European Heart Journal最新文献

{"title":"SLC31A1 loss depletes mitochondrial copper and promotes cardiac fibrosis","authors":"Bin Tu, Kai Song, Ze-Yu Zhou, Li-Chan Lin, Zhi-Yan Liu, He Sun, Yang Zhou, Ji-Ming Sha, Yan Shi, Jing-Jing Yang, Ye Zhang, Jian-Yuan Zhao, Hui Tao","doi":"10.1093/eurheartj/ehaf130","DOIUrl":"https://doi.org/10.1093/eurheartj/ehaf130","url":null,"abstract":"Background and Aims Metals serve as co-factors for a host of metalloenzymes involved in mitochondrial metabolic reprogramming. Modifications in metal homeostasis are linked to epigenetic mechanisms. However, the epigenetic mechanisms through which metal affects cardiac fibrosis (CF) remain poorly understood. Methods The metal content of mouse heart samples was measured using inductively coupled plasma mass spectrometry. Cardiac fibroblast-specific MeCP2-deficient mice and control mice were treated with isoprenaline/angiotensin II to induce CF. AAV9 carrying POSTN promoter-driven small hairpin RNA targeting MeCP2, YTHDF1, or SLC31A1 and the copper-chelating agent tetrathiomolybdate were administered to investigate their vital roles in CF. Histological and biochemical analyses were performed to determine how YTHDF1/MeCP2 regulated SLC31A1 expression in CF. The reconstitution of SLC31A1 in YTHDF1/MeCP2-deficient cardiac fibroblasts and mouse hearts was performed to study its effect on mitochondrial copper depletion and fibrosis. Human heart tissues from atrial fibrillation patients were used to validate the findings. Results Lower copper concentrations are accompanied by SLC31A1 down-regulation and mitochondrial copper depletion in CF. Fibroblast-specific SLC31A1 deficiency enhances mitochondrial copper depletion, augments glycolysis, promotes fibroblast proliferation and triggers CF. SLC31A1 inhibition due to increased MeCP2-recognized methylating CpG islands of SLC31A1 in the promoter region restrains its transcription. Conversely, MeCP2 knockdown rescued SLC31A1 expression, resulting in contradictory effects. MeCP2 up-regulation is associated with elevated m6A mRNA levels. Mechanistically, YTHDF1 recognizes target MeCP2 mRNA and induces its translation. In human heart tissues from atrial fibrillation patients, reduced copper concentrations and SLC31A1 expression, along with elevated levels of YTHDF1 and MeCP2, were observed. These changes were associated with mitochondrial copper depletion, enhanced glycolysis, and CF. Conclusions A novel epigenetic mechanism was demonstrated through which copper deficiency increases mitochondrial copper depletion and impairs CF. Findings provide new insights for the development of preventive measures for CF.","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":"18 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143570431","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":"Missing 'lncs': how insufficient scrutiny can lead to misrepresentation of long non-coding RNAs (lncRNAs) and their function in cardiovascular disease.","authors":"Matthew Bennett, Igor Ulitsky, Andrew H Baker","doi":"10.1093/eurheartj/ehaf115","DOIUrl":"https://doi.org/10.1093/eurheartj/ehaf115","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":" ","pages":""},"PeriodicalIF":37.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572042","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":"Medical therapy and outcomes in REVIVED-BCIS2 and STICHES: an individual patient data analysis","authors":"Matthew Ryan, Mark C Petrie, Evangelos Kontopantelis, Matthew Dodd, Guangyu Tong, Guillaume Marquis-Gravel, Kieran F Docherty, Tim Clayton, Alexandra J Lansky, Mamas A Mamas, Jean-Lucien Rouleau, Eric J Velazquez, Divaka Perera","doi":"10.1093/eurheartj/ehaf080","DOIUrl":"https://doi.org/10.1093/eurheartj/ehaf080","url":null,"abstract":"Background and Aims In the Surgical Treatment for Ischaemic Heart Failure Trial Extension Study (STICHES), coronary artery bypass grafting (CABG) improved outcomes of patients with ischaemic left ventricular dysfunction receiving medical therapy, whereas in the Revascularization for Ischaemia Ventricular Dysfunction trial (REVIVED-BCIS2), percutaneous coronary intervention (PCI) did not. The aim of this study was to explore differences in outcomes of participants treated with medical therapy alone in STICHES vs. REVIVED-BCIS2 and to assess the incremental benefit of CABG or PCI. Methods Pooled analysis of adjusted individual participant data from two multicentre randomized trials. All patients had left ventricular ejection fraction ≤35% and coronary artery disease and received medical therapy. Participants were randomized 1:1 to CABG (STICHES) or PCI (REVIVED-BCIS2). The primary outcome was the composite of all-cause death and hospitalization for heart failure over all available follow-up. Results A total of 1912 participants (88% male, 76% white ethnicity) were included with 98.3% completeness of follow-up for the primary outcome. The median follow-up was 118 months in STICHES and 41 months in REVIVED-BCIS2. Those receiving medical therapy alone in REVIVED-BCIS2 had fewer primary outcome events than those receiving medical therapy alone in STICHES (adjusted hazard ratio 0.60, 95% confidence interval 0.48–0.74, P < .001). Patients receiving PCI in REVIVED-BCIS2 were less likely to experience a primary outcome event than those receiving CABG in STICHES. Adjusted outcomes of patients treated with CABG in STICHES were worse than those receiving medical therapy alone in REVIVED-BCIS2. Conclusions Patients with ischaemic cardiomyopathy receiving medical therapy in REVIVED-BCIS2 had better outcomes than those in STICHES, with or without CABG surgery. Further trials comparing CABG, PCI, and medical therapy in this population are warranted.","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":"13 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143570430","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":"Common and divergent cellular aetiologies underlying hypoplastic left heart syndrome and hypoplastic right heart syndrome.","authors":"Yang Yu, Cankun Wang, Shiqiao Ye, Hannah Qin, Matthew Alonzo, Angela Onorato, Aaron Argall, Karen Texter, Qin Ma, Vidu Garg, Ming-Tao Zhao","doi":"10.1093/eurheartj/ehaf121","DOIUrl":"https://doi.org/10.1093/eurheartj/ehaf121","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":" ","pages":""},"PeriodicalIF":37.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572634","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":"A rare splice-site variant in TNNT2: the need for ancestral diversity in genomic reference data sets.","authors":"Alexandra Butters, Kate Thomson, Franki Harrington, Natasha Henden, Karen McGuire, Alicia B Byrne, Samantha Bryen, Kathryn A McGurk, Megan Leask, Michael J Ackerman, John Atherton, Johan M Bos, Colleen Caleshu, Sharlene M Day, Kyla Dunn, Ian Hayes, Jimmy Juang, Julie McGaughran, Natalie Nowak, Victoria N Parikh, Anne Ronan, Christopher Semsarian, Jil C Tardiff, Marianne Tiemensma, Tony R Merriman, James S Ware, Jonathan R Skinner, Daniel G MacArthur, Owen M Siggs, Richard D Bagnall, Jodie Ingles","doi":"10.1093/eurheartj/ehaf001","DOIUrl":"10.1093/eurheartj/ehaf001","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":" ","pages":""},"PeriodicalIF":37.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556266","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":"High intensity exercise programme in patients with hypertrophic cardiomyopathy: a randomized trial","authors":"Joyee Basu, Dimitra Nikoletou, Chris Miles, Hamish MacLachlan, Gemma Parry-Williams, Fred Tilby-Jones, Paulo Bulleros, Zephryn Fanton, Claire Baker, Shane Purcell, Carmen Lech, Tracy Chapman, Peter Sage, Shams Wahid, Nabeel Sheikh, Shruti Jayakumar, Aneil Malhotra, Tracey Keteepe-Arachi, Belinda Gray, Gherardo Finocchiaro, Gerald Carr-White, Elijah Behr, Maite Tome, Jamie O’Driscoll, Irina Chis Ster, Sanjay Sharma, Michael Papadakis","doi":"10.1093/eurheartj/ehae919","DOIUrl":"https://doi.org/10.1093/eurheartj/ehae919","url":null,"abstract":"Background and Aims The feasibility and impact of high intensity exercise programmes in patients with hypertrophic cardiomyopathy (HCM) are unknown. This study was conducted to determine the feasibility of a high intensity exercise programme and explore safety and efficacy outcomes in patients with HCM. Methods Participants were randomized to a 12-week supervised exercise programme (n = 40) in addition to usual care, or usual care alone (n = 40). All participants underwent assessment at baseline and 12 weeks. The exercise group was re-evaluated 6 months post-programme. Feasibility was assessed by (i) recruitment, adherence, and retention rates; (ii) staffing ratios; (iii) logistics; and (iv) acceptability of the intervention. The primary exploratory safety outcome was a composite of arrhythmia-related events. Exploratory secondary outcomes included changes in (i) cardiorespiratory fitness; (ii) cardiovascular risk factors; and (iii) quality of life, anxiety, and depression scores. Results Overall, 67 (84%) participants completed the study (n = 34 and n = 33 in the exercise and usual care groups, respectively). Reasons for non-adherence included travel, work, and family commitments. Resource provision complied with national cardiac rehabilitation standards. There was no difference between groups for the exploratory safety outcome (P = .99). At 12 weeks, the exercise group had a greater increase in peak oxygen consumption (VO2) [+4.1 mL/kg/min, 95% confidence interval (CI) 1.1, 7.1] and VO2 at anaerobic threshold (+2.3 mL/kg/min, 95% CI 0.4, 4.1), lower systolic blood pressure (−7.3 mmHg, 95% CI −11.7, −2.8) and body mass index (−0.8 kg/m2, 95% CI −1.1, −0.4), and greater improvement in hospital anxiety (−3, 95% CI −4.3, −1.7) and depression (−1.7, 95% CI −2.9, −0.5) scores, compared to the usual care group. Most exercise gains dissipated at 6 months. Conclusions A high intensity exercise programme is feasible in patients with HCM, with apparent cardiovascular and psychological benefits, and no increase in arrhythmias. A large-scale study is required to substantiate findings and assess long-term safety of high intensity exercise in HCM.","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":"7 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546539","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":"Empagliflozin in resistant hypertension and heart failure with preserved ejection fraction: the EMPEROR-Preserved trial.","authors":"Michael Böhm, Javed Butler, Andrew Coats, Lucas Lauder, Felix Mahfoud, Gerasimos Filippatos, João Pedro Ferreira, Stuart J Pocock, Martina Brueckmann, Sibylle J Hauske, Elke Schueler, Christoph Wanner, Subodh Verma, Faiez Zannad, Milton Packer, Stefan D Anker","doi":"10.1093/eurheartj/ehae938","DOIUrl":"https://doi.org/10.1093/eurheartj/ehae938","url":null,"abstract":"<p><strong>Background and aims: </strong>Hypertension has a high prevalence in heart failure with preserved ejection fraction (HFpEF), which can be controlled, uncontrolled, or even resistant. The effects of empagliflozin on systolic blood pressure (SBP), time in target range, incidence of hypertensive urgencies, and studied cardiovascular and renal outcomes in different hypertension categories and after treatment with empagliflozin in the EMPEROR-Preserved trial were explored.</p><p><strong>Methods: </strong>A total of 5533 patients were studied and the population was separated into resistant (resHTN), uncontrolled (uctrHTN), and controlled (ctrHTN) hypertension. The effect of SBP on outcomes and treatment effects of empagliflozin were explored. Analyses were done with Cox regression analyses adjusted for demographic and clinical confounders and with a mixed model for repeated measures.</p><p><strong>Results: </strong>Empagliflozin reduced SBP in resHTN slightly more than in the other categories in the first weeks, while thereafter there were no significant differences. The modest reduction in SBP resulted in a moderate increase in time at target and reduced hypertensive urgencies. The primary endpoint was more prevalent in resHTN (P = .0358), but the treatment effect of empagliflozin on the primary endpoint was similar in resHTN, uctrHTN, and ctrHTN (P for interaction = .92) as was the improvement of the estimated glomerular filtration rate slope (P for interaction = .95) and change in quality of life by empagliflozin.</p><p><strong>Conclusions: </strong>In HFpEF, the prevalence of resHTN is high and is associated with frequently higher outcome rates compared with ctrHTN and uctrHTN. The treatment effect was not modified by hypertension categories. This indicates that in HFpEF, moderate modifications of blood pressure do not affect overall outcomes and treatment effects of empagliflozin.</p>","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":" ","pages":""},"PeriodicalIF":37.6,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556269","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":"Distinct inflammatory pathways shape atherosclerosis in different vascular beds","authors":"Oliver Soehnlein, Esther Lutgens, Yvonne Döring","doi":"10.1093/eurheartj/ehaf054","DOIUrl":"https://doi.org/10.1093/eurheartj/ehaf054","url":null,"abstract":"Studies suggest varying atherosclerotic cardiovascular disease (ASCVD) prevalence across arterial beds. Factors such as smoking expedite ASCVD progression in the abdominal aorta, while diabetes accelerates plaque development in lower limb arteries, and hypertension plays a significant role in ASCVD development in the coronary and carotid arteries. Moreover, superficial femoral atherosclerosis advances slower compared with atherosclerosis in coronary and carotid arteries. Furthermore, femoral atherosclerosis exhibits higher levels of ossification and calcification, but lower cholesterol concentrations compared with atherosclerotic lesions of other vascular beds. Such disparities exemplify the diverse progression of ASCVD across arterial beds, pointing towards differential mechanistic pathways in each vascular bed. Hence, this review summarizes current literature on immune-inflammatory mechanisms in various arterial beds in ASCVD to advance our understanding of this disease in an aging society with increased need of vascular bed and patient-specific treatment options.","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":"97 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546538","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":"Tafamidis in octogenarians with wild-type transthyretin cardiac amyloidosis: an international cohort study","authors":"Philippe Debonnaire, Karl Dujardin, Nicolas Verheyen, Anne-Catherine Pouleur, Steven Droogmans, Mathias Claeys, Alexandre Bohyn, Kris Bogaerts, Milad El Haddad, Emma Christiaen, Nicolas Wyseure, David K Zach, Lars Buytaert, Annemie Jacobs, Ian Buysschaert, Sander Trenson, Raf Van Hoeyweghen, René Tavernier","doi":"10.1093/eurheartj/ehae923","DOIUrl":"https://doi.org/10.1093/eurheartj/ehae923","url":null,"abstract":"Background and Aims In real-world, wild-type transthyretin cardiomyopathy is increasingly diagnosed in patients ≥ 80 years old (octogenarians), although being underrepresented in randomized clinical trials. Specific data on natural course and outcome under tafamidis treatment in octogenarians are therefore scarce. The impact of tafamidis treatment on mortality in real-world wild-type transthyretin cardiomyopathy octogenarians was studied. Methods An international, multicentre cohort study of 710 consecutive wild-type transthyretin cardiomyopathy patients with mean follow-up of 2.2 ± 1.8 years for all-cause mortality endpoint was performed. Results The cohort consisted of 58.5% (415/710) octogenarians (85 ± 4 years, 74.2% male). Before tafamidis availability, natural course in octogenarians (148/257) vs. non-octogenarians (109/257) was poor, with 16% 1-year and 71% 5-year mortality vs. 8% and 47%, respectively (P &amp;lt; .001). Since tafamidis availability, 70.1% (253/361) octogenarians were initiated on tafamidis vs. 83.7% (231/276) non-octogenarians (P &amp;lt; .001). Tafamidis discontinuation was similar (octogenarians 10.3% and non-octogenarians 7.4%; P = .260). Overall tafamidis treated vs. untreated octogenarians had better unadjusted survival (P &amp;lt; .001), with 5% 1-year and 24% 3-year mortality. Tafamidis treatment associated with lower mortality after propensity score matching on baseline variables, including age, National Amyloidosis Centre stage, and New York Heart Association class in on average 394 subjects [hazard ratio (HR) = 0.53, 95% confidence interval (CI) 0.34–0.84, P = .007], also in octogenarians (HR = 0.57, 95% CI 0.33–1.01, P = .053). Neither age at diagnosis (P = .217) nor at treatment initiation (P = .154) interacted with tafamidis mortality benefit. Octogenarians had poorer survival despite tafamidis, when initiated at ≥90 years (HR = 3.3, 95% CI 1.10–9.53, P = .033) and National Amyloidosis Centre Stage ≥3 (HR = 2.4, 95% CI 0.87–6.46, P = .090). Conclusions Real-world tafamidis treatment improves survival without age affecting treatment efficacy, although mortality remains considerable in octogenarians.","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":"2 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546627","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":"Gaining the upper hand on peripheral artery disease.","authors":"Francisco Ujueta, Aaron W Aday, Marie Gerhard-Herman","doi":"10.1093/eurheartj/ehaf132","DOIUrl":"https://doi.org/10.1093/eurheartj/ehaf132","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":" ","pages":""},"PeriodicalIF":37.6,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556275","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}