Mitochondrial DNA 4977bp Deletion Mutation in Peripheral Blood Reflects Atrial Remodeling in Patients with Non-Valvular Atrial Fibrillation

Abstract

Purpose

Recently, mitochondrial DNA 4977bp deletion (mtDNA 4977 ^-mut ), a somatic mutation related to oxidative stress, has been shown to be associated with atrial fibrillation (AF). We hypothesized that patient age, as well as electroanatomical characteristics of fibrillating left atrial (LA), vary depending on the presence of mtDNA 4977 ^-mut in peripheral blood among patients with non-valvular AF.

Materials and Methods

Analyzing clinical and electroanatomical characteristics, we investigated the presence of the mtDNA 4977 ^-mut in peripheral blood of 212 patients (51.1±13.2 years old, 83.5% male) undergoing catheter ablation for non-valvular AF, as well as 212 age-matched control subjects.

Results

The overall frequency of peripheral blood mtDNA 4977 ^-mut in patients with AF and controls was not significantly different (24.5% vs. 19.3%, p=0.197). When the AF patient group was stratified according to age, mtDNA 4977 ^-mut was more common (47.4% vs. 20.0%, p=0.019) in AF patients older than 65 years than their age-matched controls. Among AF patients, those with mtDNA 4977 ^-mut were older (58.1±11.9 years old vs. 48.8±11.9 years old, p<0.001). AF patients positive for the mtDNA mutation had greater LA dimension ( p=0.014), higher mitral inflow peak velocity (E)/diastolic mitral annular velocity (Em) ratio ( p<0.001), as well as lower endocardial voltage ( p=0.035), and slower conduction velocity ( p=0.048) in the posterior LA than those without the mutation. In multivariate analysis, E/Em ratio was found to be significantly associated with the presence of mtDNA 4977 ^-mut in peripheral blood.

Conclusion

mtDNA 4977 ^-mut , an age-related somatic mutation detected in the peripheral blood, is associated with advanced age and electro-anatomical remodeling of the atrium in non-valvular AF.