Quantitative analysis of myocardial mitochondrial DNA deletion and its relationship with cardiac dysfunction in heart failure

Objective: To assess the effects of acquired myocardial mitochondrial DNA (mtDNA) damage in the development of heart failure. Methods: Twenty eight patients with congestive heart failure who underwent endomyocardial biopsy, together with 10 control hearts obtained at autopsy from people who died from accident were enrolled. The mtDNA deletions were analysed by quantitative polymerase chain reaction (PCR) technique. The frequency and extent of two commonly encountered mtDNA deletions, mtDNA 4977 bp(mtDNA⁴⁹⁷⁷) and 7436 bp(mtDNA⁷⁴³⁶) deletions were used as the damage index to assess the relationship of the extent of mtDNA damage with the degree of cardiac dysfunction in the development of heart failure. Results: mtDNA⁴⁹⁷⁷ deletion was observed in the hearts of all of the patients with congestive heart failure, accounting for 0.103 - 1.028% of the total mtDNA; mtDNA⁷⁴³⁶ deletion was found in 7 of 10 patients with dilated cardiomyopathy (DCM) and 7 of 18 patients with rheumatic heart disease (RHD), and comprised 0.009 - 0.488% of the total. Quantitatively very low mtDNA⁴⁹⁷⁷ and mtDNA⁷⁴³⁶ deletions were detected only in 2 and 2 control hearts respectively. With the rising of NYHA function class and the enlarged left atrial size, the percentage of mtDNA deletions increased markedly; and the extent of increase in DCM was more marked than that in RHD. Conclusions: The extent of myocardial mtDNA damage varied closely with the degree of cardiac dysfunction, especially in patients with DCM.