Telomere Length Is Associated With Adverse Atrial Remodeling in Patients With Atrial Fibrillation

Area of Science:

• Cardiology
• Genetics
• Aging Research

Background:

• Atrial fibrillation (AF) is a common arrhythmia, increasing with age.
• Telomeres, DNA protective caps, shorten with age and may indicate biological aging.
• Atrial remodeling and fibrosis are key factors in AF pathophysiology.

Purpose of the Study:

• To investigate the relationship between telomere length (TL) and atrial remodeling in AF patients.
• To assess gene expression profiles based on TL and left atrial fibrosis.
• To explore the mechanistic impact of telomere shortening on atrial fibrosis using mouse models.

Main Methods:

• Analysis of 72 AF patients undergoing catheter ablation.
• Quantification of TL and correlation with left atrial low voltage areas (fibrosis surrogate).
• Gene expression profiling via mRNA sequencing and assessment of clonal hematopoiesis; use of telomerase knockout mice.

Main Results:

• Patients with advanced left atrial fibrosis had shorter TL.
• Shorter TL and extensive fibrosis correlated with significantly lower success rates post-ablation.
• Gene expression and clonal hematopoiesis differed between short and long TL groups; mouse models showed fibrosis and related gene overexpression.

Conclusions:

• Telomere shortening is associated with left atrial remodeling and fibrosis in AF.
• Shorter telomeres may drive molecular changes leading to cardiac fibrosis and persistent AF.