» Articles » PMID: 18075464

Arg389Gly-beta1-adrenergic Receptors Determine Improvement in Left Ventricular Systolic Function in Nonischemic Cardiomyopathy Patients with Heart Failure After Chronic Treatment with Carvedilol

Abstract

Objective: Administration of the beta-adrenergic receptor blocker carvedilol to patients with chronic heart failure leads to clinically significant benefits, including improvement in left ventricular systolic function in some, but not all, patients. We sought to determine the basis of the variable effect obtained with carvedilol in patients with heart failure. Carvedilol blocks both beta1-adrenergic and beta2-adrenergic receptors, and both receptors exist as polymorphisms. We aimed to determine whether these polymorphisms contribute to variability in response to carvedilol in patients with chronic heart failure.

Methods: We retrospectively and prospectively investigated 135 patients with nonischemic cardiomyopathy and chronic stable heart failure (New York Heart Association class II, III) treated with carvedilol. Baseline echocardiography was obtained before introduction of carvedilol and repeated after stabilization of a maximally tolerated dose of carvedilol (50-100 mg/day) for at least 1 year. Polymerase chain reaction and restriction fragment length polymorphism analysis were used to genotype beta1-adrenergic and beta2-adrenergic receptor polymorphisms.

Results: When grouped according to receptor polymorphisms patients were well matched for severity of heart failure, comorbidity and treatment. No significant difference was observed in baseline left ventricular ejection fraction (LVEF) between groups (P>0.05). After 1.5 years of treatment with carvedilol patients with Arg389Arg-beta1-adrenergic receptors had a significantly greater improvement in LVEF compared with Gly389 carriers (Arg389Arg 18.8%; Arg389Gly 9.4%; Gly389Gly 6.0%; P<0.001) whereas there were no differences attributable to other beta1-adrenergic and beta2-adrenergic receptor polymorphisms (P>0.05).

Conclusion: In patients with nonischemic dilated cardiomyopathy, carvedilol leads to a significantly greater improvement in LVEF in patients with the Arg389Arg-beta1 adrenergic receptor phenotype.

Citing Articles

Roles of β-adrenoceptor Subtypes and Therapeutics in Human Cardiovascular Disease: Heart Failure, Tachyarrhythmias and Other Cardiovascular Disorders.

Wong Y, Haqqani H, Molenaar P Handb Exp Pharmacol. 2024; 285:247-295.

PMID: 38844580 DOI: 10.1007/164_2024_720.


Pediatric Beta Blocker Therapy: A Comprehensive Review of Development and Genetic Variation to Guide Precision-Based Therapy in Children, Adolescents, and Young Adults.

Walton M, Wagner J Genes (Basel). 2024; 15(3).

PMID: 38540438 PMC: 10969836. DOI: 10.3390/genes15030379.


Towards precision medicine in heart failure.

Weldy C, Ashley E Nat Rev Cardiol. 2021; 18(11):745-762.

PMID: 34108678 DOI: 10.1038/s41569-021-00566-9.


Variants in ADRB1 and CYP2C9: Association with Response to Atenolol and Losartan in Marfan Syndrome.

Van Driest S, Sleeper L, Gelb B, Morris S, Dietz H, Forbus G J Pediatr. 2020; 222:213-220.e5.

PMID: 32586526 PMC: 7323908. DOI: 10.1016/j.jpeds.2020.03.064.


Association of Genetic Polymorphisms in the Beta-1 Adrenergic Receptor with Recovery of Left Ventricular Ejection Fraction in Patients with Heart Failure.

Luzum J, English J, Ahmad U, Sun J, Canan B, Sadee W J Cardiovasc Transl Res. 2019; 12(4):280-289.

PMID: 30756358 PMC: 6690812. DOI: 10.1007/s12265-019-09866-5.