Clonal hematopoiesis of indeterminate potential and risk of atrial fibrillation: a meta-analysis

Abstract Background and Aims Clonal hematopoiesis of indeterminate potential (CHIP) has recently been recognized as a significant risk factor for various non-hematologic conditions, particularly cardiovascular diseases. However, the relationship between CHIP and atrial fibrillation (AF) remains underexplored to date. Given the conflicting findings in recent studies, the present meta-analysis aimed to assess the association between CHIP and the incidence or recurrence of AF. Methods Medline, Cochrane Library and Scopus were searched until October 27, 2024. Triple-independent study selection, data extraction and quality assessment were performed. Evidence was pooled using restricted maximum likelihood random-effects meta-analysis. Results Four studies comprising a total of 801,085 participants were included. Over a median follow-up period of 9 years, participants with any CHIP [variant allele fraction (VAF) ≥ 2%] exhibited a significantly elevated risk of developing incident or recurrent AF compared to those in the non-CHIP group (hazard ratio [HR] = 1.12; 95% confidence interval [CI] = [0.07 to 1.17], P < 0.0001; I² = 3%, heterogeneity P = 0.38). The presence of any CHIP was associated with a markedly increased risk for both incident and recurrent AF when these outcomes were analyzed separately. Furthermore, large CHIP (VAF ≥ 10%) was correlated with a heightened risk of incident AF, suggesting a potential dose-response relationship. Leave-one-out sensitivity analyses identified no evidence of outliers. Conclusions CHIP is associated with increased risk of incident or recurrent AF. Further research is required to clarify the mechanisms underlying the observed association and to explore interventions aimed at mitigating this risk.