Circulation最新文献

{"title":"Letter by Kornelius Regarding Article, \"Cardiovascular Disease in Anabolic Androgenic Steroid Users\".","authors":"Edy Kornelius","doi":"10.1161/circulationaha.125.074873","DOIUrl":"https://doi.org/10.1161/circulationaha.125.074873","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"28 1","pages":"e295"},"PeriodicalIF":37.8,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145331701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypercontractility and Oxidative Stress Drive Creatine Kinase Dysfunction in Hypertrophic Cardiomyopathy.","authors":"Anton Xu,David Weissman,Katharina J Ermer,Edoardo Bertero,Jan M Federspiel,Felix Stadler,Elisa Grünler,Melina Tangos,Sevasti Zervou,Mark T Waddingham,James T Pearson,Jan-Christian Reil,Smita Scholtz,Jan Dudek,Michael Kohlhaas,Alexander G Nickel,Lucie Carrier,Thomas Eschenhagen,Michelle Michels,Cris Dos Remedios,Sean Lal,Leticia Prates Roma,Nazha Hamdani,Diederik Kuster,Inês Falcão-Pires,Christopher N Johnson,Craig A Lygate,Jolanda van der Velden,Christoph Maack,Vasco Sequeira","doi":"10.1161/circulationaha.125.074120","DOIUrl":"https://doi.org/10.1161/circulationaha.125.074120","url":null,"abstract":"BACKGROUNDHypertrophic cardiomyopathy (HCM) is a prevalent inherited cardiac disorder marked by left ventricular hypertrophy and hypercontractility. This excessive mechanical workload creates an energetic mismatch in which consumption exceeds production, leading to myocardial energy depletion. Although CK (creatine kinase) plays a key role in cardiac energy homeostasis, its involvement in HCM remains unclear. This study investigates how hypercontractility-driven mitochondrial stress and the resulting increase in mitochondrial H2O2 disrupt CK function in HCM.METHODSCK function was analyzed using myocardial left ventricular tissue from 92 patients with HCM (with and without pathogenic sarcomere variants) and 30 non-failing human controls. Myofilament and mitochondrial CK isoforms were measured using mRNA analysis, protein immunoblotting, enzyme activity assays, mass spectrometry, and redox-sensitive proteomics. To explore links between hypercontractility, mitochondrial reactive oxygen species, and CK dysfunction, we used isolated cardiomyocytes from wild-type, mitochondrion-targeted catalase-overexpressing, CK knockout (myofilament and mitochondrial CK deletion), HCM-associated Mybpc3 knockin, and mito-roGFP2-Orp1 mouse models. We also tested the effects of the Ca2+ sensitizer EMD-57033, the CK inhibitor 1-fluoro-2,4-dinitrobenzene, and the myosin inhibitor MYK-581, a mavacamten derivative.RESULTSOur analysis revealed significant reductions in myofilament and mitochondrial CK protein levels, as well as CK activity, in myocardium of patients with HCM, primarily because of oxidative modifications of CK. In isolated mouse cardiomyocytes from wild-type and CK knockouts, hypercontractility induced by EMD-57033 elevated mitochondrial H2O2, causing cellular arrhythmias and CK inactivation. Hypercontractility-induced oxidative stress, arrhythmias, and CK dysfunction were also observed in Mybpc3 knockin cardiomyocytes. Mitochondrion-targeted catalase-overexpressing mice with enhanced H2O2 scavenging were protected against H2O2-induced (EMD-57033-mediated) arrhythmias and CK dysfunction. MYK-581 treatment in Mybpc3 knockin cardiomyocytes reduced hypercontractility, lowered H2O2 production and arrhythmias, and preserved CK function. CK inhibition using 1-fluoro-2,4-dinitrobenzene in wild-type cardiomyocytes elevated mitochondrial H2O2 levels and triggered cellular arrhythmias. This mitochondrial oxidation was independently confirmed in mito-roGFP2-Orp1 cardiomyocytes exposed to 1-fluoro-2,4-dinitrobenzene. Mitochondrion-targeted catalase-overexpressing mice were protected from 1-fluoro-2,4-dinitrobenzene -induced oxidative stress and arrhythmogenic events.CONCLUSIONSThis study reveals a mechanistic link between hypercontractility, mitochondrial reactive oxygen species, and CK dysfunction in HCM, perpetuating a cycle of energetic dysfunction. Targeting hypercontractility and oxidative stress through myosin inhibition offers a strategy to restore energy balance","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"99 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response by Marcus to Letter Regarding Article, \"Left Ventricular Entry to Reduce Brain Lesions During Catheter Ablation: A Randomized Trial\".","authors":"Gregory M Marcus","doi":"10.1161/circulationaha.125.076073","DOIUrl":"https://doi.org/10.1161/circulationaha.125.076073","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"15 1","pages":"e294"},"PeriodicalIF":37.8,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145331699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clear as Mud: Determining the Stage of Prevention in Cardiovascular Disease.","authors":"Ayeeshik Kole,Parag H Joshi","doi":"10.1161/circulationaha.125.074099","DOIUrl":"https://doi.org/10.1161/circulationaha.125.074099","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"19 1","pages":"1123-1125"},"PeriodicalIF":37.8,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145331702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response by Windfeld-Mathiasen et al to Letter Regarding Article, \"Cardiovascular Disease in Anabolic Androgenic Steroid Users\".","authors":"Josefine Windfeld-Mathiasen,Ida M Heerfordt,Kim Peder Dalhoff,Jon Trærup Andersen,Michael Asger Andersen,Karl Sebastian Johansson,Tor Biering-Sørensen,Flemming Javier Olsen,Henrik Horwitz","doi":"10.1161/circulationaha.125.075941","DOIUrl":"https://doi.org/10.1161/circulationaha.125.075941","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"6 1","pages":"e296-e297"},"PeriodicalIF":37.8,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145332003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Opportunistic Detection of Coronary Artery Calcium on Noncardiac Chest Computed Tomography: An Emerging Tool for Cardiovascular Disease Prevention: A Scientific Statement From the American Heart Association.","authors":"Randi Foraker,Laurence Sperling,Lisa Bratzke,Matthew Budoff,Michelle Leppert,Alexander C Razavi,Fatima Rodriguez,Michael D Shapiro,Seamus Whelton,Nathan D Wong,Eugene Yang, ","doi":"10.1161/cir.0000000000001382","DOIUrl":"https://doi.org/10.1161/cir.0000000000001382","url":null,"abstract":"Coronary artery calcium (CAC) is a marker of subclinical atherosclerosis that confers increased risk of atherosclerotic cardiovascular disease. Measured by noncontrast cardiac computed tomography, CAC improves risk stratification beyond traditional risk factors and can aid decision-making for allocation of preventive treatments. Although national guidelines recommend consideration of CAC measurement for >17 million individuals in the United States with borderline to intermediate 10-year atherosclerotic cardiovascular disease risk, adoption has been limited. A promising approach to bridge this gap is opportunistic detection of CAC using non-ECG-gated chest computed tomography scans that are performed for a noncardiac indication. Approximately 19 million non-ECG-gated chest computed tomography scans are performed per year, and reporting opportunistic detection of CAC from these scans can enhance atherosclerotic cardiovascular disease risk stratification without additional radiation exposure, cost, or burden. Estimation of risk by traditional risk factor scoring is underused, and reporting of opportunistic detection of CAC has the potential to alert physicians of risk, independent of guideline-recommended risk calculator use. Advancements in artificial intelligence allow integration of automated CAC quantification into clinical practice. Several artificial intelligence algorithms are in use to improve the likelihood of reporting opportunistic detection of CAC and appropriate allocation of preventive therapies. Systematic approaches are needed to ensure appropriate reporting, interpretation, and action while avoiding unnecessary downstream testing. Implementation that includes tailored preventive care and streamlined care pathways involving multidisciplinary clinical teams including radiology, cardiology, and primary care is essential.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"104 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145296186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contemporary Burden of Cardiovascular Disease in Pregnancy: Insights From a Real-World Pregnancy Electronic Health Record Cohort.","authors":"Emily S Lau, Valentina D'Souza, Yunong Zhao, Christopher Reeder, Rachel Goldberg, Micayla Flores, Katherine E Economy, Mahnaz Maddah, Shaan Khurshid, Patrick T Ellinor, Jennifer E Ho","doi":"10.1161/CIRCULATIONAHA.125.074692","DOIUrl":"10.1161/CIRCULATIONAHA.125.074692","url":null,"abstract":"<p><strong>Background: </strong>Cardiac and vascular complications are the leading causes of maternal mortality and morbidity, but the contemporary burden of and secular trends in pregnancy-related cardiovascular complications are not well-characterized. We developed a multi-institutional electronic health record-based pregnancy cohort with rigorously defined cardiovascular outcomes to examine trends in prevalence of maternal cardiovascular comorbidities and cardiovascular disease (CVD) and incidence of pregnancy-related cardiovascular complications.</p><p><strong>Methods: </strong>We identified pregnancy encounters that occurred between 2001 and 2019 from a primary care electronic health record cohort using International Classification of Diseases and Current Procedural Terminology codes. We used regular expressions to recover estimated gestational age from unstructured notes and used gestational age to define the pregnancy episode for each individual pregnancy. Leveraging this cohort, we quantified and examined trends in the prevalence of maternal cardiovascular comorbidities and CVD and incidence of cardiovascular complications in pregnancies over the course of 19 years of follow-up. We also compared clinical factors for pregnancies with and those without cardiovascular complications.</p><p><strong>Results: </strong>Our pregnancy cohort comprised 56 833 pregnancies among 38 996 individuals (mean age at start of pregnancy, 32±5 years). Regular expressions recovered gestational age for 75% of pregnancies, with good correlation between gestational age ascertained by regular expressions versus manual review (Pearson <i>r</i>=0.9). Among 56 833 pregnancies, overall prevalence of maternal CVD was 4% (age-adjusted 8%) and increased over 19 years (age-adjusted prevalence 1% in 2001 and 7% in 2019; <i>P</i><0.001). Incidence of pregnancy-related cardiovascular complications was 15% (age-adjusted 17%) and increased over the study follow-up period (age-adjusted incidence 11% in 2001 and 13% in 2019; <i>P</i><0.001). Cardiovascular complications within 1 year postpartum were more frequent in individuals with greater burden of maternal cardiovascular comorbidities and CVD (diabetes, 6% versus 3%; hypertension, 23% versus 5%; CVD, 10% versus 3%; <i>P</i><0.001 for all).</p><p><strong>Conclusions: </strong>In a large-scale electronic health record-based pregnancy cohort, both the prevalence of maternal cardiovascular comorbidities and CVD as well as the incidence of pregnancy-related cardiovascular complications within 1 year postpartum increased over the course of 2 decades. Our findings demonstrate an alarming rise in pregnancy-related cardiovascular complications in a contemporary real-world setting and highlight pregnancy as a crucial life opportunity for cardiovascular health optimization.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1044-1055"},"PeriodicalIF":38.6,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter by Kornelius Regarding Article, \"Risk of Incident Atrial Fibrillation in Women With a History of Hypertensive Disorders of Pregnancy: A Population-Based Retrospective Cohort Study\".","authors":"Edy Kornelius","doi":"10.1161/CIRCULATIONAHA.125.074400","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.125.074400","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"152 15","pages":"e284"},"PeriodicalIF":38.6,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-Year Outcomes of Catheter Ablation in Patients With End-Stage Heart Failure and Atrial Fibrillation.","authors":"Christian Sohns, Maximilian Moersdorf, Nassir F Marrouche, Angelika Costard-Jaeckle, Harry J G M Crijns, Leonard Bergau, Henrik Fox, Gerhard Hindricks, Nikolaos Dagres, Samuel Sossalla, Rene Schramm, Thomas Fink, Mustapha El Hamriti, Vanessa Sciacca, Maxim Didenko, Frank Konietschke, Volker Rudolph, Jan Gummert, Jan G P Tijssen, Philipp Sommer","doi":"10.1161/CIRCULATIONAHA.125.075787","DOIUrl":"10.1161/CIRCULATIONAHA.125.075787","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1118-1121"},"PeriodicalIF":38.6,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redefining the Genetic Architecture of Hypertrophic Cardiomyopathy: Role of Intermediate-Effect Variants.","authors":"Soledad García Hernandez, Luis de la Higuera Romero, Adrian Fernandez, Maria Luisa Peña Peña, Nerea Mora-Ayestaran, María Teresa Basurte-Elorz, Jose María Larrañaga-Moreira, Ivonne Cárdenas Reyes, Eduardo Villacorta, Maria Valverde-Gómez, Alicia Baustista-Paves, Elena Veira Villanueva, Martín Ortiz-Genga, Alex Lipov, Noel Brogger, María Sabater Molina, Eduardo Moreno-Escobar, Luis Ruiz-Guerrero, Petros Syrris, Xusto Fernández, Jesús Piqueras-Flores, Almudena Amor Salamanca, Connie R Bezzina, Perry M Elliott, Roberto Barriales-Villa, Juan Ramon Gimeno-Blanes, Pablo García-Pavía, Roddy Walsh, Juan Pablo Ochoa","doi":"10.1161/CIRCULATIONAHA.125.074529","DOIUrl":"10.1161/CIRCULATIONAHA.125.074529","url":null,"abstract":"<p><strong>Background: </strong>Hypertrophic cardiomyopathy (HCM) is a genetically heterogeneous disorder linked primarily to rare variants in sarcomeric genes, although recently certain nonsarcomeric genes have emerged as important contributors. Nonmendelian genetic variants with reproducible moderate-effect sizes and low penetrance, intermediate-effect variants (IEVs), can play a crucial role in modulating disease expression. Understanding the clinical impact of IEVs is crucial to unravel the complex genetic architecture of HCM.</p><p><strong>Methods: </strong>We conducted an ancestry-based enrichment analysis of 14 validated HCM genes, including the 9 core sarcomeric and 5 nonsarcomeric genes <i>(ALPK3</i>, <i>CSRP3</i>, <i>FHOD3</i>, <i>FLNC</i>, and <i>TRIM63</i>). Enrichment of intermediate frequency missense variants was evaluated in 10 981 patients with HCM, 4030 internal controls of European-ancestry, and 590 000 external controls from gnomAD non-Finnish Europeans. The population-attributable fraction was calculated to assess contribution of IEVs to HCM. Age-related disease penetrance, phenotypic severity (left ventricular maximum wall thickness), and major adverse cardiac events were analyzed in 11 991 HCM cases of the whole cohort according to 5 genetic groups: genotype negative, isolated IEV, monogenic, monogenic+IEV, and double monogenic.</p><p><strong>Results: </strong>Fourteen IEVs in 8 genes were identified in 731 individuals (6.1% of the cohort), of whom 570 patients (4.8%) had IEVs in isolation: 198 (34.7%) in sarcomeric genes and 372 (65.3%) in nonsarcomeric genes. The contribution of IEVs to HCM genetics according to population-attributable fraction was estimated to be 4.9% (95% CI, 3.2-6.7). A significant gradient in penetrance, phenotypic severity, and major adverse cardiac events was observed across genetic groups. Compared with genotype-negative patients, IEV carriers displayed a younger median age at diagnosis (59 years of age [95% CI, 46-69] versus 61 years [95% CI, 49-70]; <i>P</i>=0.0073) and a higher mean left ventricular maximum wall thickness (18.1±3.7 versus 19.0±4.3; <i>P</i>=0.0043). IEVs also modified disease expression in individuals with monogenic variants, causing a more aggressive phenotype than in individuals from the monogenic-only group with HCM onset at younger age and a higher left ventricular maximum wall thickness (all <i>P</i><0.0001), with major adverse cardiac event-free survival being significantly lower (93.3% versus 69.3% at 70 years of age; <i>P</i><0.0001).</p><p><strong>Conclusions: </strong>IEVs are present in 6.1% of HCM cases and account for 4.8% of HCM genetic burden. IEVs also influence disease severity and outcomes, particularly when combined with monogenic disease-causing variants. Evaluation of IEVs should be considered when HCM genetic testing is performed.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1060-1075"},"PeriodicalIF":38.6,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12513046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945250","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}