While genetic approaches to AF have revealed that susceptibility to AF and response to therapy are modulated in part by the underlying genetic substrate, the translation of these discoveries to the bedside management of AF patients has thus far been limited. This relates to poor understanding of the underlying mechanisms associated with common AF risk alleles, challenges associated with determining efficacy of AADs and lack of genotype-directed prospective studies. Our preliminary data showed that a common chr4q25 SNP associated with AF predicted successful symptom control in patients treated with AADs and individuals who carried the risk variant responded better to Vaughan Williams class I vs. class III AADs. Based on the information collected in this feasibility and pilot study, we propose to conduct a prospective pharmacogenomic study where a cohort of patients with frequent symptomatic paroxysmal AF will be randomized to a flecainide (class I AAD) or sotalol (class III AAD) in order to determine if response to therapy is modified by chr4q25 SNPs using AF burden as a metric of drug efficacy. This main study, like the pilot study proposed here, will utilize a crossover design to minimize inter-individual variability and maximize statistical power to detect an interaction between chr4q25 genotype and the reduction of AF burden with flecainide vs. sotalol. After a run-in period during which the AAD will be up-titrated, subjects will be monitored with the Medtronic Reveal LINQ Insertable Cardiac Monitor (ICM) system to assess AF burden. Furthermore, subjects will be asked to complete a comprehensive, validated 20-item AF specific questionnaire (AF Effect on QualiTy-of-life [AFEQT]) at baseline, and monthly thereafter for the duration of the study. At the end of the 3-month trial period, the AAD will be discontinued and participants will be switched to the other AAD and followed for another 3-month period in a crossover trial design.