Abstract:
AIMS:Clonal haematopoiesis of indeterminate potential (CHIP), defined as the presence of an expanded somatic blood cell clone without other haematological abnormalities, was recently shown to increase with age and is associated with coronary artery disease and calcification. The most commonly mutated CHIP genes, DNMT3A and TET2, were shown to regulate inflammatory potential of circulating leucocytes. The incidence of degenerative calcified aortic valve (AV) stenosis increases with age and correlates with chronic inflammation. We assessed the incidence of CHIP and its association with inflammatory blood cell phenotypes in patients with AV stenosis undergoing transfemoral aortic valve implantation (TAVI). METHODS AND RESULTS:Targeted amplicon sequencing for DNMT3A and TET2 was performed in 279 patients with severe AV stenosis undergoing TAVI. Somatic DNMT3A- or TET2-CHIP-driver mutations with a VAF ≥ 2% were detected in 93 out of 279 patients (33.3%), with an age-dependent increase in the incidence from 25% (55-69 years) to 52.9% (90-100 years). Patients with DNMT3A- or TET2-CHIP-driver mutations did not differ from patients without such mutations in clinical parameters, concomitant atherosclerotic disease, blood cell counts, inflammatory markers, or procedural characteristics. However, patients with DNMT3A- or TET2-CHIP-driver mutations had a profoundly increased medium-term all-cause mortality following successful TAVI. Differential myeloid and T-cell distributions revealed pro-inflammatory T-cell polarization in DNMT3A-mutation carriers and increased pro-inflammatory non-classical monocytes in TET2-mutation carriers. CONCLUSION:This is the first study to show that acquired somatic mutations in the most commonly mutated CHIP-driver genes occur frequently in patients with severe degenerative AV stenosis, are associated with increased pro-inflammatory leucocyte subsets, and confer a profound increase in mortality following successful TAVI.
journal_name
Eur Heart Jjournal_title
European heart journalauthors
Mas-Peiro S,Hoffmann J,Fichtlscherer S,Dorsheimer L,Rieger MA,Dimmeler S,Vasa-Nicotera M,Zeiher AMdoi
10.1093/eurheartj/ehz591subject
Has Abstractpub_date
2020-02-21 00:00:00pages
933-939issue
8eissn
0195-668Xissn
1522-9645pii
5554424journal_volume
41pub_type
杂志文章abstract:Aims:Epidemiological studies strongly suggest a link between stress, depression, and cardiovascular diseases (CVDs); the mechanistic correlation, however, is poorly understood. A single-nucleotide polymorphism in the BDNF gene (BDNFVal66Met), associated with depression and anxiety, has been proposed as a genetic risk f...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehv655
更新日期:2017-05-07 00:00:00
abstract:AIMS:Growing data suggest that antibiotic exposure is associated with a long-lasting alteration in gut microbiota, and may be related to subsequent cardiovascular disease (CVD). We investigated associations of life-stage and duration of antibiotic exposure during adulthood with subsequent CVD events. METHODS AND RESUL...
journal_title:European heart journal
pub_type: 杂志文章,多中心研究
doi:10.1093/eurheartj/ehz231
更新日期:2019-12-14 00:00:00
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journal_title:European heart journal
pub_type: 杂志文章,多中心研究
doi:10.1016/j.ehj.2004.08.006
更新日期:2004-11-01 00:00:00
abstract::The effect of diuretic dose on the haemodynamic response to captopril was assessed in nine patients with chronic cardiac failure. Each patient was given an intravenous dose of captopril while maintained on (a) a low dose diuretic regime, and (b) a high dose diuretic regime. Activity of the renin angiotensin aldosteron...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a060302
更新日期:1992-07-01 00:00:00
abstract::The non-invasive quantification of mitral and aortic regurgitation using the left-to-right stroke count ratio (SCR) calculated with gated equilibrium radionuclide ventriculography (RNV), is affected by the overlap of atria and ventricles and the consequent difficult definition of the ventricular regions of interest (R...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a062176
更新日期:1987-10-01 00:00:00
abstract::An investigation was undertaken to assess the value of adding streptokinase therapy to standard penicillin treatment of artificially induced infective endocarditis due to Streptococcus sanguis. In pigs a low-grade infection could be induced which closely simulated streptococcal endocarditis in man, but for technical r...
journal_title:European heart journal
pub_type: 临床试验,杂志文章
doi:10.1093/oxfordjournals.eurheartj.a062100
更新日期:1986-06-01 00:00:00
abstract::Reactive thrombocytosis following cardiopulmonary bypass surgery is generally considered to be a benign condition which is transient and does not require specific therapy. We describe three patients who developed stroke in association with reactive thrombocytosis in the late recovery period following cardiopulmonary b...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a060642
更新日期:1994-08-01 00:00:00
abstract::The efficacy of nifedipine and prazosin in the treatment of Raynaud's phenomenon was assessed in a prospective double-blind randomized cross-over trial in 15 patients. Each patient received one week of nifedipine 20 mg TID, one week of prazosin 1 mg TID, and 2 weeks of placebo. Nifedipine was shown to be effective in ...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a061923
更新日期:1985-08-01 00:00:00
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journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a014717
更新日期:1996-10-01 00:00:00
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journal_title:European heart journal
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2009-09-01 00:00:00
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journal_title:European heart journal
pub_type: 临床试验,杂志文章
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更新日期:2000-07-01 00:00:00
abstract:AIMS:Evidence is accumulating that inflammation plays a role in the pathophysiology of heart failure. Lipoprotein-associated phospholipase A2 (Lp-PLA2) has pro-inflammatory properties. We investigated whether Lp-PLA2 activity is associated with heart failure. METHODS AND RESULTS:Lp-PLA2 activity was determined in a ra...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehl230
更新日期:2006-10-01 00:00:00
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pub_type: 新闻
doi:
更新日期:2014-04-01 00:00:00
abstract:AIMS:Circulating progenitor cells (PC) may contribute to myocardial recovery following infarction. Growth factors including VEGF are produced during ischaemia and stimulate PC release and activation. In this study, we focused on the functional chemotactic response of PC to VEGF in subjects early after myocardial ischae...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehm542
更新日期:2008-01-01 00:00:00
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journal_title:European heart journal
pub_type: 杂志文章,评审
doi:10.1093/eurheartj/8.suppl_k.49
更新日期:1987-11-01 00:00:00
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journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehs011
更新日期:2013-06-01 00:00:00
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journal_title:European heart journal
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1053/euhj.1999.1483
更新日期:1999-10-01 00:00:00
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journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehp240
更新日期:2009-09-01 00:00:00
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journal_title:European heart journal
pub_type: 杂志文章
doi:10.1053/euhj.1998.1332
更新日期:1999-03-01 00:00:00
abstract:AIMS:Resuscitated cardiac arrest (CA), leading to harmful cardiovascular dysfunction and multiple organ failure, includes a whole-body hypoxia-reoxygenation phenomenon. Opening of the mitochondrial permeability transition pore (mPTP) appears to be a pivotal event in ischaemia-reperfusion injury. We hypothesized that ph...
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doi:10.1093/eurheartj/ehq112
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journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a060494
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journal_title:European heart journal
pub_type: 杂志文章,评审
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更新日期:1997-06-01 00:00:00
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journal_title:European heart journal
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1093/eurheartj/ehl565
更新日期:2007-03-01 00:00:00
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doi:10.1093/eurheartj/ehs459
更新日期:2015-03-14 00:00:00
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journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/14.4.474
更新日期:1993-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1093/eurheartj/ehr434
更新日期:2012-03-01 00:00:00
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journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/eht070
更新日期:2013-08-01 00:00:00
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journal_title:European heart journal
pub_type: 杂志文章,meta分析,评审
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更新日期:2007-12-01 00:00:00
abstract::Twenty-four hour Holter monitoring and symptom-limited exercise testing were carried out prior to discharge in 157 patients recovering from acute myocardial infarction. Supraventricular arrhythmias (SVT) during Holter monitoring were recorded in 15%, and ST segment depression during exercise in 27%. No association bet...
journal_title:European heart journal
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1093/oxfordjournals.eurheartj.a060078
更新日期:1992-10-01 00:00:00
abstract::The utility of high-frequency current applied through the distal electrode of a conventional electrode-catheter for altering atrio-ventricular conduction was studied in 18 anaesthetized dogs. Following adequate unipolar His bundle recording, current was applied over periods of 20-30 s, with an output power of 30 W. Co...
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pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a059450
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