Po-02-125 evaluation of a genome-wide and pitx2 polygenic risk score for the prediction of atrial fibrillation recurrence after pulmonary vein isolation

Polygenic risk scores (PRS) were recently shown to be associated with preexisting atrial fibrillation (AF) and to be predictive of incident AF. Previous studies using limited PRS to predict recurrent AF following pulmonary vein isolation (PVI) showed inconsistent results. We sought to evaluate the association of PRS with AF recurrence following ablation using a genome-wide PRS combining >6 million single nucleotide polymorphisms (PRSAF) and, in a secondary analysis, a PRS limited to a locus involved in pulmonary vein development comprising the PITX2 gene (PRSPITX2). To assess whether a genome-wide PRS was associated with time to recurrence of atrial arrhythmia following a first PVI. We included patients from our hospital biobank who underwent genome-wide array genotyping and imputation, had successful PVI performed in our center with at least 1 year of follow-up and absence of moderate-severe structural heart disease. We computed PRSAF and PRSPITX2 using weights from Khera et al (PRS catalog ID PGS000016) and assessed their association with time to first atrial arrhythmia recurrence following a blanking period of 90 days using Cox proportional hazards models (including covariables listed in table 1). A total of 411 patients in our biobank were identified to have had PVI for paroxysmal or persistent AF between 2002 and 2020. Of these, 342 met inclusion criteria (fig. 1A). Over a median follow-up time of 6.06 years (IQR 2.73-10.2), a total of 218 patients (62%) experienced atrial arrhythmia recurrence (fig. 1C). AF type (persistent vs. paroxysmal) and left atrial diameter were significantly associated with arrhythmia recurrence in univariate and multivariate analyses (table 1). Neither PRSAF (fig. 1B) nor PRSPITX2 were associated with the primary endpoint (HR 1.04, p=0.6 and HR 1.02, p=0.8, respectively). Furthermore, neither PRS was associated with recurrence in a subgroup analysis restricted to 287 patients with paroxysmal AF. A genome-wide PRS comprised of >6million markers and a targeted PITX2 PRS were not significantly associated with time to first atrial arrhythmia recurrence following a first acutely successful PVI for paroxysmal or persistent AF. These findings are in line with recent studies assessing a limited PRS. Further studies are required to explore the potential role of genetic susceptibility to AF in predicting AF recurrence in the absence of pulmonary vein reconnection and in predicting AF burden as an endpoint for PVI efficacy.