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.