Circulation最新文献

{"title":"Letter by Berry and McCartney Regarding Article, \"Effect of Cangrelor on Infarct Size in ST-Segment-Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention (The PITRI Trial)\".","authors":"Colin Berry,Peter McCartney","doi":"10.1161/circulationaha.124.071295","DOIUrl":"https://doi.org/10.1161/circulationaha.124.071295","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"135 1","pages":"e1002-e1003"},"PeriodicalIF":37.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097727","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 Bulluck and Hausenloy to Letter Regarding Article, \"Effect of Cangrelor on Infarct Size in ST-Segment-Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial (the PITRI Trial)\".","authors":"Heerajnarain Bulluck,Derek J Hausenloy,","doi":"10.1161/circulationaha.124.072689","DOIUrl":"https://doi.org/10.1161/circulationaha.124.072689","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"211 1","pages":"e1004-e1005"},"PeriodicalIF":37.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097724","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":"Partial Heart Transplantation: Early Experience With Pediatric Heart Valve Replacements That Grow.","authors":"Neel K Prabhu,Berk Aykut,Michael Mensah-Mamfo,Douglas M Overbey,Joseph W Turek","doi":"10.1161/circulationaha.124.072626","DOIUrl":"https://doi.org/10.1161/circulationaha.124.072626","url":null,"abstract":"Heart valve replacement in children is fraught with long-term morbidity and mortality rates, largely because conventional implants lack the capacity to grow with the child. Partial heart transplantation presents a potential solution by transplanting only specific segments of a donor heart, thereby providing a living and growing heart valve implant. This approach harnesses the full spectrum of cardiac tissues, which, when freshly procured and supported by immunosuppression, can integrate as functional and potentially growth-capable tissue. This state-of-the-art review discusses the history and development of partial heart transplantation, its indications, recent clinical experiences, regulation, and future directions.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"31 1","pages":"1477-1490"},"PeriodicalIF":37.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097723","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":"Factor XI Inhibition for Atrial Fibrillation: Where Do We Stand?","authors":"Siddharth M Patel,Robert P Giugliano,Christian T Ruff","doi":"10.1161/circulationaha.125.074100","DOIUrl":"https://doi.org/10.1161/circulationaha.125.074100","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"25 1","pages":"1433-1435"},"PeriodicalIF":37.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097726","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":"Diagnostic Yield and Outcomes of Incidental Thoracic Aortic Dilatation in the National Health Service Targeted Lung Health Check Program: Novel Insights from a Regional Tertiary Center in the United Kingdom.","authors":"Dalia Ahmed,Nehan Khalid,Vivek Shrivastava,Claudette Philips,Kanwal Tariq,Imran Sunderji,Oliver Byass,Raghav T Bhatia","doi":"10.1161/circulationaha.124.073264","DOIUrl":"https://doi.org/10.1161/circulationaha.124.073264","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"55 1","pages":"1491-1493"},"PeriodicalIF":37.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097728","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":"Genomic Editing of a Pathogenic Mutation in ACTA2 Rescues Multisystemic Smooth Muscle Dysfunction Syndrome in Mice.","authors":"Qianqian Ding,Peiheng Gan,Zhisheng Xu,Hui Li,Lei Guo,Camryn MacDonald,Wei Tan,Efrain Sanchez-Ortiz,John R McAnally,Yu Zhang,Dileep Karri,Lin Xu,Ning Liu,Eric N Olson","doi":"10.1161/circulationaha.125.074218","DOIUrl":"https://doi.org/10.1161/circulationaha.125.074218","url":null,"abstract":"Background: Vascular smooth muscle cells (vSMCs), the predominant cell type in the aortic wall, play a crucial role in maintaining aortic integrity, blood pressure, and cardiovascular function. vSMC contractility and function depend on smooth muscle alpha-actin 2 (ACTA2). The pathogenic variant ACTA2 c.536G>A (p. R179H) causes multisystemic smooth muscle dysfunction syndrome (MSMDS), a severe disorder marked by widespread smooth muscle abnormalities, resulting in life-threatening aortic disease and high-risk early mortality from aneurysms or stroke. No effective treatments exist for MSMDS. Methods: To develop a comprehensive therapy for MSMDS, we utilized CRISPR-Cas9 adenine base editing to correct the ACTA2 R179H mutation. We generated isogenic human induced pluripotent stem cell (iPSC) lines and humanized mice carrying this pathogenic missense mutation. iPSC-SMCs were evaluated for key functional characteristics, including proliferation, migration, and contractility. The adenine base editor (ABE) ABE8e-SpCas9-VRQR under control of either a SMC-specific promoter or a CMV promoter, and an optimized single guide RNA (sgRNA) under control of U6 promoter were delivered intravenously to humanized R179H mice using adeno-associated virus serotype 9 (AAV9) and phenotypic outcomes were evaluated. Results: The R179H mutation causes a dramatic phenotypic switch in human iPSC-SMCs from a contractile to a synthetic state, a transition associated with aneurysm formation. Base editing prevented this pathogenic phenotypic switch and restored normal SMC function. In humanized mice, the ACTA2R179H/+ mutation caused widespread smooth muscle dysfunction, manifesting as decreased blood pressure, aortic dilation and dissection, bladder enlargement, gut dilation, and hydronephrosis. In vivo base editing rescued these pathological abnormalities, normalizing smooth muscle function. Conclusions: This study demonstrates the effectiveness of adenine base editing to treat MSMDS and restore aortic smooth muscle function. By correcting the ACTA2 R179H mutation, the pathogenic phenotypic shift in SMCs was prevented, key aortic smooth muscle functions were restored, and life-threatening aortic dilation and dissection were mitigated in humanized mice. These findings underscore the promise of gene-editing therapies in addressing the underlying genetic causes of smooth muscle disorders and offer a potential transformative treatment for patients facing severe vascular complications.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"40 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066797","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":"Palliative and End-of-Life Care During Critical Cardiovascular Illness: A Scientific Statement From the American Heart Association.","authors":"Erin A Bohula,Michael J Landzberg,Venu Menon,Carlos L Alviar,Gregory W Barsness,Daniela R Crousillat,Nelia Jain,Robert Page,Rachel Wells,Abdulla A Damluji,","doi":"10.1161/cir.0000000000001334","DOIUrl":"https://doi.org/10.1161/cir.0000000000001334","url":null,"abstract":"Cardiac intensive care units are witnessing a demographic shift, characterized by patients with increasingly complex or end-stage cardiovascular disease with a greater burden of concomitant comorbid noncardiovascular disease. Despite technical advances in care that may be offered, many critically ill cardiovascular patients will nevertheless experience significant morbidity and mortality during the acute decompensation, including physical and psychological suffering. Palliative care, with its specialized focus on alleviating suffering, aligns treatments with patient and caregiver values and improves overall care planning. Integrating palliative care into cardiovascular disease management extends the therapeutic approach beyond life-sustaining measures to encompass life-enhancing goals, addressing the physical, emotional, psychosocial, and spiritual needs of critically ill patients. This American Heart Association scientific statement aims to explore the definitions and conceptual framework of palliative care and to suggest strategies to integrate palliative care principles into the management of patients with critical cardiovascular illness.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"20 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982433","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":"Dusp14-Mediated Dephosphorylation of MLKL Protects Against Cardiomyocyte Necroptosis in Hypothyroidism-Induced Heart Failure.","authors":"Yitian Zheng,Yueyue Cao,Wenyao Wang,Yicheng Tong,Shuaixing Wang,Chen Li,Mingming Zhao,Yao Song,Yuan-Geng-Shuo Wang,Jiating Qi,Chao Wu,Jie Yang,Jilin Zheng,Jun Gao,Jingjia Wang,Qing Yang,Gang Liu,Jiajun Zhao,Yan Zhang,Han Xiao,You-Yi Zhang,Yi-Da Tang","doi":"10.1161/circulationaha.125.074353","DOIUrl":"https://doi.org/10.1161/circulationaha.125.074353","url":null,"abstract":"BACKGROUNDHypothyroidism leads to multiple organ dysfunction, with the heart the most affected. However, the pathologic mechanism of hypothyroidism-induced heart failure remains to be completely elucidated. Thyroid hormone replacement therapy enhances myocardium systolic function but increases the occurrence of arrythmias. There is an urgent need to explore these mechanisms in detail and to discover and develop drugs that can target and manage heart failure in patients with hypothyroidism.METHODSIn this study, a mouse model of hypothyroidism-induced heart failure was established through the administration of propylthiouracil. Dusp14 knockout mice were generated, and adeno-associated virus-mediated cardiomyocyte-specific overexpression of Dusp14 (dual specificity phosphatase 14) was used in combination with related cellular experiments to investigate the protective effects of Dusp14 on hypothyroidism-induced heart failure. Further analyses confirmed the crucial involvement of necroptosis in the pathogenesis of hypothyroidism-induced heart failure, and demonstrated the protective role of Dusp14 in modulating necroptosis. In addition, a novel small molecule compound that effectively regulates Dusp14 activity in vitro was identified through molecular docking, providing a potential therapeutic avenue.RESULTSDusp14 regulates necroptosis and mitigates hypothyroidism-induced heart failure. Myocardial tissue sections from mice in the hypothyroidism group showed positive Evans blue dye staining, and the serum levels of the myocardial injury marker lactate dehydrogenase were significantly higher compared with the euthyroid group (n=8). In addition, phosphorylation levels of the necroptosis marker MLKL (mixed lineage kinase domain-like protein) were significantly elevated, indicating the activation of necroptosis (n=8). These findings suggest that myocardial necroptosis is activated during hypothyroidism. Myocardial-specific overexpression of Dusp14 reduced myocardial necroptosis and improved myocardial contractile function in hypothyroid mice (n=8). In contrast, Dusp14 knockout exacerbated myocardial contractile dysfunction and necroptosis in these mice (n=5-7). These results indicate that Dusp14 alleviates hypothyroidism-induced heart failure by inhibiting necroptosis. P077-0472, a small molecule compound, was identified as an activator of Dusp14, which could inhibit cardiomyocyte necroptosis from hypothyroidism (n=6).CONCLUSIONSDusp14 inhibits cardiomyocyte necroptosis from hypothyroidism and consequently rescues damaged cardiomyocytes. P077-0472, a novel small molecule compound that activates the dephosphorylation function of Dusp14, could inhibit cardiomyocyte necroptosis from hypothyroidism.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"121 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945134","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":"METTL3 Is Essential for Exercise Benefits in Diabetic Cardiomyopathy.","authors":"Chunyan Wang,Siman Shen,Jiayi Kang,Aya Sugai-Munson,Xiao Xiao,Yajing Zhang,Junyuan Zhu,Zipeng Liu,Tina B McKay,Oluwaseun Akeju,Eric R Jonas,Amrut V Ambarar,Michael R Bristow,Weifeng Yao,Haobo Li","doi":"10.1161/circulationaha.124.070279","DOIUrl":"https://doi.org/10.1161/circulationaha.124.070279","url":null,"abstract":"BACKGROUNDExercise improves functional outcomes in patients with diabetic cardiomyopathy (DiaCM). The molecular mechanism underlying cardiac benefits of exercise in DiaCM remains incompletely understood. N6-methyladenosine (m6A) is the most common form of messenger RNA modification in eukaryotes and has been implicated in cardiac development and disease. However, the role of m6A in DiaCM and in the mitigating effects of exercise on this disease are unclear.METHODSCardiomyocyte-specific N6-adenosine-methyltransferase-like 3 (METTL3, an m6A methyltransferase) knockout mice and their wild-type littermates were subjected to either chow diet or high-fat diet feeding and injection of streptozotocin to induce DiaCM, followed by an 8-week exercise training and assessment of cardiac function. Some of the mice were injected with adeno-associated viral vector encoding METTL3 to overexpress METTL3 in cardiomyocytes. Cardiac METTL3 expressions were assessed in patients with nonischemic primary dilated cardiomyopathies without or with diabetes. Potential METTL3 downstream effector YBX1 (Y-box binding protein 1) was identified through RNA sequencing. The functional role of YBX1 was examined through adeno-associated viral vector overexpression or knockdown in cardiomyocytes in DiaCM mice.RESULTSWe showed that cardiac METTL3 protein expression and m6A level were downregulated in patient with dilated cardiomyopathy and further downregulated in patients with dilated cardiomyopathy and diabetes. Consistently, cardiac METTL3 and m6A were downregulated in mouse with DiaCM, whereas they were upregulated by exercise. Cardiomyocyte-specific METTL3 knockout eliminated the cardiac benefits of exercise on DiaCM. Conversely, cardiomyocyte-specific METTL3 overexpression improved systolic and diastolic function in 2 DiaCM mouse models. We demonstrated that exercise enhanced cardiac METTL3 expression in DiaCM through signal transducer and activator of transcription 3. Moreover, METTL3 attenuated DiaCM through m6A-depdendent YBX1 upregulation and the subsequent activation of Nrf2. Cardiomyocyte-specific YBX1 overexpression promoted Nrf2 activation and attenuated oxidative stress, resulting in an improvement in cardiac function in DiaCM. In contrast, cardiomyocyte-specific YBX1 gene knockdown abolished the effect of METTL3 on cardiac improvement in mice with DiaCM. Further, pharmacological activation of METTL3 using a small molecule attenuated cardiac dysfunction in DiaCM.CONCLUSIONSThese studies reveal an essential role of METTL3 in the cardiac benefits of exercise and identify METTL3 and YBX1 as promising therapeutic targets for treating DiaCM.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"15 1 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945135","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":"Correction to: Mavacamten in Patients With Hypertrophic Cardiomyopathy Referred for Septal Reduction: Week 128 Results from VALOR-HCM.","authors":"Milind Y Desai, Kathy Wolski, Anjali Owens, Jeffrey B Geske, Sara Saberi, Andrew Wang, Mark Sherrid, Paul C Cremer, Neal K Lakdawala, Albree Tower-Rader, David Fermin, Srihari S Naidu, Nicholas G Smedira, Hartzell Schaff, Zhiqun Gong, Lana Mudarris, Kathy Lampl, Amy J Sehnert, Steven E Nissen","doi":"10.1161/CIR.0000000000001339","DOIUrl":"https://doi.org/10.1161/CIR.0000000000001339","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 19","pages":"e1001"},"PeriodicalIF":35.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975428","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}