European Heart Journal最新文献

{"title":"EP4/ANXA2 axis in pulmonary arterial hypertension: therapeutic implications.","authors":"Hu Xu,Lan Ye,Chunxiu Du,Hui Tang,Qi Zheng,Chunhua Zhu,Bo Liang,Yali Wang,Xiuhui Mao,Qing Liang,Jiayao Zhang,Huishu Shao,Xiaowan Sun,Ruqiang Yuan,Weijing Yun,Changbiao Luo,Jiaming Xiu,Wen Su,Fenling Fan,Zhiyu Dai,Lihong Chen,Youfei Guan,Xiaoyan Zhang","doi":"10.1093/eurheartj/ehaf763","DOIUrl":"https://doi.org/10.1093/eurheartj/ehaf763","url":null,"abstract":"BACKGROUND AND AIMSPulmonary arterial hypertension (PAH) is a progressive condition marked by the abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs), leading to significant remodelling of the pulmonary arteries (PAs). The cyclooxygenase metabolite of arachidonic acid prostaglandin E2 and its receptor EP4 are crucial for maintaining vascular homeostasis. This study aimed to determine the role of EP4 in the pathogenesis of PAH and evaluate the potential of EP4 as a therapeutic target for PAH.METHODSTwo well-established PAH models, the monocrotaline-induced rat model and hypoxia/Su5416-induced mouse model, were used in this study. Both pharmacological interventions (including the EP4 antagonist grapiprant and MF498 and the agonist Cay10598) and genetic strategies (including vascular smooth muscle cell [VSMC]-specific EP4 knockout mice and VSMC-specific human EP4 transgenic mice) were used to comprehensively investigate the role of EP4 in the pathogenesis of PAH. Multiple cellular and molecular biology approaches were employed to investigate the underlying mechanisms.RESULTSThe results showed that the pharmacological blockade of the EP4 receptor and genetic deletion of the EP4 gene in VSMCs led to a significant improvement in PAH and PA remodelling. Conversely, pharmacological activation and VSMC-specific overexpression of EP4 exacerbate PAH progression. Further analysis identified annexin A2 (ANXA2) as a critical downstream mediator in EP4-induced PAH progression. Mechanistically, EP4 activation was found to enhance the translation of ANXA2 and phosphorylation of ANXA2 at Thr208 via the cAMP/PKA pathway, promoting PASMC proliferation and migration through increased nuclear translocation of β-catenin, a key signalling molecule in the canonical Wnt pathway. Importantly, pharmacological inhibition or genetic deletion of ANXA2 effectively protected PAH in rodents, suggesting its pathogenic role in PAH development.CONCLUSIONSThis study reveals a crucial pathway involving EP4 and ANXA2 in PAH development and progression. Targeting EP4 and its downstream effector ANXA2 represents promising therapeutic strategies for PAH management.","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":"93 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140401","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":"Abnormal electrocardiogram findings in athletes.","authors":"Gherardo Finocchiaro, Alessandro Zorzi, Mark Abela, Aaron Baggish, Silvia Castelletti, Elena Cavarretta, Guido Claessen, Domenico Corrado, Maria Sanz de la Garza, Sabiha Gati, Viviana Maestrini, Aneil Malhotra, Josef Niebauer, David Niederseer, Michael Papadakis, Antonio Pelliccia, Sanjay Sharma, Flavio D'Ascenzi","doi":"10.1093/eurheartj/ehaf646","DOIUrl":"https://doi.org/10.1093/eurheartj/ehaf646","url":null,"abstract":"<p><p>Athletes commonly exhibit a series of electrical, structural, and functional physiological changes which may overlap with cardiac pathology. The last two decades have witnessed a progressive improvement in understanding what can be considered benign for athletes and what may be deemed as potentially pathological and require further investigations. However, diagnostic uncertainties in the cardiac assessment of athletes are often encountered. In particular, the clinical significance of some electrocardiogram (ECG) findings may be uncertain. While uncommon and suggestive of an underlying cardiac condition, they may be identified among healthy athletes without additional pathological findings to support a unifying clinical diagnosis. This creates significant dilemmas for clinicians charged with determining sports eligibility and those who have the responsibility to help athletes in the decision-making process regarding future competitive sports participation. Current guidelines, recommendations, and position papers provide a roadmap for the differential diagnosis between 'athlete's heart' and cardiac disease. However, managing ECG findings of uncertain clinical significance, especially when initial diagnostic evaluation reveals no supportive signs of pathology, has received comparatively less attention, in particular, the type of cardiac investigations, the extent of diagnostic work-up and the need for follow-up require clarification. This document aims to provide guidance based on published evidence and expert opinions to assist in the clinical decision-making regarding ECG anomalies that are common sources of uncertainty when managing asymptomatic athletes.</p>","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":" ","pages":""},"PeriodicalIF":35.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136917","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":"Simultaneous transcatheter replacement of four cardiac valves in a 58-year-old female.","authors":"Changdong Zhang,Mei Liu,Xiaoke Shang","doi":"10.1093/eurheartj/ehaf757","DOIUrl":"https://doi.org/10.1093/eurheartj/ehaf757","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":"154 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134045","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":"Rare rupture at right-noncoronary commissure in giant sinus of Valsalva pseudoaneurysm with preserved valve function.","authors":"Bangjie Xun,Haoyu Gao,Jun Shi","doi":"10.1093/eurheartj/ehaf754","DOIUrl":"https://doi.org/10.1093/eurheartj/ehaf754","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":"41 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134136","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":"Cardiovascular magnetic resonance in the assessment of the risk of fatal or life-threatening ventricular arrhythmias in suspected vs diagnosed cardiac sarcoidosis.","authors":"Pauli Pöyhönen,Riina Kandolin,Markku Kupari","doi":"10.1093/eurheartj/ehaf758","DOIUrl":"https://doi.org/10.1093/eurheartj/ehaf758","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":"13 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134044","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":"The great mimicker: aortic extramural haematoma secondary to multi-branch systemic arterial rupture.","authors":"Min Liu,Wei Yu,Ziyang Zhu","doi":"10.1093/eurheartj/ehaf752","DOIUrl":"https://doi.org/10.1093/eurheartj/ehaf752","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":"15 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134046","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":"Ascending aortic pseudoaneurysm with sternal erosion and protrusion towards the body surface in a multiply reoperated Marfan patient: multimodal imaging.","authors":"Tingting Li,Xinran Xu,Wei Yu","doi":"10.1093/eurheartj/ehaf755","DOIUrl":"https://doi.org/10.1093/eurheartj/ehaf755","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":"81 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134067","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":"Drug-coated vs non-drug-coated devices for femoropopliteal artery interventions: long-term outcomes of the SAFE-PAD study.","authors":"Joseph M Kim,Robert W Yeh,Yang Song,Eric A Secemsky","doi":"10.1093/eurheartj/ehaf721","DOIUrl":"https://doi.org/10.1093/eurheartj/ehaf721","url":null,"abstract":"BACKGROUND AND AIMSFemoropopliteal artery disease is associated with high rates of post-revascularization restenosis. Drug-coated devices (DCD), including drug-coated balloons (DCBs) and drug-eluting stents (DES), have demonstrated efficacy in reducing restenosis rates compared to non-drug-coated devices (NDCDs). However, concerns about potential long-term mortality risks have led to regulatory scrutiny. This study represents the final report from the Safety Assessment of Femoropopliteal Endovascular Treatment with Paclitaxel-Coated Devices (SAFE-PAD) study, a pre-specified analysis designed with the US Food and Drug Administration to evaluate the long-term mortality associated with femoropopliteal DCD use.METHODSSAFE-PAD was a retrospective cohort study of 168 553 Medicare fee-for-service beneficiaries (≥66 years) who underwent femoropopliteal artery revascularization between 2015 and 2018. Device exposure (DCDs vs. NDCDs) was identified using Medicare claims data. The primary outcome was all-cause mortality, assessed between treatment groups using inverse probability treatment weighting. Secondary outcomes included all-cause hospitalizations, repeat revascularization, major amputation, and cardiovascular medication use. Sensitivity analyses included instrumental variable methods, falsification endpoints, and simulation of hypothetical unmeasured confounders. Subgroup analyses examined outcomes in inpatient vs outpatient settings, in younger/low-risk populations, and in high-risk chronic limb-threatening ischaemia patients.RESULTSAt a median follow-up of 4.3 years (maximum: 9.0 years), DCD use was not associated with increased mortality (adjusted hazard ratio: 0.98; 95% confidence interval: 0.97, 0.99), meeting the pre-specified 5% non-inferiority relative margin. Sensitivity analyses supported the validity of the primary result. Secondary outcomes showed similar hospitalization and amputation rates between groups but an increase in repeat revascularization with DCDs. Subgroup analyses confirmed safety findings across high/low-risk subgroups and across clinical settings.CONCLUSIONSIn this final report from the SAFE-PAD study, there was no evidence of long-term mortality risk associated with DCDs used for femoropopliteal revascularization. The SAFE-PAD study helped inform the reversal of regulatory warnings against routine DCD use.","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":"2 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134070","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":"Sex differences in atrial fibrillation-related atrial remodelling assessed by electroanatomic mapping and biopsy.","authors":"Kana Nakashima,Takanori Yamaguchi,Yuya Takahashi,Toyokazu Otsubo,Shigeki Shichida,Ryosuke Osako,Kodai Shinzato,Kotaro Tsuruta,Yuki Nishimura,Makoto Edayoshi,Yuki Kawano,Yukako Shintani-Domoto,Kai Miyazaki,Akira Fukui,Atsushi Kawaguchi,Shigehisa Aoki,Seitaro Nomura,Naohiko Takahashi,Kyoko Soejima,Kaoru Ito,Koichi Node","doi":"10.1093/eurheartj/ehaf768","DOIUrl":"https://doi.org/10.1093/eurheartj/ehaf768","url":null,"abstract":"BACKGROUND AND AIMSHistopathological sex differences in atrial structural remodelling in patients with non-valvular atrial fibrillation (AF) require further investigation.METHODSRight atrial biopsy was performed on 282 patients undergoing AF ablation and high-density voltage mapping (66 ± 12 years; 81 women). Of the 58 patients without AF undergoing supraventricular tachycardia ablation included, 26 underwent atrial biopsy and 41 underwent voltage mapping. The voltage at the biopsy site (Vbiopsy), global left atrial voltage (VGLA), and histopathological parameters (fibrosis, intercellular space, myofibrillar loss, myocardial nuclear density, and cardiomyocyte diameter) were evaluated.RESULTSVbiopsy (7.4 ± 2.6 vs 9.3 ± 3.2 mV, P < .001) and VGLA (4.9 ± 1.8 vs 6.7 ± 2.2 mV, P < .001) were significantly lower in women with AF. A similar relationship was observed in patients without AF: Vbiopsy (7.8 ± 2.7 vs 10.9 ± 2.6 mV, P < .001) and VGLA (7.3 ± 1.7 vs 9.4 ± 1.4 mV, P < .001) were lower in women. Vbiopsy and VGLA positively correlated in both groups (r = 0.70 and 0.60, P < .001), supporting an integrated interpretation of the voltage and histopathological data. No significant sex differences were observed among the histopathological parameters. In 34 patients with minimal histological change, small cardiomyocytes (<10 μm) were more frequent in women (37% ± 23% vs 20% ± 19%, P = .029).CONCLUSIONSDespite consistently lower voltage in women, no significant histopathological sex differences were identified in non-valvular cases, likely due to their inherently smaller atrial mass.","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":"93 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140252","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":"Importance of basic science and research training for the future generation of cardiologists.","authors":"Gemma Chiva-Blanch,Elisa Liehn,Ioanna Andreadou,Julien Barc,Bianca J J M Brundel,Sean M Davidson,Perry Elliott,Paul C Evans,Zoltan Giricz,Monika Gladka,Can Gollmann-Tepeköylü,Petra Kleinbongard,Thomas Krieg,Cecilia Linde,Thomas F Lüscher,Tomasz Guzik,Ange Maguy,Theresa McDonagh,Melanie Paillard,Radoslaw Parma,Maurizio Pesce,Giulio Pompilio,Maria Rubini,Katrin Streckfuss-Bömeke,Matthias Thielmann,Carlo G Tocchetti,Sophie Van Linthout,Panagiotis Vardas,Pascal Vranckx,Johann Wojta,Cinzia Perrino","doi":"10.1093/eurheartj/ehaf738","DOIUrl":"https://doi.org/10.1093/eurheartj/ehaf738","url":null,"abstract":"Advances in the battle against cardiovascular diseases depend upon continuously translating emerging scientific knowledge from preclinical studies and clinical trials into innovative and effective therapeutic strategies. Over the past three decades, molecular and cellular biology have undergone a profound transformation, and large-scale, single-cell, and multi-omics studies have enabled investigations on cardiac disease mechanisms with unprecedented precision. However, these rapid advancements have also contributed to a divergence between the needs and aspirations of basic researchers and those of clinical scientists and practicians, to the detriment of discovery science, precision medicine, and cardiovascular healthcare. The present document highlights the importance of education and training in overcoming the gap between discovery and clinical science, by promoting a common language aimed at designing more translationally relevant and impactful discovery science. To achieve this aim, multidisciplinary efforts will be required to better define learning objectives within training programmes, including education in discovery and clinical sciences, promotion of specific mentorship paths, collaborative research efforts, promotion of equality, diversity, and inclusion, and protection of research time and activity within academic, clinical, and research careers.","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":"41 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134066","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}