Arrhythmias & electrophysiology
Association of Clonal Hematopoiesis With Silent Brain Lesions and Cognitive Decline in Patients With Atrial Fibrillation
Authors' conclusion
In patients with AF, CHIP was independently associated with a greater burden and progression of silent brain lesions and with accelerated cognitive decline.
Study context
- Population
- Patients with atrial fibrillation (AF) enrolled 2014–2017validation cohort n = 199
- Participants
- 1,572 patients
- Exposure
- Clonal hematopoiesis of indeterminate potential (CHIP) carriers vs noncarriers
- CHIP carriersn = 342
- Outcome
- Prevalent and incident silent brain lesions (large noncortical or cortical infarcts, small noncortical infarcts, microbleeds, white matter lesions (WMLs)) on MRI
- Follow-up
- Baseline and 2 years
Methodological detailsmulticentre, external validation cohort
- Multicentre
- External validation cohort
Main finding
As reported in the abstract
Silent brain lesions at baseline
CHIP carriers vs NoncarriersOdds ratio (95% CI)
Cerebral microbleeds
1.45(1.09–1.93)
WMLs
1.56(1.20–2.04)
Observational data: associations, not effects.
Further findings
| Outcome | OR (95% CI) | |
|---|---|---|
| Silent brain lesions at baseline, non-DNMT3A carriersNon-DNMT3A carriersvs NoncarriersMicrobleeds | 1.79 (1.25–2.55) | |
| Silent brain lesions at baseline, non-DNMT3A carriersNon-DNMT3A carriersvs NoncarriersWMLs | 1.80 (1.25–2.62) | |
| 0.20.5125Odds ratio (log scale) |
Multiple CHIP sequence variations · baseline
| OR (95% CI) | ||
|---|---|---|
| Multiple CHIP variationsMicrobleeds | 1.36 (1.10–1.69) | |
| Multiple CHIP variationsWMLs | 1.41 (1.15–1.75) | |
| 0.512Odds ratio (log scale) |
| Outcome | β (95% CI) |
|---|---|
| Montreal Cognitive Assessment score · 7 yearsLower score (greater decline) in carriers | −0.53 (−1.02 to −0.03) |
Multiple CHIP sequence variations · baseline
- Large CHIP clones (variant allele frequency >10%) associated with higher WML volumes
Montreal Cognitive Assessment score · 7 years
- Decline more pronounced in DNMT3A and ASXL1 carriers
External validation cohort (Korea)
- Similar trend, limited to TET2 sequence variations
Original publication
Association of Clonal Hematopoiesis With Silent Brain Lesions and Cognitive Decline in Patients With Atrial Fibrillation. Circulation. Published 18 August 2026. doi:10.
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