Circulation最新文献

{"title":"Letter by Khouri et al Regarding Article, \"CXCR6+ T Cells Drive Immune Checkpoint Inhibitor Myocarditis\".","authors":"Charles Khouri, Alex Hlavaty, Emanuel Raschi","doi":"10.1161/CIRCULATIONAHA.126.079662","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.126.079662","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"154 15","pages":"e589-e590"},"PeriodicalIF":41.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164836","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":"Prevalence, Predictors, and Clinical Implications of Residual Shunt After Patent Foramen Ovale Percutaneous Closure.","authors":"Paul Guedeney, Julio I Farjat-Pasos, Nicolas Meneveau, Claire Dauphin, Maik J Grundeken, Jeremie Abtan, Meier Elbaz, Matthieu Besutti, Jules Mesnier, Lars S Witte, Patrick Ohlmann, Gora Ndiaye, Marion Kibler, Marcel Am Beijk, Robbert J de Winter, Gaetano Maria De Ferrari, Paolo Boretto, Romain Tresorier, Thibaut Pommier, Vincent Roule, Farzin Beygui, Nicolas Martin, Paul Gabrion, Hakim Benamer, Matthieu Perier, Vincent Auffret, Emmanuel Boiffard, Fabien Arabucki, Stéphanie Rouanet, Marie Dupuy, Florent Huang, Louis Giovachini, Michel Zeitouni, Nadjib Hammoudi, Johanne Silvain, Josep Rodés-Cabau, Gilles Montalescot","doi":"10.1161/CIRCULATIONAHA.126.081160","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.126.081160","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"154 15","pages":"1515-1517"},"PeriodicalIF":41.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165199","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":"PUS7-Mediated Pseudouridylation of TGFBI Drives Vascular Remodeling in Pulmonary Hypertension.","authors":"Junting Zhang, Yiying Li, Muhua He, Jianxin Tan, Yuan Chen, Zhongyuan Lin, Hongbo Wang, Fang Liu, Xiaolin Chen, Zihui Jia, Hanbin Chen, Zhen Chen, Fanhao Kong, Jiawen Fu, Jin-Song Bian, Xiao-Wei Nie","doi":"10.1161/CIRCULATIONAHA.126.080714","DOIUrl":"10.1161/CIRCULATIONAHA.126.080714","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary hypertension (PH) is a life-threatening cardiovascular disorder characterized by irreversible pulmonary vascular remodeling and poor prognosis. RNA pseudouridylation, the most evolutionarily conserved RNA epigenetic modification, and its catalytic enzyme pseudouridine synthase 7 (PUS7) remained uncharacterized in PH, representing a major gap in the understanding of the epigenetic pathogenesis of the disease.</p><p><strong>Methods: </strong>We generated the first single-base resolution pseudouridine (Ψ) landscape in lung tissues of patients with PH using bisulfite-induced deletion sequencing. PUS7 expression was analyzed in hypoxic pulmonary artery endothelial cells, the lung tissues of patients with PH, and SU5416-hypoxia rodent model. The functional roles of PUS7 were investigated through genetic manipulation (PUS7-deficiency cells, adeno-associated virus serotype-mediated overexpression, endothelial cell-specific knockdown, and heterozygous knockout mice) and pharmacological inhibition with NSC107512.</p><p><strong>Results: </strong>Bisulfite-induced deletion sequencing revealed global Ψ dysregulation in the lung tissues of patients with PH. Among PUS family members, PUS7 was the most markedly upregulated in these tissues and in the hypoxic pulmonary artery endothelial cells. Both gene knockdown and pharmacological inhibition with NSC107512 ameliorated PH, whereas adeno-associated virus serotype-mediated PUS7 overexpression exacerbated disease progression. RNA immunoprecipitation sequencing and mutagenesis studies demonstrated that PUS7 bound to and catalyzed Ψ at position 688 of TGFBI (transforming growth factor β-induced protein) mRNA, thereby stabilizing TGFBI and activating phosphatidylinositol 3-kinase-protein kinase B signaling pathway. Furthermore, hypoxia-inducible factor 2α bound directly to the PUS7 promoter, establishing a hypoxia-inducible factor 2α/PUS7/TGFBI/phosphatidylinositol 3-kinase-protein kinase B positive feedback loop that drives PH pathogenesis.</p><p><strong>Conclusions: </strong>PUS7-mediated pseudouridylation serves as a novel epigenetic driver of PH through the hypoxia-inducible factor 2α/PUS7/TGFBI/phosphatidylinositol 3-kinase-protein kinase B axis, positioning PUS7 as a promising therapeutic target for this devastating disease.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1456-1472"},"PeriodicalIF":41.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863778","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":"Dual Control of Low-Density Lipoprotein Cholesterol Levels by ANGPTL3 and ANGPTL8.","authors":"Yanqing Xu, Fei Luo, Justin Fletcher, Melissa Inigo, Shawn Burgess, Guosheng Liang, Lisa N Kinch, Julia Kozlitina, Jonathan C Cohen, Helen H Hobbs","doi":"10.1161/CIRCULATIONAHA.126.080412","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.126.080412","url":null,"abstract":"<p><strong>Background: </strong>Inactivation of ANGPTL3 (angiopoietin-like protein 3; A3) is a proven therapeutic strategy for lowering plasma lipid levels independently of the low-density lipoprotein receptor, yet the optimal approach to inactivate A3 remains unclear. A3 is proteolytically cleaved and circulates as full-length, N-terminal, and C-terminal fragments. The specific contribution of each form of A3, and of its paralog, ANGPTL8 (angiopoietin-like protein 8; A8), in modulating circulating levels of ApoB (apolipoprotein B)-containing lipoproteins remain poorly defined. Clarifying these relationships will inform next-generation A3-directed therapies.</p><p><strong>Methods: </strong>We performed liver perfusion studies to directly compare the number and composition of very-low-density lipoprotein particles secreted from mice with and without A3. To amplify effects on cholesterol metabolism, we generated <i>Ldlr</i>^-/- mice expressing wild-type A3, full-length A3, or N-terminal A3 fragments, with or without coexpression of A8, and analyzed plasma lipids, circulating A3 and A8 complexes, and intravascular lipase activities. Complementary in vitro assays and structural modeling were used to assess relative endothelial lipase inhibition by A3 alone or in complex with A8.</p><p><strong>Results: </strong>Liver perfusion studies revealed that A3 inactivation does not alter the rates of hepatic secretion of very-low-density lipoprotein in wild-type or <i>Ldlr</i>^-/- mice. Inactivation of A8 alone lowered plasma low-density lipoprotein cholesterol levels by ≈20%, an effect dependent upon the expression of both endothelial lipase and A3. Maximal inhibition of lipoprotein lipase required coexpression of A8 plus both full-length A3 and N-terminal A3 fragments, indicating that A3 cleavage, in addition to A8 expression, is essential for maximal lipoprotein lipase inhibition. In contrast, A8 expression, but not A3 cleavage, was required for optimal endothelial lipase inhibition.</p><p><strong>Conclusions: </strong>A8 acts in concert with A3 to differentially modulate lipoprotein lipase- and endothelial lipase-mediated lipolysis, which antagonizes hepatic clearance of newly secreted atherogenic ApoB-containing lipoproteins. This mechanistic framework refines our understanding of A3-targeted lipid lowering and highlights the therapeutic potential of dual A3- plus A8-directed strategies to treat dyslipidemia and prevent atherosclerotic cardiovascular disease.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":41.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179882","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":"Approach to Heart Failure With Mildly Reduced Left Ventricular Ejection Fraction.","authors":"Felix Lindberg, Lars H Lund","doi":"10.1161/CIRCULATIONAHA.126.079813","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.126.079813","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"154 15","pages":"1537-1540"},"PeriodicalIF":41.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163811","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":"Bleeding With Asundexian Versus Placebo in Patients With Noncardioembolic Ischemic Stroke or High-Risk TIA: OCEANIC-STROKE Randomized Trial.","authors":"John W Eikelboom, Lizhen Xu, Ashkan Shoamanesh, Qiang Dong, Teruyuki Hirano, Jeffrey L Saver, Jaime Masjuan, Andrew M Demchuk, Charlotte Cordonnier, Daniel Bereczki, Georgios Tsivgoulis, Roland Veltkamp, Ivan Staikov, Hee-Joon Bae, Bruce C V Campbell, Andrea Zini, I-Hui Lee, Martin Kovář, Robert Mikulik, Robin Lemmens, José M Ferro, Thompson Robinson, Hanne Christensen, Serefnur Ozturk, Ronen R Leker, Peter Turcani, Agnieszka Slowik, Pablo Amaya, Fan Kee Hoo, Gian Marco De Marchis, Michael Knoflach, P N Sylaja, Jukka Putaala, Jonathan M Coutinho, H Bart van der Worp, Evija Miglane, Vaidas Matijošaitis, Arne G Lindgren, Gisele Sampaio Silva, Else Charlotte Sandset, Saule T Turuspekova, Pablo Colorado, Scott E Kasner, Lars Keller, Christoph Neumann, Eva Muehlhofer, Helle Klingenberg Iversen, Yolanda Silva, Oscar Ayo-Martín, Ashfaq Shuaib, Ziran Wang, Karleen Schulze, Raed A Joundi, Mukul Sharma","doi":"10.1161/CIRCULATIONAHA.126.081836","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.126.081836","url":null,"abstract":"<p><strong>Background: </strong>OCEANIC-STROKE (XXX) showed that asundexian added to antiplatelet therapy reduced ischemic stroke without significantly increasing bleeding in patients with noncardioembolic ischemic stroke or high-risk transient ischemic attack. We characterized bleeding categories, sites, and key subgroups.</p><p><strong>Methods: </strong>In the safety population, 12 254 participants received at least 1 dose of asundexian (n=6124) or placebo (n=6130). Bleeding was categorized by International Society on Thrombosis and Haemostasis criteria as major, clinically relevant nonmajor (CRNM), or minor. While-on-treatment analyses included events through 2 days after the last dose, with death and permanent discontinuation as competing risks.</p><p><strong>Results: </strong>Major bleeding occurred in 117 (1.9%) participants with asundexian and 107 (1.7%) with placebo (cause-specific hazard ratio [csHR], 1.10 [95% CI, 0.85-1.44]; <i>P</i>=0.46). Major or CRNM bleeding occurred in 339 (5.5%) and 307 (5.0%), respectively (csHR, 1.12 [95% CI, 0.96-1.30]; <i>P</i>=0.16), and any bleeding in 763 (12.5%) and 752 (12.3%) (csHR, 1.02 [95% CI, 0.93-1.13]; <i>P</i>=0.65). Treatment effects for major and major or CRNM bleeding were consistent across prespecified subgroups, including planned dual antiplatelet therapy. Symptomatic intracranial hemorrhage occurred in 41 (0.7%) and 36 (0.6%) participants. Any gastrointestinal bleeding occurred in 186 (3.0%) and 147 (2.4%) (csHR, 1.28 [95% CI, 1.03-1.59]), and lower gastrointestinal bleeding in 102 (1.7%) and 59 (1.0%) (csHR, 1.75 [95% CI, 1.27-2.41]), primarily rectal bleeding. Any procedure-related bleeding and any mucosal bleeding did not differ significantly.</p><p><strong>Conclusions: </strong>Asundexian added to antiplatelet therapy reduced ischemic stroke without significantly increasing major, major or CRNM, or any bleeding. Lower gastrointestinal bleeding was more frequent with asundexian, whereas treatment effects on major and major or CRNM bleeding were consistent across prespecified subgroups.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05686070.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":41.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179889","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":"Trends and Distribution of Low-Density Lipoprotein Cholesterol Levels Among US Adults and Adolescents Without Atherosclerotic Cardiovascular Disease, 1999 to 2023.","authors":"Shannon Lyon, Sarah D de Ferranti, Andrew E Moran, Yiyi Zhang","doi":"10.1161/CIRCULATIONAHA.126.080677","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.126.080677","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"154 15","pages":"1510-1514"},"PeriodicalIF":41.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167190","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":"METTL7B Mitigates Hypertension and Vascular Remodeling.","authors":"Zhenzhen Chen, Haizeng Zhang, Qiaoxi Yang, Luyun Fan, Xilan Dong, Qianhui Ling, Xinru Guo, Fengkai Yue, Jiarui Cui, Yan Tang, Bin Geng, Jun Cai","doi":"10.1161/CIRCULATIONAHA.126.079407","DOIUrl":"10.1161/CIRCULATIONAHA.126.079407","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Hypertension is a major risk factor for cardiovascular diseases. RNA N6-methyladenosine (m&lt;sup&gt;6&lt;/sup&gt;A) modification is closely linked to hypertension pathogenesis, but key m&lt;sup&gt;6&lt;/sup&gt;A-related factors that regulate blood pressure remain unclear. This study aims to identify these regulators and evaluate their therapeutic potential.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We assessed RNA m&lt;sup&gt;6&lt;/sup&gt;A changes and METTL (methyltransferase-like) expression in hypertensive aortas via methylated RNA immunoprecipitation sequencing and RNA sequencing (RNA-seq). Global &lt;i&gt;Mettl7b&lt;/i&gt; knockout mice and vascular smooth muscle cell (VSMC)-specific &lt;i&gt;Mettl7b&lt;/i&gt; knockin and knockout mice were used to evaluate its in vivo role. Downstream target genes were identified via methylated RNA immunoprecipitation sequencing, enhanced cross-linking and immunoprecipitation sequencing, and RNA-seq. METTL7B activators were screened using molecular docking and surface plasmon resonance and validated in vivo via intraperitoneal injection.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Under hypertensive stress, METTL7B expression positively correlated with global RNA m&lt;sup&gt;6&lt;/sup&gt;A content, exhibiting concurrent depletion in VSMCs. In vitro biochemical assays revealed that recombinant METTL7B significantly increased RNA m&lt;sup&gt;6&lt;/sup&gt;A levels. Crucially, METTL7B overexpression in METTL3 knockout cells robustly upregulated m&lt;sup&gt;6&lt;/sup&gt;A levels, definitively establishing METTL7B as a novel, METTL3-independent RNA m&lt;sup&gt;6&lt;/sup&gt;A methyltransferase. Physiologically, VSMC-specific Mettl7b ablation exacerbated angiotensin II-induced hypertensive pathogenesis, structural arterial remodeling, and vascular tone, whereas its overexpression exerted potent vasoprotective effects. Mechanistically, METTL7B recruited HNRNPH1 to catalyze m&lt;sup&gt;6&lt;/sup&gt;A deposition at the 3' untranslated region of FILIP1L mRNA, facilitating its maturation. Importantly, the expression of FILIP1L was positively correlated with blood pressure reduction in humans and mice. Elevated FILIP1L downregulated the expression of its binding protein FLNA (Filamin A), reducing F-actin polymerization, attenuating VSMC contractility, and ultimately lowering blood pressure. Furthermore, FILIP1L overexpression reversed the detrimental effects of &lt;i&gt;Mettl7b&lt;/i&gt; knockout on hypertension and vascular remodeling, whereas these effects were not rescued by the mutation of FILIP1L's m&lt;sup&gt;6&lt;/sup&gt;A site. Elucidating the upstream pathology, we found that stress-induced KLF4 directly bound the METTL7B promoter, transcriptionally repressing its expression. Finally, the Food and Drug Administration-approved drug netarsudil exerted preventive and therapeutic effects on hypertension and vascular remodeling by activating METTL7B; notably, these therapeutic benefits were completely abolished in VSMC-specific &lt;i&gt;Mettl7b&lt;/i&gt; knockout mice.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Collectively, our study identifies a novel RNA m&lt;sup&gt;6&lt;","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1473-1493"},"PeriodicalIF":41.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812441","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":"Under Pressure: Right Ventricular Obstruction by Pericardial Cyst.","authors":"Anika Shah, Gregory Troutman, Yoshiya Toyoda, Pravin Patil","doi":"10.1161/CIRCULATIONAHA.126.081912","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.126.081912","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"154 15","pages":"1541"},"PeriodicalIF":41.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165228","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":"Noninvasive Thrombus Imaging in Patients With Ischemic Stroke.","authors":"Beth Whittington, Craig Balmforth, Alessandro Giaj Levra, Laura Clark, Neil Craig, Audrey White, Krithika Loganath, Evangelos Tzolos, Allison Winarski, Rachael O Forsythe, Michael McDermott, Tariq Ramtoola, Phyo H Khaing, Sphamandla Ntshangase, Mark G Macaskill, Stefan Veizades, Mairi Brittan, Tim Clark, Michelle Rooney, Christophe Lucatelli, Piotr J Slomka, Norman Koglin, Andrew W Stephens, Iris Hardewig, Edwin J R van Beek, Marc R Dweck, Joanna Wardlaw, Michelle C Williams, William N Whiteley, David E Newby","doi":"10.1161/CIRCULATIONAHA.126.080420","DOIUrl":"10.1161/CIRCULATIONAHA.126.080420","url":null,"abstract":"<p><strong>Background: </strong>Determining the source of thromboembolism in patients with acute ischemic stroke remains challenging because current diagnostic approaches rely largely on circumstantial and inferential associations rather than direct identification of the cause of stroke. Fluorine-18 GP1 ([¹⁸F]GP1) is a novel radiotracer that binds with high affinity and specificity to activated glycoprotein IIb/IIIa receptors on activated platelets. We aimed to determine whether hybrid [¹⁸F]GP1 positron emission tomography (PET) and computed tomography angiography could identify in vivo cardiovascular thromboembolism in patients with acute ischemic stroke and provide a mechanism-based assessment of stroke etiology.</p><p><strong>Methods: </strong>In a single-center prospective observational cohort study, 100 patients presenting with acute ischemic stroke underwent hybrid [¹⁸F]GP1 PET/computed tomography angiography within 21 days of symptom onset in addition to standard-of-care stroke investigations. Stroke etiology was classified using the causative classification system by an expert stroke physician blinded to [¹⁸F]GP1 PET findings. In parallel, [¹⁸F]GP1 PET/computed tomography angiography images were analyzed independently by readers who were blinded to all clinical data and causative classification system classification. We assessed whether [¹⁸F]GP1 PET/computed tomography angiography could identify the source of in vivo cardiovascular thromboembolism, influence stroke classification, and predict recurrent cerebrovascular events.</p><p><strong>Results: </strong>Cardiovascular [¹⁸F]GP1 uptake indicative of thrombosis was identified in nearly two-thirds (n=63) of participants, changing stroke classification in over a quarter (n=26) of patients. In those with stroke of undetermined cause, the source of thrombus was identified in 18 of 41 (44%) participants, which included nonstenotic carotid atherothrombosis, native cardiac valve thrombosis, and paradoxical thromboembolism. During a median follow-up of 613 (interquartile interval, 251-788) days, recurrent stroke or transient ischemic attack occurred in 14 patients, 13 (93%) of whom had cardiovascular [¹⁸F]GP1 uptake at baseline. Cardiovascular [¹⁸F]GP1 uptake was associated with a 10.4-fold increased risk of recurrent events (95% CI, 1.35-79.40; <i>P</i>=0.024).</p><p><strong>Conclusions: </strong>Noninvasive thrombosis imaging is a novel technique that enables direct in vivo identification of thrombus formation and frequently reveals the source of thromboembolism in patients with acute ischemic stroke. This approach represents a shift from inference-based to mechanism-based stroke classification with potential implications for targeted prevention strategies and better patient outcomes.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05636748.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1424-1440"},"PeriodicalIF":41.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863831","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}