Abstract 15314: Differential Association of Polymorphic Genetic Variants With Non-Pulmonary Vein Triggers in Patients With Non-Paroxysmal Atrial Fibrillation: Results From a Prospective Study (DECAF)

Abstract

Introduction: Earlier evidences support the origin of ectopic beats from non-pulmonary vein (non-PV) areas that initiate and maintain AF and elimination of these triggers is known to provide better arrhythmia-free survival. Of the different types, non-paroxysmal AF (NPAF) are more prevalently associated with non-PV drivers. Although emerging data on myocytes-fibroblast interactions provide some insight into the pathophysiology of non-PV triggers, the exact mechanism of origin of these ectopic foci is still unknown. Therefore, we examined the association of several AF-specific genetic variants with prevalence of non-PV triggers in NPAF patients undergoing catheter ablation. Methods: Four hundred AF patients (67% male, 62±12 year, left atrial size 45.3±7 mm, 64% non-paroxysmal) undergoing catheter ablation were prospectively enrolled at our center. DNA extraction and genotyping for 16 AF-associated SNPS from collected blood samples were performed using Qiagen QiaAMP 96 well blood 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. Result: In the non-paroxysmal AF population, significant allelic association was detected between non-PV triggers and rs6599230 (OR 0.57 [95% CI 0.31-0.88], p=0.042) and rs1448817 (OR 1.82 [95%CI 1.12-3.40], p=0.034). Interestingly, rs6599230 suggested a protective effect with 43% risk reduction while rs1448817 was an independent predictor of higher risk of developing non-PV triggers. Conclusion: Our results identified predictive association of two genetic variants, rs6599230 and rs1448817, with non-PV triggers in non-paroxysmal AF patients. Interestingly, the association was distinctive. The SNP, rs6599230 located in close proximity to SCN5A gene, was found to have a protective effect against development of arrhythmogenic triggers in the extra-PV sites whereas rs1448817 on chromosome 4q25 increased the risks of having non-PV triggers.