Abstract 10066: Clonal Hematopoiesis of Indeterminate Potential is Not Associated With Incident Atrial Fibrillation

Introduction: Inflammation is involved in the initiation and maintenance of atrial fibrillation (AF). Clonal hematopoiesis of indeterminate potential (CHIP) increases cardiovascular risk through pro-inflammatory mechanisms. Hypothesis: The presence of CHIP is associated with increased risk of incident AF. Methods: Individuals with AF were identified from the CATHGEN cohort, a study of 9,334 sequential individuals undergoing cardiac catheterization at Duke University Hospital, using ICD-9/10 codes and ECG interpretations. Incident AF was defined as AF diagnosed after blood sample collection. Individuals with predisposing or provoking conditions leading to AF (i.e., cardiomyopathy, valve disease, congenital heart disease, thyroid disease, and recent STEMI or cardiac surgery) were excluded. The remaining individuals with incident AF were matched 1:1 to controls without an AF diagnosis based on age, sex, ancestry-defined race, BMI, diabetes, hypertension, and smoking status. Whole exome sequencing was performed in DNA extracted from whole blood, and CHIP carriers in 68 genes of interest were identified. Results: Among 1,716 individuals with incident AF, 335 had no predisposing or provoking conditions leading to AF. Among these individuals, 17 (5.1%) were CHIP carriers, compared to 18 (5.4%) matched controls (odds ratio, 0.94; 95% confidence interval [CI], 0.48-1.86; p =0.9). Ten individuals (3.0%) with incident AF were carriers of a CHIP clone with variant allele fraction >10%, compared to 11 (3.3%) matched controls (odds ratio 0.90; 95% CI, 0.37-2.22; p =0.8). Restriction to the two most common genes ( DNMT3A or TET2 ) also did not show an association between CHIP and AF ( Table 1 ). Conclusions: There is no association between CHIP carrier status, high burden of CHIP, or CHIP in DNMT3A or TET2 and incident AF in the CATHGEN cohort.