Cardiac Involvement in Mitochondrial Diseases, and Vice Versa

Abstract

In this issue of Circulation , Anan et al1 describe cardiac abnormalities occurring in a small group of patients with well-defined defects in mitochondrial DNA (mtDNA). Abnormal cardiac findings, as assessed by ECG, chest radiograph, echocardiography, and His bundle electrograms, were detected in patients within each of four categories of mitochondrial diseases. Conduction disturbances were observed uniformly in patients with Kearns-Sayre syndrome, while some patients with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) exhibited symmetric left ventricular hypertrophy with either normal or abnormal wall motion. Asymmetric septal hypertrophy with a hypokinetic ventricle was present in a majority of patients with MERRF (myoclonus epilepsy with ragged red fibers) and progressed over time to dilated cardiomyopathy in one individual. Cardiac abnormalities were less prevalent in patients with ocular myopathy, but diffuse hypokinesis was noted in 1 of 6 patients. Kearns-Sayre syndrome and ocular myopathy result from accumulation of deleted forms of mtDNA in affected tissues, whereas MERRF and MELAS are caused by single nucleotide substitutions in the mitochondrial tRNALys and tRNALeu genes, respectively. Cardiac dysfunction occurring in conjuction with neuropathic and skeletal myopathic symptoms in patients with mitochondrial gene defects has been described previously in case and kindred reports, as reviewed by Wallace,2 but this recent work analyzes a somewhat larger set of patients from several diagnostic categories. The authors conclude that mitochondrial gene defects cause specific cardiac abnormalities that are characteristic of the particular molecular pathology. Only a small number of patients within each category of mitochondrial disease were studied, and the clinical assessments were neither comprehensive nor highly detailed. Patients with apparently normal hearts were not subjected to provocative stimuli that may have unmasked more subtle abnormalities. Nevertheless, this …