TOPLINE

Patients with atrial fibrillation (AF) who carry clonal hematopoiesis of indeterminate potential (CHIP) genetic variations showed significantly higher rates of silent brain lesions, including cerebral microbleeds and white matter lesions (WMLs), compared with noncarriers.

METHODOLOGY

• Researchers assessed 1572 patients with AF (mean age, 72.5 years; 72.8% men) enrolled in the Swiss-AF cohort study between 2014 and 2017.
• Participants underwent deep-targeted sequencing to detect CHIP-associated sequence variations, brain MRI to identify silent brain lesions, and standardized cognitive assessments using the Montreal Cognitive Assessment.
• Silent brain lesions were defined as large noncortical or cortical infarcts, small noncortical infarcts, microbleeds, and WMLs, assessed at baseline and after 2 years.
• Findings were externally validated in an independent East Asian cohort of 199 patients with AF from Korea.

TAKEAWAY

• CHIP was identified in 342 patients (22%), most commonly in DNMT3A (49.4%) and TET2 (28.3%), and ASXL1 (12%).
• CHIP was associated with a higher burden of microbleeding and WMLs, particularly in non-DNMT3A carriers (odds ratio [OR], 1.70; P = .004 and OR, 1.80; P = .002, respectively).
• Presence of higher burden of CHIP variations was associated with increased odds of microbleeds (OR, 1.37; P = .005) and WMLs (OR, 1.41; P = .002).
• Over 7 years, CHIP carriers exhibited greater cognitive decline, with a lower MoCA score compared with noncarriers (β, -0.53; P = .037), with the decline more pronounced in DNMT3A variation carriers.

IN PRACTICE

"These findings suggest that CHIP contributes to small vessel disease and may play a role in vascular cognitive impairment in AF," the authors wrote.

SOURCE

The study was led by Pascal B. Meyre, University Hospital Basel, Switzerland. It was published online on August 18 in Circulation.

LIMITATIONS

Inclusion of predominantly male European patients could limit generalizability to other populations. The observational design may limit causal inference. Residual confounding from unmeasured variables cannot be excluded.

DISCLOSURES

The study received funding from the Swiss National Science Foundation, Swiss Heart Foundation, the Foundation for Cardiovascular Research Basel, and the University of Basel. Multiple authors reported receiving fees, research support, or grants from pharmaceutical and medical device companies including Medtronic, Abbott, Biosense Webster, Biotronik, Boston Scientific, AstraZeneca, Bayer, Novartis, and others. Additional author disclosures are reported in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.