Pub Date : 2026-02-01DOI: 10.1001/jamacardio.2025.4739
Sarah A Abramowitz, Lily Hoffman-Andrews, David Zhang, Renae Judy, Thomas P Cappola, Sharlene M Day, Nosheen Reza, Anjali T Owens, Scott M Damrauer, Michael G Levin
<p><strong>Importance: </strong>Polygenic background modifies variant penetrance in hypertrophic (HCM) and dilated (DCM) cardiomyopathies, diseases with opposing morphologic characteristics and inversely related genetic pathways. Whether polygenic susceptibility for one disease protects against monogenic risk for the other remains uncertain.</p><p><strong>Objective: </strong>To characterize if polygenic background bidirectionally modifies pathogenicity of established rare variants associated with HCM and DCM.</p><p><strong>Design, setting, and participants: </strong>This cross-sectional study was conducted using data from the Penn Medicine BioBank (PMBB). Volunteers enrolled in PMBB between November 1994 and July 2022 with available electronic health record and genotyping data through September 2024 were included. Analysis was performed in June 2025.</p><p><strong>Exposures: </strong>Normalized polygenic scores (PGSs) for HCM and DCM as well as carrier status of pathogenic variants in established HCM or DCM genes.</p><p><strong>Main outcomes and measures: </strong>HCM and DCM defined using electronic health record diagnosis and procedure codes, as well as echocardiogram measurements obtained from medical records.</p><p><strong>Results: </strong>This study included 49 434 PMBB participants (median (IQR) age, 57 [42-67] years; 24 886 male [50.3%]). An increased HCM PGS was associated with a 1.1% increase in left ventricular ejection fraction (LVEF; 95% CI, 0.9 to 1.3; P = 7.3 × 10-31), a 0.79-mm decrease in left ventricular internal diameter at end-diastole (LVIDd; 95% CI, -0.92 to -0.67; P = 2.3 × 10-36), and a 0.18-mm increase in interventricular septal (IVS) thickness (95% CI, 0.14 to 0.22; P = 9.3 × 10-19). A 1-SD increase in DCM PGS was associated with a 2.0% decrease in LVEF (95% CI, -2.2 to -1.8; P = 3.3 × 10-83) and a 1.0-mm increase in LVIDd (95% CI, 0.93 to 1.1; P = 3.2 × 10-78) and was not significantly associated with IVS (estimate, -1.3 × 10⁻3 mm; 95% CI, -0.04 to 0.03; P = .94). A 1-SD increase in HCM PGS was associated with an increased risk of HCM (odds ratio [OR], 1.8; 95% CI, 1.6-2.0; P = 9.6 × 10-25) and decreased risk of DCM (OR, 0.69; 95% CI, 0.64-0.74; P = 4.3 × 10-22). A 1-SD increase in DCM PGS was associated with an increased risk of DCM (OR, 1.6; 95% CI, 1.5-1.7; P = 1.7 × 10-40) and decreased risk of HCM (OR, 0.69; 95% CI, 0.63-0.76; P = 3.0 × 10-13). Monogenic and polygenic risk terms had significant independent effects when combined in models of disease status and echocardiographic measurements; the inclusion of either an HCM or DCM PGS improved the discrimination (area under the receiving operating characteristic curve) of models of HCM (0.043; 95% credible interval, 0.034-0.053) and DCM (0.045; 95% credible interval, 0.039-0.051) beyond models including age, sex, and monogenic variant status.</p><p><strong>Conclusions and relevance: </strong>The findings in this study indicate that HCM and DCM risk were modified by po
{"title":"Polygenic Background and Penetrance of Pathogenic Variants in Hypertrophic and Dilated Cardiomyopathies.","authors":"Sarah A Abramowitz, Lily Hoffman-Andrews, David Zhang, Renae Judy, Thomas P Cappola, Sharlene M Day, Nosheen Reza, Anjali T Owens, Scott M Damrauer, Michael G Levin","doi":"10.1001/jamacardio.2025.4739","DOIUrl":"10.1001/jamacardio.2025.4739","url":null,"abstract":"<p><strong>Importance: </strong>Polygenic background modifies variant penetrance in hypertrophic (HCM) and dilated (DCM) cardiomyopathies, diseases with opposing morphologic characteristics and inversely related genetic pathways. Whether polygenic susceptibility for one disease protects against monogenic risk for the other remains uncertain.</p><p><strong>Objective: </strong>To characterize if polygenic background bidirectionally modifies pathogenicity of established rare variants associated with HCM and DCM.</p><p><strong>Design, setting, and participants: </strong>This cross-sectional study was conducted using data from the Penn Medicine BioBank (PMBB). Volunteers enrolled in PMBB between November 1994 and July 2022 with available electronic health record and genotyping data through September 2024 were included. Analysis was performed in June 2025.</p><p><strong>Exposures: </strong>Normalized polygenic scores (PGSs) for HCM and DCM as well as carrier status of pathogenic variants in established HCM or DCM genes.</p><p><strong>Main outcomes and measures: </strong>HCM and DCM defined using electronic health record diagnosis and procedure codes, as well as echocardiogram measurements obtained from medical records.</p><p><strong>Results: </strong>This study included 49 434 PMBB participants (median (IQR) age, 57 [42-67] years; 24 886 male [50.3%]). An increased HCM PGS was associated with a 1.1% increase in left ventricular ejection fraction (LVEF; 95% CI, 0.9 to 1.3; P = 7.3 × 10-31), a 0.79-mm decrease in left ventricular internal diameter at end-diastole (LVIDd; 95% CI, -0.92 to -0.67; P = 2.3 × 10-36), and a 0.18-mm increase in interventricular septal (IVS) thickness (95% CI, 0.14 to 0.22; P = 9.3 × 10-19). A 1-SD increase in DCM PGS was associated with a 2.0% decrease in LVEF (95% CI, -2.2 to -1.8; P = 3.3 × 10-83) and a 1.0-mm increase in LVIDd (95% CI, 0.93 to 1.1; P = 3.2 × 10-78) and was not significantly associated with IVS (estimate, -1.3 × 10⁻3 mm; 95% CI, -0.04 to 0.03; P = .94). A 1-SD increase in HCM PGS was associated with an increased risk of HCM (odds ratio [OR], 1.8; 95% CI, 1.6-2.0; P = 9.6 × 10-25) and decreased risk of DCM (OR, 0.69; 95% CI, 0.64-0.74; P = 4.3 × 10-22). A 1-SD increase in DCM PGS was associated with an increased risk of DCM (OR, 1.6; 95% CI, 1.5-1.7; P = 1.7 × 10-40) and decreased risk of HCM (OR, 0.69; 95% CI, 0.63-0.76; P = 3.0 × 10-13). Monogenic and polygenic risk terms had significant independent effects when combined in models of disease status and echocardiographic measurements; the inclusion of either an HCM or DCM PGS improved the discrimination (area under the receiving operating characteristic curve) of models of HCM (0.043; 95% credible interval, 0.034-0.053) and DCM (0.045; 95% credible interval, 0.039-0.051) beyond models including age, sex, and monogenic variant status.</p><p><strong>Conclusions and relevance: </strong>The findings in this study indicate that HCM and DCM risk were modified by po","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":" ","pages":"147-155"},"PeriodicalIF":14.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12728730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1001/jamacardio.2025.4668
Faraz S Ahmad, Sadiya S Khan, Michael G Levin
{"title":"Implementation Intelligence With AI-Prospective Evaluations Needed.","authors":"Faraz S Ahmad, Sadiya S Khan, Michael G Levin","doi":"10.1001/jamacardio.2025.4668","DOIUrl":"10.1001/jamacardio.2025.4668","url":null,"abstract":"","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":" ","pages":"125"},"PeriodicalIF":14.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145488714","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 : 2026-01-30DOI: 10.1001/jamacardio.2026.0119
Robert O Bonow
{"title":"The First Decade of JAMA Cardiology.","authors":"Robert O Bonow","doi":"10.1001/jamacardio.2026.0119","DOIUrl":"https://doi.org/10.1001/jamacardio.2026.0119","url":null,"abstract":"","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"82 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073209","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 : 2026-01-28DOI: 10.1001/jamacardio.2025.5339
Stephen J Greene,Haolin Xu,Karen Chiswell,G Michael Felker,Sabra C Lewsey,Punag H Divanji,Hans-Peter Goertz,Stephen B Heitner,Sanatan Shreay,Ambarish Pandey,Clyde W Yancy,Javed Butler,Gregg C Fonarow
ImportanceAmong patients with heart failure with reduced ejection fraction (HFrEF) in US clinical practice, the residual risk of poor clinical outcomes despite quadruple medical therapy is not well characterized.ObjectiveTo evaluate clinical outcomes and health care costs among patients hospitalized for HFrEF prescribed quadruple medical therapy at discharge.Design, Setting, and ParticipantsThis retrospective cohort study examined Medicare beneficiaries hospitalized for HFrEF in the Get With The Guidelines-Heart Failure registry and discharged from US hospitals receiving any dose of quadruple medical therapy (angiotensin receptor-neprilysin inhibitor, β-blocker, mineralocorticoid receptor antagonist, and sodium-glucose cotransporter 2 inhibitor) between July 1, 2021, and December 31, 2023. Data analysis was conducted from October 2024 through March 2025.ExposurePrescription of quadruple medical therapy (angiotensin receptor-neprilysin inhibitor, β-blocker, mineralocorticoid receptor antagonist, and sodium-glucose cotransporter 2 inhibitor) at time of hospital discharge.Main Outcomes and MeasuresThe primary outcomes were mortality, HF hospitalization, mortality or HF hospitalization, and per-patient health care expenditure (Medicare Part A and B inpatient and outpatient costs, in 2023 US dollars).ResultsAmong 20 651 patients with HFrEF eligible for quadruple medical therapy across 532 US hospitals, 1490 (7.2%) were prescribed quadruple therapy at discharge, with high between-hospital variance (median odds ratio, 2.04; 95% CI, 1.89-2.24). Median (IQR) age of patients prescribed quadruple therapy was 74 (69-81) years, and 543 patients (36.4%) were women. Over 12-month follow-up, cumulative incidences of all-cause mortality, HF hospitalization, and all-cause mortality or HF hospitalization were 19.3% (95% CI, 17.3%-21.4%), 26.0% (95% CI, 23.6%-28.5%), and 37.1% (95% CI, 34.4%-39.8%), respectively. Median (IQR) 12-month per-patient health care expenditure was $27 956 ($7478-$61 126). Twelve-month mortality and HF hospitalization outcomes were similar for patients prescribed quadruple medical therapy at discharge in the first half vs the second half of the study period.Conclusions and RelevanceIn this nationwide cohort study, even when prescribed quadruple medical therapy, older patients hospitalized for HFrEF in US clinical practice face substantial residual risk of death and HF readmission and often accrue high health care costs.
{"title":"One-Year Outcomes in Patients Hospitalized for Heart Failure With Reduced Ejection Fraction Prescribed Quadruple Medical Therapy at Discharge.","authors":"Stephen J Greene,Haolin Xu,Karen Chiswell,G Michael Felker,Sabra C Lewsey,Punag H Divanji,Hans-Peter Goertz,Stephen B Heitner,Sanatan Shreay,Ambarish Pandey,Clyde W Yancy,Javed Butler,Gregg C Fonarow","doi":"10.1001/jamacardio.2025.5339","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.5339","url":null,"abstract":"ImportanceAmong patients with heart failure with reduced ejection fraction (HFrEF) in US clinical practice, the residual risk of poor clinical outcomes despite quadruple medical therapy is not well characterized.ObjectiveTo evaluate clinical outcomes and health care costs among patients hospitalized for HFrEF prescribed quadruple medical therapy at discharge.Design, Setting, and ParticipantsThis retrospective cohort study examined Medicare beneficiaries hospitalized for HFrEF in the Get With The Guidelines-Heart Failure registry and discharged from US hospitals receiving any dose of quadruple medical therapy (angiotensin receptor-neprilysin inhibitor, β-blocker, mineralocorticoid receptor antagonist, and sodium-glucose cotransporter 2 inhibitor) between July 1, 2021, and December 31, 2023. Data analysis was conducted from October 2024 through March 2025.ExposurePrescription of quadruple medical therapy (angiotensin receptor-neprilysin inhibitor, β-blocker, mineralocorticoid receptor antagonist, and sodium-glucose cotransporter 2 inhibitor) at time of hospital discharge.Main Outcomes and MeasuresThe primary outcomes were mortality, HF hospitalization, mortality or HF hospitalization, and per-patient health care expenditure (Medicare Part A and B inpatient and outpatient costs, in 2023 US dollars).ResultsAmong 20 651 patients with HFrEF eligible for quadruple medical therapy across 532 US hospitals, 1490 (7.2%) were prescribed quadruple therapy at discharge, with high between-hospital variance (median odds ratio, 2.04; 95% CI, 1.89-2.24). Median (IQR) age of patients prescribed quadruple therapy was 74 (69-81) years, and 543 patients (36.4%) were women. Over 12-month follow-up, cumulative incidences of all-cause mortality, HF hospitalization, and all-cause mortality or HF hospitalization were 19.3% (95% CI, 17.3%-21.4%), 26.0% (95% CI, 23.6%-28.5%), and 37.1% (95% CI, 34.4%-39.8%), respectively. Median (IQR) 12-month per-patient health care expenditure was $27 956 ($7478-$61 126). Twelve-month mortality and HF hospitalization outcomes were similar for patients prescribed quadruple medical therapy at discharge in the first half vs the second half of the study period.Conclusions and RelevanceIn this nationwide cohort study, even when prescribed quadruple medical therapy, older patients hospitalized for HFrEF in US clinical practice face substantial residual risk of death and HF readmission and often accrue high health care costs.","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"74 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056843","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 : 2026-01-28DOI: 10.1001/jamacardio.2025.5305
Louisa A Mounsey,Mandana Chitsazan,Ivy Shi,Pedro H Ribeiro,Juhi K Parekh,Athar Roshandelpoor,Chiadi Ndumele,Norrina B Allen,Sadiya S Khan,Bruce M Psaty,James S Floyd,Daniel Levy,Rudolf A de Boer,Navin Suthahar,Kevin Damman,Michelle C Odden,Ron T Gansevoort,Kunihiro Matsushita,Carine Hamo,Issa J Dahabreh,Robert W Yeh,Mahnaz Maddah,Shaan Khurshid,Patrick T Ellinor,Emily S Lau,Dhruv S Kazi,Jennifer E Ho
ImportanceThe prevalence of obesity and cardiovascular-kidney-metabolic (CKM) syndrome continues to rise. Indications for novel CKM therapies, including glucagonlike peptide 1 receptor agonists (GLP-1RAs), sodium-glucose cotransporter-2 inhibitors (SGLT2is), and nonsteroidal mineralocorticoid antagonists (nsMRAs) continue to expand, yet the proportion of adults meeting expanded indications, including for multiple medications remains unclear.ObjectiveTo examine proportion of adults meeting US Food and Drug Administration (FDA)-approved indications for GLP1-RAs, SGLT2is, and nsMRAs across national survey, community-based, and ambulatory health care samples.Design, Setting, and ParticipantsThis study used a representative cross-sectional survey of US adults (National Health and Nutrition Examination Survey [NHANES], weighted 245 million; mean [SD] age, 47 [18] years; 126.8 million [52%] female), 5 pooled community-based cohort studies (the Framingham Heart Study, the Multi-Ethnic Study of Atherosclerosis, the Prevention of Renal and Vascular Endstage Disease Study, the Atherosclerosis Risk in Communities Study, and the Cardiovascular Health Study; n = 30 929; mean [SD] age, 63 [14] years; 16 749 [54%] female), and 2 ambulatory health care samples (the Beth Israel Deaconess Medical Center cohort [BIDMC], n = 84 714; mean [SD] age, 46 [17] years; 51 113 [60%] female] and the Mass General Brigham cohort [MGB], n = 362 485; mean [SD] age, 48 [17] years; 227 206 [61%] female). Data were analyzed from November 2024 to November 2025.ExposuresFDA-approved indications for GLP-1RAs, SGLT2is, and nsMRAs.Main Outcomes and MeasuresMedication class eligibility within each study sample.ResultsThe proportion of individuals who met current FDA-approved indications for 1 or more CKM medication was 60% in NHANES (representing 148 million US adults), 61% in the pooled cohorts, 42% in the BIDMC ambulatory cohort, and 46% in the MGB ambulatory cohort. Eligibility for GLP-1RA therapy was most common, with 56% (representing 137.1 million US adults) in NHANES, 49% in the pooled cohorts, 41% in the BIDMC cohort, and 46% in the MGB cohort. This was followed by SGLT2i therapy (24% [57.9 million] in NHANES, 33% in the pooled cohorts, 14% for both BIDMC and MGB) and nsMRA (5% [11.7 million] in NHANES, 5% in the pooled cohorts, and 1% to 2% in ambulatory samples). Overlapping eligibility for multiple classes was common, with 12% to 17% for GLP1-RA and SGLT2i therapies and 1% to 5% for all 3 classes (an estimated 11.7 million US adults in NHANES).Conclusions and RelevanceThis study found that up to 61% of adults met FDA-approved indications for at least 1 of 3 novel CKM therapy classes. This represents an estimated 148 million US adults, including 11.7 million US adults with potential FDA indications for triple therapy, highlighting the urgent need to optimize implementation and utilization of CKM syndrome therapies.
肥胖症和心血管肾代谢综合征（CKM）的患病率持续上升。新型CKM治疗的适应症，包括胰高血糖素样肽1受体激动剂（GLP-1RAs）、钠-葡萄糖共转运蛋白-2抑制剂（SGLT2is）和非甾体矿皮质激素拮抗剂（nsMRAs）继续扩大，但符合扩大适应症的成人比例，包括多种药物治疗仍不清楚。目的研究在全国调查、社区调查和门诊医疗样本中，符合美国食品和药物管理局（FDA）批准的GLP1-RAs、SGLT2is和nsra适应症的成年人比例。设计、环境和参与者本研究采用了一项具有代表性的美国成年人横断面调查（全国健康与营养调查[NHANES]，加权2.45亿；平均年龄[SD] 47岁；1.268亿[52%]女性），5项基于社区的队列研究(弗雷明汉心脏研究、多种族动脉粥样硬化研究、肾脏和血管终末期疾病预防研究、社区动脉粥样硬化风险研究和心血管健康研究；n = 30 929；平均[SD]年龄63岁；16例 749例[54%]女性)和2例门诊医疗样本（Beth Israel Deaconess Medical Center队列[BIDMC]， n = 84 714；平均[SD]年龄46亿岁；51例 113例[60%]女性]和麻省总医院Brigham队列[MGB]， n = 362 485；平均[SD]年龄48亿岁；227 206例[61%]女性）。数据分析时间为2024年11月至2025年11月。fda批准GLP-1RAs、SGLT2is和nsra的适应症。主要结果和测量方法每个研究样本的药物类别合格性。结果符合目前fda批准的1种或1种以上CKM药物适应症的个体比例在NHANES中为60%（代表1.48亿美国成年人），在合并队列中为61%，在BIDMC流动队列中为42%，在MGB流动队列中为46%。GLP-1RA治疗的资格是最常见的，在NHANES中有56%（代表1.371亿美国成年人），在合并队列中有49%，在BIDMC队列中有41%，在MGB队列中有46%。其次是SGLT2i治疗（在NHANES中占24%[5790万]，在合并队列中占33%，在BIDMC和MGB中占14%）和nsMRA（在NHANES中占5%[1170万]，在合并队列中占5%，在流动样本中占1%至2%）。多个类别的重叠资格很常见，GLP1-RA和SGLT2i治疗的重叠资格为12%至17%，所有3个类别的重叠资格为1%至5% （NHANES估计有1170万美国成年人）。结论和相关性本研究发现，高达61%的成年人符合fda批准的3种新型CKM治疗类别中至少1种的适应症。这意味着估计有1.48亿美国成年人，其中包括1170万美国成年人具有潜在的FDA三联疗法适应症，突出了优化CKM综合征治疗的实施和利用的迫切需要。
{"title":"Cardiovascular-Kidney-Metabolic Medication Eligibility Across National Survey, Community-Based, and Ambulatory Healthcare Samples.","authors":"Louisa A Mounsey,Mandana Chitsazan,Ivy Shi,Pedro H Ribeiro,Juhi K Parekh,Athar Roshandelpoor,Chiadi Ndumele,Norrina B Allen,Sadiya S Khan,Bruce M Psaty,James S Floyd,Daniel Levy,Rudolf A de Boer,Navin Suthahar,Kevin Damman,Michelle C Odden,Ron T Gansevoort,Kunihiro Matsushita,Carine Hamo,Issa J Dahabreh,Robert W Yeh,Mahnaz Maddah,Shaan Khurshid,Patrick T Ellinor,Emily S Lau,Dhruv S Kazi,Jennifer E Ho","doi":"10.1001/jamacardio.2025.5305","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.5305","url":null,"abstract":"ImportanceThe prevalence of obesity and cardiovascular-kidney-metabolic (CKM) syndrome continues to rise. Indications for novel CKM therapies, including glucagonlike peptide 1 receptor agonists (GLP-1RAs), sodium-glucose cotransporter-2 inhibitors (SGLT2is), and nonsteroidal mineralocorticoid antagonists (nsMRAs) continue to expand, yet the proportion of adults meeting expanded indications, including for multiple medications remains unclear.ObjectiveTo examine proportion of adults meeting US Food and Drug Administration (FDA)-approved indications for GLP1-RAs, SGLT2is, and nsMRAs across national survey, community-based, and ambulatory health care samples.Design, Setting, and ParticipantsThis study used a representative cross-sectional survey of US adults (National Health and Nutrition Examination Survey [NHANES], weighted 245 million; mean [SD] age, 47 [18] years; 126.8 million [52%] female), 5 pooled community-based cohort studies (the Framingham Heart Study, the Multi-Ethnic Study of Atherosclerosis, the Prevention of Renal and Vascular Endstage Disease Study, the Atherosclerosis Risk in Communities Study, and the Cardiovascular Health Study; n = 30 929; mean [SD] age, 63 [14] years; 16 749 [54%] female), and 2 ambulatory health care samples (the Beth Israel Deaconess Medical Center cohort [BIDMC], n = 84 714; mean [SD] age, 46 [17] years; 51 113 [60%] female] and the Mass General Brigham cohort [MGB], n = 362 485; mean [SD] age, 48 [17] years; 227 206 [61%] female). Data were analyzed from November 2024 to November 2025.ExposuresFDA-approved indications for GLP-1RAs, SGLT2is, and nsMRAs.Main Outcomes and MeasuresMedication class eligibility within each study sample.ResultsThe proportion of individuals who met current FDA-approved indications for 1 or more CKM medication was 60% in NHANES (representing 148 million US adults), 61% in the pooled cohorts, 42% in the BIDMC ambulatory cohort, and 46% in the MGB ambulatory cohort. Eligibility for GLP-1RA therapy was most common, with 56% (representing 137.1 million US adults) in NHANES, 49% in the pooled cohorts, 41% in the BIDMC cohort, and 46% in the MGB cohort. This was followed by SGLT2i therapy (24% [57.9 million] in NHANES, 33% in the pooled cohorts, 14% for both BIDMC and MGB) and nsMRA (5% [11.7 million] in NHANES, 5% in the pooled cohorts, and 1% to 2% in ambulatory samples). Overlapping eligibility for multiple classes was common, with 12% to 17% for GLP1-RA and SGLT2i therapies and 1% to 5% for all 3 classes (an estimated 11.7 million US adults in NHANES).Conclusions and RelevanceThis study found that up to 61% of adults met FDA-approved indications for at least 1 of 3 novel CKM therapy classes. This represents an estimated 148 million US adults, including 11.7 million US adults with potential FDA indications for triple therapy, highlighting the urgent need to optimize implementation and utilization of CKM syndrome therapies.","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"102 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056844","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 : 2026-01-28DOI: 10.1001/jamacardio.2025.5536
{"title":"Error in Abstract and Text.","authors":"","doi":"10.1001/jamacardio.2025.5536","DOIUrl":"10.1001/jamacardio.2025.5536","url":null,"abstract":"","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":" ","pages":""},"PeriodicalIF":14.1,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12853280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146063576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-21DOI: 10.1001/jamacardio.2025.5241
Robert O Bonow,Patrick T O'Gara
{"title":"Sex Differences in Left Ventricular Remodeling and Outcomes in Aortic Regurgitation.","authors":"Robert O Bonow,Patrick T O'Gara","doi":"10.1001/jamacardio.2025.5241","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.5241","url":null,"abstract":"","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"31 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005164","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 : 2026-01-21DOI: 10.1001/jamacardio.2025.5249
Pilar Lopez Santi,Federico Fortuni,Jérémy Bernard,Camille Sarrazyn,Aileen P Chua,Steele C Butcher,Maria C Meucci,Jingnan Zhang,Roxana Enache,Edgar Tay,Alice Bergeron,Kai-Hang Yiu,Marie-Annick Clavel,Philippe Pibarot,Jeroen J Bax,Nina Ajmone Marsan
ImportanceLeft ventricular (LV) dilatation is an established prognosticator in aortic regurgitation (AR). Current guidelines recommend aortic valve surgery (AVS) using LV end-systolic diameter index (LVESDi) with a uniform threshold, irrespective of sex. While LV end-systolic volume index (LVESVi) may better characterize LV remodeling, it was only recently included in European guideline recommendations, with a threshold of 45 mL/m2 for both men and women.ObjectiveTo assess sex differences in LV remodeling using linear and volumetric dimensions and their association with outcomes in AR.Design, Setting, and ParticipantsThis was a multicenter cohort study of patients with moderate-severe AR and preserved LV ejection fraction (LVEF) between December 2003 and December 2022, with a median (IQR) follow-up of 7 (4-11) years. The study took place at 5 centers in the Netherlands, Singapore, Hong Kong, Canada, and Romania. Patients with at least moderate-severe AR and preserved LVEF (≥50%) were included. Those with symptoms, acute AR, significant other valvular disease, or prior valve surgery were excluded. Data were analyzed from January to November 2024.ExposureLV dilatation assessed by LVESDi and LVESVi.Main Outcomes and MeasuresAll-cause mortality during medical management and following AVS.ResultsA total of 808 patients (mean [SD] age, 56 [19] years; 488 men and 320 women) were included, 323 of whom underwent AVS. Mean (SD) baseline LVESDi did not differ between sexes (women: 20 [5] mm/m2 vs men: 20 [4] mm/m2; P = .77), whereas men had larger mean (SD) LVESVi (39 [16] mL/m2 vs 31 [15] mL/m2; P < .001). During follow-up under medical management, 74 patients died. Adjusted 6-year survival was lower in women (80% vs 89%; P = .001). Receiver operating characteristic curve analysis identified LVESDi 20 mm/m2 or greater for both sexes, LVESVi 40 mL/m2 or greater for women, and LVESVi 45 mL/m2 or greater for men as thresholds associated with mortality. These cutoffs were validated using age-adjusted cubic splines and remained associated with outcomes after multivariable adjustment, with a differential effect by sex for LVESVi but not for LVESDi. After AVS, survival did not differ by sex (85% women vs 89% men; P = .31). Only preoperative LVESVi was associated with mortality, with a significant sex interaction (HR, 1.03; 95% CI, 1.00-1.06; P = .04).Conclusions and RelevanceIn this study among individuals with moderate-severe AR, similar LVESDi thresholds (20 mm/m2) for both sexes, but lower than currently recommended by guidelines, were independently associated with mortality. In turn, LVESVi thresholds were 40 mL/m2 for women and 45 mL/m2 for men, suggesting the need for sex-specific cutoffs to improve risk stratification.
左室（LV）扩张是主动脉瓣反流（AR）的预后指标。目前的指南推荐主动脉瓣手术（AVS）使用具有统一阈值的左室收缩末期直径指数（LVESDi），而不考虑性别。虽然左室收缩末期容积指数（LVESVi）可以更好地表征左室重构，但直到最近才被纳入欧洲指南建议，男性和女性的阈值均为45 mL/m2。目的利用线性和体积尺寸评估左室重构的性别差异及其与AR结局的关系。设计、环境和参与者：这是一项多中心队列研究，研究对象为2003年12月至2022年12月期间中重度AR患者和保留左室射血分数（LVEF），中位（IQR）随访时间为7（4-11）年。这项研究在荷兰、新加坡、香港、加拿大和罗马尼亚的5个中心进行。包括至少有中重度AR和LVEF保存（≥50%）的患者。排除有症状、急性急性变应性鼻炎、显著其他瓣膜疾病或既往瓣膜手术的患者。数据分析时间为2024年1月至11月。通过LVESDi和LVESVi评估暴露。主要结局和测量方法：医疗管理期间和AVS后的全因死亡率。结果共纳入808例患者（平均[SD]年龄56岁，男性488例，女性320例），其中323例患者行AVS。平均（SD）基线LVESDi在性别之间没有差异(女性：20 [5]mm/m2 vs男性：20 [5]mm/m2； P =。77)，而男性的平均（SD） LVESVi更大（39 [15]mL/m2 vs 31 [15] mL/m2; P < 0.001）。在医疗管理的随访期间，74名患者死亡。女性的调整后6年生存率较低（80% vs 89%; P = 0.001）。受试者工作特征曲线分析确定，男女的LVESDi为20 mm/m2或更高，女性的LVESVi为40 mL/m2或更高，男性的LVESVi为45 mL/m2或更高，这是与死亡率相关的阈值。使用年龄调整三次样条验证了这些截断值，并且在多变量调整后仍然与结果相关，LVESVi的性别差异影响，而LVESDi则没有。AVS后，生存率无性别差异（85%女性vs 89%男性；P = 0.31）。只有术前LVESVi与死亡率相关，且存在显著的性别交互作用（HR, 1.03; 95% CI, 1.00-1.06; P = 0.04）。在本研究中，在中重度AR患者中，男女LVESDi阈值相似（20 mm/m2），但低于目前指南推荐值，与死亡率独立相关。反过来，LVESVi阈值女性为40 mL/m2，男性为45 mL/m2，这表明需要性别特异性的截止值来改善风险分层。
{"title":"Sex Differences in Left Ventricular Remodeling for Risk Stratification of Patients With Aortic Regurgitation.","authors":"Pilar Lopez Santi,Federico Fortuni,Jérémy Bernard,Camille Sarrazyn,Aileen P Chua,Steele C Butcher,Maria C Meucci,Jingnan Zhang,Roxana Enache,Edgar Tay,Alice Bergeron,Kai-Hang Yiu,Marie-Annick Clavel,Philippe Pibarot,Jeroen J Bax,Nina Ajmone Marsan","doi":"10.1001/jamacardio.2025.5249","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.5249","url":null,"abstract":"ImportanceLeft ventricular (LV) dilatation is an established prognosticator in aortic regurgitation (AR). Current guidelines recommend aortic valve surgery (AVS) using LV end-systolic diameter index (LVESDi) with a uniform threshold, irrespective of sex. While LV end-systolic volume index (LVESVi) may better characterize LV remodeling, it was only recently included in European guideline recommendations, with a threshold of 45 mL/m2 for both men and women.ObjectiveTo assess sex differences in LV remodeling using linear and volumetric dimensions and their association with outcomes in AR.Design, Setting, and ParticipantsThis was a multicenter cohort study of patients with moderate-severe AR and preserved LV ejection fraction (LVEF) between December 2003 and December 2022, with a median (IQR) follow-up of 7 (4-11) years. The study took place at 5 centers in the Netherlands, Singapore, Hong Kong, Canada, and Romania. Patients with at least moderate-severe AR and preserved LVEF (≥50%) were included. Those with symptoms, acute AR, significant other valvular disease, or prior valve surgery were excluded. Data were analyzed from January to November 2024.ExposureLV dilatation assessed by LVESDi and LVESVi.Main Outcomes and MeasuresAll-cause mortality during medical management and following AVS.ResultsA total of 808 patients (mean [SD] age, 56 [19] years; 488 men and 320 women) were included, 323 of whom underwent AVS. Mean (SD) baseline LVESDi did not differ between sexes (women: 20 [5] mm/m2 vs men: 20 [4] mm/m2; P = .77), whereas men had larger mean (SD) LVESVi (39 [16] mL/m2 vs 31 [15] mL/m2; P < .001). During follow-up under medical management, 74 patients died. Adjusted 6-year survival was lower in women (80% vs 89%; P = .001). Receiver operating characteristic curve analysis identified LVESDi 20 mm/m2 or greater for both sexes, LVESVi 40 mL/m2 or greater for women, and LVESVi 45 mL/m2 or greater for men as thresholds associated with mortality. These cutoffs were validated using age-adjusted cubic splines and remained associated with outcomes after multivariable adjustment, with a differential effect by sex for LVESVi but not for LVESDi. After AVS, survival did not differ by sex (85% women vs 89% men; P = .31). Only preoperative LVESVi was associated with mortality, with a significant sex interaction (HR, 1.03; 95% CI, 1.00-1.06; P = .04).Conclusions and RelevanceIn this study among individuals with moderate-severe AR, similar LVESDi thresholds (20 mm/m2) for both sexes, but lower than currently recommended by guidelines, were independently associated with mortality. In turn, LVESVi thresholds were 40 mL/m2 for women and 45 mL/m2 for men, suggesting the need for sex-specific cutoffs to improve risk stratification.","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"39 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005166","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 : 2026-01-21DOI: 10.1001/jamacardio.2025.5196
Ozan Unlu,David Zelle,Christopher P Cannon,Simin Lee,Marian McPartlin,Samantha Subramaniam,Michela Tucci,Michael Oates,Christian Figueroa,Hunter Nichols,Tabitha V Rutkowski,Alexander J Blood,Benjamin M Scirica,Naomi D L Fisher
ImportanceHome blood pressure monitoring (HBPM) is essential and universally recommended for hypertension management, but patterns of real-world patient engagement with HBPM have not been studied and remain largely unknown.ObjectiveTo evaluate patient engagement with HBPM in a remote hypertension management program.Design, Setting, and ParticipantsThis retrospective cohort study analyzing prospectively collected program data was conducted within a remote hypertension management program at a large academic health care system, Mass General Brigham, in Boston, Massachusetts. Data were collected from from September 2018 to June 2022. Adults with uncontrolled hypertension enrolled in the program were eligible for inclusion. Data analyses were conducted from February to April 2025.InterventionsPatients received free automated HBPM devices, education, and ongoing personalized support from health care navigators via telephone and messaging, with algorithm-guided medication titration.Main Outcomes and MeasuresThe primary outcome was engagement at baseline. Weekly HBPM frequency was categorized as no engagement (0 measurements), low engagement (1-11 measurements/week), intermediate engagement (12-23 measurements/week), and high engagement (24-28 measurements/week).ResultsA total of 3390 patients were enrolled in the remote hypertension program; median (IQR) patient age was 61 (52-69) years, with 1958 (57.8%) female patients. Mean (SD) systolic BP at baseline was 143 (13) mm Hg, and most patients had comorbidities, including 1369 patients (40.4%) with atherosclerotic cardiovascular disease and 996 (29.4%) with diabetes. At baseline, 1107 patients (32.7%) had no engagement, 484 (14.3%) had low engagement, 618 (18.2%) had intermediate engagement, and 1181 (34.8%) had high engagement.Conclusions and RelevanceIn this cohort study of a remote hypertension management program, patient engagement with HBPM was suboptimal despite free devices, education, and personalized support with a navigator. To support optimal HBPM, innovative methods of BP monitoring that are more convenient and less burdensome for patients may enhance engagement and improve hypertension management outcomes.
家庭血压监测（HBPM）是必不可少的，并且被普遍推荐用于高血压管理，但现实世界中患者参与HBPM的模式尚未研究，并且在很大程度上仍然未知。目的评估远程高血压管理项目中HBPM的患者参与情况。设计、环境和参与者本回顾性队列研究分析了前瞻性收集的项目数据，在马萨诸塞州波士顿的大型学术卫生保健系统Mass General Brigham的一个远程高血压管理项目中进行。数据收集时间为2018年9月至2022年6月。参加该项目的高血压未控制的成年人符合入选条件。数据分析时间为2025年2月至4月。干预措施：患者接受了免费的自动HBPM设备、教育和医疗导航员通过电话和短信提供的持续个性化支持，并使用算法指导的药物滴定。主要结果和测量主要结果是基线时的参与度。每周HBPM频率分为无参与度（0次测量）、低参与度（1-11次测量/周）、中等参与度（12-23次测量/周）和高参与度（24-28次测量/周）。结果远程高血压项目共纳入3390例患者；中位（IQR）患者年龄61岁（52 ~ 69岁），女性1958例（57.8%）。基线时平均收缩压（SD）为143 (13)mm Hg，大多数患者有合并症，其中1369例（40.4%）患有动脉粥样硬化性心血管疾病，996例（29.4%）患有糖尿病。基线时，1107例（32.7%）患者无敬业度，484例（14.3%）患者敬业度低，618例（18.2%）患者敬业度中等，1181例（34.8%）患者敬业度高。结论和相关性在这项远程高血压管理项目的队列研究中，尽管有免费设备、教育和导航个性化支持，但患者参与HBPM的效果并不理想。为了支持最佳HBPM，对患者来说更方便、负担更少的创新血压监测方法可能会提高患者的参与度并改善高血压管理结果。
{"title":"Patient Engagement With Home Blood Pressure Monitoring.","authors":"Ozan Unlu,David Zelle,Christopher P Cannon,Simin Lee,Marian McPartlin,Samantha Subramaniam,Michela Tucci,Michael Oates,Christian Figueroa,Hunter Nichols,Tabitha V Rutkowski,Alexander J Blood,Benjamin M Scirica,Naomi D L Fisher","doi":"10.1001/jamacardio.2025.5196","DOIUrl":"https://doi.org/10.1001/jamacardio.2025.5196","url":null,"abstract":"ImportanceHome blood pressure monitoring (HBPM) is essential and universally recommended for hypertension management, but patterns of real-world patient engagement with HBPM have not been studied and remain largely unknown.ObjectiveTo evaluate patient engagement with HBPM in a remote hypertension management program.Design, Setting, and ParticipantsThis retrospective cohort study analyzing prospectively collected program data was conducted within a remote hypertension management program at a large academic health care system, Mass General Brigham, in Boston, Massachusetts. Data were collected from from September 2018 to June 2022. Adults with uncontrolled hypertension enrolled in the program were eligible for inclusion. Data analyses were conducted from February to April 2025.InterventionsPatients received free automated HBPM devices, education, and ongoing personalized support from health care navigators via telephone and messaging, with algorithm-guided medication titration.Main Outcomes and MeasuresThe primary outcome was engagement at baseline. Weekly HBPM frequency was categorized as no engagement (0 measurements), low engagement (1-11 measurements/week), intermediate engagement (12-23 measurements/week), and high engagement (24-28 measurements/week).ResultsA total of 3390 patients were enrolled in the remote hypertension program; median (IQR) patient age was 61 (52-69) years, with 1958 (57.8%) female patients. Mean (SD) systolic BP at baseline was 143 (13) mm Hg, and most patients had comorbidities, including 1369 patients (40.4%) with atherosclerotic cardiovascular disease and 996 (29.4%) with diabetes. At baseline, 1107 patients (32.7%) had no engagement, 484 (14.3%) had low engagement, 618 (18.2%) had intermediate engagement, and 1181 (34.8%) had high engagement.Conclusions and RelevanceIn this cohort study of a remote hypertension management program, patient engagement with HBPM was suboptimal despite free devices, education, and personalized support with a navigator. To support optimal HBPM, innovative methods of BP monitoring that are more convenient and less burdensome for patients may enhance engagement and improve hypertension management outcomes.","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"3 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005230","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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