title: Cardiomyopathy is common in patients with the mitochondrial DNA m.3243A>G mutation and correlates with mutation load.
abstract: Although neuromuscular clinical features often dominate the clinical presentation of mitochondrial disease due to the m.3243A>G mitochondrial DNA (mtDNA) mutation, many patients develop cardiac failure, which is often overlooked until it reaches an advanced stage. We set out to determine whether cardiac complications are sufficiently common to warrant prospective screening in all mutation carriers. Routine clinical echocardiography and 3 Tesla cardiac MRI were performed on ten m.3243A>G mutation carriers and compared to age and gender matched controls, with contemporaneous quadriceps muscle biopsies to measure respiratory chain activity and mtDNA mutation levels. Despite normal echocardiography, all ten m.3243A>G mutation carriers had evidence of abnormal cardiac function on MRI. The degree of cardiac dysfunction correlated with the percentage level of mutant mtDNA in skeletal muscle. Sub-clinical cardiac dysfunction was a universal finding in this study, adding weight to the importance of screening for cardiac complications in patients with m.3243A>G. The early detection of cardiac dysfunction with MRI opens up opportunities to prevent heart failure in these patients through early intervention.
authors.affiliation: Newcastle Magnetic Resonance Centre, Institute of Cellular Medicine, Newcastle University, Campus for Ageing and Vitality, NE4 5PL, UK.
authors.forename: Kieren G
authors.initials: KG
authors.lastname: Hollingsworth
authors.forename: Grainne S
authors.initials: GS
authors.lastname: Gorman
authors.forename: Michael I
authors.initials: MI
authors.lastname: Trenell
authors.forename: Robert
authors.initials: R
authors.lastname: McFarland
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
authors.forename: Douglass M
authors.initials: DM
authors.lastname: Turnbull
authors.forename: Guy A
authors.initials: GA
authors.lastname: MacGowan
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Blamire
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Chinnery
mesh_terms: D000328:Adult; D009202:Cardiomyopathies / Q000150:complications* / Q000175:diagnosis; D004272:DNA, Mitochondrial / Q000235:genetics*; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000235:genetics; D006352:Heart Ventricles / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000150:complications* / Q000235:genetics*; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D014102:Torsion Abnormality / Q000209:etiology / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial