Clonal haematopoiesis of indeterminate potential (CHIP) mutations were more prevalent in patients with atrial fibrillation than non-AF subjects (adjusted OR 1.38; 95% CI 1.10-1.74; P<0.01).
Cohort (n=25,631)
Yes
Are CHIP mutations associated with the development, progression, and adverse clinical outcomes of atrial fibrillation?
CHIP mutations are associated with a higher prevalence, more progressive nature, and worse clinical outcomes in patients with atrial fibrillation.
Effect estimate: adjusted OR 1.38 (95% CI 1.10-1.74)
Absolute Event Rate: 23.6% vs 10.7%
p-value: p=< .01
BACKGROUND AND AIMS: Both clonal haematopoiesis of indeterminate potential (CHIP) and atrial fibrillation (AF) are age-related conditions. This study investigated the potential role of CHIP in the development and progression of AF. METHODS: Deep-targeted sequencing of 24 CHIP mutations (a mean depth of coverage = 1000×) was performed in 1004 patients with AF and 3341 non-AF healthy subjects. Variant allele fraction ≥ 2.0% indicated the presence of CHIP mutations. The association between CHIP and AF was evaluated by the comparison of (i) the prevalence of CHIP mutations between AF and non-AF subjects and (ii) clinical characteristics discriminated by CHIP mutations within AF patients. Furthermore, the risk of clinical outcomes-the composite of heart failure, ischaemic stroke, or death-according to the presence of CHIP mutations in AF was investigated from the UK Biobank cohort. RESULTS: The mean age was 67.6 ± 6.9 vs. 58.5 ± 6.5 years in AF (paroxysmal, 39.0%; persistent, 61.0%) and non-AF cohorts, respectively. CHIP mutations with a variant allele fraction of ≥2.0% were found in 237 (23.6%) AF patients (DNMT3A, 13.5%; TET2, 6.6%; and ASXL1, 1.5%) and were more prevalent than non-AF subjects 356 (10.7%); P < .001 across the age. After multivariable adjustment (age, sex, smoking, body mass index, diabetes, and hypertension), CHIP mutations were 1.4-fold higher in AF adjusted odds ratio (OR) 1.38; 95% confidence interval 1.10-1.74, P < .01. The ORs of CHIP mutations were the highest in the long-standing persistent AF (adjusted OR 1.50; 95% confidence interval 1.14-1.99, P = .004) followed by persistent (adjusted OR 1.44) and paroxysmal (adjusted OR 1.33) AF. In gene-specific analyses, TET2 somatic mutation presented the highest association with AF (adjusted OR 1.65; 95% confidence interval 1.05-2.60, P = .030). AF patients with CHIP mutations were older and had a higher prevalence of diabetes, a longer AF duration, a higher E/E', and a more severely enlarged left atrium than those without CHIP mutations (all P < .05). In UK Biobank analysis of 21 286 AF subjects (1297 with CHIP and 19 989 without CHIP), the CHIP mutation in AF is associated with a 1.32-fold higher risk of a composite clinical event (heart failure, ischaemic stroke, or death). CONCLUSIONS: CHIP mutations, primarily DNMT3A or TET2, are more prevalent in patients with AF than non-AF subjects whilst their presence is associated with a more progressive nature of AF and unfavourable clinical outcomes.
Ahn et al. (Wed,) conducted a cohort in Atrial fibrillation (n=25,631). Clonal haematopoiesis of indeterminate potential (CHIP) mutations vs. Absence of CHIP mutations / non-AF subjects was evaluated on Prevalence of CHIP mutations (adjusted OR 1.38, 95% CI 1.10-1.74, p=< .01). Clonal haematopoiesis of indeterminate potential (CHIP) mutations were more prevalent in patients with atrial fibrillation than non-AF subjects (adjusted OR 1.38; 95% CI 1.10-1.74; P<0.01).