Circulation最新文献

{"title":"Letter by Gu and Shu Regarding Article, \"Association of Pre-Fontan Hemodynamics With Long-Term Outcomes After Fontan Palliation: A Study From the Pediatric Cardiac Care Consortium\".","authors":"Bingyan Gu, Jianlong Shu","doi":"10.1161/CIRCULATIONAHA.126.080139","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.126.080139","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"154 13","pages":"e409-e410"},"PeriodicalIF":41.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073721","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":"Modeling Heart Failure With Preserved Ejection Fraction Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.","authors":"Brian Yu, Lu Ren, Yu Liu, Chengyi Tu, Ana Kojic, Yuanyuan Dai, Ravichandra Venkateshappa, Mengcheng Shen, Shane R Zhao, Joseph C Wu","doi":"10.1161/CIRCULATIONAHA.126.081881","DOIUrl":"10.1161/CIRCULATIONAHA.126.081881","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"154 13","pages":"1261-1264"},"PeriodicalIF":41.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13623075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073726","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":"The Association Between Hospital Comprehensive Stroke Center Designation Status and Stroke Rate Reporting in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry After Transcatheter Aortic Valve Replacement: Implications for Hospital Performance Assessment.","authors":"G Michael Deeb, P Michael Grossman, Pratik Manandbar, Joseph E Bavaria, John Carroll, Mohamad A Alkhouli, Joseph C Cleveland, Kim Guibone, Deana Harbach, Tsuyoshi Kaneko, Neil S Kleiman, Dharam J Kumbhani, Joan Michaels, Wayne Batchelor, Vinod H Thourani, Sreekanth Vemulapalli","doi":"10.1161/CIRCULATIONAHA.125.078584","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.125.078584","url":null,"abstract":"<p><strong>Background: </strong>The Michigan Structural Heart Consortium showed that transcatheter aortic valve replacement (TAVR) stroke rates were associated with hospital Comprehensive Stroke Center (CSC) designation, suggesting that hospital structural factors affect stroke reporting. We sought to determine whether CSC designation is nationally associated with reported stroke rates and the potential impact on hospital performance and Transcatheter Valve Therapy National Data Registry (TVTR) public reporting.</p><p><strong>Methods: </strong>Consecutive TVTR cases from January 2016 through June 2023 were included, excluding sites reporting to the TVTR <1 year or performing <20 total TAVR procedures. The primary outcome was in-hospital stroke rate. Secondary outcomes were disabling stroke and 30-day stroke. Major bleeding, death, acute renal failure, and a composite end point were falsification end points to determine whether CSC status was uniquely associated with stroke. Multivariable hierarchical models were created starting with patient covariates and sequentially adding hospital variables to account for determinants of stroke. The impact of CSC status on hospital performance was estimated by correcting CSC hospital stroke rates in the validated TVTR 30-day composite model.</p><p><strong>Results: </strong>A total of 525 919 TAVRs at 800 sites were included, and 10 963 strokes (2.1%) were reported within 30 days: 8284 (1.6%) in-hospital and 2679 (0.5%) after discharge. A total of 4733 (0.9%) were disabling strokes. Multivariate analysis showed that CSC status and participation in TAVR trials were independent predictors of in-hospital stroke rate (<i>P</i>=0.033 and 0.012) and disabling stroke (<i>P</i>=0.033 and 0.007), but not falsification end points (<i>P</i>=NS). Participation in TAVR trials and operator volume were independent predictors of 30-day stroke (<i>P</i>=0.039 and <i>P</i>=0.041). The impact of CSC status on the 30-day composite model showed performance improvement for 8 of 153 CSC hospitals.</p><p><strong>Conclusions: </strong>CSC hospital status and participation in TAVR trials are significant predictors unique for stroke. Correcting for the association of CSC status on stroke rate resulted in an estimated 8 of 153 hospitals improving their TVTR 30-day composite model performance. Further work is needed to account for potential ascertainment bias for stroke in public reporting.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":41.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073723","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":"Novel mTORC1 Booster LAPTM4A Potentiates Pathological Cardiac Hypertrophy.","authors":"Yufeng Hu, Wei Li, Manli Hu, Song Tian, Siyi Zhou, Jiayi Liu, Xu Cheng, Changjiang Zhang, Yingjie Zuo, Jiaxing Zhang, Dianyu Liu, Yang Hu, Yuanbao Chen, Xin Li, Lei Luo, Hailong Yang, Lan Bai, Hui Liu, Péter Ferdinandy, Mario Chiong, Mayarling Francisca Troncoso, Jinying Wen, Jingjing Cai, Xiao-Jing Zhang, Zhi-Gang She, Xin Zhang, Hongliang Li","doi":"10.1161/CIRCULATIONAHA.126.080371","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.126.080371","url":null,"abstract":"<p><strong>Background: </strong>Excessive unnecessary protein accumulation in cardiomyocyte is a leading contributor for pathological cardiac hypertrophy and has been found closely regulated by the mTORC1 (mechanistic target of rapamycin complex 1) signaling and lysosome transmembrane proteins. However, the precise regulatory mechanism stratifying mTORC1 signaling and the specific functions of lysosomal proteins in protein homeostasis of cardiomyocytes remain largely unidentified.</p><p><strong>Methods: </strong>We screened lysosomal genes conserved in mice, rats, and humans. Adenoviral infection of rat cardiomyocytes was used to assess the functional role of LAPTM4A (lysosome-associated protein transmembrane 4A). To evaluate its effects in vivo, adeno-associated virus 9 driven by the cardiac troponin T promoter was used for cardiomyocyte-specific expression. RNA sequencing and mass spectrometry-based proteomics were performed to elucidate the underlying molecular mechanisms. Last, a dual-luciferase reporter assay was used to screen a Food and Drug Administration-approved drug library for compounds that suppress LAPTM4A expression.</p><p><strong>Results: </strong>Lysosomal transmembrane proteins expressed in cardiomyocytes were screened for their roles in regulating hypertrophy, and LAPTM4A emerged as a potent promoter of cardiomyocyte hypertrophy and prohypertrophic gene expression. Overexpression of LAPTM4A aggravated cardiac remodeling and dysfunction by enhancing mTORC1-p70S6K (70-kDa ribosomal protein S6 kinase)/4EBP1 (eukaryotic translation initiation factor 4E-binding protein 1)-mediated protein synthesis, without affecting lysosomal autophagy, in a NEDD4L (neural precursor cell expressed developmentally downregulated 4-like)-dependent manner. Mechanistically, LAPTM4A directly interacted with NEDD4L, facilitating K63-linked ubiquitination of AKT (protein kinase B [v-akt murine thymoma viral oncogene homolog]) and subsequent activation of mTORC1 signaling. Cardiomyocyte-specific deletion of LAPTM4A significantly attenuated myocardial hypertrophy and fibrosis induced by transverse aortic constriction in mice. Furthermore, a dual-luciferase reporter screen identified magnolol, a Food and Drug Administration-approved compound, as a suppressor of LAPTM4A expression with marked cardioprotective effects in vivo.</p><p><strong>Conclusions: </strong>Our study identified a novel mTORC1 booster LAPTM4A and verified interrupting the LAPTM4A-mTORC1 axis can significantly inhibit excessive protein synthesis and pathological cardiac hypertrophy, which might represent an attractive therapeutic approach for this disease.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":41.3,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015875","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":"New Bundle Branch Block: Diagnosis and Interpretation.","authors":"Jeremy S Treger, Karol Čurila, Gaurav A Upadhyay","doi":"10.1161/CIRCULATIONAHA.126.079784","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.126.079784","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"154 12","pages":"1151-1154"},"PeriodicalIF":41.3,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015896","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":"Postpartum Care for Hypertensive Disorders of Pregnancy.","authors":"Tracy Hampton","doi":"10.1161/CIRCULATIONAHA.126.082893","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.126.082893","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"154 12","pages":"1162-1163"},"PeriodicalIF":41.3,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015836","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":"Concordance, Not Cacophony: Nutrition Is Not as Confusing as You Think.","authors":"Valerie K Sullivan, Lawrence J Appel","doi":"10.1161/CIRCULATIONAHA.126.081223","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.126.081223","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"154 12","pages":"1085-1087"},"PeriodicalIF":41.3,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015866","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":"Site-Specific Apo AI Glycation Impairs HDL Function and Promotes Atherosclerosis in Diabetes.","authors":"Yang Dai, Qingrun Li, Fenghua Ding, Shuai Chen, Feifei Li, Ruoxu Gu, Qingqing Wang, Leying Li, Jianwen Zhang, Xiaoqun Wang, Chengshuang Chu, Qingyun Zheng, Ying Shen, Qiujing Chen, Jingmeng Liu, Xuefeng Wang, Yan Peng, Songlin Zhuang, Weifeng Shen, Man Pan, Ruiyan Zhang, Guoyu Meng, Rong Zeng, Lin Lu","doi":"10.1161/CIRCULATIONAHA.125.078171","DOIUrl":"10.1161/CIRCULATIONAHA.125.078171","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Apo (apolipoprotein) AI glycation has been implicated in HDL (high-density lipoprotein) dysfunction, but its site-resolved landscape, clinical relevance, relationship with diabetic atherosclerosis, and underlying mechanisms remain incompletely defined.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We performed unbiased site-resolved glycation proteomics in 860 patients with type 2 diabetes and coronary atherosclerosis (CAS) and 294 controls with type 2 diabetes without CAS to define the plasma apo AI glycation landscape. Apo AI glycation signatures associated with diabetic CAS were identified using integrated unsupervised and supervised analyses. An Apo AI Glycation Index was developed using least absolute shrinkage and selection operator regression and evaluated in training, testing, and independent validation cohorts. To assess functional relevance, a glycation-resistant apo AI mutant, cross-linked apo AI (apo AI&lt;sub&gt;CL&lt;/sub&gt;), was engineered and tested under glycation conditions using surface plasmon resonance, in vitro and in vivo reverse cholesterol transport assays, HDL remodeling analyses, and atherosclerosis models. RNA sequencing, macrophage-specific knockout models, receptor-binding assays, signaling inhibition, and cholesterol efflux rescue experiments were used to investigate the underlying macrophage pathway.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Apo AI glycation patterns differed between patients with type 2 diabetes with and without CAS, with K96 and K106/107 emerging as prominent disease-associated glycation sites. The Apo AI Glycation Index was independently associated with CAS and coronary artery disease in patients with type 2 diabetes and was inversely associated with HDL-mediated reverse cholesterol transport and lecithin-cholesterol acyltransferase activity. Compared with native apo AI, apo AI&lt;sub&gt;CL&lt;/sub&gt; showed reduced key-site glycation, preserved structural stability, enhanced binding affinity to lecithin-cholesterol acyltransferase, and improved HDL-mediated reverse cholesterol transport under glycation conditions. In diabetic mouse models, apo AI&lt;sub&gt;CL&lt;/sub&gt; attenuated HDL dysfunction and atherosclerotic lesion formation compared with glycated apo AI. These data support a candidate mechanism in which glycated apo AI enhances RAGE (receptor for advanced glycation end products) interaction and activates ERK1/2 (extracellular signal-regulated kinase 1/2)-NF-κB (nuclear factor κB)/p65 signaling, leading to upregulation of NR2C2 (nuclear receptor subfamily 2 group C member 2). LXRα (liver X receptor α) activation and macrophage NR2C2 deficiency restored cholesterol efflux in glycated apo AI-treated macrophages.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study provides a comprehensive site-resolved map of apo AI glycation in patients with diabetes and identifies the Apo AI Glycation Index as a glycation signature associated with diabetic CAS and impaired HDL function. Experimental data support a mechanism in which","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1088-1108"},"PeriodicalIF":41.3,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812370","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":"Acute Coronary Syndrome in Kawasaki Disease From Infancy to Adulthood.","authors":"Pei-Ni Jone, Jane W Newburger, Jane C Burns, Matthew I Tomey, André Jakob, Yasutsugu Shiono, Satsuki Fukushima, Yoshihide Mitani, Ming-Tai Lin, Alain Fraisse, Hirosyohi Yokoi, Tosihiro Tamura, Nadine Choueiter, Jiken Bhatt, Luis G Quinonez, Etsuko Tsuda, Nagib Dahdah, John B Gordon, Kenji Suda","doi":"10.1161/CIRCULATIONAHA.126.080727","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.126.080727","url":null,"abstract":"<p><p>Acute coronary syndrome (ACS) remains underrecognized in patients with Kawasaki disease (KD). The population at risk for KD-associated ACS is increasing, yet current ACS guidelines are largely derived from atherosclerotic disease and do not adequately address the distinctive mechanisms, anatomy, and thrombosis risk associated with KD. Because the pathophysiology and management of KD-associated ACS differ in fundamental ways from those of atherosclerotic coronary artery disease, its management requires a coordinated team response, with collaboration between pediatric and adult cardiologists. Recent advances in coronary imaging, interventional techniques, and antithrombotic therapies provide an opportunity to establish a more disease-specific approach. This review synthesizes current evidence on the epidemiology and pathophysiology of coronary artery aneurysms, interventional coronary imaging, acute management, revascularization strategies, antithrombotic therapy, and post-ACS surveillance in patients with KD to guide clinical decision-making and treatment for patients with KD presenting with ACS.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"154 12","pages":"1135-1150"},"PeriodicalIF":41.3,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015868","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":"ALKBH5-Dependent m⁶A Demethylation Promotes Cardiac Aging Through SLC38A3 Reduction and Glutamine Metabolic Alteration.","authors":"Kun Liu, Chi-Qian Liang, Hong-Ji Li, Cheng Li, Qian-Yu Huang, Jin-Hua Lin, Jia-Xuan Chen, Ze-Bing Ye, Hui Zhao, Kyu-Sang Park, Shuang Liu, Meng Wang, Qing-Hua Zhou, Yan-Mei Li, Hao Wang, Zhen-Yu Ju, Xu-Feng Qi","doi":"10.1161/CIRCULATIONAHA.125.079193","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.125.079193","url":null,"abstract":"<p><strong>Background: </strong><i>N</i>⁶-methyladenosine (m⁶A) modification has been linked to various types of physiological and pathological bioprocesses. However, the exact role of m⁶A mRNA methylation in cardiac aging is largely unknown. Here, we show that ALKBH5 (alpha-ketoglutarate-dependent dioxygenase AlkB homolog 5), an m⁶A demethylase, plays a critical role in regulating cardiac aging.</p><p><strong>Methods: </strong>Physiologically aged and paraquat-induced mouse models of cardiac aging as well as senescent cardiomyocyte cell cultures were used to evaluate the expression and function of ALKBH5 in cardiac aging. The adeno-associated virus serotype 9 and small interfering RNAs were used to modulate ALKBH5 expression in vivo and in vitro, respectively. Cardiac aging and function were evaluated by histological analysis, immunostaining, and echocardiography. Methylated RNA immunoprecipitation sequencing and functional screening were performed to identify potential targets of ALKBH5 in regulating cardiac aging.</p><p><strong>Results: </strong>ALKBH5 expression was increased in aged hearts and in senescent-like cardiomyocyte models, accompanied by reduced m⁶A levels. ALKBH5 knockdown attenuated senescence-associated phenotypes in cardiomyocytes and reduced aging-associated cardiac remodeling and dysfunction in physiological aging and paraquat-challenged mouse models when adeno-associated virus serotype 9-short hairpin RNA targeting ALKBH5 gene was delivered beginning in young adulthood, whereas ALKBH5 knockdown initiated in already aged hearts did not reverse established phenotypes. Mechanistically, ALKBH5-dependent m⁶A demethylation reduced the expression of SLC38A3 (solute carrier family 38-member 3), which suggested a YTHDC2 (YTH domain-containing protein 2)-dependent mechanism, thereby contributing to reduced glutamine accumulation, impaired mitochondrial homeostasis, and increased oxidative stress. SLC38A3 overexpression attenuated aging-associated cardiac phenotypes in vivo. In addition, glutamine supplementation reduced senescence-associated and cardiac aging-related phenotypes.</p><p><strong>Conclusions: </strong>Our study demonstrates that ALKBH5-SLC38A3 axis is an important regulator of m⁶A-linked, glutamine-associated pathways in aging-related cardiac phenotypes. These findings support a role for ALKBH5 as a contributor to cardiac aging-associated remodeling and dysfunction and suggest this pathway as a candidate target for further mechanistic and translational investigation.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":41.3,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015919","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}