Heart Rhythm. 2025 May 12. pii: S1547-5271(25)02434-8. [Epub ahead of print]
Atrial fibrillation (AF) is the most common sustained arrhythmia. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by the clonal expansion of hematopoietic stem cells due to acquired mutations without hematologic malignancies, has emerged as a potential risk factor for AF. This narrative review summarizes the shared risk factors between CHIP and AF, including age, lifestyle behaviors and cardiometabolic conditions. It then explores the underlying mechanisms including inflammation, atrial fibrosis and abnormal red cell distribution width. Among these, inflammation is a central driver that promotes abnormal calcium handling, which further accelerates atrial remodeling. For specific mutations, TET2 mutations correlate strongest with AF, with other mutations in genes such as ASXL1, JAK2, TP53, PPM1D and spliceosomes, may also modulate AF susceptibility, though their precise roles require further investigation.
Keywords: Aging; Atrial fibrillation; Atrial fibrosis; Clonal hematopoiesis; Clonal hematopoiesis of indeterminate potential; Inflammation; Somatic mutation