Abstract:
Aim:Hypertrophic cardiomyopathy (HCM) exhibits genetic heterogeneity that is dominated by variation in eight sarcomeric genes. Genetic variation in a large number of non-sarcomeric genes has also been implicated in HCM but not formally assessed. Here we used very large case and control cohorts to determine the extent to which variation in non-sarcomeric genes contributes to HCM. Methods and results:We sequenced known and putative HCM genes in a new large prospective HCM cohort (n = 804) and analysed data alongside the largest published series of clinically genotyped HCM patients (n = 6179), previously published HCM cohorts and reference population samples from the exome aggregation consortium (ExAC, n = 60 706) to assess variation in 31 genes implicated in HCM. We found no significant excess of rare (minor allele frequency < 1:10 000 in ExAC) protein-altering variants over controls for most genes tested and conclude that novel variants in these genes are rarely interpretable, even for genes with previous evidence of co-segregation (e.g. ACTN2). To provide an aid for variant interpretation, we integrated HCM gene sequence data with aggregated pedigree and functional data and suggest a means of assessing gene pathogenicity in HCM using this evidence. Conclusion:We show that genetic variation in the majority of non-sarcomeric genes implicated in HCM is not associated with the condition, reinforce the fact that the sarcomeric gene variation is the primary cause of HCM known to date and underscore that the aetiology of HCM is unknown in the majority of patients.
journal_name
Eur Heart Jjournal_title
European heart journalauthors
Walsh R,Buchan R,Wilk A,John S,Felkin LE,Thomson KL,Chiaw TH,Loong CCW,Pua CJ,Raphael C,Prasad S,Barton PJ,Funke B,Watkins H,Ware JS,Cook SAdoi
10.1093/eurheartj/ehw603subject
Has Abstractpub_date
2017-12-07 00:00:00pages
3461-3468issue
46eissn
0195-668Xissn
1522-9645pii
ehw603journal_volume
38pub_type
杂志文章abstract::The 18 month mortality rate in 2180 patients excluded from the Danish Verapamil Infarction Trail II (DAVIT II) was 25.6%. In non-consenters (n = 368) this was 15.0% compared with 13.85 in 897 placebo-treated patients (hazard ratio 1.09 [P = 0.60] when adjusting for sex and age). The increased mortality rate in exclude...
journal_title:European heart journal
pub_type: 临床试验,杂志文章
doi:10.1093/eurheartj/14.3.377
更新日期:1993-03-01 00:00:00
abstract:AIMS:Short QT syndrome (SQTS) is a genetically determined ion-channel disorder, which may cause malignant tachyarrhythmias and sudden cardiac death. Thus far, mutations in five different genes encoding potassium and calcium channel subunits have been reported. We present, for the first time, a novel loss-of-function mu...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehr076
更新日期:2011-05-01 00:00:00
abstract::The choice of oral anticoagulant (OAC) for patients with atrial fibrillation (AF) may be influenced by individual clinical features or by patterns of risk factors and comorbidities. We reviewed analyses of subgroups of patients from trials of vitamin K antagonists vs. non-vitamin K oral anticoagulants (NOACs) for stro...
journal_title:European heart journal
pub_type: 杂志文章,评审
doi:10.1093/eurheartj/ehw069
更新日期:2017-03-21 00:00:00
abstract:AIMS:Exposure of tissue factor (TF) is a critical proximal step in the pathogenesis of acute coronary syndromes. Sunol-cH36, a chimaeric monoclonal antibody to TF, blocks binding of factor X to the TF:VIIa complex. This report describes the first completed trial of Sunol-cH36 in humans. METHODS AND RESULTS:We assessed...
journal_title:European heart journal
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1093/eurheartj/ehi094
更新日期:2005-04-01 00:00:00
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...
journal_title:European heart journal
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更新日期:2020-02-21 00:00:00
abstract:Aims:Pulmonary hypertension (PH) and pulmonary vascular disease (PVD) are common and associated with adverse outcomes in heart failure with preserved ejection fraction (HFpEF). Little is known about the impact of PVD on the pathophysiology of exercise intolerance. Methods and results:Heart failure with preserved eject...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehy331
更新日期:2018-08-07 00:00:00
abstract:AIMS:Phenotypic heterogeneity and incomplete penetrance are common in patients with hypertrophic cardiomyopathy (HCM). We aim to improve the understanding in genotype-phenotype correlations in HCM, particularly the contribution of an MYL2 founder mutation and risk factors to left ventricular hypertrophic remodelling. ...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehv522
更新日期:2016-06-14 00:00:00
abstract::Atrial fibrillation is often associated with atrial enlargement and stretch is known to cause electrophysiological alterations. Acute stretch may, depending on the moment at which it is applied, cause action potential shortening or induce both early and delayed afterdepolarizations which, when large enough, may initia...
journal_title:European heart journal
pub_type: 杂志文章,评审
doi:10.1093/eurheartj/18.suppl_c.12
更新日期:1997-05-01 00:00:00
abstract::Advances in molecular genetics present new opportunities and challenges for cardiologists who manage patients and families with cardiomyopathies. The aims of this position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases are to review the general issues related to ge...
journal_title:European heart journal
pub_type: 共识发展会议,杂志文章
doi:10.1093/eurheartj/ehq271
更新日期:2010-11-01 00:00:00
abstract::MitraClip therapy consists of percutaneous edge-to-edge coaptation of the mitral leaflets that is analogous to the surgical Alfieri technique. The safety profile of the MitraClip device is favourable, and survival outcomes in high-surgical-risk patients are superior to historical controls. However, questions remain re...
journal_title:European heart journal
pub_type: 杂志文章,评审
doi:10.1093/eurheartj/ehr101
更新日期:2011-10-01 00:00:00
abstract::Strong experimental evidence links ventricular fibrillation to an increased temporal dispersion of the recovery of excitability. The effect of an overall prolongation of repolarization and an increased basic dispersion of repolarization on premature dispersion was studied on ventricular surface in 10 dogs. Our observa...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/6.suppl_d.15
更新日期:1985-11-01 00:00:00
abstract:AIMS:Although cerebral blood flow (CBF) is known to be low in patients with advanced systolic heart failure (HF), little is known of the prognostic significance of this observation. We investigated whether CBF might be associated with the development of adverse outcomes in systolic HF, and whether it might provide prog...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehr345
更新日期:2012-02-01 00:00:00
abstract::Approximately 20% of patients undergoing diagnostic coronary arteriography for acute or chronic cardiac ischaemia have angiographically normal coronary arteries. The mechanism behind this phenomenon is likely to be the result of a combination of functional or anatomical abnormalities in the coronary microcirculation, ...
journal_title:European heart journal
pub_type: 杂志文章,评审
doi:10.1093/eurheartj/17.suppl_g.14
更新日期:1996-12-01 00:00:00
abstract:AIMS:To assess the diagnostic accuracy of 256-row computed tomographic angiography (CTA) in patients with suspected coronary artery disease (CAD). Non-invasive imaging of the coronary artery by CTA has increasingly been used in recent years. The accuracy of 256-row CTA has not yet been studied. We sought to assess the ...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehq072
更新日期:2010-08-01 00:00:00
abstract:AIMS:Psoriasis is a chronic inflammatory disease and inflammation contributes to the pathogenesis of atrial fibrillation (AF) and ischaemic stroke. We therefore investigated the risk of these endpoints in patients with psoriasis. METHODS AND RESULTS:Cohort study of the entire Danish population followed from 1997 to 20...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehr285
更新日期:2012-08-01 00:00:00
abstract:AIMS:The risk of stroke is greater among women with atrial fibrillation (AF) than men. Warfarin protects against stroke, but treatment-related bleeding occurs more often in women than in men. METHODS AND RESULTS:SPORTIF III (open label, n=3410) and V (double-blind, n=3922) included 2257 women with AF and one or more s...
journal_title:European heart journal
pub_type: 杂志文章,随机对照试验
doi:10.1093/eurheartj/ehl103
更新日期:2006-08-01 00:00:00
abstract::Hemodynamic variables were measured in 34 patients with isolated systolic hypertension before and after acute administration of propranolol. The patients were separated into two groups, those younger than and those older than 45 years of age, respectively. After drug administration, systolic pressure decreased signifi...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/4.suppl_g.51
更新日期:1983-11-01 00:00:00
abstract::Diagnosis of myocarditis has improved with the application of new techniques such as immunohistochemistry, polymerase chain reaction, in situ hybridization and Southern blot in endomyocardial biopsies. Treatment of inflammatory heart disease is still difficult and not yet validated by a study with patient numbers suff...
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/eurheartj/16.suppl_o.173
更新日期:1995-12-01 00:00:00
abstract::Degenerative mitral valve disease has become the major cause of mitral regurgitation in North America; it is incumbent on surgeons to know repair techniques and to document their results. Fortunately, improvements in myocardial protection have been concurrent with the evolution of mitral valve repair in our country. T...
journal_title:European heart journal
pub_type: 杂志文章,评审
doi:10.1093/eurheartj/12.suppl_b.30
更新日期:1991-07-01 00:00:00
abstract::The feasibility of transcatheter laser coagulation of atrial myocardium was tested in a canine model by using a combined electrode-laser catheter. In 17 anaesthetized beagles a total of 264 lesions, 12-19 per dog, and 3-5 in each area were produced in: (1) the lateral walls, (2) the posterior right atrial walls, (3) t...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a060618
更新日期:1994-07-01 00:00:00
abstract::Among 101 consecutive patients operated on for native infective aortic valve endocarditis (53 males, 48 females, mean age 39 years), 69 presented various forms of infectious extension to the surrounding areas. Twenty-six lesions were noted in the aortic roots: 18 annular abscesses, one abscess of the Valsalva sinus an...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/16.suppl_b.103
更新日期:1995-04-01 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
abstract:AIMS:Short-QT syndrome 1 (SQT1) is an inherited channelopathy with accelerated repolarization due to gain-of-function in HERG/IKr. Patients develop atrial fibrillation, ventricular tachycardia (VT), and sudden cardiac death with pronounced inter-individual variability in phenotype. We generated and characterized transg...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehy761
更新日期:2019-03-07 00:00:00
abstract:AIM:We sought to evaluate the incidence and electrophysiological features of the local slow potential preceding the surface QRS complex (pre-QRS potential) which was detected more frequently at successful sites of catheter ablation of left parietal concealed accessory pathways, than at unsuccessful sites. METHODS AND ...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1053/euhj.1999.1688
更新日期:1999-12-01 00:00:00
abstract::From January 1978 to August 1983, 41 prosthetic valve thromboses in 34 patients were operated upon in our service. They comprised 15 aortic, 25 mitral and one tricuspid valve thromboses. Seven patients had massive thrombus with dysfunction of the prosthesis; others had small and disseminated thrombi on their prosthesi...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/5.suppl_d.39
更新日期:1984-10-01 00:00:00
abstract:AIMS:To investigate the efficacy and outcome of emergency percutaneous coronary interventions (PCI) in patients with stent thrombosis. METHODS AND RESULTS:Between 1995 and 2003, 6058 patients underwent bare-metal stent implantation, of which 95 (1.6%) patients suffered from stent thrombosis. The timing of stent thromb...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehi135
更新日期:2005-06-01 00:00:00
abstract:AIMS:The objectives of this study were to determine the association of waist circumference (WC) and waist-to-hip ratio (WHR) with the risk of incident cardiovascular disease (CVD) events and to determine whether the strength of association of WC and WHR with CVD risk is different. METHODS AND RESULTS:This meta-regress...
journal_title:European heart journal
pub_type: 杂志文章,meta分析,评审
doi:10.1093/eurheartj/ehm026
更新日期:2007-04-01 00:00:00
abstract:AIMS:To investigate whether an ambulance crew's length of experience affected the outcome of out-of-hospital cardiac arrest. METHODS AND RESULTS:This was a population-based, retrospective observational study of attempted resuscitations in 1547 consecutive arrests of cardiac aetiology by Nottinghamshire Emergency Ambul...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1053/euhj.1998.1334
更新日期:1999-04-01 00:00:00
abstract:AIMS:Patients with chronic heart failure (CHF) exhibit detrimental changes in skeletal muscle that contribute to their impaired physical performance. This study investigates the possibility of counteracting these changes by chronic low-frequency electrical stimulation (CLFS) of left and right thigh muscles. METHODS AN...
journal_title:European heart journal
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/j.ehj.2003.09.027
更新日期:2004-01-01 00:00:00
abstract:AIM:Short-term psychological stress is associated with an immediate physiological response and may be associated with a transiently higher risk of cardiovascular events. The aim of this study was to determine whether brief episodes of anger trigger the onset of acute myocardial infarction (MI), acute coronary syndromes...
journal_title:European heart journal
pub_type: 杂志文章,meta分析,评审
doi:10.1093/eurheartj/ehu033
更新日期:2014-06-01 00:00:00