European heart journal open最新文献

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Testing if vitamin K1 reduces the progression of non-severe calcific aortic stenosis: design and rationale of the Prevention of Aortic Stenosis Progression Phylloquinone Ossification Reduction Trial (PASSPORT). 测试维生素K1是否能减少非严重钙化性主动脉狭窄的进展:预防主动脉狭窄进展叶绿醌骨化减少试验(PASSPORT)的设计和基本原理。
European heart journal open Pub Date : 2025-12-05 eCollection Date: 2025-11-01 DOI: 10.1093/ehjopen/oeaf144
William A Courtney, Jarryd Walker, Aindreas Dorai-Raj, Tom Gilbert, Adil Rajwani, Jamie W Bellinge, Jonathan M Hodgson, Graham S Hillis, Carl J Schultz
{"title":"Testing if vitamin K1 reduces the progression of non-severe calcific aortic stenosis: design and rationale of the Prevention of Aortic Stenosis Progression Phylloquinone Ossification Reduction Trial (PASSPORT).","authors":"William A Courtney, Jarryd Walker, Aindreas Dorai-Raj, Tom Gilbert, Adil Rajwani, Jamie W Bellinge, Jonathan M Hodgson, Graham S Hillis, Carl J Schultz","doi":"10.1093/ehjopen/oeaf144","DOIUrl":"10.1093/ehjopen/oeaf144","url":null,"abstract":"<p><strong>Aims: </strong>Calcific aortic stenosis (CAS) is the most common heart valvulopathy in high-income countries. There is no known treatment for CAS other than replacement of the valve in severe, symptomatic disease. Observational studies and a small openlabel randomized trial have reported that vitamin K1 supplementation may reduce the progression rate of calcification and obstruction in CAS.</p><p><strong>Methods and results: </strong>3PASSPORT(ACTRN12622000447752) will be a prospective, randomized, double-blind, placebo-controlled clinical trial investigating if nutritional supplementation with 10 mg of vitamin K1 can reduce the rate of valvular calcification and haemodynamic progression in CAS. Patients identified to have mild or moderate CAS based on standard echocardiographic criteria will be randomized 1:1 to vitamin K1 10 mg per day or matched placebo, and followed-up for a mean period of 16 months, ranging from 12 to 21 months. The primary endpoint will be the difference in aortic valve calcification volume, measured by computed tomography aortic valve calcium score, from baseline to follow-up, and secondary endpoints will include the change in echocardiographic progression of CAS, including peak flow velocity, mean pressure gradient, and aortic valve area. The trial is registered with the Australian New Zealand. Clinical Trials Registry (ACTRN12622000447752). The trial has met its recruitment target of 108 participants.</p><p><strong>Conclusion: </strong>PASSPORT will be prospective, randomized, double-blind clinical trial powered to demonstrate if oral supplementation with vitamin K1 reduces the progression of valvular calcification and echocardiographic severity of disease in patients with non-severe CAS. The trial results will have implications for the management of CAS, for which there is currently no medical treatment.</p>","PeriodicalId":93995,"journal":{"name":"European heart journal open","volume":"5 6","pages":"oeaf144"},"PeriodicalIF":0.0,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12715181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145806929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inflammation-resolution signalling in cardiac repair, remodelling, and heart failure. 心脏修复、重构和心力衰竭中的炎症消退信号。
European heart journal open Pub Date : 2025-12-04 eCollection Date: 2025-11-01 DOI: 10.1093/ehjopen/oeaf157
Ganesh V Halade, Magnus Bäck, Vasundhara Kain
{"title":"Inflammation-resolution signalling in cardiac repair, remodelling, and heart failure.","authors":"Ganesh V Halade, Magnus Bäck, Vasundhara Kain","doi":"10.1093/ehjopen/oeaf157","DOIUrl":"10.1093/ehjopen/oeaf157","url":null,"abstract":"<p><p>Chronic unresolved inflammation is a major driver for the genesis of cardiovascular disease, originating from unhealthy lifestyle interactions with a network of metabolic genes impacting overall immune fitness. Acute inflammation is a host defence response overlapping with safe clearance of inflammation, termed as resolution of inflammation, co-ordinated by nutritionally originated fatty acid's interaction with immune-responsive enzymes. Especially processing of polyunsaturated fatty acids by immune-responsive lipoxygenase and cyclooxygenase orchestrates the biosynthesis of specialized proresolving mediators. In contrast, dysregulation due to an imbalanced lifestyle, such as an unhealthy diet, lack of sleep, and exercise/low physical activity, drives non-resolving inflammation. Overall, the quality of fatty acids, enzymatic processing, on-time biosynthesis of SPMs, and precise activation of SPM-specific receptors operate cardiac repair in heart failure with reduced ejection fraction; however, the dysfunction of specific receptors, such as FPR2, drives obesogenic ageing and heart failure with preserved ejection fraction. Thus, the overlapping inflammation-resolution signalling pathways that are essential for cardiac repair and the prevention of cardiac damage are highly relevant to cardiometabolic disorders and the subsequent development of heart failure. Therefore, future research is warranted to study lifestyle factors that maintain the balance of inflammation-resolution signalling in cardiac health and develop new therapeutic targets for resolution medicine.</p>","PeriodicalId":93995,"journal":{"name":"European heart journal open","volume":"5 6","pages":"oeaf157"},"PeriodicalIF":0.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12728415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145835757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sex differences in the progression of cardiovascular-kidney-metabolic syndrome. 心肾代谢综合征进展的性别差异。
European heart journal open Pub Date : 2025-12-04 eCollection Date: 2025-11-01 DOI: 10.1093/ehjopen/oeaf162
Satoshi Taya, Kentaro Ejiri, Hidehiro Kaneko, Yuta Suzuki, Toru Miyoshi, Atsushi Mizuno, Toshiyuki Ko, Takahiro Jimba, Tatsuhiko Azegami, Akira Okada, Katsuhito Fujiu, Norifumi Takeda, Hiroyuki Morita, Kaori Hayashi, Koichi Node, Masaomi Nangaku, Hideo Yasunaga, Norihiko Takeda, Shinsuke Yuasa
{"title":"Sex differences in the progression of cardiovascular-kidney-metabolic syndrome.","authors":"Satoshi Taya, Kentaro Ejiri, Hidehiro Kaneko, Yuta Suzuki, Toru Miyoshi, Atsushi Mizuno, Toshiyuki Ko, Takahiro Jimba, Tatsuhiko Azegami, Akira Okada, Katsuhito Fujiu, Norifumi Takeda, Hiroyuki Morita, Kaori Hayashi, Koichi Node, Masaomi Nangaku, Hideo Yasunaga, Norihiko Takeda, Shinsuke Yuasa","doi":"10.1093/ehjopen/oeaf162","DOIUrl":"10.1093/ehjopen/oeaf162","url":null,"abstract":"<p><strong>Aims: </strong>Cardiovascular-kidney-metabolic (CKM) syndrome is a novel disease concept; however, sex differences in its progression remain uncertain. This study aimed to quantify the risk of cardiovascular disease (CVD) events across CKM stages and to explore sex differences in this association.</p><p><strong>Methods and results: </strong>We included 1 332 436 individuals (581 423 males and 751 013 females) from the DeSC database between 2014 and 2023 who had no prior CVD (i.e. CKM Stage 4). CKM stages were categorized as follows: Stage 0 (no CKM risk factors); Stage 1 (excess or dysfunctional adiposity); Stage 2 [metabolic risk factors and chronic kidney diseases (CKD)], and Stage 3 (subclinical CVD). We used Cox models to examine the association of CKM stages with the risk of CVD events (newly developed CKM Stage 4), including myocardial infarction, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The progression from CKM Stages 0 to 3 showed a dose-dependent increase in adjusted hazard ratios (HR) for developing CVD events, with the highest risk at Stage 3 [1.85 (95% CI: 1.80-1.90)]. A similar pattern was observed in both males and females. However, the magnitude of associations for CKM stages 1-3 differed between the sexes: HR by Stage 1, 1.12 (1.04-1.21) vs. 1.12 (1.07-1.16); by Stage 2, 1.78 (1.69-1.88) vs. 1.43 (1.39-1.48); by Stage 3, 1.99 (1.89-2.10) vs. 1.82 (1.76-1.88); and <i>P</i>-for-interaction values were 0.87, < 0.001, and 0.005, respectively.</p><p><strong>Conclusion: </strong>In this large nationwide cohort, CKM stage progression was associated with higher CVD risk in both sexes, with modest sex-specific differences. These findings highlight the value of CKM staging for early risk assessment, regardless of sex.</p>","PeriodicalId":93995,"journal":{"name":"European heart journal open","volume":"5 6","pages":"oeaf162"},"PeriodicalIF":0.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12728414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145835742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Setting the stage for cardiomyopathy gene editing trials: a systematic review of isogenic pair use in human induced pluripotent stem cell-derived cardiomyocyte research. 为心肌病基因编辑试验奠定基础:在人类诱导多能干细胞衍生的心肌细胞研究中使用等基因对的系统回顾。
European heart journal open Pub Date : 2025-12-03 eCollection Date: 2026-01-01 DOI: 10.1093/ehjopen/oeaf161
C Nina van der Wilt, Rogier J A Veltrop, Maaike H Janssens, Iara Bakker, Francesca Stillitano, Joost P G Sluijter, Linda W van Laake, Jolanda van der Velden, Eric Villard, Judith Montag, Chris Denning, J Peter van Tintelen, Anneline S J M Te Riele, Pim van der Harst, Leon J Schurgers, Frank G van Steenbeek, Magdalena Harakalova
{"title":"Setting the stage for cardiomyopathy gene editing trials: a systematic review of isogenic pair use in human induced pluripotent stem cell-derived cardiomyocyte research.","authors":"C Nina van der Wilt, Rogier J A Veltrop, Maaike H Janssens, Iara Bakker, Francesca Stillitano, Joost P G Sluijter, Linda W van Laake, Jolanda van der Velden, Eric Villard, Judith Montag, Chris Denning, J Peter van Tintelen, Anneline S J M Te Riele, Pim van der Harst, Leon J Schurgers, Frank G van Steenbeek, Magdalena Harakalova","doi":"10.1093/ehjopen/oeaf161","DOIUrl":"10.1093/ehjopen/oeaf161","url":null,"abstract":"<p><p><i>In vitro</i> gene editing using isogenic pairs of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) has demonstrated the feasibility of introducing or correcting specific pathogenic variants. These successes represent a key first step towards therapeutic genome editing for cardiomyopathies, showing that precise, variant-specific interventions are achievable. To translate <i>in vitro</i> findings to the clinic, it is essential to develop robust disease models that yield meaningful, translatable data. The next challenge is systematically identifying disease-causing variants amenable to gene editing with strong pre-clinical support. Therefore, we conducted a systematic search of published studies on isogenic hiPSC-CM pairs in cardiomyopathy research with specific criteria, including (likely) pathogenic variants causing cardiomyopathy, correction and/or introduction of variants, differentiation into CMs, and functional follow-up. We systematically assessed 785 papers and highlighted 101 studies meeting our inclusion criteria reporting 69 patients carrying 56 unique variants across 31 genes, most commonly <i>MYH7</i>, <i>MYBPC3</i>, and <i>DMD</i>. This expanded to 91 variants across 38 genes upon inclusion of the introduced variants in a donor line. However, reported clinical data were often incomplete, underscoring the need for standardized phenotypic documentation. We reveal a lack of patient details, which creates an incomplete picture of underlying disease variables that hinder the design of targeted personalized treatments. Omitted key clinical data can lead to misinterpretations or overlooked variables that impact treatment outcomes. This systematic review integrates current evidence from successful <i>in vitro</i> studies using isogenic hiPSC-CM models and proposes a reporting framework for variant prioritization and the rigorous application of isogenic controls in cardiomyopathy research.</p>","PeriodicalId":93995,"journal":{"name":"European heart journal open","volume":"6 1","pages":"oeaf161"},"PeriodicalIF":0.0,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12796640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145971740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prediction of major bleeding events for patients with dual antiplatelet therapy after myocardial infarction-a validation of the PRECISE-DAPT cancer score. 预测心肌梗死后双重抗血小板治疗患者的大出血事件——对PRECISE-DAPT癌症评分的验证
European heart journal open Pub Date : 2025-12-02 eCollection Date: 2025-11-01 DOI: 10.1093/ehjopen/oeaf137
Sacharias von Koch, Mamas A Mamas, Mohamed Dafaalla, Francesco Costa, Sasha Koul, Tomas Jernberg, David Erlinge, Moman A Mohammad
{"title":"Prediction of major bleeding events for patients with dual antiplatelet therapy after myocardial infarction-a validation of the PRECISE-DAPT cancer score.","authors":"Sacharias von Koch, Mamas A Mamas, Mohamed Dafaalla, Francesco Costa, Sasha Koul, Tomas Jernberg, David Erlinge, Moman A Mohammad","doi":"10.1093/ehjopen/oeaf137","DOIUrl":"10.1093/ehjopen/oeaf137","url":null,"abstract":"","PeriodicalId":93995,"journal":{"name":"European heart journal open","volume":"5 6","pages":"oeaf137"},"PeriodicalIF":0.0,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12671399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145673269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Association of pericoronary adipose tissue inflammation with coronary collateral vessel formation in patients with chronic left anterior descending occlusion. 慢性左前降闭塞患者冠状动脉旁支血管形成与冠状动脉周围脂肪组织炎症的关系。
European heart journal open Pub Date : 2025-11-27 eCollection Date: 2025-11-01 DOI: 10.1093/ehjopen/oeaf155
Chen Lv, Kang Zhou, Xing-Dou Chen, Qi-Ying Wu, Jin-Chang Li, Xian-Ming Fu
{"title":"Association of pericoronary adipose tissue inflammation with coronary collateral vessel formation in patients with chronic left anterior descending occlusion.","authors":"Chen Lv, Kang Zhou, Xing-Dou Chen, Qi-Ying Wu, Jin-Chang Li, Xian-Ming Fu","doi":"10.1093/ehjopen/oeaf155","DOIUrl":"10.1093/ehjopen/oeaf155","url":null,"abstract":"<p><strong>Aims: </strong>The role of pericoronary adipose tissue (PCAT) inflammation in coronary collateral circulation (CCC) development remains unclear. This study compared PCAT characteristics in chronic total occlusion (CTO) patients with good vs. poor collaterals.</p><p><strong>Methods and results: </strong>Twenty left anterior descending CTO patients were stratified into poor (P-CCC, <i>n</i> = 8) and good collateral (G-CCC, <i>n</i> = 12) groups per Rentrop classification. CT-derived fat attenuation index (FAI), epicardial adipose tissue (EAT) volume, and histologic markers (macrophage polarization, microvascular density) were analyzed. Compared with the P-CCC group, the G-CCC group exhibited significantly lower FAI (-93.6 ± 7.2 vs. -70.8 ± 2.4 HU, <i>P</i> < 0.05) but higher EAT volume [8491.3 (7951.6-13060.0) vs. 3452.8 (1741.7-6425.4) mm³, <i>P</i> < 0.05]. Histologically, relative to P-CCC PCAT, G-CCC PCAT showed increased M2 macrophage density (14.47 ± 2.87 vs. 3.47 ± 1.63, <i>P</i> < 0.05), a higher M2/M1 ratio (4.40 ± 2.17 vs. 0.95 ± 0.61, <i>P</i> < 0.05), and greater microvascular density (4.69 ± 1.11 vs. 2.21 ± 0.50, <i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>PCAT inflammation is associated with enhanced collateral vessel formation. These findings highlight PCAT's potential as a therapeutic target for collateral promotion, warranting further investigation into its molecular mechanisms.</p>","PeriodicalId":93995,"journal":{"name":"European heart journal open","volume":"5 6","pages":"oeaf155"},"PeriodicalIF":0.0,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12700156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145758788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Acute pharmacologic management of myocardial infarction in patients undergoing percutaneous coronary intervention: insights from the Italian nationwide EYESHOT-2 prospective registry. 经皮冠状动脉介入治疗患者心肌梗死的急性药物治疗:来自意大利全国EYESHOT-2前瞻性登记的见解
European heart journal open Pub Date : 2025-11-25 eCollection Date: 2025-11-01 DOI: 10.1093/ehjopen/oeaf154
Marco Zuin, Donata Lucci, Paolo Calabrò, Antonino Nicosia, Emanuele Tizzani, Ciro Mauro, Pier Luigi Temporelli, Lucio Gonzini, Aldo Pietro Maggioni, Massimo Grimaldi, Furio Colivicchi, Domenico Gabrielli, Fabrizio Oliva, Leonardo De Luca
{"title":"Acute pharmacologic management of myocardial infarction in patients undergoing percutaneous coronary intervention: insights from the Italian nationwide EYESHOT-2 prospective registry.","authors":"Marco Zuin, Donata Lucci, Paolo Calabrò, Antonino Nicosia, Emanuele Tizzani, Ciro Mauro, Pier Luigi Temporelli, Lucio Gonzini, Aldo Pietro Maggioni, Massimo Grimaldi, Furio Colivicchi, Domenico Gabrielli, Fabrizio Oliva, Leonardo De Luca","doi":"10.1093/ehjopen/oeaf154","DOIUrl":"10.1093/ehjopen/oeaf154","url":null,"abstract":"<p><strong>Aims: </strong>International guidelines recommend specific antithrombotic strategies for acute myocardial infarction (AMI) patients undergoing percutaneous coronary intervention (PCI). However, real-world practice often diverges. This study aimed to assess antithrombotic therapy use in AMI patients admitted to cardiac care units (CCUs) across Italy.</p><p><strong>Methods and results: </strong>The EmploYEd Antithrombotic Therapies in Patients with Acute Coronary Syndromes Hospitalized in Italian Cardiac Care Units (EYESHOT-2) registry (NCT06316128) is an Italian nationwide, prospective study evaluating AMI management, focusing primarily on PCI-treated patients. Between 1 and 29 February 2024, 2806 patients were enrolled across 183 Italian CCUs. Percutaneous coronary intervention was performed in 83.5% of cases, while 16.5% received conservative treatment. Patients not undergoing PCI were older, more often female, had more comorbidities, and were more frequently diagnosed with NSTEMI. Pre-treatment with dual antiplatelet therapy before angiography was administered in 58.4% of PCI-treated patients. In the cath lab, most received oral P2Y<sub>12</sub> inhibitors post-procedure. In-hospital outcomes favoured PCI, with lower rates of mortality, re-infarction, and major bleeding. Independent predictors of in-hospital bleeding among PCI patients included older age [odds ratio (OR) 1.05, 95% confidence interval (CI) 1.03-1.07, <i>P</i> < 0.0001], prior bleeding (OR 2.38, 95% CI 1.02-5.59, <i>P</i> = 0.046), recent surgery (OR 3.47, 95% CI 1.28-9.42, <i>P</i> = 0.01), Killip class III/IV (OR 1.75, 95% CI 1.00-3.05, <i>P</i> = 0.049), and femoral access (OR 2.85, 95% CI 1.80-4.49, <i>P</i> < 0.0001), while, among patients treated conservatively, included history of anaemia (OR 4.83, 95% CI 2.24-10.41, <i>P</i> < 0.0001) and peripheral vascular disease (OR 2.75, 95% 1.24-6.12, <i>P</i> = 0.01).</p><p><strong>Conclusion: </strong>This nationwide registry highlights improvements in AMI care in Italy but reveals persistent discrepancies between guideline-recommended and actual practice, underscoring the need for broader adoption of evidence-based strategies.</p><p><strong>Registration: </strong>URL: http://www.clinicaltrials.gov. NCT06316128.</p>","PeriodicalId":93995,"journal":{"name":"European heart journal open","volume":"5 6","pages":"oeaf154"},"PeriodicalIF":0.0,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12686988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145727912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
3D immunolabelling of human aortic valves by optimized CUBIC tissue clearing and its application for neural mapping in aortic stenosis. 优化立方组织清除的人主动脉瓣三维免疫标记及其在主动脉狭窄神经定位中的应用。
European heart journal open Pub Date : 2025-11-25 eCollection Date: 2026-01-01 DOI: 10.1093/ehjopen/oeaf156
Justine Bergeon, David Hupin, Jianjiang Hu, Sylvie Le Guyader, Anders Franco-Cereceda, Magnus Bäck
{"title":"3D immunolabelling of human aortic valves by optimized CUBIC tissue clearing and its application for neural mapping in aortic stenosis.","authors":"Justine Bergeon, David Hupin, Jianjiang Hu, Sylvie Le Guyader, Anders Franco-Cereceda, Magnus Bäck","doi":"10.1093/ehjopen/oeaf156","DOIUrl":"https://doi.org/10.1093/ehjopen/oeaf156","url":null,"abstract":"<p><p>Calcific aortic valve stenosis (CAVS) is characterized by significant structural alterations in the aortic valve. However, its neuroanatomical landscape remains poorly understood. In this study, we developed an optimized three-dimensional (3D) imaging approach that combined enhanced Clear, Unobstructed Brain Imaging Cocktails and Computational (CUBIC) tissue clearing and SWITCH-Off/On to visualize the neuronal architecture within calcified human aortic valves derived from patients undergoing aortic valve replacement surgery. Standard CUBIC analysis protocols have shown limited efficacy owing to poor clearing and antibody penetration in mineralized tissues. By integrating SWITCH chemistry before decalcification and refractive index matching, we achieved uniform delipidation, fluorescence preservation, and deep tissue labelling. Light-sheet fluorescence microscopy enabled high-resolution 3D reconstructions with an 80% success rate, revealing heterogeneous and spatially organized neuronal distributions across the aortic valve. This method offers a robust platform for studying valve innervation and its potential role in mechanosensing and disease progression, opening perspectives for neuro-targeted interventions in valvular heart disease.</p>","PeriodicalId":93995,"journal":{"name":"European heart journal open","volume":"6 1","pages":"oeaf156"},"PeriodicalIF":0.0,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12915582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146230347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mapping cardiac drug transport: In vitro assessment of cardiac P-glycoprotein function with [18F]MC225 by using µ-engineered heart tissues. 绘制心脏药物转运图:微工程心脏组织用[18F]MC225体外评估心脏p -糖蛋白功能
European heart journal open Pub Date : 2025-11-25 eCollection Date: 2025-11-01 DOI: 10.1093/ehjopen/oeaf150
Wanling Liu, Maureen Dannenberg, Pascalle Mossel, Zeyu Cai, Inês Farinha Antunes, Jurgen Sijbesma, Chantal Kwizera, Lu Cao, Andries van der Meer, Robert Passier, Riemer H J A Slart, Verena Schwach, Gert Luurtsema
{"title":"<i>Mapping cardiac drug transport: In vitro</i> assessment of cardiac P-glycoprotein function with [<sup>18</sup>F]MC225 by using µ-engineered heart tissues.","authors":"Wanling Liu, Maureen Dannenberg, Pascalle Mossel, Zeyu Cai, Inês Farinha Antunes, Jurgen Sijbesma, Chantal Kwizera, Lu Cao, Andries van der Meer, Robert Passier, Riemer H J A Slart, Verena Schwach, Gert Luurtsema","doi":"10.1093/ehjopen/oeaf150","DOIUrl":"10.1093/ehjopen/oeaf150","url":null,"abstract":"<p><strong>Aims: </strong>P-glycoprotein (P-gp), an efflux transporter with diverse compound effects, is a vital part of cardiac function. To determine if the selective substrate tracer [<sup>18</sup>F]MC225 also functions in cardiac P-gp, micro-engineered heart tissues (µ-EHTs) utilizing human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes were used. This model offers advantages in potentially reducing animal experiments and allowing direct evaluation on human cells. However, its adoption in nuclear medicine remains very limited. This study aims to evaluate [<sup>18</sup>F]MC225 as a measurement method for cardiac P-gp function using a heart-on-chip model.</p><p><strong>Methods and results: </strong>µ-EHTs were treated with the P-gp inhibitor Tariquidar (200 nM for 30 min) or the P-gp inducer Doxorubicin (1 µM for 24 h) and incubated with [<sup>18</sup>F]MC225 (1 MBq/mL for 30 min). First, we identified and confirmed the expression of P-gp in the µ-EHTs using immunofluorescent staining, which showed an increase of P-gp expression after Doxorubicin treatment. According to γ-counter measurements, Tariquidar-treated tissues exhibited a higher uptake (117.5 ± 33.67%, <i>n</i> = 24) (<i>P</i> = 0.035) than the control, compared to Doxorubicin-treated tissues which exhibited a lower uptake (63.97 ± 21.89%, <i>n</i> = 20) (<i>P</i> < 0.001) compared to its controls. Autoradiography visualized radioactive distribution in each µ-EHT and confirmed the γ-counter measurements.</p><p><strong>Conclusion: </strong>[<sup>18</sup>F]MC225 effectively evaluates and measures cardiac P-gp function in µ-EHTs on the heart-on-chip platform. This research sets the stage for future studies using P-gp function to evaluate the efficacy and safety of novel cardiovascular drugs using µ-EHTs.</p>","PeriodicalId":93995,"journal":{"name":"European heart journal open","volume":"5 6","pages":"oeaf150"},"PeriodicalIF":0.0,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12662796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145650549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characteristics, trends, and outcomes of ablation for persistent atrial fibrillation: a Danish cohort study. 持续性房颤消融的特点、趋势和结果:丹麦队列研究。
European heart journal open Pub Date : 2025-11-19 eCollection Date: 2025-11-01 DOI: 10.1093/ehjopen/oeaf148
Lise Da Riis-Vestergaard, Jacob Tønnesen, Martin H Ruwald, Regitze Hein, Christopher Ryan Zörner, Charlotte Middelfart, Arne Johannessen, Jim Hansen, Rene Husted Worck, Gunnar Gislason, Morten Lock Hansen
{"title":"Characteristics, trends, and outcomes of ablation for persistent atrial fibrillation: a Danish cohort study.","authors":"Lise Da Riis-Vestergaard, Jacob Tønnesen, Martin H Ruwald, Regitze Hein, Christopher Ryan Zörner, Charlotte Middelfart, Arne Johannessen, Jim Hansen, Rene Husted Worck, Gunnar Gislason, Morten Lock Hansen","doi":"10.1093/ehjopen/oeaf148","DOIUrl":"https://doi.org/10.1093/ehjopen/oeaf148","url":null,"abstract":"<p><strong>Aims: </strong>Catheter ablation (CA) is widely used for atrial fibrillation (AF), but pulmonary vein isolation (PVI) alone is less effective in persistent AF (peAF) than paroxysmal AF (PAF). Real-world data on patient selection, outcomes, and complications with PVI or PVI plus (≥1 additional line or CFAE/ganglionated plexi ablation) are limited. We examined characteristics, trends, recurrence, and complications in peAF ablations.</p><p><strong>Methods and results: </strong>Patients with peAF undergoing first-time catheter ablation between 2010 and 2020 were identified from the Danish National Ablation Database. They were categorized by ablation strategy (PVI or PVI plus), and baseline characteristics and trends were assessed. AF recurrence was analysed using cumulative incidence at one and five years, and across procedural years. Major adverse cardiovascular events (MACE) and procedure-related complications were also examined. Among 4144 peAF patients, 3.417 received PVI and 727 PVI plus. Baseline characteristics were similar, except the PVI plus group had longer diagnosis-to-ablation-time (mean 5.67 years vs. 3.9 years, <i>P</i> < 0.001) and more severe atrial enlargement (14.8% vs. 9.8%, <i>P</i> < 0.001). AF recurrence was higher with PVI plus at one- and five-years (54% vs. 46%, 77% vs. 68%). Recurrence rates declined over time (2010-2013 vs. 2018-2020). PVI plus use decreased from 58% to 15%. MACE and complication rates were low and similar.</p><p><strong>Conclusion: </strong>PVI plus was used less frequently over time and was associated with longer diagnosis-to-ablation times and larger left atria. We observed a proportional decline for both groups in AF recurrence across procedural years, and complication rates were low and similar.</p>","PeriodicalId":93995,"journal":{"name":"European heart journal open","volume":"5 6","pages":"oeaf148"},"PeriodicalIF":0.0,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12646157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145644026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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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