposition to DCM also contributes to these conditions.ObjectiveTo assess the association of a DCM polygenic score with PPCM, ACM, and CCM, and to evaluate the contributions of monogenic and polygenic susceptibilities to these secondary cardiomyopathies.Design, Setting, and ParticipantsThis was a retrospective genetic association analysis of data from the Mass General Brigham (MGB) Biobank (n = 42 137, 2008-2025), with replication in the UK Biobank (n = 295 160, 2005-2010), FinnGen (n = 417 950, 2017-2025), and the Veterans Affairs Million Veteran Program (n = 516 066, 2011-2025). In MGB Biobank, medical records were reviewed to ascertain secondary cardiomyopathy cases and antecedent clinical risk factors.ExposuresDCM polygenic risk score and DCM monogenic variants.Main Outcomes and MeasuresThe primary outcomes were the association of the DCM polygenic risk score with PPCM, ACM, and CCM and the prevalence of monogenic variants and a high polygenic score among individuals with cardiomyopathy.ResultsThe mean (SD) age in the MGB Biobank was 55.7 (17.0) years at enrollment, and 24 551 (58.3%) were female. Across the 4 study cohorts, 3414 individuals with secondary cardiomyopathy were identified, including 70 with PPCM, 2281 with ACM, and 1063 with CCM. The DCM polygenic score was associated with PPCM (odds ratio [OR], 1.82 per SD; 95% CI, 1.43-2.30), ACM (OR, 1.56; 95% CI,1.34-1.82), and CCM (OR, 1.64; 95% CI,1.24-2.15) (all with P < .001). Monogenic variants were enriched but present in 7 of 113 individuals with medical record-reviewed cardiomyopathy in MGB, while 66 had a high polygenic score, which conferred an approximately 3-fold increased odds of cardiomyopathy. Most individuals with cardiomyopathy lacked antecedent clinical risk factors.Conclusions and RelevanceIn this cohort study, individuals with PPCM, ACM, and CCM were enriched for monogenic DCM variants and a high DCM polygenic score, suggesting a shared genetic susceptibility influenced by distinct environmental precipitants. These findings support a shared genetic architecture between secondary cardiomyopathies and DCM, although additional work with larger numbers of individuals with cardiomyopathy is needed to confirm these findings.","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"78 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194882","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}
Pub Date : 2025-10-01DOI: 10.1001/jamacardio.2025.3269
Jong Hyun Jhee,Kyoung Hwa Ha,Dasom Son,Hyeok-Hee Lee,Eun-Jin Kim,Hyeon Chang Kim,Hokyou Lee
ImportancePositive health outcomes of a high cardiovascular health (CVH) score have been demonstrated largely with single CVH assessments in midlife, whereas the association of cumulative CVH during young adulthood with premature cardiovascular disease (CVD) and particularly kidney outcomes remains unclear.ObjectiveTo examine the association of cumulative CVH from 30 to 40 years of age with the risk of CVD and kidney events in midlife.Design, Setting, and ParticipantsThis population-based cohort study used Korean National Health Insurance health screening and claims data on adults aged 40 years without prior CVD or chronic kidney disease (CKD). Data were analyzed from May 1, 2024, to April 30, 2025.ExposureTen-year cumulative CVH score, calculated as the area under the CVH score curve from 30 to 40 years of age (range, 0-100 per visit; cumulative range, 0-1000 points × years), based on the American Heart Association's Life's Essential 8 construct.Main Outcomes and MeasuresThe primary outcomes were CVD events (myocardial infarction, ischemic stroke, heart failure, or cardiovascular death) and kidney events (incident CKD, kidney replacement therapy, or kidney-related death) after 40 years of age among participants.ResultsAmong 241 924 adults (78.1% male [n = 188 871]; all aged 40 years) with 3 or more examination visits (at 30 and 40 years of age and ≥1 visits in between; median number of visits, 8 [IQR, 6-10]), 2748 CVD events and 2085 kidney events occurred over a median follow-up of 9.2 years (IQR, 8.4-10.1). The highest quintile (quintile 5 [Q5]; ≥735 points × years) of cumulative CVH from 30 to 40 years of age was associated with a very low incidence of CVD (0.05% per year; adjusted hazard ratio [HR], 0.27 [95% CI, 0.22-0.32] vs Q1) and kidney events (0.05% per year; adjusted HR, 0.25 [95% CI, 0.21-0.31] vs Q1) in midlife. Each 100-point × year higher cumulative CVH (eg, 10-point higher CVH score × 10 years) was associated with a 34% lower hazard of CVD events and a 35% lower hazard of kidney events. The associations were similar by sex and for event subtypes and remained significant after adjustment for CVH score at 40 years of age or the slope of CVH change.Conclusions and RelevanceThese findings suggest that a higher cumulative CVH score from 30 to 40 years of age was associated with markedly lower risks of CVD and kidney events in midlife, highlighting the importance of sustained primordial prevention efforts throughout early life.
{"title":"Cumulative Cardiovascular Health Score Through Young Adulthood and Cardiovascular and Kidney Outcomes in Midlife.","authors":"Jong Hyun Jhee,Kyoung Hwa Ha,Dasom Son,Hyeok-Hee Lee,Eun-Jin Kim,Hyeon Chang Kim,Hokyou Lee","doi":"10.1001/jamacardio.2025.3269","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.3269","url":null,"abstract":"ImportancePositive health outcomes of a high cardiovascular health (CVH) score have been demonstrated largely with single CVH assessments in midlife, whereas the association of cumulative CVH during young adulthood with premature cardiovascular disease (CVD) and particularly kidney outcomes remains unclear.ObjectiveTo examine the association of cumulative CVH from 30 to 40 years of age with the risk of CVD and kidney events in midlife.Design, Setting, and ParticipantsThis population-based cohort study used Korean National Health Insurance health screening and claims data on adults aged 40 years without prior CVD or chronic kidney disease (CKD). Data were analyzed from May 1, 2024, to April 30, 2025.ExposureTen-year cumulative CVH score, calculated as the area under the CVH score curve from 30 to 40 years of age (range, 0-100 per visit; cumulative range, 0-1000 points × years), based on the American Heart Association's Life's Essential 8 construct.Main Outcomes and MeasuresThe primary outcomes were CVD events (myocardial infarction, ischemic stroke, heart failure, or cardiovascular death) and kidney events (incident CKD, kidney replacement therapy, or kidney-related death) after 40 years of age among participants.ResultsAmong 241 924 adults (78.1% male [n = 188 871]; all aged 40 years) with 3 or more examination visits (at 30 and 40 years of age and ≥1 visits in between; median number of visits, 8 [IQR, 6-10]), 2748 CVD events and 2085 kidney events occurred over a median follow-up of 9.2 years (IQR, 8.4-10.1). The highest quintile (quintile 5 [Q5]; ≥735 points × years) of cumulative CVH from 30 to 40 years of age was associated with a very low incidence of CVD (0.05% per year; adjusted hazard ratio [HR], 0.27 [95% CI, 0.22-0.32] vs Q1) and kidney events (0.05% per year; adjusted HR, 0.25 [95% CI, 0.21-0.31] vs Q1) in midlife. Each 100-point × year higher cumulative CVH (eg, 10-point higher CVH score × 10 years) was associated with a 34% lower hazard of CVD events and a 35% lower hazard of kidney events. The associations were similar by sex and for event subtypes and remained significant after adjustment for CVH score at 40 years of age or the slope of CVH change.Conclusions and RelevanceThese findings suggest that a higher cumulative CVH score from 30 to 40 years of age was associated with markedly lower risks of CVD and kidney events in midlife, highlighting the importance of sustained primordial prevention efforts throughout early life.","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"31 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194877","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}
Pub Date : 2025-10-01DOI: 10.1001/jamacardio.2025.3276
Sarah Haeger,Nisha Bansal
{"title":"How Cardiovascular Health in Young Adulthood Affects Kidney and Cardiovascular Risk Later in Life-Lifespan Lessons.","authors":"Sarah Haeger,Nisha Bansal","doi":"10.1001/jamacardio.2025.3276","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.3276","url":null,"abstract":"","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"23 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194880","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}
Pub Date : 2025-09-24DOI: 10.1001/jamacardio.2025.3168
Rohan G Reddy,David A Danford,Shelby Kutty
{"title":"Pathway to Risk Stratification in Tricuspid Regurgitation.","authors":"Rohan G Reddy,David A Danford,Shelby Kutty","doi":"10.1001/jamacardio.2025.3168","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.3168","url":null,"abstract":"","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"24 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127144","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}
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