title: Impaired myocardial perfusion reserve and fibrosis in Friedreich ataxia: a mitochondrial cardiomyopathy with metabolic syndrome.
abstract: OBJECTIVE
  Cardiomyopathy produces significant mortality in patients with Friedreich ataxia (FA), a genetic disorder that produces intra-mitochondrial iron accumulation. We sought to test the hypothesis that abnormal myocardial perfusion reserve and fibrosis represent early manifestations of cardiomyopathy.
  
  
  RESULTS
  Twenty-six patients with genetically proven FA ages 36 ± 12 years without cardiomyopathy and eight controls underwent cardiac magnetic resonance with adenosine. Precontrast imaging for myocardial iron estimation was performed. Myocardial perfusion reserve index (MPRI) was quantified using the normalized upslope of myocardial enhancement during vasodilator stress vs. rest. Left ventricular (LV) mass and volumes were computed from short-axis cine images. Serologies included lipids, and platelets were isolated for iron quantification using inductively coupled plasma mass spectrometry. Left ventricular ejection fraction and mass averaged 64.1 ± 8.3% and 62.7 ± 16.7 g/m², respectively, indicating preserved systolic function and absence of significant hypertrophy. Myocardial perfusion reserve index quantification revealed significantly lower endocardial-to-epicardial perfusion reserve in patients vs. controls (0.80 ± 0.18 vs. 1.22 ± 0.36, P = 0.01). Lower MPRI was predicted by increased number of metabolic syndrome (met-S) features (P < 0.01). Worse concentric remodelling occurred with increased GAA repeat length (r = 0.64, P < 0.001). Peripheral platelet iron measurement showed no distinction between patients and controls (5.4 ± 8.5 × 10⁻⁷ vs. 5.5 ± 2.9 × 10⁻⁷ ng/platelet, P = 0.88), nor did myocardial T2* measures.
  
  
  CONCLUSIONS
  Patients with FA have abnormal myocardial perfusion reserve that parallels met-S severity. Impaired perfusion reserve and fibrosis occur in the absence of significant hypertrophy and prior to clinical heart failure, providing potential therapeutic targets for stage B cardiomyopathy in FA and related myocardial diseases.
authors.affiliation: The Ohio State University, Columbus, OH 43210, USA. raman.1@osu.edu
authors.forename: Subha V
authors.initials: SV
authors.lastname: Raman
authors.forename: Kavita
authors.initials: K
authors.lastname: Phatak
authors.forename: J Chad
authors.initials: JC
authors.lastname: Hoyle
authors.forename: Michael L
authors.initials: ML
authors.lastname: Pennell
authors.forename: Beth
authors.initials: B
authors.lastname: McCarthy
authors.forename: Tam
authors.initials: T
authors.lastname: Tran
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Prior
authors.forename: John W
authors.initials: JW
authors.lastname: Olesik
authors.forename: Anthony
authors.initials: A
authors.lastname: Lutton
authors.forename: Chelsea
authors.initials: C
authors.lastname: Rankin
authors.forename: John T
authors.initials: JT
authors.lastname: Kissel
authors.forename: Roula
authors.initials: R
authors.lastname: Al-Dahhak
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000737:chemistry; D009202:Cardiomyopathies / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology; D016022:Case-Control Studies; D003326:Coronary Circulation / Q000502:physiology*; D005355:Fibrosis / Q000209:etiology; D005621:Friedreich Ataxia / Q000150:complications*; D006801:Humans; D007501:Iron / Q000378:metabolism; D018810:Magnetic Resonance Angiography; D008833:Microcirculation / Q000502:physiology; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D013318:Stroke Volume / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000503:physiopathology; D055815:Young Adult
chemical_list: D007501:Iron