Shen Li,Hongbo Liu,Sujin Lee,Eunji Ha,Bernhard Dumoulin,Matthew B Palmer,Clint L Miller,Scott M Damrauer,Rajeev Malhotra,Katalin Susztak
{"title":"Transcription factor TBX2 is a key regulator of vascular calcification","authors":"Shen Li,Hongbo Liu,Sujin Lee,Eunji Ha,Bernhard Dumoulin,Matthew B Palmer,Clint L Miller,Scott M Damrauer,Rajeev Malhotra,Katalin Susztak","doi":"10.1093/eurheartj/ehag756","DOIUrl":"https://doi.org/10.1093/eurheartj/ehag756","url":null,"abstract":"Abstract Background and Aims Vascular calcification predicts cardiovascular mortality more strongly than traditional risk factors, yet its molecular basis remains poorly understood. The burden is greatest in chronic kidney disease (CKD), where disordered mineral metabolism accelerates arterial mineral deposition. Methods Cross-trait genome-wide and phenome-wide association analyses were combined with single-cell RNA-seq and ATAC-seq from human kidneys and coronary arteries to identify upstream regulators. Chromatin immunoprecipitation sequencing and expression profiling were used to assess direct transcriptional control. Functional relevance was evaluated in multiple gene-edited mouse lines and in primary vascular smooth muscle cells (VSMCs) targeting T-box transcription factor 2 (TBX2), Runt-related transcription factor 2 (RUNX2), NLRP3, CASP1, and GSDMD. Results GWAS followed by expression quantitative trait loci (eQTL) and Bayesian colocalization analysis prioritized TBX2 as a shared genetic locus associated with kidney function and calcification-related cardiometabolic traits. TBX2-deficient mice exhibited increased susceptibility to vascular calcification, hypercalciuria, kidney injury, bone demineralization, and systemic phosphate dysregulation under CKD-like phosphate stress conditions. TBX2 deficiency promoted VSMC calcification and osteochondrogenic differentiation in vitro. Mechanistically, TBX2 acted as a transcriptional repressor by binding the promoter of RUNX2, a key osteogenic transcription factor, and suppressing its expression. Deletion of RUNX2 in TBX2-deficient VSMCs abolished TBX2 loss–induced calcification. TBX2-deficient VSMCs were also more sensitive to activation of the NLRP3 inflammasome by microcrystals generated from osteogenic VSMCs. Genetic deletion of NLRP3, CASP1, or GSDMD in TBX2-deficient mice attenuated vascular calcification and renal injury. In human samples, TBX2 expression inversely correlated with the severity of kidney fibrosis and was reduced in calcified vascular lesions. Conclusions Integrative genetic, cellular, and animal studies identify TBX2 as a central transcriptional repressor linking mineral dysregulation, osteogenic signalling, and sterile inflammation in CKD-associated vascular calcification. Therapeutic strategies that restore TBX2 function or target its RUNX2–NLRP3 axis may reduce cardiovascular risk in patients with CKD.","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":"58 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087958","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}
Masahiko Umei,Gerhard-Paul Diller,Margarita Brida,Tuan-Chen Aw,Andreas Hoschtitzky,Aleksander Kempny,Michael A Gatzoulis
{"title":"Adults with congenital heart disease: the growing impact of acquired cardiovascular risk factors on late mortality","authors":"Masahiko Umei,Gerhard-Paul Diller,Margarita Brida,Tuan-Chen Aw,Andreas Hoschtitzky,Aleksander Kempny,Michael A Gatzoulis","doi":"10.1093/eurheartj/ehag787","DOIUrl":"https://doi.org/10.1093/eurheartj/ehag787","url":null,"abstract":"Abstract Background and Aims With improved survival, adults with congenital heart disease (ACHD) increasingly face acquired cardiovascular risk factors; however, their impact on late mortality remains incompletely defined. This study aimed to evaluate the contribution of acquired cardiovascular risk factors to mortality in ACHD. Methods A total of 9826 ACHD patients (mean age 39.0 ± 16.4 years; 50.3% male) who attended our tertiary centre between 2000 and 2024 were retrospectively analysed. Clinical and demographic data were obtained from a prospectively maintained database. Cox proportional hazards models were used to assess associations between risk factors and all-cause mortality. Results During a median follow-up of 10.0 years (98 764 patient-years), 1371 patients died (mortality rate 1.39% per patient-year). In multivariable analysis, older age (hazard ratio [HR] 1.07 per year; P < .001), male sex (HR 1.30; P = .026), greater lesion complexity (HR 2.12; P < .001), coronary artery disease (HR 1.78; P = .005), sleep apnoea (HR 2.22; P < .001), depression (HR 1.45; P = .010), and current smoking (HR 1.67; P < .001) were independently associated with higher mortality, while higher income was associated with lower mortality risk. Conclusions Both congenital lesion complexity and acquired comorbidities are associated with late mortality in ACHD. These data support the need for comprehensive, multidisciplinary management that incorporates timely modification of general cardiovascular and other risk factors alongside congenital heart disease-specific care.","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":"75 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087960","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":"Accidental stent-graft deployment into the false lumen during thoracic endovascular aortic repair for Stanford type B aortic dissection after Bentall procedure, salvaged by re-stenting via the true lumen","authors":"Youyi Zhu,Hongwei Zhang,Zihao Li","doi":"10.1093/eurheartj/ehag798","DOIUrl":"https://doi.org/10.1093/eurheartj/ehag798","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":"15 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087962","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":"Biventricular vs conduction system pacing after atrioventricular node ablation for heart failure with atrial fibrillation: the CONDUCT-AF trial","authors":"David Žižek,Maja Ivanovski,Miha Mrak,Catalin Pestrea,Ecaterina Cicala,Sandro Brusich,Ivana Grgić Romić,Peter Bógyi,Gábor Zoltán Duray,Sebastiaan Dhont,Vassil Traykov,Josip Kedžo,Matevž Jan,Miroslav Krpan,Luka Klemen,Bor Antolič,Jakob Peterlin,Tadej Žlahtič,Tomaž Podlesnikar,Wilfried Mullens,Anja Zupan Mežnar,of CONDUCT-AF Investigators,David Žižek,Anja Zupan Mežnar,Wilfried Mullens,Miha Mrak,Sandro Brusich,Matjaž Šinkovec,Andrej Pernat,Zlatko Fras,Maja Ivanovski,Tomaž Podlesnikar,Jakob Peterlin,Tadej Žlahtič,Bor Antolič,Martin Rauber,Luka Klemen,Nastja Žgalin,Kristian Franić,Tanja Andoljšek Simonič,Matevž Jan,Jernej Štublar,Catalin Pestrea,Ecaterina Cicala,Roxana Enache,Peter Bogyi,Gabor Zoltan Duray,Balazs Polgar,Nikolett Vigh,Ivana Grgić Romić,Ana Lanča Bastiančić,David Židan,Zrinka Jurišić,Josip Kedžo,Borka Pezo Nikolić,Miroslav Krpan,Vassil Traykov,Momchil Marinov,Denislav Boychev,Emiliyan Martinov,Daniel Marchov,Gergana Litsova,Vyara Konstantinova,Sebastiaan Dhont,Jonas Erzeel,Günther Prenner","doi":"10.1093/eurheartj/ehag699","DOIUrl":"https://doi.org/10.1093/eurheartj/ehag699","url":null,"abstract":"Abstract Background and Aims Randomized evidence comparing conduction system pacing (CSP) and biventricular pacing (BVP) following atrioventricular node ablation in patients with refractory atrial fibrillation (AF) and heart failure (HF) remains limited. This study evaluated whether CSP with left bundle branch area pacing is non-inferior to BVP in patients undergoing atrioventricular node ablation. Methods CONDUCT-AF was an investigator-initiated, multicentre, randomized trial conducted across 10 European centres. Patients with refractory AF, HF with left ventricular ejection fraction (LVEF) < 50%, narrow QRS duration (≤120 ms), and N-terminal pro-B-type natriuretic peptide > 600 ng/L were randomized 1:1 to CSP or BVP. The primary endpoint was the change in LVEF after 6 months, assessed by an independent core laboratory. Secondary endpoints included echocardiographic, clinical, and procedural outcomes. Analyses followed the intention-to-treat principle. Results Eighty-two patients were randomized (mean age 72 ± 7 years, 46% male). At 6 months, LVEF improved similarly in CSP {from 36% [95% confidence interval (CI) 33–39] to 46% [95% CI 44–49]; P < .001} and BVP group [from 34% (95% CI 31–36) to 46% (95% CI 43–49); P < .001]. The between-group difference was .4% (95% CI −3.1–3.8; P = .002 for non-inferiority). Changes in left ventricular volumes, clinical parameters, and composite endpoint of worsening HF or cardiovascular death were comparable between groups. Paced QRS [mean difference −14 ms (95% CI −19 to −9; P < .001)] and procedural and fluoroscopy times were significantly shorter with CSP compared with BVP. Conclusions In HF patients with refractory AF undergoing atrioventricular node ablation, CSP with left bundle branch area pacing was non-inferior to BVP for LVEF improvement at 6 months, providing comparable clinical outcomes and a favourable procedural profile.","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":"13 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087955","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}
Carlo Di Mario,Giulia Nardi,Niccolò Ciardetti,Alessio Mattesini
{"title":"Intravascular imaging from research tool to guidelines: a 35-year long journey","authors":"Carlo Di Mario,Giulia Nardi,Niccolò Ciardetti,Alessio Mattesini","doi":"10.1093/eurheartj/ehag237","DOIUrl":"https://doi.org/10.1093/eurheartj/ehag237","url":null,"abstract":"Abstract Initially developed to overcome the limitations of angiography in visualizing plaque morphology, intravascular ultrasound and optical coherence tomography have advanced dramatically in resolution, acquisition speed, and analytical automation. These techniques now provide detailed, real-time assessment of coronary artery structure, enabling precise stent sizing, calcium characterization, and optimization of percutaneous coronary interventions. Clinical trials and meta-analyses demonstrated that intravascular imaging-guided PCI significantly reduces restenosis, thrombosis, target lesion failure, and cardiac mortality compared with angiography-guided approaches. These achievements underpin the current Class I, Level A recommendations for intravascular imaging-guidance of complex PCI in the most recent ESC and ACC/AHA/SCAI guidelines. Intravascular imaging has also become instrumental in studying atherosclerosis regression, plaque vulnerability, and the effects of lipid-lowering therapies such as statins and PCSK9 inhibitors, allowing the implementation of personalized prevention and intervention strategies. Intravascular imaging remains grossly underused in clinical practice but better reimbursement, improved and mandatory training and the integration of artificial intelligence for image interpretation may facilitate a wider application.","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":"83 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149092288","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}
Thomas W Johnson, Nieves Gonzalo, Jose M de la Torre Hernandez, Nicolas Amabile, Peter O'Kane, Mirvat Alasnag, Robert-Jan van Geuns, Niels Ramsing Holm, Salvatore Brugaletta, Lorenz Raber, Remo Albiero, Miroslaw Ferenc, Manuel Pan, Valeria Paradies, Ziad A Ali, Haibo Jia, Pedro Lemos, Rony Mathew, Jun Jie Zhang, Joo-Yoong Hahn, Yiannis S Chiatzizisis, Francesco Burzotta, Adrian P Banning, Giulio Guagliumi, David Hildick-Smith, Alaide Chieffo, Takashi Akasaka, Gary Mintz, Yves Louvard, Jens Flensted Lassen, Goran Stankovic
{"title":"Intracoronary imaging for left main percutaneous coronary intervention: a clinical consensus statement of the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC and the European Bifurcation Club (EBC).","authors":"Thomas W Johnson, Nieves Gonzalo, Jose M de la Torre Hernandez, Nicolas Amabile, Peter O'Kane, Mirvat Alasnag, Robert-Jan van Geuns, Niels Ramsing Holm, Salvatore Brugaletta, Lorenz Raber, Remo Albiero, Miroslaw Ferenc, Manuel Pan, Valeria Paradies, Ziad A Ali, Haibo Jia, Pedro Lemos, Rony Mathew, Jun Jie Zhang, Joo-Yoong Hahn, Yiannis S Chiatzizisis, Francesco Burzotta, Adrian P Banning, Giulio Guagliumi, David Hildick-Smith, Alaide Chieffo, Takashi Akasaka, Gary Mintz, Yves Louvard, Jens Flensted Lassen, Goran Stankovic","doi":"10.1093/eurheartj/ehag353","DOIUrl":"10.1093/eurheartj/ehag353","url":null,"abstract":"<p><p>Left main disease represents one of the most complex lesion subsets for percutaneous coronary intervention, associated with an increased risk of serious late complications. The recent endorsement of intracoronary imaging for the guidance of left main bifurcation percutaneous coronary intervention in both acute and chronic coronary syndrome, with respective recommendations in American and European guidelines, reflects the results of recent studies. Patient benefit can only be realized through the interventional community embracing the need for intracoronary imaging-guided planning, guidance and optimization of left main stenting. This clinical consensus statement summarizes the views of a global expert panel, coordinated by the European Association of Percutaneous Cardiovascular Interventions (EAPCI), in collaboration with the European Bifurcation Club (EBC). The document includes an appraisal of the most contemporary evidence and provides clinical guidance on how to maximize the benefit of intravascular ultrasound or optical coherence tomography in the treatment of left main bifurcation disease.</p>","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":" ","pages":"5247-5265"},"PeriodicalIF":45.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940620","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}
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