Myocardial blood flow and oxygen consumption in patients with Friedreich's ataxia prior to the onset of cardiomyopathy.
OBJECTIVE
We tested the hypothesis, in patients with Friedreich's ataxia and no overt structural heart disease, that impairment of cardiac oxidative metabolism may be compensated for either by increased rest myocardial blood flow or more efficient oxygen consumption in performance of external work.


BACKGROUND
Friedreich's ataxia is characterized by a mutant frataxin gene, which causes mitochondrial iron overload and impaired energy production. Further, it is frequently associated with cardiomyopathy. Studies using magnetic resonance spectroscopy, however, suggest impaired cardiac energetics even in the absence of structural heart disease.


METHODS
Positron emission tomography measured rest myocardial blood flow (N-13-ammonia method) and myocardial oxygen consumption (11-C-acetate, Kmono) in Friedreich's ataxia patients (n=8; 31+/-5 years, mean+/-SD, four women) and healthy controls (n=8; 30+/-7 years, five women) matched for stroke work index and age. Stroke work index and power were determined by electrocardiogram gated positron emission tomography N-13-ammonia using modified Simpson's rule to compute left ventricular volumes.


RESULTS
Neither stroke work index nor rest myocardial blood flow differed significantly between the groups. Although myocardial oxygen consumption was lower in Friedreich's ataxia (P<0.001), Kmono/rest myocardial blood flow, an index of myocardial oxygen extraction, did not differ between the groups. Power/Kmono, an index of the efficiency of myocardial oxygen consumption, was greater in Friedreich's ataxia (P<0.04). Rest myocardial blood flow normalized to rate pressure product was lower in Friedreich's ataxia (P<0.05).


CONCLUSIONS
Prior to the onset of cardiomyopathy, selected patients with Friedreich's ataxia may compensate for impaired cardiac energetics through more efficient oxygen consumption rather than increased rest myocardial blood flow. The data illustrate a more general mechanism pertaining to metabolic regulation of myocardial blood flow and myocardial oxygen consumption.
Gregory
Shawn A
SA
Departments of Medicine (Cardiology Division), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
MacRae
Calum A
CA
Aziz
Kusai
K
Sims
Katherine B
KB
Schmahmann
Jeremy D
JD
Kardan
Arash
A
Morss
Alexander M
AM
Ellinor
Patrick T
PT
Tawakol
Ahmed
A
Fischman
Alan J
AJ
Gewirtz
Henry
H
D000328:Adult; D001794:Blood Pressure / Q000502:physiology; D049628:Body Size / Q000502:physiology; D009202:Cardiomyopathies / Q000150:complications* / Q000503:physiopathology*; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000502:physiology; D004553:Electric Conductivity; D005260:Female; D005621:Friedreich Ataxia / Q000150:complications* / Q000235:genetics / Q000503:physiopathology*; D006321:Heart / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology; D009929:Organ Size / Q000502:physiology; D010101:Oxygen Consumption / Q000502:physiology*; D049268:Positron-Emission Tomography