Atrial fibrillation is associated with accumulation of aging-related common type mitochondrial DNA deletion mutation in human atrial tissue

Study objective: Accumulation of somatic mutations of mitochondrial DNA (mtDNA) contributes to the aging process and progressive organ dysfunction. We investigated the mitochondrial DNA with 4977-base-pair mtDNA deletion mutation (mtDNA⁴⁹⁷⁷) in human atrial tissue and correlated the amount of mtDNA⁴⁹⁷⁷ to clinical atrial fibrillation (AF). Methods and results: Atrial tissue from the right atrial appendage was obtained in 88 patients during open-heart surgery (22 children/adolescents and 66 adults). The amount of mtDNA⁴⁹⁷⁷ was measured using a nested polymerase chain reaction protocol and normalized to wild-type mtDNA. We found that the mtDNA⁴⁹⁷⁷ was absent in all 22 pediatric/adolescent patients. In the adult group, the relative amount of mtDNA⁴⁹⁷⁷ was significantly higher in patients with AF than in patients without AF (0.55 ± 0.26 vs 0.35 ± 0.29, p < 0.007) [mean ± SD]. The amount of mtDNA⁴⁹⁷⁷ was also positively associated with age (r = 0.29, p < 0.01). Left and right atrial pressures, left atrial dimension, hypertension, and cardiac diagnosis did not influence the amount of mtDNA⁴⁹⁷⁷ significantly. Further multivariate analysis showed that both aging and AF contributed independently to the accumulation of mtDNA⁴⁹⁷⁷. Conclusion: AF is associated with an increase of mtDNA⁴⁹⁷⁷. This change is similar to the aging process of atrial tissue and might contribute to atrial dysfunction in AF.