Abstract 4099: Genetic and Clinical Predictors of Response to Rate Control Therapy in Patients with Atrial Fibrillation
Background: Randomized studies have now shown that ventricular rate control is an acceptable strategy in patients with atrial fibrillation (AF). Beta-blockers are the first line pharmacologic agent used for ventricular rate control. Recently, a non-synonymous polymorphism (G389R) in the beta-1-adrenergic receptor has been found to modulate the outcome of beta-blockade in heart failure patients. Accordingly, in this study we evaluated the impact of clinical factors and of two common polymorphisms in the β1-adrenergic receptor (G389R and S49G) on response to ventricular rate control therapy in patients with AF.
Methods and Results: We studied 279 patients (200 men, 79 women, ages 55 ± 13 years) prospectively enrolled in the Vanderbilt AF Registry, and managed with rate control. Ventricular rate control was prospectively defined as adequate based on the AFFIRM criteria:
Average heart rate (HR) at rest ≤80 bpm and
Maximum HR during 6-min walk test ≤110 bpm or average HR during 24-hr Holter ≤100 bpm.
Non-response was defined when the ventricular rate was inadequately controlled necessitating a change in therapy. In 151 (54.1%) patients, ventricular rate control was classified as adequate. Although the frequencies of the two â1-adrenergic polymorphisms were in Hardy-Weinberg equilibrium (G389R: 0.25 [cases] vs 0.26 [controls]; S49R: 0.14 [cases] vs. 0.24 [controls], both P>0.05), they were not significantly associated with ventricular rate control (P>0.05 for both). However, a history of hypertension, hyperlipidemia, valvular heart disease and cardiomyopathy were significantly associated with inadequate ventricular rate control. Conversely, prior stroke was more common in patients with adequate ventricular rate control (odds ratio [OR] = 0.29; P<0.01).
Conclusions: We have identified clinical predictors of response to ventricular rate therapy in patients with AF. However, common β1-adrenergic receptor polymorphisms did not modulate response to rate control therapy. Future studies are needed to confirm these findings in other cohorts and to elucidate potential clinical decision-making tools to predict response to rate control therapy in AF patients.