INTRODUCTION
Atrial fibrillation (AF) is the most common atrial arrhythmia and confers increased risk of cardiovascular morbidity and mortality. AF carries a significantly increased risk of incident and recurrent ischemic stroke1,2, myocardial infarction, heart failure3, and all-cause mortality.4In addition, AF directly impacts patient outcomes and quality of life, and, over the past few decades, multiple randomized trials have been aimed at evaluating the effects of various antiarrhythmic drugs (AAD) and procedural interventions to affect these outcomes.5-10 However, there is significant heterogeneity in the clinical phenotype of, as well as management strategies for, AF.11-13 Given the rising prevalence14 of and significant public health burden incurred by AF and its associated heterogeneity, recent work has focused on the genetic underpinnings of AF and its implications on diagnosis and treatment-specific outcomes.15
Genetic analysis has largely been focused on the clinical subgroup of ‘early onset AF’ or ‘lone AF,’ typically defined as clinically recognized AF in a patient <66 years old and in the absence of structural heart disease.16 This work has resulted in the identification of multiple genes in familial forms of AF and single nucleotide polymorphisms (SNPs) associated with the development of this clinical sub-phenotype of AF17,18; additionally, many of the same genetic loci have been identified as modulators of clinical response to AF therapeutics. Despite these advances, contemporary guidelines do not support the routine use of genetic testing in AF patients.19 Herein, we describe the current understanding of the association between genetic susceptibility and AF, review challenges related to patient selection for genetic testing, and describe the outcomes of AAD and catheter interventions for genetically mediated AF. Further, we propose potential next steps in the understanding and integration of genetics into clinical AF care.