Circulation最新文献

{"title":"Letter by Xu et al Regarding Article, \"Intracranial Atherosclerotic Disease and Incident Dementia: The ARIC Study (Atherosclerosis Risk in Communities)\".","authors":"Lingyu Xu, Yanfei Wang, Yan Xu","doi":"10.1161/CIRCULATIONAHA.124.072061","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.072061","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 12","pages":"e765"},"PeriodicalIF":35.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699748","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":"Clinical Interpretation of Statistical Interaction.","authors":"Andrea Bellavia, Sabina A Murphy","doi":"10.1161/CIRCULATIONAHA.125.073644","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.125.073644","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 12","pages":"811-813"},"PeriodicalIF":35.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699789","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":"Coupling Interval Counts in Ventricular Premature Depolarizations During Acute Ischemia.","authors":"Yusuke Yamazaki, Hideo Mitamura, Toru Egashira","doi":"10.1161/CIRCULATIONAHA.124.073654","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.073654","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 12","pages":"884-886"},"PeriodicalIF":35.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699792","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":"Left Ventricular Ejection Fraction and Implantable Cardioverter Defibrillator in Nonischemic Heart Failure With Reduced Ejection Fraction: Insights From DANISH.","authors":"Seiko N Doi, Jawad H Butt, Jens Jakob Thune, Jens C Nielsen, Jens Haarbo, Niels E Bruun, Line L Olesen, Lars Videbæk, Finn Gustafsson, Hans Eiskjær, Christian Hassager, Jesper H Svendsen, Dan E Høfsten, Steen Pehrson, Lars Køber","doi":"10.1161/CIRCULATIONAHA.124.071777","DOIUrl":"10.1161/CIRCULATIONAHA.124.071777","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"887-889"},"PeriodicalIF":35.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806350","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 Zhao et al to Letters Regarding Article, \"Intracranial Atherosclerotic Disease and Incident Dementia: The ARIC Study (Atherosclerosis Risk in Communities)\".","authors":"Di Zhao, Eliseo Guallar, Bruce A Wasserman","doi":"10.1161/CIRCULATIONAHA.125.073361","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.125.073361","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 12","pages":"e766"},"PeriodicalIF":35.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699752","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":"XBP1s-EDEM2 Prevents the Onset and Development of HFpEF by Ameliorating Cardiac Lipotoxicity.","authors":"Oveena Fonseka, Rida Raja, Claire Ross, Sanskruti R Gare, Jiayan Zhang, Susanne S Hille, Katharine King, Andrea Ruiz-Velasco, Namrita Kaur, Xinyi Chen, Jessica M Miller, Riham R E Abouleisa, Qinghui Ou, Zhiyong Zou, Xiangjun Zhao, Cristian Sotomayor-Flores, Derk Frank, Eileithyia Swanton, Martin R Pool, Sara Missaglia, Daniela Tavian, Gabriele G Schiattarella, Tao Wang, Luigi Venetucci, Christian Pinali, Martin K Rutter, Bernard D Keavney, Elizabeth J Cartwright, Tamer M A Mohamed, Oliver J Müller, Wei Liu","doi":"10.1161/CIRCULATIONAHA.124.072194","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.072194","url":null,"abstract":"<p><strong>Background: </strong>Morbidity and mortality of heart failure with preserved ejection fraction (HFpEF) is increased in metabolic disorders. However, options for preventing and treating these prevalent outcomes are limited. Intramyocardial lipotoxicity contributes to cardiac dysfunction. Here, we investigate the mechanisms underlying endoplasmic reticulum degradation enhancing EDEM2 (endoplasmic reticulum degradation-enhancing alpha-mannosidase-like protein 2) regulation of cardiac lipid homeostasis and assess strategies that inhibit the incidence and progression of HFpEF.</p><p><strong>Methods: </strong>Metabolic stress was induced in C57BL/6 male mice using a high-fat diet and Nω-nitro-l-arginine methyl ester. The recombinant adeno-associated virus 9 delivery system was used for loss- and gain-of-function studies. Palmitic acid and oleic acid stimulation of rat cardiomyocytes and human induced pluripotent stem cell-derived cardiomyocytes imitated a condition of high lipids in vitro. Molecular mechanisms were investigated via RNA sequencing, mass spectrometry proteomics, lipidomic analyses, transmission electron microscopy, histology, and luciferase reporter assays.</p><p><strong>Results: </strong>In the human heart, we first detected lipid overload accompanied by a reduction of XBP1 (X-box binding protein 1) under metabolic stress. Thereafter, a decrease in EDEM2 was confirmed in human and mouse HFpEF hearts. Given that the spliced form of XBP1 (XBP1s) is a transcription factor, EDEM2 was identified as its new target in cardiomyocytes. EDEM2 knockdown mice manifested lipid droplet accumulation and higher levels of triglycerides and diglycerides in the myocardium, aggravating oxidative stress, hypertrophy, and the onset and progression of HFpEF under metabolic stress. XBP1s ablation mice displayed a similar myocardial lipid disturbance and cardiac phenotypes, which were reversed by EDEM2 overexpression. Mechanistically, the findings obtained from rat cardiomyocytes and human induced pluripotent stem cell-derived cardiomyocytes demonstrated that, in the presence of EDEM2, SEC23A mediated intracellular translocation of ATGL (adipose triglyceride lipase) under fatty acid stimulation, inhibiting ATGL degradation and excessive intracellular lipid droplets. Furthermore, the functional studies supported that EDEM2 prevention of lipid overload occurred in an ATGL-dependent manner. Therapeutically, cardiac XBP1s or EDEM2 restoration mitigated lipid deposition and preserved lipid profiles in the myocardium, thus preventing the development of HFpEF.</p><p><strong>Conclusions: </strong>We demonstrate a cardioprotective mechanism regulating myocardial lipid homeostasis. The findings provide a promising therapeutic target to prevent and treat HfpEF, a condition with limited treatment options.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":35.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699786","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":"Inositol 1,4,5-Trisphosphate Receptor 1 Gain-of-Function Increases the Risk for Cardiac Arrhythmias in Mice and Humans.","authors":"Bo Sun, Mingke Ni, Yanhui Li, Zhenpeng Song, Hui Wang, Hai-Lei Zhu, Jinhong Wei, Darrell Belke, Shitian Cai, Wenting Guo, Jinjing Yao, Shanshan Tian, John Paul Estillore, Ruiwu Wang, Mads Toft Søndergaard, Malene Brohus, Palle Duun Rohde, Yongxin Mu, Alexander Vallmitjana, Raul Benitez, Leif Hove-Madsen, Michael Toft Overgaard, Glenn I Fishman, Ju Chen, Shubhayan Sanatani, Arthur A M Wilde, Michael Fill, Josefina Ramos-Franco, Mette Nyegaard, S R Wayne Chen","doi":"10.1161/CIRCULATIONAHA.124.070563","DOIUrl":"10.1161/CIRCULATIONAHA.124.070563","url":null,"abstract":"<p><strong>Background: </strong>Ca²⁺ mishandling in cardiac Purkinje cells is a well-known cause of cardiac arrhythmias. The Purkinje cell resident inositol 1,4,5-trisphosphate receptor 1 (ITPR1) is believed to play an important role in Ca²⁺ handling, and ITPR1 gain-of-function (GOF) has been implicated in cardiac arrhythmias. However, nearly all known disease-associated ITPR1 variants are loss-of-function and are primarily linked to neurological disorders. Whether ITPR1 GOF has pathological consequences, such as cardiac arrhythmias, is unclear. This study aimed to identify human ITPR1 GOF variants and determine the impact of ITPR1 GOF on Ca²⁺ handling and arrhythmia susceptibility.</p><p><strong>Methods: </strong>There are a large number of rare ITPR1 missense variants reported in open data repositories. Based on their locations in the ITPR1 channel structure, we selected and characterized 33 human ITPR1 missense variants from open databases and identified 21 human ITPR1 GOF variants. We generated a mouse model carrying a human ITPR1 GOF variant, ITPR1-W1457G (W1447G in mice).</p><p><strong>Results: </strong>We showed that the ITPR1-W1447G^+/- and recently reported ITPR1-D2594K^+/- GOF mutant mice were susceptible to stress-induced ventricular arrhythmias. Confocal Ca²⁺ and voltage imaging in situ in heart slices and Ca²⁺ imaging and patch-clamp recordings of isolated Purkinje cells showed that ITPR1-W1447G^+/- and ITPR1-D2594K^+/- variants increased the occurrence of stress-induced spontaneous Ca²⁺ release, delayed afterdepolarization, and triggered activity in Purkinje cells. To assess the potential role of ITPR1 variants in arrhythmia susceptibility in humans, we looked up a gene-based association study in the UK Biobank data set and identified 7 rare ITPR1 missense variants showing potential association with cardiac arrhythmias. Remarkably, in vitro functional characterization revealed that all these 7 ITPR1 variants resulted in GOF.</p><p><strong>Conclusions: </strong>Our studies in mice and humans reveal that enhanced function of <i>ITPR1</i>, a well-known movement disorder gene, increases the risk for cardiac arrhythmias.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"847-862"},"PeriodicalIF":35.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799421","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}

{"title":"Differences in Pediatric and Adult Heart Allocation Policies and Some of the Reasons Why.","authors":"Ryan R Davies, Maryjane Farr","doi":"10.1161/CIRCULATIONAHA.125.072978","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.125.072978","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 12","pages":"825-827"},"PeriodicalIF":35.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699795","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":"Ganglionic Inflammation in a Patient With Takotsubo Syndrome.","authors":"Karin A Ziegler, Manuel Zeitler, Sandro Meunier, Inga Sinicina, Tim P Hasenbein, Daniel Andergassen, Anton Bomhard, Reginald V C T van der Kwast, Stefan Engelhardt","doi":"10.1161/CIRCULATIONAHA.124.070862","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.070862","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 12","pages":"890-892"},"PeriodicalIF":35.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699796","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":"Natural History and Clinical Outcomes of Patients With <i>DSG2/DSC2</i> Variant-Related Arrhythmogenic Right Ventricular Cardiomyopathy.","authors":"Liang Chen, Yuxiao Hu, Ardan M Saguner, Barbara Bauce, Yaxin Liu, Anteng Shi, Fu Guan, Zhongli Chen, Maria Bueno Marinas, Lingmin Wu, Deborah Foltran, Alexis Hermida, Veronique Fressart, Serena Pinci, Rudy Celeghin, Zixian Chen, Baowei Zhang, Lin Yubi, Xiaorui Liu, Marco Cason, Marika Martini, Ilaria Rigato, Corinna Brunckhorst, Ruth Biller, Cristina Basso, Bing Yang, Xiaoyan Zhao, Julia Cadrin-Tourigny, Alessio Gasperetti, Cynthia A James, Xianliang Zhou, Estelle Gandjbakhch, Kalliopi Pilichou, Firat Duru, Shengshou Hu","doi":"10.1161/CIRCULATIONAHA.124.072226","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.072226","url":null,"abstract":"<p><strong>Background: </strong>Genetic variants in desmosomal cadherins, desmoglein 2 (<i>DSG2</i>) and desmocollin 2 (<i>DSC2</i>), cause a distinct form of arrhythmogenic right ventricular cardiomyopathy (ARVC), which remains poorly reported. In this study, we aimed to provide a comprehensive description of the phenotypic expression, natural history, and clinical outcomes of patients with this ARVC subset.</p><p><strong>Methods: </strong>Genetic and clinical data of <i>DSG2</i> and <i>DSC2</i> variant carriers were collected from 5 countries in Europe and Asia. We assessed the phenotypic profile of these patients and their clinical outcomes, focusing on heart failure and ventricular arrhythmia events.</p><p><strong>Results: </strong>Overall, 271 subjects, 254 with <i>DSG2</i> variants, were included in this study (median age, 38 years [interquartile range, 25-52]; 62.7% male). Of these, 165 were probands, and 200 were diagnosed with definite ARVC. A total of 181 (66.8%) individuals carried missense variants, mainly distributed in the extracellular domains. Notably, we included 78 (28.8%) individuals with multiple variants. Of the 200 cases with diagnosed ARVC, 41 (20.5%) experienced premature cardiac death before the age of 65. Among the 81 individuals for whom both left ventricular ejection fraction and right ventricular fractional area change data were available at presentation, 29 (35.8%) had isolated right ventricular dysfunction, and 16 (19.8%) had biventricular dysfunction. Single-variant carriers who engaged in intense physical exercise were younger at disease onset compared with those who did not (<i>P</i>=0.001). Compared with single-variant carriers, those with multiple variants were more likely to be diagnosed with ARVC (96.2% versus 64.8%; <i>P</i><0.001) and exhibited more severe left ventricular dysfunction (44.4% versus 22.1%; <i>P</i>=0.001) and right ventricular dilation (88.9% versus 55.8%, <i>P</i><0.001). Multiple-variant carriers were significantly younger at ARVC diagnosis compared with single-variant carriers (33 [18-49] years versus 42 [27-54] years; <i>P</i><0.001]. During follow-up, end-stage heart failure (<i>P</i><0.001) and malignant ventricular arrhythmias (<i>P</i>=0.004) were significantly more frequent in multiple-variant compared with single-variant carriers. Compared with <i>PKP2</i> patients, <i>DSG2/DSC2</i> patients exhibited a significantly higher risk of end-stage heart failure (<i>P</i><0.001).</p><p><strong>Conclusions: </strong>ARVC attributable to variants in desmosomal cadherins mostly present with right ventricular or biventricular disease. Multiple variants are common in these patients and are associated with more frequent clinical penetrance, earlier onset of disease, and adverse clinical outcomes.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":35.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691367","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}