PO-01-153 HIGHER PREVALENCE OF CLONAL HEMATOPOIESIS OF INDETERMINATE POTENTIAL IN ATRIAL FIBRILLATION

Abstract

Both clonal hematopoiesis of indeterminate potential (CHIP) and atrial fibrillation (AF) are age-related conditions. CHIP is associated with increased cardiovascular disease risk, contributing to AF development. However, the association between CHIP and AF is unknown. To investigate the prevalence of CHIP mutations in patients with AF and their clinical characteristics differentiated by CHIP. Deep-targeted sequencing of 24 CHIP mutations was performed and compared in 690 patients with AF and 3,341 non-AF healthy adults. Variant allele fraction (VAF) ≥2.0% indicated CHIP presence. The baseline characteristics of the AF cohort were as follows: mean age, 67.5±6.7 years; male, 474 (68.7%); and persistent AF, 316 (45.8%) cases. Twenty-four CHIP mutations with a VAF of at least 0.02 were found in 160 (23.3%) AF patients and 356 (10.7%) non-AF adults (p<0.001). The most commonly occurring somatic mutation genes in AF were DNMT3A (13.5%), TET2 (7.0%), and ASXL1 (1.7%). After multivariable adjustment, CHIP mutations were 1.3-fold higher in AF patients than in non-AF adults: odds ratio (OR), 1.34 and 95% confidence interval (CI), 1.04-1.73, p=0.026. In gene-specific analyses, TET2 somatic mutation presented the highest association with AF (OR, 1.71; 95% CI, 1.05–2.81, p=0.033). AF patients with CHIP mutations showed older age, more diabetes, a longer AF duration, a severely enlarged left atrium, and a higher E/E’ than those without CHIP mutations. CHIP mutations, primarily DNMT3A or TET2, are 1.3–1.7-fold more prevalent in patients with AF and related to more progressed AF. Further studies are required to understand the genetic architecture of AF.