A common β1-adrenergic receptor polymorphism predicts favorable response to rate-control therapy in atrial fibrillation.

Parvez B, Chopra N, Rowan S, Vaglio JC, Muhammad R, Roden DM, Darbar D
J Am Coll Cardiol. 2012 59 (1): 49-56

PMID: 22192668 · PMCID: PMC3245828 · DOI:10.1016/j.jacc.2011.08.061

OBJECTIVES - In this study, we evaluated the impact of 2 common β1-adrenergic receptor (β1-AR) polymorphisms (G389R and S49G) in response to ventricular rate control therapy in patients with atrial fibrillation (AF).

BACKGROUND - Randomized studies have shown that ventricular rate control is an acceptable treatment strategy in patients with AF. However, identification of patients who will adequately respond to rate-control therapy remains a challenge.

METHODS - We studied 543 subjects (63% men; age 61.8 ± 14 years) prospectively enrolled in the Vanderbilt AF registry and managed with rate-control strategy. A "responder" displayed adequate ventricular rate control based on the AFFIRM (Atrial Fibrillation Follow-Up Investigation of Rhythm Management) criteria: average heart rate (HR) at rest ≤80 beats/min; and maximum HR during a 6-min walk test ≤110 beats/min or average HR during 24-h Holter ≤100 beats/min.

RESULTS - A total of 295 (54.3%) patients met the AFFIRM criteria. Baseline clinical characteristics were similar in responders and nonresponders except for mean resting HR (76 ± 20 beats/min vs. 70 ± 15 beats/min; p < 0.01) and smoking (6% vs. 1%; p < 0.01). Multiple clinical variables (age, gender, hypertension) failed to predict response to rate-control therapy. By contrast, carriers of Gly variant at 389 were more likely to respond favorably to rate-control therapy; 60% versus 51% in the Arg389Arg genotype, p = 0.04. This association persisted after correction for multiple clinical factors (odds ratio: 1.42, 95% confidence interval: 1.00 to 2.03, p < 0.05). Among responders, subjects carrying the Gly389 variant required the lowest doses of rate-control medications; atenolol: 92 mg versus 68 mg; carvedilol: 44 mg versus 20 mg; metoprolol: 80 mg versus 72 mg; diltiazem: 212 mg versus 180 mg, and verapamil: 276 mg versus 200 mg, respectively (p < 0.01 for all comparisons).

CONCLUSIONS - We have identified a common β1-AR polymorphism, G389R, that is associated with adequate response to rate-control therapy in AF patients. Gly389 is a loss-of-function variant; consequently, for the same adrenergic stimulation, it produces reduced levels of adenyl cyclase, and hence, attenuates the β-adrenergic cascade. Mechanistically, the effect of rate-control drugs will be synergistic with that of the Gly389 variant, which could possibly explain our findings. These findings represent a step forward in the development of a long-term strategy of selecting treatment options in AF based on genotype.

Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

MeSH Terms (24)

Adrenergic beta-1 Receptor Antagonists Aged Anti-Arrhythmia Agents Atrial Fibrillation Cohort Studies Confidence Intervals Dose-Response Relationship, Drug Drug Administration Schedule Electrocardiography Female Follow-Up Studies Heart Rate Humans Logistic Models Male Middle Aged Odds Ratio Polymorphism, Genetic Predictive Value of Tests Prospective Studies Receptors, Adrenergic, beta-1 Registries Severity of Illness Index Treatment Outcome

Connections (1)

This publication is referenced by other Labnodes entities:

Links