Po-01-002 association of novel combined genetic polymorphisms with risk of thromboembolism in patients with atrial fibrillation

AF patients remain on oral anticoagulation (OAC) or left atrial appendage (LAA) closure is performed for thromboprophylaxis. However, clots on the closure device as well as stroke/transient ischemic attack (TIA) are observed to occur in some patients despite of being on blood thinners or after being off-OAC for a very brief period. Therefore, we evaluated if genetic variants were associated with TE events in this subset of AF population. This prospective study (NCT04115436) included consecutive AF patients that were managed for AF at our center. SNP Genotyping Analysis was performed on the blood sample of the study participants using a combination of microarray and next-generation sequencing (NGS). We screened for common single nucleotide polymorphisms (SNPs) reported in the literature to be associated with stroke and thromboembolism at a genome-wide significance level. We genotyped 29 AF patients (age: 66.5±3.53 years; female: 6 (20.7%)) with thromboembolic events following AF ablation. Of these patients, device (Watchman)-associated thrombus was reported in 13 (44.8%), stroke/TIA off-OAC in 14 (48.3%) and left atrial appendage thrombus while on OAC in 2 (6.9%). One or more of the following 4 SNPs were detected in 27/29 patients (93.1%): rs11833579, rs12476527, rs505922 and rs6891174. They were homozygous for the recessive allele in all 27 patients. Of the 27, 19 (70.3%) patients including the 13 with device-clot had >2 of the 4 genetic variants reported. Location of these SNPs and their clinical significance is provided in table 1. Our findings, for the first time, document the association of four stroke-related genetic variants with prothrombotic events such as device-related clot in patients with atrial fibrillation.