MITOCHONDRIAL-DNA DELETIONS IN DILATED CARDIOMYOPATHY - A CLINICAL-STUDY EMPLOYING ENDOMYOCARDIAL SAMPLING

Objectives. The aim of this study was to assess the occurrence of the two most commonly encountered mitochondrial DNA (mtDNA) deletions in t he hearts of patients with idiopathic dilated cardiomyopathy. Backgrou nd. The mutation frequency of mtDNA is high, and sporadic cases of car diomyopathies associated with mtDNA deletions have been described. Rep orts of increases in mtDNA deletions with advancing age also exist. Me thods. We studied 15 consecutive patients with typical signs of idiopa thic dilated cardiomyopathy, without a family history, together with 1 6 control hearts obtained at autopsy from patients who died of noncard iac causes. The patients underwent both right and left heart catheteri zation, during which endomyocardial biopsy samples were taken. The mtD NA in these samples and in the control hearts was analyzed by the poly merase chain reaction technique for the occurrence and proportion of 5 and 7.4 kilobase (kb) deletions; (Cambridge sequence map positions fr om nucleotides 8469 to 13447 and 8637 to 16084, respectively).Results. The 5 kb mtDNA deletion was observed in the hearts of all of the pati ents with idiopathic dilated cardiomyopathy, accounting for 0.32 +/- 0 .05% (mean +/- SEM) of the total mtDNA. The 7.4-kb deletion was found in 7 of the 15 patients with idiopathic dilated cardiomyopathy and com prised 0.28 +/- 0.08% of the total. The 5- and 7.4-kb deletions were d etected in 12 and 9 control hearts, respectively, quantitatively simil ar to the patients with idiopathic dilated cardiomyopathy. A sigmoidal age dependency of the mtDNA deletions was found both in the patients with cardiomyopathy and in the control hearts, but after elimination o f the confounding age variable, there was no difference between these groups. Conclusions. Because of the similarity of the age dependent in crease in the frequency of mtDNA deletions in cardiomyopathic and cont rol hearts, the deletions have no causal relation with idiopathic dila ted cardiomyopathy. The present results confirm the notion of an incre ase in mtDNA deletions with advancing age and show that endomyocardial tissue sampling is a feasible method for detecting mtDNA defects in a ffected hearts.