Abstract 18539: Atrial Fibrillation and Sleep Apnea: Modulation of Response to Drug Therapy by Common Genetic Variants
Background: Severe obstructive sleep apnea (OSA) is associated with a decreased response of atrial fibrillation (AF) to anti-arrhythmic drugs (AADs). Whether common AF susceptibility alleles or common single nucleotide polymorphisms (SNPs) in the β1-adrenoreceptor (ADR) modulate response to AADs in patients with OSA is unknown.
Hypothesis: Common genetic variants associated with AF decrease the efficacy of AADs to a greater degree in severe OSA as compared to non-severe OSA.
Methods: We analyzed 84 individuals that had polysomnography, genotyping, and a comprehensive evaluation of AF status over time. Response to AADs was defined as a decrease in AF burden score by ≥ 75% on a validated symptom scoring tool or the combination of sinus rhythm on follow-up EKGs, stable AAD therapy, AF burden below the ASSERT threshold on device diagnostics or ambulatory monitoring, and the absence of non-pharmacologic therapies (cardioversion, nodal ablation, AF ablation). Severe OSA was defined as an apnea-hypopnea index (AHI) ≥ 30 events/hour. We analyzed common AF susceptibility alleles (rs2200733 and rs10033464 at 4q25, rs7193343 in ZFHX3, rs13376333 in KCNN3) and common SNPs in the β1-ADR (rs1801252 and rs1801253 at ADRB1).
Results: Over an average follow-up period of 9.0 ± 4.5 months, 41 participants (49%) responded to AADs and 37 (44%) had severe OSA. For the β1-ADR SNP rs1801252, the AHI was higher in those with the variant compared to wild-type (37 ± 25 vs 23 ± 20 events/hour; p = 0.03 by Mann-Whitney test). Individuals with non-severe OSA and this variant were more likely to not respond to AADs when compared to wild-type allele (OR 2.0; 95% CI 0.5-7.8; Figure).
Conclusions: In a cohort receiving AAD therapy for AF, OSA severity was associated with a functional variant in the β1-ADR An unfavorable genotype may contribute to decreased response to AADs in those with AF and non-severe OSA. Genotype may play less of a role in the response to AADs in severe OSA.
- © 2012 by American Heart Association, Inc.