Abstract:
:Nucleic acid-based therapeutics are currently developed at large scale for prevention and management of cardiovascular diseases (CVDs), since: (i) genetic studies have highlighted novel therapeutic targets suggested to be causal for CVD; (ii) there is a substantial recent progress in delivery, efficacy, and safety of nucleic acid-based therapies; (iii) they enable effective modulation of therapeutic targets that cannot be sufficiently or optimally addressed using traditional small molecule drugs or antibodies. Nucleic acid-based therapeutics include (i) RNA-targeted therapeutics for gene silencing; (ii) microRNA-modulating and epigenetic therapies; (iii) gene therapies; and (iv) genome-editing approaches (e.g. CRISPR-Cas-based): (i) RNA-targeted therapeutics: several large-scale clinical development programmes, using antisense oligonucleotides (ASO) or short interfering RNA (siRNA) therapeutics for prevention and management of CVD have been initiated. These include ASO and/or siRNA molecules to lower apolipoprotein (a) [apo(a)], proprotein convertase subtilisin/kexin type 9 (PCSK9), apoCIII, ANGPTL3, or transthyretin (TTR) for prevention and treatment of patients with atherosclerotic CVD or TTR amyloidosis. (ii) MicroRNA-modulating and epigenetic therapies: novel potential therapeutic targets are continually arising from human non-coding genome and epigenetic research. First microRNA-based therapeutics or therapies targeting epigenetic regulatory pathways are in clinical studies. (iii) Gene therapies: EMA/FDA have approved gene therapies for non-cardiac monogenic diseases and LDL receptor gene therapy is currently being examined in patients with homozygous hypercholesterolaemia. In experimental studies, gene therapy has significantly improved cardiac function in heart failure animal models. (iv) Genome editing approaches: these technologies, such as using CRISPR-Cas, have proven powerful in stem cells, however, important challenges are remaining, e.g. low rates of homology-directed repair in somatic cells such as cardiomyocytes. In summary, RNA-targeted therapies (e.g. apo(a)-ASO and PCSK9-siRNA) are now in large-scale clinical outcome trials and will most likely become a novel effective and safe therapeutic option for CVD in the near future. MicroRNA-modulating, epigenetic, and gene therapies are tested in early clinical studies for CVD. CRISPR-Cas-mediated genome editing is highly effective in stem cells, but major challenges are remaining in somatic cells, however, this field is rapidly advancing.
journal_name
Eur Heart Jjournal_title
European heart journalauthors
Landmesser U,Poller W,Tsimikas S,Most P,Paneni F,Lüscher TFdoi
10.1093/eurheartj/ehaa229subject
Has Abstractpub_date
2020-10-21 00:00:00pages
3884-3899issue
40eissn
0195-668Xissn
1522-9645pii
5827044journal_volume
41pub_type
杂志文章abstract::Atrial fibrillation (AF) and chronic heart failure (CHF) are two major and even growing cardiovascular conditions that often coexist. However, few data are available to guide treatment of AF in patients with CHF. This review summarizes current literature concerning the following topics: (i) prognostic relevance of AF ...
journal_title:European heart journal
pub_type: 杂志文章,评审
doi:10.1093/eurheartj/ehm341
更新日期:2007-11-01 00:00:00
abstract:AIMS:We investigated the influence of type one cannabinoid receptor (CB1) deficiency on acute heart failure (AHF) and the underlying mechanism. Acute heart failure syndrome is an important clinical problem because of its high morbidity and mortality rates. Activation of CB1 induces vascular dilation and reinforces the ...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehr246
更新日期:2012-12-01 00:00:00
abstract::A 35-year-old man developed giant cell myocarditis resulting in severe congestive cardiac failure. He needed urgent orthotopic cardiac transplantation despite maximal doses of inotropes and augmentation with an intra-aortic balloon pump. The patient presented with rhythm disturbances and echocardiographically diminish...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a059938
更新日期:1991-04-01 00:00:00
abstract::The clinical expert consensus statement on takotsubo syndrome (TTS) part II focuses on the diagnostic workup, outcome, and management. The recommendations are based on interpretation of the limited clinical trial data currently available and experience of international TTS experts. It summarizes the diagnostic approac...
journal_title:European heart journal
pub_type: 共识发展会议,杂志文章
doi:10.1093/eurheartj/ehy077
更新日期:2018-06-07 00:00:00
abstract:AIMS:Hypertrophic cardiomyopathy (HCM) is a disease with marked regional differences in wall thickness. However, the relation between myocardial function and wall thickness has not been well studied. Ultrasonic strain rate (SR) imaging makes it possible to study the regional myocardial deformation. We investigated whet...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehm444
更新日期:2007-12-01 00:00:00
abstract:AIMS:The importance of heart rate in the pathophysiology of heart failure with reduced LVEF has recently attracted attention. In particular, the findings of the Systolic Heart failure treatment with the I(f) inhibitor ivabradine Trial (SHIFT) have put special emphasis on heart rate reduction with ivabradine for improve...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehs004
更新日期:2012-05-01 00:00:00
abstract::Alterations in the right ventricular function may or may not contribute to progressive cardiac dysfunction after left ventricular infarction. Ligation of the left coronary artery (LCAL) was lethal within 24 h for 25% of 100 rats, whereas none of 21 sham-operated rats died. No rats died during the following 4 weeks, af...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/14.11.1554
更新日期:1993-11-01 00:00:00
abstract::Earlier studies have shown that return to work following PTCA is frequent; however PTCA is now performed in patients with more extensive coronary artery disease. The present study was designed to compare the vocational outcome of patients who underwent PTCA in 1980-1982 with that of patients who underwent the procedur...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/10.suppl_g.54
更新日期:1989-12-01 00:00:00
abstract:Aims:Primary prevention implantable cardioverter defibrillators (ICDs) are established therapy for reducing mortality in patients with left ventricular systolic dysfunction and ischaemic heart disease (IHD). However, their efficacy in patients without IHD has been controversial. We undertook a meta-analysis of the tota...
journal_title:European heart journal
pub_type: 杂志文章,meta分析,评审
doi:10.1093/eurheartj/ehx028
更新日期:2017-06-07 00:00:00
abstract:AIMS:Aspirin combined with clopidogrel is the treatment of choice for acute coronary syndromes. Although the maintenance of aspirin until surgery does not affect postoperative bleeding after coronary artery bypass graft (CABG) surgery, the latter may be dramatically increased when clopidogrel is continued over a period...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehm049
更新日期:2007-04-01 00:00:00
abstract::Contrary to most prospective epidemiologic studies, an earlier report from the British Regional Heart Study (BRHS) suggested that high density lipoprotein (HDL)-cholesterol in men aged 40-59 years was not a significant, independent, predictive risk factor for coronary heart disease (CHD), controlling for the composite...
journal_title:European heart journal
pub_type: 杂志文章,评审
doi:10.1093/eurheartj/11.suppl_h.21
更新日期:1990-12-01 00:00:00
abstract:Aims:Atrial fibrillation (AFib) and atrial flutter (AFlut) are common arrhythmias with increased use of invasive procedures. A steady re-evaluation of relevant safety endpoints is recommended and both quality management and pay-for-performance programs are evolving. Therefore, the aims of this study were (i) to investi...
journal_title:European heart journal
pub_type: 杂志文章,多中心研究
doi:10.1093/eurheartj/ehy528
更新日期:2018-11-21 00:00:00
abstract::Arbutamine (Gensia, Inc., San Diego, CA) is a newly-developed sympathomimetic agent specifically designed for cardiovascular stress testing. It has been successfully used for the detection of coronary artery disease in conjunction with electrocardiography, echocardiographic and radionuclide techniques. Arbutamine incr...
journal_title:European heart journal
pub_type: 杂志文章,评审
doi:10.1093/eurheartj/16.suppl_m.24
更新日期:1995-11-01 00:00:00
abstract::Temporal signal averaging of the surface QRS (V1 + V3 + V5) was performed in 16 patients with arrhythmogenic right ventricular dysplasia and in 16 normal subjects. The differences between ARVD patients and normals were large for the filtered QRS duration (FQRSd) (146.2 +/- 18.9 ms vs. 91.8 +/- 4.1 ms, P less than 0.00...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a062501
更新日期:1988-03-01 00:00:00
abstract::The purpose of this study was to describe the mechanism and determine predictive factors of mitral valve rupture requiring valve replacement following percutaneous mitral commissurotomy. Of the 350 consecutive patients treated by balloon mitral commissurotomy, the procedure was not completed in 16, and 11 developed ac...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/16.1.43
更新日期:1995-01-01 00:00:00
abstract:AIM:Cardiosphere-derived cells (CDCs) produce regenerative effects in the post-infarct setting. However, it is unclear whether CDCs are beneficial in non-ischaemic dilated cardiomyopathy (DCM). We tested the effects of CDC transplantation in mice with cardiac-specific Gαq overexpression, which predictably develop progr...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehu196
更新日期:2015-03-21 00:00:00
abstract:AIMS:Prognostic importance of coronary vessel dominance in patients with ST-elevation myocardial infarction (STEMI) remains uncertain. The aim of this study was to assess influence of coronary vessel dominance on the short- and long-term outcome after STEMI. METHODS AND RESULTS:Coronary angiographic images of consecut...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehu236
更新日期:2015-05-01 00:00:00
abstract::Aims Abciximab has previously been shown to enhance thrombolysis and improve myocardial perfusion when combined with reduced doses of alteplase. The purpose of the reteplase phase of TIMI 14 was to evaluate the effects of abciximab when used in combination with a reduced dose of reteplase for ST-elevation myocardial i...
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.2000.2243
更新日期:2000-12-01 00:00:00
abstract::The study was designed to examine the safety and efficacy of acute interventional use of captopril on left ventricular volumes, ventricular arrhythmias and neurohormones during thrombolysis in patients with a first anterior myocardial infarction, within 6 h of onset of symptoms. Left ventricular dysfunction and progno...
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.a060608
更新日期:1994-07-01 00:00:00
abstract::Randomized clinical trials (RCTs) are the definitive contributors to evidence-based medicine. RCTs assessing serious outcomes in cardiovascular disease have grown, with 'megatrials' becoming more common with the realization that wrong conclusions resulted from random error in inadequately sized trials. Simple design a...
journal_title:European heart journal
pub_type: 杂志文章,评审
doi:10.1093/eurheartj/ehl152
更新日期:2006-09-01 00:00:00
abstract:AIMS:To document the impact of intensive insulin therapy during intensive care on long-term (4 years) outcome of high-risk cardiac surgery patients. METHODS AND RESULTS:In this pre-planned sub-analysis and follow-up study of a large, randomized controlled trial on the effects of intensive insulin therapy during critic...
journal_title:European heart journal
pub_type: 杂志文章,随机对照试验
doi:10.1093/eurheartj/ehi855
更新日期:2006-11-01 00:00:00
abstract:AIMS:To evaluate the efficacy of atrial pacing in the suppression of early reinitiation of atrial fibrillation after successful internal cardioversion. METHODS AND RESULTS:The efficacy of atrial pacing in suppressing early reinitiation of atrial fibrillation was studied in 12 of 45 (29%) patients with early reinitiati...
journal_title:European heart journal
pub_type: 临床试验,杂志文章
doi:10.1053/euhj.1999.1991
更新日期:2000-07-01 00:00:00
abstract:AIMS:Because benefits of cardiac resynchronization therapy (CRT) appear to be less favourable in non-left bundle branch block (LBBB) patients, this prospective longitudinal study tested the hypothesis that QRS morphology and echocardiographic mechanical dyssynchrony were associated with long-term outcome after CRT. ME...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehs013
更新日期:2012-11-01 00:00:00
abstract::This study describes the clinical profile and prognosis of elderly patients not eligible for predischarge exercise testing. The database consisted of 133 patients 55-64 years of age, and 111 patients older than 64 years of age who survived an acute myocardial infarction. Follow-up was one year. In the younger age grou...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/5.suppl_e.97
更新日期:1984-11-01 00:00:00
abstract:AIMS:Previous analyses suggest only modest agreement between local site and core-laboratory (core-lab) electrocardiogram (ECG) interpretation in patients with acute coronary syndromes (ACSs); however, this has not been well examined outside of clinical trial populations. METHODS AND RESULTS:Patients (n = 5277 from 51 ...
journal_title:European heart journal
pub_type: 杂志文章,多中心研究
doi:10.1093/eurheartj/ehm503
更新日期:2008-01-01 00:00:00
abstract::The prevalence of left ventricular (LV) thrombosis and incidence of arterial embolism after acute anterior myocardial infarction (AAMI) treated with streptokinase 1.5 x 10(6) IU intravenously was studied in 136 patients enrolled consecutively in five cardiological centres. Adjunctive antithrombotic therapy was adminis...
journal_title:European heart journal
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1093/eurheartj/14.11.1489
更新日期:1993-11-01 00:00:00
abstract::To study the effect of heart rate changes on Doppler measurements of mitral valve area atrial pacing was performed in 14 patients with mitral stenosis and sinus rhythm. Continuous wave Doppler and haemodynamic measurements were performed simultaneously at rest and during pacing-induced tachycardia. (1) Mitral valve ar...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a060139
更新日期:1992-02-01 00:00:00
abstract::The diagnosis and management of patients with renovascular disease and hypertension continue to elude healthcare providers. The advent of novel imaging and interventional techniques, and increased understanding of the pathways leading to irreversible renal injury and renovascular hypertension, have ushered in commenda...
journal_title:European heart journal
pub_type: 杂志文章,评审
doi:10.1093/eurheartj/ehq510
更新日期:2011-07-01 00:00:00
abstract:AIMS:Previous studies have suggested that a high body mass index (BMI) is associated with an improved outcome in congestive heart failure (CHF). However, the studies addressing this problem have not included enough patients with non-systolic heart failure to evaluate how left ventricular systolic function interacts wit...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehi022
更新日期:2005-01-01 00:00:00
abstract::AIMS More intense platelet-directed therapy for acute coronary syndrome (ACS) may increase bleeding risk. The aim of the current analysis was to determine the rate, clinical impact, and predictors of major and fatal bleeding complications in the PLATO study. METHODS AND RESULTS PLATO was a randomized, double-blind, ac...
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/ehr422
更新日期:2011-12-01 00:00:00