title: The cardiomyopathy in Friedreich's ataxia - New biomarker for staging cardiac involvement.
abstract: BACKGROUND
  Patients with autosomal-recessively inherited Friedreich's ataxia (FA) may develop a hypertrophic cardiomyopathy (CM), which potentially progresses towards a life-limiting problem. The typical features of this CM and the sequence of progression are widely unknown.
  
  
  METHODS
  Thirty-two consecutive patients with genetically confirmed FA were included. All patients received resting electrocardiogram (ECG), 24-hour Holter-ECG, echocardiography with speckle tracking imaging, cardiac magnetic resonance imaging (cMRI) with late enhancement imaging (for replacement fibrosis), and measurement of high-sensitive troponin-T (hsTNT). In addition, morphological parameters were retrospectively compared to data obtained five years before.
  
  
  RESULTS
  Based on criteria comprising ejection fraction (<55%), left ventricular end-diastolic posterior wall thickness (LVPWT ≥ 11 mm), fibrosis on cMRI, hsTNT ≥ 14 ng/ml, or T-wave-inversion, in all but two patients a CM could be detected (94%). Using these criteria we propose the following staging: a) mild CM (n=5, 16%; T-wave-inversion only); b) intermediate CM (n=4, 13%; T-wave-inversion with hypertrophy but no fibrosis); c) severe CM (n=13, 41%; fibrosis with raised hsTNT); and d) end-stage CM (n=8; 25%; ejection-fraction<55%). All patients with end-stage CM also showed fibrosis on cMRI, T-wave-inversion, marked elevation in hsTNT, and a decrease in LVPWT during the last five years (from 10.7 ± 1.2mm to 9.5 ± 1.3mm, p=0.025). In addition, 38% suffered from supraventricular tachycardia on Holter-ECG.
  
  
  CONCLUSIONS
  A comprehensive cardiac assessment will unravel established CM in almost all patients with FA with electrocardiographic abnormalities as earliest signs. Advanced stages can be characterized by elevated hsTNT and replacement fibrosis leading to recession of hypertrophy, reduction of global myocardial function, and electrical instability.
authors.affiliation: Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany; Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany; Medical Clinic II, Katharinen-Hospital, Unna, Germany. Electronic address: f.weidemann@katharinen-hospital.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Weidemann
authors.affiliation: Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany; Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany; Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Hu
authors.affiliation: Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Florescu
authors.affiliation: Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany; Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Niemann
authors.affiliation: Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany; Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Herrmann
authors.affiliation: Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany; Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Kramer
authors.affiliation: Department of Neurology, University of Würzburg, Würzburg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Klebe
authors.affiliation: Department of Neurology, University of Würzburg, Würzburg, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Doppler
authors.affiliation: Department of Neurology, University of Würzburg, Würzburg, Germany.
authors.forename: Nurcan
authors.initials: N
authors.lastname: Üçeyler
authors.affiliation: Department of Radiology, University of Würzburg, Würzburg, Germany.
authors.forename: Christian Oliver
authors.initials: CO
authors.lastname: Ritter
authors.affiliation: Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany; Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Ertl
authors.affiliation: Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany; Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Störk
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D018660:Blood Pressure Monitoring, Ambulatory; D002312:Cardiomyopathy, Hypertrophic / Q000097:blood / Q000235:genetics / Q000473:pathology*; D004452:Echocardiography; D004562:Electrocardiography; D015716:Electrocardiography, Ambulatory; D005260:Female; D005621:Friedreich Ataxia / Q000097:blood / Q000145:classification / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D020107:Troponin T / Q000378:metabolism
chemical_list: D015415:Biomarkers; D020107:Troponin T
keywords: Cardiomyopathy; Fibrosis; Friedreich's ataxia