title: Analysis of the factors influencing the cardiac phenotype in Friedreich's ataxia.
abstract: Friedreich's ataxia (FRDA) has been associated with both cardiac hypertrophy and to a lesser degree dilated cardiomyopathy. We have conducted a cross sectional magnetic resonance imaging (MRI) study of 25 patients with clinically and genetically confirmed FRDA and 24 healthy controls to analyse how disease parameters influence cardiac features in FRDA. MR cine imaging in the long and short axis planes was performed alongside clinical assessments. LV mass was most pronounced in FRDA patients with a larger genetic mutation (GAA1 repeats >600), earlier age of onset (<16years) and a shorter disease duration (<15 years). LV mass decreased with longer disease duration (>15 years), and independent of GAA1 repeat size and age of onset, suggesting cardiac thinning occurred with prolonged disease. Heart function was lower in patients with larger GAA1 repeat number and longer disease duration. Consequently, cardiac hypertrophy was more marked in FRDA patients with a larger GAA1 repeat number and younger age of onset, while prolonged disease duration was associated with lower LV mass and decreased heart function. It is important not only to understand the biochemical basis for these cardiac changes but also allow for these changes when assessing the effect of treatment of FRDA patients.
authors.affiliation: Nuffield Department of Medicine, Department of Biochemistry, University of Oxford, Oxford, UK.
authors.forename: Bheeshma
authors.initials: B
authors.lastname: Rajagopalan
authors.forename: Jane M
authors.initials: JM
authors.lastname: Francis
authors.forename: Fraser
authors.initials: F
authors.lastname: Cooke
authors.forename: L V Prasad
authors.initials: LV
authors.lastname: Korlipara
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Blamire
authors.forename: Anthony H V
authors.initials: AH
authors.lastname: Schapira
authors.forename: Jason
authors.initials: J
authors.lastname: Madan
authors.forename: Stefan
authors.initials: S
authors.lastname: Neubauer
authors.forename: J Mark
authors.initials: JM
authors.lastname: Cooper
mesh_terms: D000328:Adult; D006332:Cardiomegaly / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D004562:Electrocardiography; D005260:Female; D005621:Friedreich Ataxia / Q000453:epidemiology*; D005838:Genotype; D006801:Humans; D033862:Iron-Binding Proteins / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics; D012307:Risk Factors; D013997:Time Factors; D018911:Trinucleotide Repeats / Q000235:genetics; D000096923:Frataxin
chemical_list: D033862:Iron-Binding Proteins; D008562:Membrane Glycoproteins; D000096923:Frataxin; C093316:GPAA1 protein, human