In conclusion, patients with heart failure and reduced ejection fraction that are homozygous for ADRB1 Ser49 were significantly more likely to experience LVEF recovery than Gly49 carriers.
Bucindolol is a beta-blocker whose unique pharmacologic properties provide greater benefit in HF patients with reduced ejection fraction (HFrEF) who have the beta<sub>1</sub>-adrenergic receptor (ADRB1) Arg389Arg genotype.
GENETIC-AF is the first randomized trial of pharmacogenetic guided rhythm control, and will test the safety and efficacy of bucindolol compared with metoprolol succinate for the prevention of recurrent symptomatic AF/AFL in patients with HFrEF and an ADRB1 Arg389Arg genotype.(ClinicalTrials.govNCT01970501).
Results Subjects in each trial had less all-cause mortality with high- versus no/low-dose BB if they had ADRB1 Arg389Arg (BEST: hazard ratio [HR]=0.40, P=0.002; HF-ACTION: HR=0.45, P=0.005) but not Arg389Gly genotype (both P>0.2).
The lack of cardiac β1-adrenergic receptors (β1-AR) negatively affects the regulation of both cardiac inotropy and lusitropy, leading, in the long term, to heart failure (HF).
More consistent to mammalians, adult zebrafish developed significant heart failure in concert with β1-AR downregulation, and GRK2 and brain natriuretic peptide (BNP) upregulation in response to prolonged, 14d ISO-stimulation.
Data from our study suggest that the β adrenoreceptor Gly 49 allele of the β1 -adrenergic receptorSer(49) Gly polymorphisms may increase the risk of ICD shock in patients with heart failure, independent of beta-blocker dosage.
Impact of the β-1 adrenergic receptor polymorphism on tolerability and efficacy of bisoprolol therapy in Korean heart failure patients: association between β adrenergic receptor polymorphism and bisoprolol therapy in heart failure (ABBA) study.
Our findings that BAG3 is localized at the sarcolemma and t-tubules while modulating myocyte contraction and action potential duration through specific interaction with the β1-adrenergic receptor and L-type Ca(2+) channel provide novel insight into the role of BAG3 in cardiomyopathies and increased arrhythmia risks in heart failure.
We demonstrate that restoration of cardiac plasma membrane levels of S1PR1 produces beneficial effects that counterbalance the deleterious β1AR overstimulation in heart failure.
The present study sought to investigate whether ADRB1Arg389Gly (rs1801253), GNAS -1211 G/A (rs6123837) and GNAS 2291 C/T (rs6026584) variants are associated with left ventricular function and exercise tolerance in heart failure patients.
The common polymorphisms producing changes in the β(1)-ARs, and their signaling pathways, have been associated with clinical outcomes in several studies in hypertension and heart failure.
This pharmacogenetic substudy of the prospective, double-blind, randomized CIBIS-ELD trial determined the impact of the β1-adrenoceptorArg189Gly polymorphism on heart-rate responses to bisoprolol or carvedilol in elderly patients with heart failure (421 with sinus rhythm, 107 with atrial fibrillation).
Downregulation of β(1)- adrenergic receptors (β(1)-ARs) and increased expression/function of G-protein-coupled receptor kinase 2 (GRK2) have been observed in human heart failure, but changes in expression of other ARs and GRKs have not been established.
Thus, we performed a meta-analysis of studies to evaluate the impact of β1-AR polymorphisms on susceptibility to HF, the response to β-blocker therapy and the prognosis of HF.
The authors' laboratory has thus pursued genetic variation of the beta(1)-AR gene at the molecular, cellular, physiologic, and clinical levels as the potential basis for interindividual variability in the response to beta-blocker treatment during heart failure.
The purpose of the present study was to determine whether specific genetic polymorphisms in ADRB1 (encoding the beta1-adrenergic receptor), CYP2D6, and UGT1A1 correlated with dose of, or response to, metoprolol or carvedilol treatment in patients with heart failure.
During long-term carvedilol therapy, CHF patients with the Arg/Arg genotype of the ADRB1 gene were observed to have a more pronounced decrease in the functional class of heart failure, a significant increase in left ventricular ejection, and a decrease in left ventricular end-systolic and end-diastolic sizes as compared with patients with the Gly/Arg genotype.
Therapeutic efficacy of a combination of a beta1-adrenoreceptor (AR) blocker and beta2-AR agonist in a rat model of postmyocardial infarction dilated heart failure exceeds that of a beta1-AR blocker plus angiotensin-converting enzyme inhibitor.