Severity of obstructive sleep apnea influences the effect of genotype on response to anti-arrhythmic drug therapy for atrial fibrillation

摘要

Study Objectives: To examine the impact of genotype on the relationship between obstructive sleep apnea (OSA) and anti-arrhythmic drug (AAD) efficacy in atrial fibrillation (AF). Design: Registry based. Setting: Clinic-based. Participants: Eighty-four individuals from Vanderbilt AF registry who had polysomnography, genotyping, and serial comprehensive evaluations of AF status. Interventions: None. Measurements and Results: Response to AADs was defined as a decrease in AF burden score by ≥ 75% or the combination of sinus rhythm on follow-up EKGs, stable AAD therapy for at least 6 months, objective AF burden below an established threshold, and the absence of non-pharmacologic therapies. Participants were genotyped for common AF susceptibility alleles at chromosomes 4q25 (near PITX2), 16q22 (in ZFHX3), and 1q21 (in KCNN3), and common SNPs in the β1-adrenergic receptor (ARDB1). Wild-type status for rs10033464 at 4q25 was associated with increased success of AAD therapy in patients with no or mild OSA (odds ratio: 10.0, 95% confidence interval: 1.03 to 97.5; p < 0.05), but did not influence response to AAD therapy in those with moderate-severe OSA. A similar trend was observed for rs1801252 on ARDB1. Conclusion: In this hypothesis-generating pilot study of predominantly Caucasian men, the effect on AF response to AAD therapy of rs10033464 at 4q25 varied based on OSA status. The impact of genotype on AAD efficacy may be greatest in mild OSA and attenuated in more severe disease.