title: A 22-Year Follow-up Study of Long-term Cardiac Outcome and Predictors of Survival in Friedreich Ataxia.
abstract: OBJECTIVE
  Friedreich ataxia (FRDA) is the most common genetic sensory ataxia, and myocardial involvement is a major determinant of survival.
  
  
  OBJECTIVE
  To assess FRDA survival and cardiac outcome to adapt future therapeutic trials.
  
  
  METHODS
  In a longitudinal follow-up study, all patients with genetically confirmed FRDA seen in the reference center and referred for cardiac evaluation (standard 12-lead electrocardiogram and transthoracic echocardiography) to the cardiology department were enrolled and followed up from April 27, 1990, to July 31, 2013. The setting was the French National Reference Center for Rare Diseases and the Department of Cardiology, Salpêtrière University Hospital, Paris, France. In total, 138 patients with FRDA were followed up. Among 133 patients homozygous for expanded GAA repeats, the mean (SD) age was 31 (10) years (age range, 11-62 years), with a mean (SD) age at disease onset of 16 (8) years (age range, 3-50 years) and a mean (SD) age at first wheelchair use of 26 (9) years (age range, 11-64 years). Cardiac hypertrophy was present in 57.9% (77 of 133), and electrocardiography was normal in 6.8% (9 of 133).
  
  
  METHODS
  Long-term cardiac outcome and predictors of survival in FRDA.
  
  
  RESULTS
  After a mean (SD) follow-up of 10.5 (5.5) years (range, 0.6-23.0 years), the 10-year survival rate was 88.5%. In 80.0% of patients (12 of 15), death was due to cardiac causes. Predictors of survival were a shorter GAA repeat length on the smaller allele of the frataxin gene (hazard ratio [HR], 1.85; 95% CI, 1.28-2.69), left ventricular ejection fraction (HR, 0.42; 95% CI, 0.20-0.89), and left ventricular mass index (HR, 1.19; 95% CI, 1.04-1.36). Two cardiac evolutions were distinguished with a group-based trajectory model, including a low-risk cardiac group (78.6% [81 of 103] with normal ejection fraction at baseline that declined slightly over time but remained within the normal range) and a high-risk cardiac group (21.4% [22 of 103] in which the ejection fraction progressively declined during follow-up). The patients with the worse cardiac evolution had longer GAA repeats. Neurological impairment was not predictive of cardiac change over time.
  
  
  CONCLUSIONS
  Survival in FRDA is determined by cardiac complications, which are dependent on the mutation (ie, the size of the expanded GAA repeat). Patients with progressive decline of the left ventricular ejection fraction had a worse prognosis. This finding demonstrates that cardiac follow-up is important in FRDA to identify individuals at risk for further cardiac complications.
authors.affiliation: Department of Cardiology, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière Charles-Foix, Paris, France.
authors.forename: Francoise
authors.initials: F
authors.lastname: Pousset
authors.affiliation: Department of Cardiology, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière Charles-Foix, Paris, France.
authors.forename: Lise
authors.initials: L
authors.lastname: Legrand
authors.affiliation: Department of Genetics and Cytogenetics, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière Charles-Foix, Paris, France3Institut du Cerveau et de la Moelle Epinière, Sorbonne Universités, Université Pierre et Marie Curie, Universi.
authors.forename: Marie-Lorraine
authors.initials: ML
authors.lastname: Monin
authors.affiliation: Department of Genetics and Cytogenetics, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière Charles-Foix, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Ewenczyk
authors.affiliation: Department of Genetics and Cytogenetics, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière Charles-Foix, Paris, France.
authors.forename: Perrine
authors.initials: P
authors.lastname: Charles
authors.affiliation: Department of Cardiology, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière Charles-Foix, Paris, France4Sorbonne Universités, Université Pierre et Marie Curie, University Paris 06, UMR 1166, INSERM, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Komajda
authors.affiliation: Department of Genetics and Cytogenetics, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière Charles-Foix, Paris, France3Institut du Cerveau et de la Moelle Epinière, Sorbonne Universités, Université Pierre et Marie Curie, Universi.
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.affiliation: Department of Neurology, Université Libre de Bruxelles, Hôpital Erasme, Brussels, Belgium.
authors.forename: Massimo
authors.initials: M
authors.lastname: Pandolfo
authors.affiliation: Department of Cardiology, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière Charles-Foix, Paris, France4Sorbonne Universités, Université Pierre et Marie Curie, University Paris 06, UMR 1166, INSERM, Paris, France6Institute for Ca.
authors.forename: Richard
authors.initials: R
authors.lastname: Isnard
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie, University Paris 06, UMR 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France8INSERM, UMR 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France9Bi.
authors.forename: Sophie
authors.initials: S
authors.lastname: Tezenas du Montcel
authors.affiliation: Department of Genetics and Cytogenetics, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière Charles-Foix, Paris, France3Institut du Cerveau et de la Moelle Epinière, Sorbonne Universités, Université Pierre et Marie Curie, Universi.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D005621:Friedreich Ataxia / Q000150:complications / Q000235:genetics / Q000401:mortality; D006331:Heart Diseases / Q000175:diagnosis / Q000209:etiology / Q000401:mortality; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000175:diagnosis / Q000209:etiology / Q000401:mortality; D033862:Iron-Binding Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019680:Trinucleotide Repeat Expansion; D055815:Young Adult; D000096923:Frataxin
chemical_list: D033862:Iron-Binding Proteins; D000096923:Frataxin