Clonal Hematopoiesis of Intermediate Potential in Atrial Fibrillation: A Critical View of Current Knowledge as a Springboard for Future Research
- PMID: 40804878
- PMCID: PMC12346490
- DOI: 10.3390/diagnostics15151915
Clonal Hematopoiesis of Intermediate Potential in Atrial Fibrillation: A Critical View of Current Knowledge as a Springboard for Future Research
Abstract
Clonal hematopoiesis of intermediate potential (CHIP) is the presence of a clonally expanded hematopoietic stem cell because of a mutation in individuals without evidence of hematologic malignancy, dysplasia, or cytopenia. Interestingly, CHIP is associated with a two-fold increase in cardiovascular risk, independently of traditional risk factors. Recent studies using deep-targeted sequencing have revealed that CHIP mutations, primarily TET2 and DNMT3A, present a higher incidence in patients with AF compared to healthy controls. Moreover, the presence of the aforementioned mutations is positively correlated with the progression and the severity of the AF clinical course. Regarding the predisposition of AF, it has been proven that TET2 and ASXL1 mutations, and not DNMT3A mutation, are associated with higher interleukin-6 (IL-6) levels. IL-6 levels, being indices of cardiac remodeling, predispose to an elevated risk for AF in healthy subjects. Currently conducted research has focused on elaborating the mechanisms driving the association between AF and CHIP and on the evaluation of potential interventions to reduce the risk of AF development. The aims of our review are (i) to summarize published evidence regarding the presence of CHIP mutations as a contributor to AF severity and predisposition, and (ii) to highlight the potential benefits of investigating the correlations between CHIP and AF for AF-diagnosed patients.
Keywords: CHIP; DNMT3A mutation; TET2 mutation; atrial fibrillation; cardiovascular remodeling.
Conflict of interest statement
The authors declare no conflicts of interest.
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