Arrhythmias & electrophysiologyCohort study

Association of Clonal Hematopoiesis With Silent Brain Lesions and Cognitive Decline in Patients With Atrial Fibrillation

CirculationPublished

  • Prospective cohort study
  • multicentre
  • external validation cohort

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

Main finding

As reported in the abstract

Silent brain lesions at baseline · 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

OutcomeOR (95% CI)
Silent brain lesions at baseline, non-DNMT3A carriers — Non-DNMT3A carriers vs Noncarriers · microbleeds1.79 (1.25–2.55)
Silent brain lesions at baseline, non-DNMT3A carriers — Non-DNMT3A carriers vs Noncarriers · WMLs1.80 (1.25–2.62)
Multiple CHIP sequence variations · baseline — Multiple CHIP variations vs Noncarriers · microbleeds1.36 (1.10–1.69)
Multiple CHIP sequence variations · baseline — Multiple CHIP variations vs Noncarriers · WMLs1.41 (1.15–1.75)
Outcomeβ (95% CI)
Montreal Cognitive Assessment score · 7 years · lower 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:10.1161/circulationaha.126.079459

Summarised from the published abstract; every number is checked against it