Association of Atrial Fibrillation Risk Alleles and Response to Acute Rate Control Therapy

Abstract Objectives Given the sparse evidence for selection of first-line therapy for acute atrial fibrillation (AF) based on clinical factors alone, incorporation of genotype data may improve the effectiveness of treatment algorithms and advance the understanding of inter-patient heterogeneity. We tested whether candidate nucleotide polymorphisms (SNPs) related to AF physiologic responses are associated with ventricular rate control after intravenous diltiazem in the emergency department (ED). Methods We conducted an analysis within a prospective observational cohort of ED patients with acute symptomatic AF, ventricular rate > 110 beats per minute within the first 2 hours, initially treated with intravenous diltiazem, and who had DNA available for analysis. We evaluated 24 candidate SNPs that were grouped into 3 categories based on their phenotype response (atrioventricular nodal (AVN) conduction, resting heart rate, disease susceptibility) and calculated 3 genetic scores for each patient. Our primary outcome was maximum heart rate reduction within 4 hours of diltiazem administration. Multivariable regression was used to identify associations with the outcome while adjusting for age, sex, baseline heart rate, and diltiazem dose. Results Of the 142 patients, 127 had complete data for the primary outcome. None of the genetic scores for AVN conduction, resting heart rate, or AF susceptibility showed a significant association with maximal heart rate response. Conclusion Using a candidate SNP approach, screening for genetic variants associated with AVN conduction, resting heart rate, or AF susceptibility failed to provide significant data for predicting successful rate control response to intravenous diltiazem for treating acute AF in the ED.