title: Early changes in left ventricular long-axis function in Friedreich ataxia: relation with the FXN gene mutation and cardiac structural change.
abstract: OBJECTIVE
  Friedreich ataxia (FRDA) is an autosomal recessive condition due to a GAA triplet expansion in the FXN gene that causes increased left ventricular (LV) wall thickness and can progress to LV systolic dysfunction. However, the changes in myocardial function that occur before a reduction in LV ejection fraction are incompletely understood.
  
  
  METHODS
  LV long-axis function was assessed by measurement of tissue Doppler imaging (TDI) peak systolic (S`), early diastolic (E`), and atrial velocities (A`) at the septal and lateral borders of the mitral annulus in 60 subjects homozygous for a GAA expansion in the FXN gene who had preserved LV ejection fraction. Comparison was made with 60 sex- and age-matched controls. TDI velocities at 5 years were compared with baseline values in 17 FRDA subjects with follow-up studies who still had preserved ejection fraction.
  
  
  RESULTS
  S` and E` were reduced in FRDA subjects at both the septal and the lateral mitral annular borders. Lateral E` was independently and inversely related to age, blood pressure, septal wall thickness, and the number of GAA repeats in the smaller allele of the FXN gene, whereas septal E` was not correlated with GAA repeat number. At 5 years, there was a reduction in lateral S` and E` but no change in septal TDI velocities.
  
  
  CONCLUSIONS
  Subjects with FRDA have impairment of septal and lateral long-axis LV function, but there also seem to be regional differences in the effects of this condition that are at least partly related to the degree of genetic abnormality.
authors.affiliation: Monash Cardiovascular Research Centre, Monash Heart, Monash University Department of Medicine, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria 3168, Australia.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Mottram
authors.forename: Martin B
authors.initials: MB
authors.lastname: Delatycki
authors.forename: Lesley
authors.initials: L
authors.lastname: Donelan
authors.forename: John S
authors.initials: JS
authors.lastname: Gelman
authors.forename: Louise
authors.initials: L
authors.lastname: Corben
authors.forename: Roger E
authors.initials: RE
authors.lastname: Peverill
mesh_terms: D000328:Adult; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D015150:Echocardiography, Doppler; D005260:Female; D005500:Follow-Up Studies; D005621:Friedreich Ataxia / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D006352:Heart Ventricles / Q000000981:diagnostic imaging* / Q000503:physiopathology; D006801:Humans; D033862:Iron-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009154:Mutation; D012307:Risk Factors; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000502:physiology*; D000096923:Frataxin
chemical_list: D004247:DNA; D033862:Iron-Binding Proteins; D000096923:Frataxin