Pub Date : 2026-03-11DOI: 10.1001/jamacardio.2026.0101
André Zimerman,Alexander Dal Forno,Luis E Rohde,Caique M Ternes,Fernanda D Alves,Lucas P Damiani,Martino Martinelli-Filho,Roberto Costa,Alexsandro A Fagundes,Rodrigo M Barbosa,Eduardo B Gadelha,Carlos Eduardo Lima,Márcio A Silva,Jaime A Maldonado,Julio César de Oliveira,Fabricio Mallmann,José M Baggio Júnior,Carlos E Duarte,Liliane A de Souza,Juliana S Santos,Anderson D Silveira,Sérgio R R Decker,Leandro I Zimerman,Carisi A Polanczyk,André d'Avila
ImportanceConduction system pacing (CSP) is a promising and potentially cost-effective alternative to biventricular pacing (BiVP) in patients with heart failure with reduced ejection fraction (HFrEF) and left bundle-branch block (LBBB), but its impact on heart failure (HF) outcomes remains uncertain.ObjectiveTo compare CSP vs BiVP on an HF-related outcome in patients with HFrEF and LBBB.Design, Setting, and ParticipantsPhysioSync-HF (Conduction System Pacing Versus Biventricular Resynchronization in Patients With Chronic Heart Failure) was an investigator-initiated, multicenter, noninferiority randomized clinical trial enrolling participants from November 2022 to December 2023 with 12 months of follow-up at 14 hospitals across all regions of Brazil. Adults with symptomatic HFrEF (New York Heart Association NYHA] classes II through III), left ventricular ejection fraction (LVEF) of 35% or less, and LBBB (QRS duration ≥130 milliseconds) were eligible for inclusion. Data were analyzed from May to August 2025.InterventionPatients were randomized 1:1 to either CSP (preferentially left bundle-branch area pacing) or BiVP.Main Outcomes and MeasuresThe primary outcome was a hierarchical composite of death, HF hospitalizations, urgent HF visits, and change in LVEF at 12 months. The prespecified noninferiority margin for the odds ratio (OR) was 1.2.ResultsA total of 173 patients (median [IQR] age, 62 years [56-68]; 86 female patients [49.7%]; 115 (66.5%) with dilated cardiomyopathy; median [IQR] LVEF, 26% [22%-31%]; median [IQR] QRS, 180 milliseconds [170-200]) were included. At 12 months, CSP failed to meet noninferiority and was inferior to BiVP for the primary end point (OR, 2.36; 95% CI, 1.37-4.06; P = .99 for noninferiority; P = .002 for between-group difference). The time-to-event composite of death, HF hospitalizations, or urgent HF visits was higher in CSP (hazard ratio, 2.35; 95% CI, 0.99-5.61). Mean (SD) LVEF increased to 35% (12%) with CSP and 39% (12%) with BiVP (mean difference, 3.8%; 95% CI, 0.3%-7.3%). Relative to baseline, both groups had comparable improvements in QRS duration, Kansas City Cardiomyopathy Questionnaire Overall Summary Score, NYHA class, and natriuretic peptide levels. Total direct medical cost related to the procedure and heart failure care was the equivalent of $7090 (95% CI, $5779-$8648) lower in patients randomized to CSP at 12 months.Conclusions and RelevanceIn patients with HFrEF and LBBB, CSP was inferior to BiVP for a composite of death, HF hospitalizations, urgent HF visits, and change in LVEF at 12 months. These findings do not support the routine use of CSP as the first-line resynchronization strategy in this population.Trial RegistrationClinicalTrials.gov Identifier: NCT05572736.
{"title":"Conduction System vs Biventricular Pacing in Heart Failure: The PhysioSync-HF Randomized Clinical Trial.","authors":"André Zimerman,Alexander Dal Forno,Luis E Rohde,Caique M Ternes,Fernanda D Alves,Lucas P Damiani,Martino Martinelli-Filho,Roberto Costa,Alexsandro A Fagundes,Rodrigo M Barbosa,Eduardo B Gadelha,Carlos Eduardo Lima,Márcio A Silva,Jaime A Maldonado,Julio César de Oliveira,Fabricio Mallmann,José M Baggio Júnior,Carlos E Duarte,Liliane A de Souza,Juliana S Santos,Anderson D Silveira,Sérgio R R Decker,Leandro I Zimerman,Carisi A Polanczyk,André d'Avila","doi":"10.1001/jamacardio.2026.0101","DOIUrl":"https://doi.org/10.1001/jamacardio.2026.0101","url":null,"abstract":"ImportanceConduction system pacing (CSP) is a promising and potentially cost-effective alternative to biventricular pacing (BiVP) in patients with heart failure with reduced ejection fraction (HFrEF) and left bundle-branch block (LBBB), but its impact on heart failure (HF) outcomes remains uncertain.ObjectiveTo compare CSP vs BiVP on an HF-related outcome in patients with HFrEF and LBBB.Design, Setting, and ParticipantsPhysioSync-HF (Conduction System Pacing Versus Biventricular Resynchronization in Patients With Chronic Heart Failure) was an investigator-initiated, multicenter, noninferiority randomized clinical trial enrolling participants from November 2022 to December 2023 with 12 months of follow-up at 14 hospitals across all regions of Brazil. Adults with symptomatic HFrEF (New York Heart Association NYHA] classes II through III), left ventricular ejection fraction (LVEF) of 35% or less, and LBBB (QRS duration ≥130 milliseconds) were eligible for inclusion. Data were analyzed from May to August 2025.InterventionPatients were randomized 1:1 to either CSP (preferentially left bundle-branch area pacing) or BiVP.Main Outcomes and MeasuresThe primary outcome was a hierarchical composite of death, HF hospitalizations, urgent HF visits, and change in LVEF at 12 months. The prespecified noninferiority margin for the odds ratio (OR) was 1.2.ResultsA total of 173 patients (median [IQR] age, 62 years [56-68]; 86 female patients [49.7%]; 115 (66.5%) with dilated cardiomyopathy; median [IQR] LVEF, 26% [22%-31%]; median [IQR] QRS, 180 milliseconds [170-200]) were included. At 12 months, CSP failed to meet noninferiority and was inferior to BiVP for the primary end point (OR, 2.36; 95% CI, 1.37-4.06; P = .99 for noninferiority; P = .002 for between-group difference). The time-to-event composite of death, HF hospitalizations, or urgent HF visits was higher in CSP (hazard ratio, 2.35; 95% CI, 0.99-5.61). Mean (SD) LVEF increased to 35% (12%) with CSP and 39% (12%) with BiVP (mean difference, 3.8%; 95% CI, 0.3%-7.3%). Relative to baseline, both groups had comparable improvements in QRS duration, Kansas City Cardiomyopathy Questionnaire Overall Summary Score, NYHA class, and natriuretic peptide levels. Total direct medical cost related to the procedure and heart failure care was the equivalent of $7090 (95% CI, $5779-$8648) lower in patients randomized to CSP at 12 months.Conclusions and RelevanceIn patients with HFrEF and LBBB, CSP was inferior to BiVP for a composite of death, HF hospitalizations, urgent HF visits, and change in LVEF at 12 months. These findings do not support the routine use of CSP as the first-line resynchronization strategy in this population.Trial RegistrationClinicalTrials.gov Identifier: NCT05572736.","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"45 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147383540","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 : 2026-03-11DOI: 10.1001/jamacardio.2026.0080
Colin A Raelson,Kristen K Patton,Jacob A Doll
{"title":"Alternative Certification Methods for Cardiac Proceduralists.","authors":"Colin A Raelson,Kristen K Patton,Jacob A Doll","doi":"10.1001/jamacardio.2026.0080","DOIUrl":"https://doi.org/10.1001/jamacardio.2026.0080","url":null,"abstract":"","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"226 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147383542","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 : 2026-03-11DOI: 10.1001/jamacardio.2026.0083
Xueying Chen,Xi Liu,Ruogu Li,Zhongkai Wang,Yixiu Liang,Lei Zhang,Wei Wang,Jin Bai,Jingfeng Wang,Shengmei Qin,Weiwei Zhang,Tianbao Yao,Dong Huang,Ting Chen,Xianxian Zhao,Dening Liao,Jingbo Li,Jialiang Mao,Mihail G Chelu,Yangang Su,Kenneth A Ellenbogen,Junbo Ge
ImportanceLeft bundle-branch pacing (LBBP) has been proposed as an alternative to biventricular pacing (BiVP) for patients with heart failure with left bundle-branch block (LBBB). However, robust clinical evidence from randomized clinical trials is lacking.ObjectiveTo evaluate the long-term clinical outcomes of LBBP and BiVP.Design, Setting, and ParticipantsThis multicenter, prospective, randomized clinical trial enrolled 200 patients at 6 centers in China with a left ventricular ejection fraction (LVEF) of 35% or less and LBBB from October 2020 to March 2022. This study was took place from October 2020 to September 2024. These data were analyzed September 2024 to December 2024.InterventionsPatients were randomly assigned in a 1:1 ratio to receive either LBBP or BiVP.Main Outcomes and MeasuresThe primary end point was the time to death from any cause or heart failure hospitalization (HFH). The secondary end points included all-cause death, HFH, echocardiographic response (absolute increase in LVEF ≥5%), and super response (absolute increase in LVEF ≥15% or improvement of LVEF to ≥50%) rates.ResultsOf the 200 included patients, 136 were male and 64 were female. The success rate was 98% in the LBBP group and 94% in the BiVP group (P = .28). The median follow-up duration was 36 (range, 33-39) months. The primary end point of time to death or HFH was significantly lower in the LBBP group compared with BiVP (8% vs 28%; hazard ratio [HR], 0.26; 95% CI, 0.12-0.57; P < .001). There was no significant difference in all-cause mortality between the groups (2.0% vs 5.0%; HR, 0.40; 95% CI, 0.08-2.04; P = .25). However, LBBP significantly reduced the risk of HFH (7.0% vs 28.0%; HR, 0.23; 95% CI, 0.10-0.52; P < .001). The echocardiographic response rates were similar in both groups (86.0% vs 81.0%; P = .34) but the super-response rate was higher in the LBBP group (55.0% vs 36.0%; P < .007).Conclusions and RelevanceIn this study, LBBP was superior to BiVP in reducing the risk of death or HFH in patients with LBBB and severely reduced LVEF. Further trials are warranted in this patient population.Trial RegistrationChinese Clinical Trial Registry identifier: ChiCTR2000036554.
左束支起搏（LBBP）已被提议作为双心室起搏（BiVP）的替代方案，用于左束支传导阻滞（LBBB）心力衰竭患者。然而，缺乏随机临床试验的有力临床证据。目的评价LBBP与BiVP的长期临床疗效。设计、环境和参与者这项多中心、前瞻性、随机临床试验从2020年10月至2022年3月在中国6个中心招募了200名左室射血分数（LVEF）为35%或更低、LBBB的患者。该研究于2020年10月至2024年9月进行。这些数据是在2024年9月至2024年12月期间进行分析的。患者按1:1的比例随机分配接受LBBP或BiVP治疗。主要结局和测量主要终点是任何原因导致的死亡时间或心力衰竭住院（HFH）。次要终点包括全因死亡、HFH、超声心动图反应（LVEF绝对增加≥5%）和超反应（LVEF绝对增加≥15%或LVEF改善至≥50%）率。结果200例患者中，男性136例，女性64例。LBBP组和BiVP组的成功率分别为98%和94% （P = 0.28）。中位随访时间为36个月（范围33-39）。与BiVP相比，LBBP组的主要死亡终点或HFH显著低于BiVP组（8% vs 28%；风险比[HR]， 0.26; 95% CI, 0.12-0.57; P < 0.001）。两组之间的全因死亡率无显著差异（2.0% vs 5.0%； HR, 0.40; 95% CI, 0.08-2.04; P = 0.25）。然而，LBBP显著降低HFH的风险（7.0% vs 28.0%； HR, 0.23; 95% CI, 0.10-0.52; P < 0.001）。两组超声心动图反应率相似(86.0% vs 81.0%; P =。（34）但LBBP组超有效率更高（55.0% vs 36.0%; P < .007）。结论和相关性在本研究中，LBBP在降低LBBB和LVEF严重降低患者的死亡或HFH风险方面优于BiVP。在该患者群体中需要进一步的试验。中国临床试验注册号：ChiCTR2000036554。
{"title":"Long-Term Outcomes of Left Bundle-Branch Pacing vs Biventricular Pacing in Heart Failure: The HeartSync-LBBP Randomized Clinical Trial.","authors":"Xueying Chen,Xi Liu,Ruogu Li,Zhongkai Wang,Yixiu Liang,Lei Zhang,Wei Wang,Jin Bai,Jingfeng Wang,Shengmei Qin,Weiwei Zhang,Tianbao Yao,Dong Huang,Ting Chen,Xianxian Zhao,Dening Liao,Jingbo Li,Jialiang Mao,Mihail G Chelu,Yangang Su,Kenneth A Ellenbogen,Junbo Ge","doi":"10.1001/jamacardio.2026.0083","DOIUrl":"https://doi.org/10.1001/jamacardio.2026.0083","url":null,"abstract":"ImportanceLeft bundle-branch pacing (LBBP) has been proposed as an alternative to biventricular pacing (BiVP) for patients with heart failure with left bundle-branch block (LBBB). However, robust clinical evidence from randomized clinical trials is lacking.ObjectiveTo evaluate the long-term clinical outcomes of LBBP and BiVP.Design, Setting, and ParticipantsThis multicenter, prospective, randomized clinical trial enrolled 200 patients at 6 centers in China with a left ventricular ejection fraction (LVEF) of 35% or less and LBBB from October 2020 to March 2022. This study was took place from October 2020 to September 2024. These data were analyzed September 2024 to December 2024.InterventionsPatients were randomly assigned in a 1:1 ratio to receive either LBBP or BiVP.Main Outcomes and MeasuresThe primary end point was the time to death from any cause or heart failure hospitalization (HFH). The secondary end points included all-cause death, HFH, echocardiographic response (absolute increase in LVEF ≥5%), and super response (absolute increase in LVEF ≥15% or improvement of LVEF to ≥50%) rates.ResultsOf the 200 included patients, 136 were male and 64 were female. The success rate was 98% in the LBBP group and 94% in the BiVP group (P = .28). The median follow-up duration was 36 (range, 33-39) months. The primary end point of time to death or HFH was significantly lower in the LBBP group compared with BiVP (8% vs 28%; hazard ratio [HR], 0.26; 95% CI, 0.12-0.57; P < .001). There was no significant difference in all-cause mortality between the groups (2.0% vs 5.0%; HR, 0.40; 95% CI, 0.08-2.04; P = .25). However, LBBP significantly reduced the risk of HFH (7.0% vs 28.0%; HR, 0.23; 95% CI, 0.10-0.52; P < .001). The echocardiographic response rates were similar in both groups (86.0% vs 81.0%; P = .34) but the super-response rate was higher in the LBBP group (55.0% vs 36.0%; P < .007).Conclusions and RelevanceIn this study, LBBP was superior to BiVP in reducing the risk of death or HFH in patients with LBBB and severely reduced LVEF. Further trials are warranted in this patient population.Trial RegistrationChinese Clinical Trial Registry identifier: ChiCTR2000036554.","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"5 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147383539","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 : 2026-03-04DOI: 10.1001/jamacardio.2026.0068
Mats C H Lassen,John W Ostrominski,Brian L Claggett,Magnus O Wijkman,Justin Lee,Jeremy R Van't Hof,Amil M Shah,Tor Biering-Sørensen,Scott D Solomon,Jenifer M Brown,Muthiah Vaduganathan
ImportanceMounting evidence suggests that renin-independent aldosteronism is common and often underrecognized. Yet, whether aldosteronism across this broader spectrum is associated with incident cardiovascular disease (CVD) has not, to the authors' knowledge, been comprehensively evaluated.ObjectiveTo determine whether aldosterone measures are associated with incident CVD events in community-dwelling older adults.Design, Setting, and ParticipantsThis prospective cohort analysis included participants from the Atherosclerosis Risk in Communities (ARIC) study with serum aldosterone and renin levels measured in 2011 to 2013. Longitudinal analyses were conducted in March to September 2025 using Cox regression to assess associations between aldosterone parameters and incident CVD among participants free of heart failure (HF), myocardial infarction (MI), stroke, and potassium-sparing diuretic use at ARIC visit 5 (2011-2013).ExposuresSerum aldosterone level and aldosterone-renin ratio (ARR).Main Outcomes and MeasuresIncident HF hospitalization, atrial fibrillation (AF), ischemic stroke, MI, and a composite of these events plus all-cause death.ResultsAmong 3477 individuals free of baseline CVD (mean [SD] age, 74.8 [4.9] years; 2139 female [61.5%]), the median (IQR) aldosterone level was 5.1 (3.0-8.3) ng/dL (to convert to picomoles per liter, multiply by 27.74), renin activity was 0.78 (0.41-1.90) ng/mL per hour, and ARR was 5.9 (2.2-12.3) ng/dL per ng/mL/h. Over 9 years of follow-up, higher ARR was associated with the composite outcome (adjusted hazard ratio [aHR], 1.04; 95% CI, 1.01-1.08 per doubling), stroke (aHR, 1.13; 95% CI, 1.02-1.26), and AF (aHR, 1.10; 95% CI, 1.05-1.15) but not with incident HF hospitalization (aHR, 1.02; 95% CI, 0.96-1.07) or MI (aHR, 1.01; 95% CI, 0.92-1.12).Conclusions and RelevanceThe findings of this cohort study underscore a spectrum of primary aldosteronism, in which higher ARR was independently associated with increased risks of AF and ischemic stroke among older adults, supporting the aldosterone pathway as a potential target for CVD prevention.
{"title":"Spectrum of Primary Aldosteronism and Risk of Cardiovascular Outcomes: The Atherosclerosis Risk in Communities Study.","authors":"Mats C H Lassen,John W Ostrominski,Brian L Claggett,Magnus O Wijkman,Justin Lee,Jeremy R Van't Hof,Amil M Shah,Tor Biering-Sørensen,Scott D Solomon,Jenifer M Brown,Muthiah Vaduganathan","doi":"10.1001/jamacardio.2026.0068","DOIUrl":"https://doi.org/10.1001/jamacardio.2026.0068","url":null,"abstract":"ImportanceMounting evidence suggests that renin-independent aldosteronism is common and often underrecognized. Yet, whether aldosteronism across this broader spectrum is associated with incident cardiovascular disease (CVD) has not, to the authors' knowledge, been comprehensively evaluated.ObjectiveTo determine whether aldosterone measures are associated with incident CVD events in community-dwelling older adults.Design, Setting, and ParticipantsThis prospective cohort analysis included participants from the Atherosclerosis Risk in Communities (ARIC) study with serum aldosterone and renin levels measured in 2011 to 2013. Longitudinal analyses were conducted in March to September 2025 using Cox regression to assess associations between aldosterone parameters and incident CVD among participants free of heart failure (HF), myocardial infarction (MI), stroke, and potassium-sparing diuretic use at ARIC visit 5 (2011-2013).ExposuresSerum aldosterone level and aldosterone-renin ratio (ARR).Main Outcomes and MeasuresIncident HF hospitalization, atrial fibrillation (AF), ischemic stroke, MI, and a composite of these events plus all-cause death.ResultsAmong 3477 individuals free of baseline CVD (mean [SD] age, 74.8 [4.9] years; 2139 female [61.5%]), the median (IQR) aldosterone level was 5.1 (3.0-8.3) ng/dL (to convert to picomoles per liter, multiply by 27.74), renin activity was 0.78 (0.41-1.90) ng/mL per hour, and ARR was 5.9 (2.2-12.3) ng/dL per ng/mL/h. Over 9 years of follow-up, higher ARR was associated with the composite outcome (adjusted hazard ratio [aHR], 1.04; 95% CI, 1.01-1.08 per doubling), stroke (aHR, 1.13; 95% CI, 1.02-1.26), and AF (aHR, 1.10; 95% CI, 1.05-1.15) but not with incident HF hospitalization (aHR, 1.02; 95% CI, 0.96-1.07) or MI (aHR, 1.01; 95% CI, 0.92-1.12).Conclusions and RelevanceThe findings of this cohort study underscore a spectrum of primary aldosteronism, in which higher ARR was independently associated with increased risks of AF and ischemic stroke among older adults, supporting the aldosterone pathway as a potential target for CVD prevention.","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"42 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147350283","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 : 2026-03-04DOI: 10.1001/jamacardio.2026.0017
Ashwin Bhaskaran, Karim Wahbi, Neal K Lakdawala
{"title":"Location of LMNA Variants and Clinical Outcomes in Cardiomyopathy-Reply.","authors":"Ashwin Bhaskaran, Karim Wahbi, Neal K Lakdawala","doi":"10.1001/jamacardio.2026.0017","DOIUrl":"https://doi.org/10.1001/jamacardio.2026.0017","url":null,"abstract":"","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":" ","pages":""},"PeriodicalIF":14.1,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147354957","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}
ImportanceFamilial hypercholesterolemia (FH) is a common genetic condition that causes hypercholesterolemia and increased risk for premature atherosclerotic cardiovascular disease (ASCVD). The prevalence, management, and consequences of genetically confirmed FH across the US are poorly understood.ObjectiveTo identify genotype-positive FH in a national US cohort and describe its prevalence, consequences, and lipid-lowering management.Design, Setting, and ParticipantsIn the All of Us (AoU) cohort study, whole-genome sequencing and phenotypic data from US adult participants enrolled between May 2018 and July 2022 were analyzed to identify and study genotype-positive FH. Data were analyzed between May 2024 and May 2025.ExposureFH variants (pathogenic or likely pathogenic) in LDLR, APOB, and PCSK9 genes were manually classified with standard criteria.Main Outcomes and MeasuresThe primary outcomes were demographic characteristics, lipid measurements, ASCVD, and prevalence of FH and noncarriers in AoU. Lipid management was then characterized among individuals with FH through lipid-lowering therapy (LLT) documentation and guideline-based low-density lipoprotein cholesterol (LDL-C) targets.ResultsA total of 245 388 participants were included, with mean (SD) age of 56.5 (16.9) years and 145 563 female participants (59.3%). Genotype-positive FH was identified in 865 participants (prevalence, 0.35%; 95% CI, 0.33%-0.38%; 1 in 287 participants). Among individuals with genotype-positive FH, 349 (40%) were prescribed statins, and 332 (38.4%) had LDL-C measured. Coronary artery disease, peripheral artery disease, and transient ischemic attack or stroke were significantly more common in genotype-positive FH carriers compared to noncarriers (coronary artery disease: odds ratio [OR], 2.91; 95% CI, 2.34-3.58; peripheral artery disease: OR, 1.51; 95% CI, 1.16-1.96; and transient ischemic attack or stroke: OR, 1.54; 95% CI, 1.11-2.09). Only 30.1% of participants positive for FH variants had LDL-C less than 100 mg/dL at their most recent result compared to 48.2% of noncarriers (P < .001). Of the total participants with ASCVD and LLT prescription, significantly fewer individuals with FH met the secondary prevention LDL-C target (<70 mg/dL; 19.33% vs 43.12%; P < .001) compared to noncarriers.Conclusions and RelevanceThis cohort study finds a prevalence of genotype-positive FH in All of Us participants of 0.35% (95% CI, 0.33%-0.38%), with state-level variation. A minority of individuals with genotype-positive FH met guideline-recommended LDL-C targets and had increased rates of ASCVD.
{"title":"Management and Consequences of Genotype-Positive Familial Hypercholesterolemia.","authors":"Catherine Spinks,Margaret Sunitha Selvaraj,Christopher Robinson,Gina M Peloso,Courtney Gwynne,Sarah Urbut,Buu Truong,Kaavya Paruchuri,Whitney Hornsby,Pradeep Natarajan","doi":"10.1001/jamacardio.2026.0006","DOIUrl":"https://doi.org/10.1001/jamacardio.2026.0006","url":null,"abstract":"ImportanceFamilial hypercholesterolemia (FH) is a common genetic condition that causes hypercholesterolemia and increased risk for premature atherosclerotic cardiovascular disease (ASCVD). The prevalence, management, and consequences of genetically confirmed FH across the US are poorly understood.ObjectiveTo identify genotype-positive FH in a national US cohort and describe its prevalence, consequences, and lipid-lowering management.Design, Setting, and ParticipantsIn the All of Us (AoU) cohort study, whole-genome sequencing and phenotypic data from US adult participants enrolled between May 2018 and July 2022 were analyzed to identify and study genotype-positive FH. Data were analyzed between May 2024 and May 2025.ExposureFH variants (pathogenic or likely pathogenic) in LDLR, APOB, and PCSK9 genes were manually classified with standard criteria.Main Outcomes and MeasuresThe primary outcomes were demographic characteristics, lipid measurements, ASCVD, and prevalence of FH and noncarriers in AoU. Lipid management was then characterized among individuals with FH through lipid-lowering therapy (LLT) documentation and guideline-based low-density lipoprotein cholesterol (LDL-C) targets.ResultsA total of 245 388 participants were included, with mean (SD) age of 56.5 (16.9) years and 145 563 female participants (59.3%). Genotype-positive FH was identified in 865 participants (prevalence, 0.35%; 95% CI, 0.33%-0.38%; 1 in 287 participants). Among individuals with genotype-positive FH, 349 (40%) were prescribed statins, and 332 (38.4%) had LDL-C measured. Coronary artery disease, peripheral artery disease, and transient ischemic attack or stroke were significantly more common in genotype-positive FH carriers compared to noncarriers (coronary artery disease: odds ratio [OR], 2.91; 95% CI, 2.34-3.58; peripheral artery disease: OR, 1.51; 95% CI, 1.16-1.96; and transient ischemic attack or stroke: OR, 1.54; 95% CI, 1.11-2.09). Only 30.1% of participants positive for FH variants had LDL-C less than 100 mg/dL at their most recent result compared to 48.2% of noncarriers (P < .001). Of the total participants with ASCVD and LLT prescription, significantly fewer individuals with FH met the secondary prevention LDL-C target (<70 mg/dL; 19.33% vs 43.12%; P < .001) compared to noncarriers.Conclusions and RelevanceThis cohort study finds a prevalence of genotype-positive FH in All of Us participants of 0.35% (95% CI, 0.33%-0.38%), with state-level variation. A minority of individuals with genotype-positive FH met guideline-recommended LDL-C targets and had increased rates of ASCVD.","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"15 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147350286","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 : 2026-03-04DOI: 10.1001/jamacardio.2026.0014
Matteo Castrichini,Michael J Ackerman,John R Giudicessi
{"title":"Location of LMNA Variants and Clinical Outcomes in Cardiomyopathy.","authors":"Matteo Castrichini,Michael J Ackerman,John R Giudicessi","doi":"10.1001/jamacardio.2026.0014","DOIUrl":"https://doi.org/10.1001/jamacardio.2026.0014","url":null,"abstract":"","PeriodicalId":14657,"journal":{"name":"JAMA cardiology","volume":"42 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147350287","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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