Novel association of polymorphic genetic variants with predictors of outcome of catheter ablation in atrial fibrillation: new directions from a prospective study (DECAF)

background: Non-pulmonary vein (non-PV) triggers and left atrial (LA) scars perpetuate atrial fibrillation (AF) and limit the success rate of catheter ablation. As these risk factors manifest in some AF patients and not in all, understanding their genetic basis will offer insight into the inter-individual differences in the clinical presentation and therapeutic approaches of this complex arrhythmia. We examined the association of selected single nucleotide polymorphisms (SNPs) with scar and non-PV triggers. Methods: Four hundred AF patients (67% male, 62±12 year, LA size 45.3±7 mm, 64% non-paroxysmal) undergoing catheter ablation were prospectively enrolled at our center. DNA extraction and genotyping for 16 AF-related SNPS from blood samples were performed using Qiagen QiaAMP kit and TaqMan assay respectively. Three hundred seventy two DNA samples were available for genotyping. Multivariate logistic regression analysis (adjusted covariates: age, gender, LA size, hypertension and diabetes) was used for assessing predictive role of individual SNP; and logistic kernel-machine approach was applied to test the cumulative effect of multiple SNPs as a group with non-PV triggers and LA scar. results: SNPs, rs6599230, rs6843082, were inversely associated (OR 0.68, p= 0.04; and 0.62, p=0.01 respectively) whereas rs1448817 (OR 1.74, p= 0.04), and rs7193343 (OR 1.66, p= 0.02) predicted higher risk of non-PV triggers. Genotypes for rs6599230 and rs6843082 conferred 51% reduction in the odds for non-PV triggers (combined OR 0.49, p=0.019), while rs1448817 and rs7193343 demonstrated a combined OR of 1.93, p=0.025. For LA scar, inverse association was observed with rs1448817 (OR 0.29, p=0.006), rs17042171 (OR 0.27, p=0.032), rs3807989 (OR 0.54, p=0.017), and rs6843082 (OR 0.56, p=0.009). Two SNPs were associated with increased scar risk; rs17375901 (OR 3.68, p=0.03), and rs7193343 (OR 1.74, p=0.037). Conclusion: We identified novel genetic markers that influence the risk for non-PV triggers and LA scar in atrial fibrillation patients. Our results suggest that in patients carrying those risk variants, operators may need to adopt individualized ablation strategies to maximize procedural success.