Determining the Association of Chromosomal Variants With Non-PV Triggers and Ablation-outcome in AF (DECAF)

Specific Aim: This prospective pilot study aims to examine the association of specific genetic variants (single nucleotide polymorphisms) namely rs2200733, rs6843082, rs10033464, rs17042171, rs2106261 and rs13376333 on chromosome 1, 4 and 16, with presence of non-pulmonary vein triggers (NPVT) as well as ablation-outcome in AF patients.

Hypothesis: Genetic variants predict prevalence of non-PV triggers as well as long-term procedure-outcome.

Background: Atrial fibrillation (AF) is the most common clinical arrhythmia affecting nearly 3.0 million people in the United States. Its significant contribution to population morbidity and mortality is amplified by the fact that AF is associated with 3-5 fold increase in the prevalence of cerebrovascular stroke and 2-fold increase in the risk of death. Limited efficacy of the available therapeutic strategies makes the matter worse; failures being attributed to lack of clear-understanding of the pathophysiology of this complex arrhythmia. In addition to the traditional risk factors including advancing age, obesity, metabolic syndrome, ischemic/valvular heart disease and hyperthyroidism etc that predict the occurrence of AF, genetic predisposition to AF has been reported in recent years.

Common AF often occurs with structural heart diseases but not all individuals with the same cardiac pathology develop AF, indicating that there must be genetic factors predisposing some individuals to AF. In 2007, the first Genome wide association study (GWAS) for AF in subjects of European descent was reported by investigators from Iceland. Two common variants on chromosome 4q25 were found that were strongly associated with AF. Following this initial report, several research groups provided independent replication analyses. So far, there are at least three distinct genomic loci, 4q25, 16q22, and 1q21 that have a strong association with AF.

Although an SNP is generally not sufficient to cause AF, it may act in combination with other SNPs or pathological conditions (e.g., ischemia and stretch) to increase susceptibility to AF or it may have some regulatory role in the expression of nearby genes that are potential candidate genes for AF.