title: Concentric hypertrophic remodelling and subendocardial dysfunction in mitochondrial DNA point mutation carriers.
abstract: OBJECTIVE
  Hypertrophic remodelling and systolic dysfunction are common in patients with mitochondrial disease and independent predictors of morbidity and early mortality. Screening strategies for cardiac disease are unclear. We investigated whether myocardial abnormalities could be identified in mitochondrial DNA mutation carriers without clinical cardiac involvement.
  
  
  RESULTS
  Cardiac magnetic resonance imaging was performed in 22 adult patients with mitochondrial disease due to the m.3243A>G mutation, but no known cardiac involvement, and 22 age- and gender-matched control subjects: (i) Phosphorus-31- magnetic resonance spectroscopy, (ii) cine imaging (iii), cardiac tagging and (iv) late gadolinium enhancement (LGE) imaging. Disease burden was determined using the Newcastle Mitochondrial Disease Adult Scale (NMDAS) and urinary mutation load. Compared with control subjects, patients had an increased left ventricular mass index (LVMI), LV mass to end-diastolic volume (M/V) ratio, wall thicknesses (all P < 0.01), torsion and torsion to endocardial strain ratio (both P < 0.05). Longitudinal shortening was decreased in patients (P < 0.0001) and correlated with an increased LVMI (r = -0.52, P < 0.03), but there were no differences in the diastolic function. Among patients there was no correlation of LVMI or the M/V ratio with diabetic or hypertensive status, but the mutation load and NMDAS correlated with the LVMI (r = 0.71 and r = 0.79, respectively, both P < 0.001). The phosphocreatine/adenosine triphosphate ratio was decreased in patients (P < 0.001) but did not correlate with other parameters. No patients displayed focal LGE.
  
  
  CONCLUSIONS
  Concentric remodelling and subendocardial dysfunction occur in patients carrying m.3243A>G mutation without clinical cardiac disease. Patients with higher mutation loads and disease burden may be at increased risk of cardiac involvement.
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK. matthew.bates@newcastle.ac.uk
authors.forename: Matthew G D
authors.initials: MG
authors.lastname: Bates
authors.forename: Kieren G
authors.initials: KG
authors.lastname: Hollingsworth
authors.forename: Jane H
authors.initials: JH
authors.lastname: Newman
authors.forename: Djordje G
authors.initials: DG
authors.lastname: Jakovljevic
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Blamire
authors.forename: Guy A
authors.initials: GA
authors.lastname: MacGowan
authors.forename: Bernard D
authors.initials: BD
authors.lastname: Keavney
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Chinnery
authors.forename: Douglass M
authors.initials: DM
authors.lastname: Turnbull
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
authors.forename: Michael I
authors.initials: MI
authors.lastname: Trenell
authors.forename: Grainne S
authors.initials: GS
authors.lastname: Gorman
mesh_terms: D000328:Adult; D009202:Cardiomyopathies / Q000175:diagnosis / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D003287:Contrast Media; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D019786:Gadolinium DTPA; D006579:Heterozygote; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000175:diagnosis* / Q000235:genetics*; D019028:Magnetic Resonance Imaging, Cine / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000235:genetics*; D017354:Point Mutation; D011379:Prognosis; D012016:Reference Values; D018709:Statistics, Nonparametric; D020257:Ventricular Remodeling / Q000235:genetics* / Q000502:physiology
chemical_list: D003287:Contrast Media; D004272:DNA, Mitochondrial; D019786:Gadolinium DTPA
keywords: Cardiac tagging; Cardiomyopathy; Magnetic resonance imaging; Magnetic resonance spectroscopy; Mitochondrial disease