Mitochondrial Cardiomyopathy Evaluated With Cardiac Magnetic Resonance
A 68-year-old woman was admitted complaining of exertional dyspnea. Ten years earlier, a diagnosis of diabetes had been made and hearing loss had developed. Echocardiography and cine magnetic resonance imaging (Movie I, left) showed asymmetric septal hypertrophy with a mildly hypokinetic left ventricle (LV) (ejection fraction =48%); coronary angiography showed no significant stenosis in any major artery. Electron microscopic examination of a LV endomyocardial biopsy specimen revealed mitochondrial enlargement (Figure 1A, arrows) with concentrically arrayed cristae (Figure 1A, arrow head) and crystalline inclusions (Figure 1B, arrow). The patient was diagnosed with mitochondrial disease after a mitochondrial DNA mutation, an A to G transition at nucleotide position 3243 in the tRNALeu gene, was detected in her leukocytes. Treatment with ubiquinone (coenzyme Q10) for the primary disorder and with carvedilol and enalapril for the secondary heart failure was initiated.
Fifteen months later, however, her exertional dyspnea had worsened. In addition, 12-lead ECG showed remarkable changes in QRS-T patterns, including QRS axis deviation and increased duration (Figure 2), and cine magnetic resonance imaging revealed a further decreased LV ejection fraction (35%) due to severely hypokinetic motion in the inferior to lateral region (Movie I, right). Although a recent myocardial infarction in the region was suspected, coronary angiography again showed no significant stenosis in any major artery (Movie II and III). Cardiac magnetic resonance imaging with gadolinium contrast revealed focal perfusion defects at the interventricular septal and lateral walls (Figure 3A, arrows, and Movie IV) and contrast enhancement in the delayed -enhanced images of the corresponding areas (Figure 3B, arrows), indicating scar tissue within the myocardium.
Mitochondrial disorders are degenerative diseases characterized by heterogeneous phenotypes and genotypes; they usually present with multiorgan involvement and follow a chronic, slowly progressive course.1,2 Although various respiratory chain cofactors and vitamins are widely used in the treatment of patients with these disorders, these standard treatments do not have similar effects in all mitochondrial disorders, because of the heterogeneity.3 The current case presented with diabetes, deafness and cardiomyopathy that developed despite medical therapy. Deterioration of cardiac function with marked ECG changes appears to be attributable to mitochondria-derived injury to the myocardium, including the conduction system, eventually leading to the formation of a fibrotic scar revealed by gadolinium-enhanced cardiac magnetic resonance imaging.
The online-only Data Supplement, which contains a movie, can be found at http://circ.ahajournals.org/cgi/content/full/116/2/e25/DC1.