scholarly journals Meta-Analysis of 26 638 Individuals Identifies Two Genetic Loci Associated With Left Ventricular Ejection Fraction

2020 ◽  
Vol 13 (4) ◽  
Author(s):  
Hélène Choquet ◽  
Khanh K. Thai ◽  
Chen Jiang ◽  
Dilrini K. Ranatunga ◽  
Thomas J. Hoffmann ◽  
...  
Keyword(s):  
Heart Failure ◽  
Genetic Epidemiology ◽  
Meta Analysis ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Adult Health ◽  
Uk Biobank ◽  
Ventricular Ejection Fraction ◽  
Genome Wide ◽  
A Genome

Background: Left ventricular ejection fraction (EF) is an indicator of cardiac function, usually assessed in individuals with heart failure and other cardiac conditions. Although family studies indicate that EF has an important genetic component with heritability estimates up to 0.61, to date only 6 EF-associated loci have been reported. Methods: Here, we conducted a genome-wide association study (GWAS) of EF in 26 638 adults from the Genetic Epidemiology Research on Adult Health and Aging and the UK Biobank cohorts. Results: A meta-analysis combining results from Genetic Epidemiology Research on Adult Health and Aging and UK Biobank identified a novel locus: TMEM40 on chromosome 3p25 (rs11719526; β=0.47 and P =3.10×10 −8 ) that replicated in Biobank Japan and confirmed recent findings implicating the BAG3 locus on chromosome 10q26 in EF variation, with the strongest association observed for rs17617337 (β=−0.83 and P =8.24×10 −17 ). Although the minor allele frequencies of TMEM40 rs11719526 were generally common (between 0.13 and 0.44) in different ethnic groups, BAG3 rs17617337 was rare (minor allele frequencies<0.05) in Asian and African ancestry populations. These associations were slightly attenuated, after considering antecedent cardiac conditions (ie, heart failure/cardiomyopathy, hypertension, myocardial infarction, atrial fibrillation, valvular disease, and revascularization procedures). This suggests that the effects of the lead variants at TMEM40 or BAG3 on EF are largely independent of these conditions. Conclusions: In this large and multiethnic study, we identified 2 loci, TMEM40 and BAG3 , associated with EF at a genome-wide significance level. Identifying and understanding the genetic determinants of EF is important to better understand the pathophysiology of this strong correlate of cardiac outcomes and to help target the development of future therapies.

1384MitraClip treatment of functional mitral regurgitation - A meta-analysis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Noutsias ◽  
M Matiakis ◽  
M Ali ◽  
E Abate ◽  
B Ahmadzada ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mitral Regurgitation ◽  
Meta Analysis ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Functional Mitral Regurgitation ◽  
Clinical Effects ◽  
Ventricular Ejection Fraction ◽  
Heart Failure Patients ◽  
All Cause Mortality

Abstract Moderate-to-severe or severe functional mitral regurgitation (FMR) is associated with higher rates of hospitalizations and with increased mortality in heart failure with reduced left ventricular ejection fraction (HFrEF). Transcatheter mitral valve repair by MitraClip® implantation (TMVrMC) may effectively reduce severe MR, and is associated with symptomatic improvement. However, the long-term clinical effects of this procedure are not well defined. Aims We analyzed outcomes for rehospitalization and survival in heart failure patients with moderate-to-severe or severe functional mitral regurgitation (FMR) treated by either medical treatment (MT) only TMVrMC+MT by meta-analysis. Methods and results By systematic search of bibliographic databases, we evaluated publications comparing heart failure patients with FMR treated by MT only versus treatment by MT combined with TMVrMC. Studies with a minimum of 25 enrolled patients and a follow/up period of at least 12 months were deemed eligible for this meta-analysis. We identified n=7 studies enrolling 2,884 HFrEF patients, divided into two study arms: TMVrMC+MT (n=1,618), versus FMR patients receiving MT only (n=1,266). At 12 months, there was a significant reduction in all-cause mortality favoring TMVR+MT (OR: 0.67; CI 95% 0.55–0.81), as well as a reduction of unplanned rehospitalizations (OR: 0.69; 95%; CI 0.53–0.89), compared with the MT only patients. At 24 months, there was a significant reduction of all-cause mortality in the TMVrMC+MT patient group (OR: 0.50; CI: 95%: 0.38–0.66; p<0.001). TMVrMC+MT was associated with significantly lower rates of unplanned re-admissions for heart failure compared with MT only at 12 months (OR: 0.69; 95% CI: 0.53–0.89; p<0.001) and at 24 months (OR: 0.53; 95% CI: 0.39–0.71; p<0.001). In one publication, a survival benefit of TMVrMC+MT over MT alone was shown at 5 years post intervention (HR: 0.75; 95% CI: 0.69–0.94; p=0.012) after weighting for propensity score and controlling for age. Conclusions This meta-analysis on n=2,884 patients with moderate-to-severe or severe FMR reveals that TMVrMC+MT, as compared with MT alone, is associated with a significant reduction of rehospitalizations and improvement of survival. These data imply additional evidence for TMVrMC in eligible heart failure patients with relevant FMR, which might be important for an update of the corresponding guidelines.

scholarly journals Association of statin use and clinical outcomes in heart failure patients: a systematic review and meta-analysis

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Agata Bielecka-Dabrowa ◽  
Ibadete Bytyçi ◽  
Stephan Von Haehling ◽  
Stefan Anker ◽  
Jacek Jozwiak ◽  
...  
Keyword(s):  
Heart Failure ◽  
Clinical Outcomes ◽  
Meta Analysis ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Patients With Heart Failure ◽  
All Cause Mortality ◽  
Meta Analyses ◽  
Statin Use

Abstract Background The role of statins in patients with heart failure (HF) of different levels of left ventricular ejection fraction (LVEF) remains unclear especially in the light of the absence of prospective data from randomized controlled trials (RCTs) in non-ischemic HF, and taking into account potential statins’ prosarcopenic effects. We assessed the association of statin use with clinical outcomes in patients with HF. Methods We searched PubMed, EMBASE, Scopus, Google Scholar and Cochrane Central until August 2018 for RCTs and prospective cohorts comparing clinical outcomes with statin vs non-statin use in patients with HF at different LVEF levels. We followed the guidelines of the 2009 PRISMA statement for reporting and applied independent extraction by multiple observers. Meta-analyses of hazard ratios (HRs) of effects of statins on clinical outcomes used generic inverse variance method and random model effects. Clinical outcomes were all-cause mortality, cardiovascular (CV) mortality and CV hospitalization. Results Finally we included 17 studies (n = 88,100; 2 RCTs and 15 cohorts) comparing statin vs non-statin users (mean follow-up 36 months). Compared with non-statin use, statin use was associated with lower risk of all-cause mortality (HR 0.77, 95% confidence interval [CI], 0.72–0.83, P < 0.0001, I2 = 63%), CV mortality (HR 0.82, 95% CI: 0.76–0.88, P < 0.0001, I2 = 63%), and CV hospitalization (HR 0.78, 95% CI: 0.69–0.89, P = 0.0003, I2 = 36%). All-cause mortality was reduced on statin therapy in HF with both EF < 40% and ≥ 40% (HR: 0.77, 95% Cl: 0.68–0.86, P < 0.00001, and HR 0.75, 95% CI: 0.69–0.82, P < 0.00001, respectively). Similarly, CV mortality (HR 0.86, 95% CI: 0.79–0.93, P = 0.0003, and HR 0.83, 95% CI: 0.77–0.90, P < 0.00001, respectively), and CV hospitalizations (HR 0.80 95% CI: 0.64–0.99, P = 0.04 and HR 0.76 95% CI: 0.61–0.93, P = 0.009, respectively) were reduced in these EF subgroups. Significant effects on all clinical outcomes were also found in cohort studies’ analyses; the effect was also larger and significant for lipophilic than hydrophilic statins. Conclusions In conclusion, statins may have a beneficial effect on CV outcomes irrespective of HF etiology and LVEF level. Lipophilic statins seem to be much more favorable for patients with heart failure.

GENECHOC study: genetic markers of arrhythmic risk in heart failure

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Anys ◽  
S Rigade ◽  
S Rigade ◽  
E Baron ◽  
E Baron ◽  
...  
Keyword(s):  
Heart Failure ◽  
Genetic Markers ◽  
Left Ventricular ◽  
European Ancestry ◽  
Left Ventricular Ejection ◽  
P Value ◽  
Funding Source ◽  
Ventricular Ejection Fraction ◽  
Cardioverter Defibrillator ◽  
Genome Wide

Abstract Background Ventricular arrhythmic events are responsible for 50% of death in heart failure but no reliable predictive marker is known to discriminate patients at risk of fatal arrhythmia. Interestingly, familial predisposition has been reported suggesting a role of genetic factors. Purpose Identify genetic markers increasing the arrhythmic risk in heart failure population. Method We prospectively included heart failure patients with left ventricular ejection fraction (LVEF) under 35% and a cardioverter defibrillator in primary prevention in 22 French centres between 2009 and 2017. Patients were followed for 72 months and divided into two groups: cases with an arrhythmic event during follow-up and controls. A Genome Wide Association Study (GWAS) was done. Single Nucleotide Polymorphisms (SNPs) genotyping was performed on Affymetrix Axiom Precision Medicine Research Array plates. To complement the directly genotyped SNPs we performed large-scale imputation based on the Haplotype Reference Consortium European ancestry panel leading to a dataset of 7,5 million of SNPs. Results 332 cases and 567 controls were included (86% men, mean age at implantation 52±11 years). 78% of patients had ischaemic cardiopathy, 20% had dilated cardiomyopathy. Mean LVEF was 27±5%. No statistical difference was found between cases and controls on clinical parameters, biological results, electrocardiographic measures. No locus shows genome-wide significant association (p&lt;5.10–8) on the GWAS analysis. However, 16 signals with a p-value between 5.10–8 and 5.10–5 were investigated. eQTL and chromatin conformation point to 35 genes with cardiac expression previously associated with heart failure, cardiomyopathies, cardiogenesis, arrhythmias and inflammation. Variants identified point to regulatory regions of the genome and may then propose a molecular mechanism predisposing patients to arrhythmias. Conclusion No locus raises genome-wide significance, but several signals with a nominal p-value point to relevant genes and pathways. Replication of the GWAS is ongoing on a cohort of 156 new patients with a less severe cardiopathy implanted with a cardioverter defibrillator in secondary prevention. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Nantes University Hospital

Sign in / Sign up

Export Citation Format

Share Document