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Clinical Considerations for Competitive Sports Participation for Athletes With Cardiovascular Abnormalities: A Scientific Statement From the American Heart Association and American College of Cardiology.
IF 35.5 1区 医学
Circulation Pub Date : 2025-03-18 Epub Date: 2025-02-20 DOI: 10.1161/CIR.0000000000001297
Jonathan H Kim, Aaron L Baggish, Benjamin D Levine, Michael J Ackerman, Sharlene M Day, Elizabeth H Dineen, J Sawalla Guseh, Andre La Gerche, Rachel Lampert, Matthew W Martinez, Michael Papadakis, Dermot M Phelan, Keri M Shafer
{"title":"Clinical Considerations for Competitive Sports Participation for Athletes With Cardiovascular Abnormalities: A Scientific Statement From the American Heart Association and American College of Cardiology.","authors":"Jonathan H Kim, Aaron L Baggish, Benjamin D Levine, Michael J Ackerman, Sharlene M Day, Elizabeth H Dineen, J Sawalla Guseh, Andre La Gerche, Rachel Lampert, Matthew W Martinez, Michael Papadakis, Dermot M Phelan, Keri M Shafer","doi":"10.1161/CIR.0000000000001297","DOIUrl":"10.1161/CIR.0000000000001297","url":null,"abstract":"<p><strong>Collaborators: </strong>Larry A. Allen, MD, MHS, FAHA, FACC; Mats Börjesson, MD, PhD, FACC; Alan C. Braverman, MD, FACC; Julie A. Brothers, MD; Silvia Castelletti, MD, MSc, FESC; Eugene H. Chung, MD, MPH, FHRS, FAHA, FACC; Timothy W. Churchill, MD, FACC; Guido Claessen, MD, PhD; Flavio D'Ascenzi, MD, PhD; Douglas Darden, MD; Peter N. Dean, MD, FACC; Neal W. Dickert, MD, PhD, FACC; Jonathan A. Drezner, MD; Katherine E. Economy, MD, MPH; Thijs M.H. Eijsvogels, PhD; Michael S. Emery, MD, MS, FACC; Susan P. Etheridge, MD, FHRS, FAHA, FACC; Sabiha Gati, BSc (Hons), MBBS, PhD, MRCP, FESC; Belinda Gray, BSc (Med), MBBS, PhD; Martin Halle, MD; Kimberly G. Harmon, MD; Jeffrey J. Hsu, MD, PhD, FAHA, FACC; Richard J. Kovacs, MD, FAHA, MACC; Sheela Krishnan, MD, FACC; Mark S. Link, MD, FHRS, FAHA, FACC; Martin Maron, MD; Silvana Molossi, MD, PhD, FACC; Antonio Pelliccia, MD; Jack C. Salerno, MD, FACC, FHRS; Ankit B. Shah, MD, MPH, FACC; Sanjay Sharma, BSc (Hons), MBChB, MRCP (UK), MD; Tamanna K. Singh, MD, FACC; Katie M. Stewart, NP, MS; Paul D. Thompson, MD, FAHA, FACC; Meagan M. Wasfy, MD, MPH, FACC; Matthias Wilhelm, MD.</p><p><p>This American Heart Association/American College of Cardiology scientific statement on clinical considerations for competitive sports participation for athletes with cardiovascular abnormalities or diseases is organized into 11 distinct sections focused on sports-specific topics or disease processes that are relevant when considering the potential risks of adverse cardiovascular events, including sudden cardiac arrest, during competitive sports participation. Task forces comprising international experts in sports cardiology and the respective topics covered were assigned to each section and prepared specific clinical considerations tables for practitioners to reference. Comprehensive literature review and an emphasis on shared decision-making were integral in the writing of all clinical considerations presented.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"e716-e761"},"PeriodicalIF":35.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457096","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}
引用次数: 0
Atrial Translocation of Porphyromonas gingivalis Exacerbates Atrial Fibrosis and Atrial Fibrillation.
IF 35.5 1区 医学
Circulation Pub Date : 2025-03-18 DOI: 10.1161/CIRCULATIONAHA.124.071310
Shunsuke Miyauchi, Miki Kawada-Matsuo, Hisako Furusho, Hiromi Nishi, Ayako Nakajima, Pham Trong Phat, Fumie Shiba, Masae Kitagawa, Kazuhisa Ouhara, Noboru Oda, Takehito Tokuyama, Yousaku Okubo, Sho Okamura, Taiichi Takasaki, Shinya Takahashi, Toru Hiyama, Hiroyuki Kawaguchi, Hitoshi Komatsuzawa, Mutsumi Miyauchi, Yukiko Nakano
{"title":"Atrial Translocation of <i>Porphyromonas gingivalis</i> Exacerbates Atrial Fibrosis and Atrial Fibrillation.","authors":"Shunsuke Miyauchi, Miki Kawada-Matsuo, Hisako Furusho, Hiromi Nishi, Ayako Nakajima, Pham Trong Phat, Fumie Shiba, Masae Kitagawa, Kazuhisa Ouhara, Noboru Oda, Takehito Tokuyama, Yousaku Okubo, Sho Okamura, Taiichi Takasaki, Shinya Takahashi, Toru Hiyama, Hiroyuki Kawaguchi, Hitoshi Komatsuzawa, Mutsumi Miyauchi, Yukiko Nakano","doi":"10.1161/CIRCULATIONAHA.124.071310","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.071310","url":null,"abstract":"<p><strong>Background: </strong>Recent studies have indicated an association between periodontitis and atrial fibrillation (AF), although the underlying mechanisms remain unclear. <i>Porphyromonas gingivalis</i> is a causative agent of periodontal disease and is highly pathogenic. This study focused on <i>P gingivalis</i> and aimed to investigate the relationship among periodontitis, atrial translocation of <i>P</i> <i>gingivalis</i>, and atrial fibrosis and AF.</p><p><strong>Methods: </strong>An experiment was conducted using <i>P</i> <i>gingivalis</i>-infected C57BL/6J mice, in which <i>P</i> <i>gingivalis</i> was inoculated into the pulp of the molars. Immunohistochemistry was used to visualize the localization of <i>P</i> <i>gingivalis</i>, and loop-mediated isothermal amplification was employed to detect <i>P</i> <i>gingivalis</i> DNA in the left atrium. AF inducibility was examined by intracardiac stimulation. Moreover, left atrial appendage specimens were obtained from 68 patients with AF. A periodontal examination was conducted before the surgery, and the periodontal epithelial surface area and periodontal inflamed surface area, which are quantitative indices used to determine the clinical severity of periodontitis, were measured. The bacterial number of <i>P</i> <i>gingivalis</i> in human atrial tissue was analyzed via quantitative polymerase chain reaction. Atrial fibrosis was assessed using Azan-Mallory staining.</p><p><strong>Results: </strong>The translocation path of <i>P</i> <i>gingivalis</i> from the dental granuloma to the left atrium via the circulatory system was demonstrated by immunohistochemistry and loop-mediated isothermal amplification in <i>P</i> <i>gingivalis</i>-infected mice, which showed a higher degree of atrial fibrosis (21.9% versus 16.3%; <i>P</i>=0.0003) and a higher AF inducibility (30.0% versus 5.0%; <i>P</i>=0.04) than the control mice. Upregulation of GAL3 (galectin 3) and transforming growth factor-beta 1 in the left atrium was observed in <i>P</i> <i>gingivalis</i>-infected mice. Moreover, immunohistochemistry revealed that <i>P</i> <i>gingivalis</i> was also present in human atrial tissue. The number of <i>P</i> <i>gingivalis</i> in the human atrial tissue was positively correlated with periodontal epithelial surface area (ρ=0.35; <i>P</i>=0.004), periodontal inflamed surface area (ρ=0.52, <i>P</i><0.0001), and the degree of atrial fibrosis (ρ=0.38; <i>P</i>=0.002).</p><p><strong>Conclusions: </strong><i>P</i> <i>gingivalis</i> translocation to the left atrium correlates with the clinical severity of periodontitis, which may exacerbate atrial fibrosis and AF. Atrial translocation of <i>P</i> <i>gingivalis</i> is a potential pathway explaining the causal relationship between periodontitis and AF.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":35.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647520","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}
引用次数: 0
Covered Stent Correction for Sinus Venosus Atrial Septal Defects, an Emerging Alternative to Surgical Repair: Results of an International Registry. 静脉窦房间隔缺损的覆膜支架矫正,外科手术修复的新选择:国际注册的结果。
IF 35.5 1区 医学
Circulation Pub Date : 2025-03-18 Epub Date: 2024-12-19 DOI: 10.1161/CIRCULATIONAHA.124.070271
Eric Rosenthal, Shakeel A Qureshi, Kothandam Sivakumar, Matthew Jones, San-Fui Yong, Saleha Kabir, Pramod Sagar, Puthiyedath Thejaswi, Sebastien Hascoet, Clement Batteux, Younes Boudjemline, Ziyad M Hijazi, Jamil A Aboulhosn, Daniel S Levi, Morris M Salem, Edwin Francis, Aleksander Kempny, Alain Fraisse, Carles Bautista-Rodriguez, Kevin Walsh, Damien Kenny, Brian Traynor, Salim N Al Maskari, James R Bentham, László Környei, Muthukumaran C Sivaprakasam, Ata Firouzi, Zahra Khajali, Lee Benson, Mark Osten, Alban-Elouen Baruteau, Matthew A Crystal, Thomas J Forbes, Stanimir Georgiev, Horst Sievert, Do Nguyen Tin, Daniel Springmuller, Anand Subramanian, Hussein A M Abdullah, Radwa Bedair, Francisco Chamié, Ahmet Celebi, Jesus Damsky Barbosa, Pieter De Meester, Luca Giugno, Zakaria Jalal, Clement Karsenty, Anastasia Schleiger, Gregory Fleming, Andre Jakob, Tevfik Karagoaz, Gur Mainzer, Gareth J Morgan, Nazmi Narin, Shabana Shahanavaz, Zachary L Steinberg, Osamah Aldoss, Elnur Alizade, Oliver Aregullin, Hélène Bouvaist, Thilo Fleck, Francois Godart, Sophie Malekzadeh-Milani, Paulo Motta, Angel Sanchez-Recalde, Juan Pablo Sandoval, Weiyi Tan, John Thomson, Pablo Tomé Teixeirense, Evan M Zahn
{"title":"Covered Stent Correction for Sinus Venosus Atrial Septal Defects, an Emerging Alternative to Surgical Repair: Results of an International Registry.","authors":"Eric Rosenthal, Shakeel A Qureshi, Kothandam Sivakumar, Matthew Jones, San-Fui Yong, Saleha Kabir, Pramod Sagar, Puthiyedath Thejaswi, Sebastien Hascoet, Clement Batteux, Younes Boudjemline, Ziyad M Hijazi, Jamil A Aboulhosn, Daniel S Levi, Morris M Salem, Edwin Francis, Aleksander Kempny, Alain Fraisse, Carles Bautista-Rodriguez, Kevin Walsh, Damien Kenny, Brian Traynor, Salim N Al Maskari, James R Bentham, László Környei, Muthukumaran C Sivaprakasam, Ata Firouzi, Zahra Khajali, Lee Benson, Mark Osten, Alban-Elouen Baruteau, Matthew A Crystal, Thomas J Forbes, Stanimir Georgiev, Horst Sievert, Do Nguyen Tin, Daniel Springmuller, Anand Subramanian, Hussein A M Abdullah, Radwa Bedair, Francisco Chamié, Ahmet Celebi, Jesus Damsky Barbosa, Pieter De Meester, Luca Giugno, Zakaria Jalal, Clement Karsenty, Anastasia Schleiger, Gregory Fleming, Andre Jakob, Tevfik Karagoaz, Gur Mainzer, Gareth J Morgan, Nazmi Narin, Shabana Shahanavaz, Zachary L Steinberg, Osamah Aldoss, Elnur Alizade, Oliver Aregullin, Hélène Bouvaist, Thilo Fleck, Francois Godart, Sophie Malekzadeh-Milani, Paulo Motta, Angel Sanchez-Recalde, Juan Pablo Sandoval, Weiyi Tan, John Thomson, Pablo Tomé Teixeirense, Evan M Zahn","doi":"10.1161/CIRCULATIONAHA.124.070271","DOIUrl":"10.1161/CIRCULATIONAHA.124.070271","url":null,"abstract":"<p><strong>Background: </strong>Covered stent correction for a sinus venosus atrial septal defect (SVASD) was first performed in 2009. This innovative approach was initially viewed as experimental and was reserved for highly selected patients with unusual anatomic variants. In 2016, increasing numbers of procedures began to be performed, and in several centers, it is now offered as a standard of care option alongside surgical repair. However, covered stent correction for SVASD is not recognized by regulatory authorities, and in the minds of many pediatric and adult congenital cardiologists and surgeons, the condition is viewed as treatable only by cardiac surgery with cardiopulmonary bypass.</p><p><strong>Methods: </strong>In April 2023, all centers identified from international conferences, publications, and colleague networks to be undertaking covered stent correction for SVASD were invited to participate in a retrospective audit of their procedures.</p><p><strong>Results: </strong>Data were received on 381 patients from 54 units over a 12-year period with 90% of procedures being performed over the past 5 years. Balloon-expandable stents (8 types) were used in the majority; self-expanding stents (4 types) were used in 4.5%. The commonest stent was the 10-zig covered Cheatham Platinum stent in 62% of cases. In 10 procedures, the stent embolized requiring surgical retrieval and repair of the defect, resulting in technically successful implantation in 371 of 381 (97.4%). Major complications (surgical drainage of tamponade, pacemaker implantation, surgery for pulmonary vein occlusion, and late stent removal) occurred in 5 patients (1.3%). Repeat catheterization to correct residual leaks was required in 7 patients (1.8%). Thus, 359 of 381 patients (94.2%) had successful correction without major complications or additional catheter interventions.</p><p><strong>Conclusions: </strong>This article details the exponential uptake of covered stent correction for SVASD during the past 5 years. Cardiopulmonary bypass was avoided in the majority of patients, and major complications were infrequent. Prospective registries with standardized definitions, inclusion criteria, and follow-up and comparative studies with surgery are now required to help support the extension of covered stent correction as an alternative standard-of-care option for patients with an SVASD.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"744-756"},"PeriodicalIF":35.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853043","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}
引用次数: 0
Correction to: Tadalafil for Treatment of Combined Postcapillary and Precapillary Pulmonary Hypertension in Patients With Heart Failure and Preserved Ejection Fraction: A Randomized Controlled Phase 3 Study.
IF 35.5 1区 医学
Circulation Pub Date : 2025-03-18 Epub Date: 2025-03-17 DOI: 10.1161/CIR.0000000000001321
Marius M Hoeper, Britta Oerke, Max Wissmüller, Hanno Leuchte, Christian Opitz, Michael Halank, Hans-Juergen Seyfarth, Stephan Baldus, Johann Bauersachs, Michael Böhm, Hossein-Ardeschir Ghofrani, Stavros Konstantinides, Karen M Olsson, Rolf Wachter, Carolyn S P Lam, Behnaz Aminossadati, Stephan Rosenkranz
{"title":"Correction to: Tadalafil for Treatment of Combined Postcapillary and Precapillary Pulmonary Hypertension in Patients With Heart Failure and Preserved Ejection Fraction: A Randomized Controlled Phase 3 Study.","authors":"Marius M Hoeper, Britta Oerke, Max Wissmüller, Hanno Leuchte, Christian Opitz, Michael Halank, Hans-Juergen Seyfarth, Stephan Baldus, Johann Bauersachs, Michael Böhm, Hossein-Ardeschir Ghofrani, Stavros Konstantinides, Karen M Olsson, Rolf Wachter, Carolyn S P Lam, Behnaz Aminossadati, Stephan Rosenkranz","doi":"10.1161/CIR.0000000000001321","DOIUrl":"https://doi.org/10.1161/CIR.0000000000001321","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 11","pages":"e763"},"PeriodicalIF":35.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647532","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}
引用次数: 0
Bleeding and New Malignancy Diagnoses After Anticoagulation for Atrial Fibrillation: A Population-Based Cohort Study.
IF 35.5 1区 医学
Circulation Pub Date : 2025-03-18 Epub Date: 2025-02-20 DOI: 10.1161/CIRCULATIONAHA.124.070865
Kavi Grewal, Xuesong Wang, Peter C Austin, Cynthia A Jackevicius, Inbar Nardi-Agmon, Dennis T Ko, Douglas S Lee, Paaladinesh Thavendiranathan, Michael Fradley, Paul Dorian, Husam Abdel-Qadir
{"title":"Bleeding and New Malignancy Diagnoses After Anticoagulation for Atrial Fibrillation: A Population-Based Cohort Study.","authors":"Kavi Grewal, Xuesong Wang, Peter C Austin, Cynthia A Jackevicius, Inbar Nardi-Agmon, Dennis T Ko, Douglas S Lee, Paaladinesh Thavendiranathan, Michael Fradley, Paul Dorian, Husam Abdel-Qadir","doi":"10.1161/CIRCULATIONAHA.124.070865","DOIUrl":"10.1161/CIRCULATIONAHA.124.070865","url":null,"abstract":"<p><strong>Background: </strong>Bleeding after starting anticoagulation for atrial fibrillation (AF) may be the first sign of malignancy, especially in elderly individuals. There are no recommendations to guide investigations for malignancy after new-onset bleeding after anticoagulation for AF. Our objective was to determine the association of bleeding after starting oral anticoagulation for AF with new diagnoses of malignancy in a population-wide sample.</p><p><strong>Methods: </strong>We conducted a population-based cohort study using linked administrative data sets of people ≥66 years of age who newly initiated warfarin or direct oral anticoagulants after diagnosis with AF between 2008 and 2022. Follow-up was 2 years after starting anticoagulation. We excluded patients with valvular disease, chronic dialysis, venous thromboembolism, previous cancer, or previously documented bleeding. Bleeding was identified from hospital/emergency department discharge records and physician billings, then handled as a time-varying covariate in cause-specific regression models while adjusting for baseline characteristics. The primary outcome was incident malignancy. We also determined the site of origin of the malignancy and the stage at diagnosis if indicated in the Ontario Cancer Registry. Analyses were repeated while limiting the exposure to specific bleeding sites.</p><p><strong>Results: </strong>Among 119 480 people (mean age, 77.4 years; 52% men) who started anticoagulants, 26 037 (21.8%) had documented bleeding, and 5800 (4.9%) were diagnosed with malignancy within the next 2 years. Bleeding was associated with a higher hazard of cancer diagnosis with a hazard ratio (HR) of 4.0 (95% CI, 3.8-4.3). The HRs for any malignancy were 5.0 (95% CI, 4.6-5.5) for gastrointestinal, 5.0 (95% CI, 4.4-5.7) for genitourinary, 4.0 (95% CI, 3.5-4.6) for respiratory, 1.8 (95% CI, 1.4-2.2) for intracranial, and 1.5 (95% CI, 1.2-2.0) for nasopharyngeal bleeds. The HRs were substantially higher for cancers concordant with the bleeding site (gastrointestinal, 15.4; genitourinary, 11.8; respiratory, 10.1). Cancers were diagnosed at an earlier stage after bleeding (27.6% stage 4 after bleeding versus 31.3% without bleeding; <i>P</i>=0.029).</p><p><strong>Conclusions: </strong>In anticoagulated patients with AF, bleeding was strongly associated with new cancer diagnoses. Antecedent bleeding was associated with cancer diagnosis at an earlier stage. This highlights the importance of timely investigations in patients with bleeding after anticoagulation for AF, rather than attributing bleeding as an expected adverse effect.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"773-782"},"PeriodicalIF":35.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457091","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}
引用次数: 0
Response by Chan et al to Letters Regarding Article, "Race and Sex Differences in the Association of Bystander CPR for Cardiac Arrest".
IF 35.5 1区 医学
Circulation Pub Date : 2025-03-18 Epub Date: 2025-03-17 DOI: 10.1161/CIRCULATIONAHA.124.073360
Paul S Chan, Saket Girotra, Monique A Starks
{"title":"Response by Chan et al to Letters Regarding Article, \"Race and Sex Differences in the Association of Bystander CPR for Cardiac Arrest\".","authors":"Paul S Chan, Saket Girotra, Monique A Starks","doi":"10.1161/CIRCULATIONAHA.124.073360","DOIUrl":"10.1161/CIRCULATIONAHA.124.073360","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 11","pages":"e714-e715"},"PeriodicalIF":35.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647560","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}
引用次数: 0
Letter by Tamirisa et al Regarding Article, "Race and Sex Differences in the Association of Bystander CPR for Cardiac Arrest".
IF 35.5 1区 医学
Circulation Pub Date : 2025-03-18 Epub Date: 2025-03-17 DOI: 10.1161/CIRCULATIONAHA.124.071883
Ketan Tamirisa, Ethan Lowder, Jim P Stimpson
{"title":"Letter by Tamirisa et al Regarding Article, \"Race and Sex Differences in the Association of Bystander CPR for Cardiac Arrest\".","authors":"Ketan Tamirisa, Ethan Lowder, Jim P Stimpson","doi":"10.1161/CIRCULATIONAHA.124.071883","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.071883","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 11","pages":"e710-e711"},"PeriodicalIF":35.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647469","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}
引用次数: 0
Nrf3-Mediated Mitochondrial Superoxide Promotes Cardiomyocyte Apoptosis and Impairs Cardiac Functions by Suppressing Pitx2.
IF 35.5 1区 医学
Circulation Pub Date : 2025-03-18 DOI: 10.1161/CIRCULATIONAHA.124.070286
Qishan Chen, Ancheng Zheng, Xiaolei Xu, Zhenning Shi, Mei Yang, Shasha Sun, Leyu Wang, Yumeng Wang, Haige Zhao, Qingzhong Xiao, Li Zhang
{"title":"Nrf3-Mediated Mitochondrial Superoxide Promotes Cardiomyocyte Apoptosis and Impairs Cardiac Functions by Suppressing Pitx2.","authors":"Qishan Chen, Ancheng Zheng, Xiaolei Xu, Zhenning Shi, Mei Yang, Shasha Sun, Leyu Wang, Yumeng Wang, Haige Zhao, Qingzhong Xiao, Li Zhang","doi":"10.1161/CIRCULATIONAHA.124.070286","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.070286","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Myocardial infarction (MI) elicits mitochondria reactive oxygen species (ROS) production and cardiomyocyte (CM) apoptosis. Nrf3 (nuclear factor erythroid 2-related factor 3) has an established role in regulating redox signaling and tissue homeostasis. Here, we aimed to evaluate the role and mechanism of Nrf3 in injury-induced pathological cardiac remodeling.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Global (Nrf3-KO) and CM-specific (Nrf3&lt;sup&gt;△CM&lt;/sup&gt;) Nrf3 knockout mice were subjected to MI or ischemia/reperfusion injury, followed by functional and histopathological analysis. Primary neonatal mouse and rat ventricular myocytes and CMs derived from human induced pluripotent stem cells were used to evaluate the impact of Nrf3 on CM apoptosis and mitochondrial ROS production. Chromatin immunoprecipitation sequencing and immunoprecipitation-mass spectrometry analysis were used to uncover potential targets of Nrf3. MitoParaquat administration and CM-specific adeno-associated virus vectors were used to further confirm the &lt;i&gt;i&lt;/i&gt;n vivo relevance of the identified signal pathways.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Nrf3 was expressed mainly in CMs in healthy human hearts, and an increased level of Nrf3 was observed in CMs within the border zone of infarcted human hearts and murine cardiac tissues after MI. Both global and CM-specific Nrf3 knockout significantly decreased injury-induced mitochondrial ROS production, CM apoptosis, and pathological cardiac remodeling, consequently improving cardiac functions. In addition, cardiac-specific Nrf3 overexpression reversed the ameliorative cardiac phenotypes observed in Nrf3-KO mice. Functional studies showed that Nrf3 promoted neonatal mouse ventricular myocyte, neonatal rat ventricular myocyte, and CMs derived from human induced pluripotent stem cell apoptosis by increasing mitochondrial ROS production. Critically, augmenting mitochondrial ROS with MitoParaquat blunted the beneficial effects of Nrf3 deletion on cardiac function and remodeling. Mechanistically, a redox regulator Pitx2 (paired-like homeodomain transcription factor 2) was identified as one of the main target genes of Nrf3. Specifically, Nrf3 binds to &lt;i&gt;Pitx2&lt;/i&gt; promoter, where it increases DNA methylation through recruiting heterogeneous nuclear ribonucleoprotein K and DNA-methyltransferase 1 complex, thereby inhibiting Pitx2 expression. CM-specific knockdown of Pitx2 blunted the beneficial effects of Nrf3 deletion on cardiac function and remodeling, and cardiac-specific Pitx2 overexpression attenuated MI-induced mitochondrial ROS production and CM apoptosis, as well as preserved cardiac functions after MI.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Nrf3 promotes injury-induced CM apoptosis and deteriorates cardiac functions by increasing mitochondrial ROS production through suppressing Pitx2 expression. Targeting the Nrf3-Pitx2-mitochondrial ROS signal axis may therefore represent a novel therapeutic approach for MI treatment.&lt;/p","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":35.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647524","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}
引用次数: 0
The Role of Race in Cardiovascular Disease Risk Prediction.
IF 35.5 1区 医学
Circulation Pub Date : 2025-03-18 Epub Date: 2025-03-17 DOI: 10.1161/CIRCULATIONAHA.124.071233
Chiadi E Ndumele, Keith C Ferdinand, Sadiya S Khan
{"title":"The Role of Race in Cardiovascular Disease Risk Prediction.","authors":"Chiadi E Ndumele, Keith C Ferdinand, Sadiya S Khan","doi":"10.1161/CIRCULATIONAHA.124.071233","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.071233","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 11","pages":"741-743"},"PeriodicalIF":35.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647569","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}
引用次数: 0
Low Penetrance Sarcomere Variants Contribute to Additive Risk in Hypertrophic Cardiomyopathy. 低外显率肌瘤变异增加肥厚性心肌病的附加风险。
IF 35.5 1区 医学
Circulation Pub Date : 2025-03-18 Epub Date: 2024-12-05 DOI: 10.1161/CIRCULATIONAHA.124.069398
Joshua K Meisner, Aaron Renberg, Eric D Smith, Yao-Chang Tsan, Brynn Elder, Abbey Bullard, Owen L Merritt, Sean L Zheng, Neal K Lakdawala, Anjali T Owens, Thomas D Ryan, Erin M Miller, Joseph W Rossano, Kimberly Y Lin, Brian L Claggett, Euan A Ashley, Michelle Michels, Rachel Lampert, John C Stendahl, Dominic Abrams, Christopher Semsarian, Victoria N Parikh, Matthew T Wheeler, Jodie Ingles, Iacopo Olivotto, Sharlene M Day, Sara Saberi, Mark W Russell, Michael Previs, Carolyn Y Ho, James S Ware, Adam S Helms
{"title":"Low Penetrance Sarcomere Variants Contribute to Additive Risk in Hypertrophic Cardiomyopathy.","authors":"Joshua K Meisner, Aaron Renberg, Eric D Smith, Yao-Chang Tsan, Brynn Elder, Abbey Bullard, Owen L Merritt, Sean L Zheng, Neal K Lakdawala, Anjali T Owens, Thomas D Ryan, Erin M Miller, Joseph W Rossano, Kimberly Y Lin, Brian L Claggett, Euan A Ashley, Michelle Michels, Rachel Lampert, John C Stendahl, Dominic Abrams, Christopher Semsarian, Victoria N Parikh, Matthew T Wheeler, Jodie Ingles, Iacopo Olivotto, Sharlene M Day, Sara Saberi, Mark W Russell, Michael Previs, Carolyn Y Ho, James S Ware, Adam S Helms","doi":"10.1161/CIRCULATIONAHA.124.069398","DOIUrl":"10.1161/CIRCULATIONAHA.124.069398","url":null,"abstract":"<p><strong>Background: </strong>Classically, hypertrophic cardiomyopathy (HCM) has been viewed as a single-gene (monogenic) disease caused by pathogenic variants in sarcomere genes. Pathogenic sarcomere variants are individually rare and convey high risk for developing HCM (highly penetrant). Recently, important polygenic contributions have also been characterized. Low penetrance sarcomere variants (LowSVs) at intermediate frequencies and effect sizes have not been systematically investigated. We hypothesize that LowSVs may be common in HCM with substantial influence on disease risk and severity.</p><p><strong>Methods: </strong>Among all sarcomere variants observed in the Sarcomeric Human Cardiomyopathy Registry (SHaRe), we identified putative LowSVs defined by (1) population frequency greater than expected for highly penetrant (monogenic) HCM (allele frequency >5×10<sup>-5</sup> in the Genome Aggregation Database, gnomAD) and (2) moderate enrichment (>2×) in patients with HCM compared with gnomAD. LowSVs were examined for their association with disease severity and clinical outcomes. Functional effects of selected LowSVs were assessed using induced pluripotent stem cell-derived cardiomyocytes. Association of LowSVs with HCM-adjacent traits in the general population was tested using UK Biobank cardiac magnetic resonance imaging data.</p><p><strong>Results: </strong>Among 6045 patients and 1159 unique variants in sarcomere genes, 12 LowSVs were identified. LowSVs were collectively common in the general population (1:350) and moderately enriched in HCM (aggregate odds ratio, 14.9 [95% CI, 12.5-17.9]). Isolated LowSVs were associated with an older age of HCM diagnosis and fewer adverse events. However, LowSVs in combination with a pathogenic sarcomere variant conferred higher morbidity (eg, composite adverse event hazard ratio, 5.4 [95% CI, 3.0-9.8] versus single pathogenic sarcomere variant, 2.0 [95% CI, 1.8-2.2]; <i>P</i><0.001). An intermediate functional impact was validated for 2 specific LowSVs-<i>MYBPC3</i> c.442G>A (partial splice gain) and <i>TNNT2</i> c.832C>T (intermediate effect on contractile mechanics). Cardiac magnetic resonance imaging analysis of the general population revealed 5 of 12 LowSVs were significantly associated with HCM-adjacent traits without overt HCM.</p><p><strong>Conclusions: </strong>This study establishes a new class of low penetrance sarcomere variants that are relatively common in the population. When penetrant, isolated LowSVs cause mild HCM. In combination with pathogenic sarcomere variants, LowSVs markedly increase disease severity, supporting a clinically significant additive effect. Last, LowSVs also contribute to age-related remodeling even in the absence of overt HCM.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"783-798"},"PeriodicalIF":35.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779449","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}
引用次数: 0
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