(Circulation. 2001;103:2441.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
From the William S. Middleton Veterans Hospital, Madison, Wis (T.R.W., D.C.R.); the Department of Medical Physics, University of WisconsinMadison, Madison, Wis (M.T., R.J.N.); the Department of Medical Physics, Duke University, Durham, NC (T.R.D.); and the Department of Medicine, University of WisconsinMadison, Madison Wis (T.R.W., D.C.R., P.S., C.K.S.).
Correspondence and reprint requests to Thomas R. Wallhaus, MD, 600 Highland Ave, H6/349, University of Wisconsin Hospital and Clinics, Department of Medicine, Cardiology Section, Madison, WI 53792-3248. E-mail trw{at}medicine.wisc.edu
BackgroundUse of ß-adrenoreceptor blockade in the treatment of heart failure has been associated with a reduction in myocardial oxygen consumption and an improvement in myocardial energy efficiency. One potential mechanism for this beneficial effect is a shift in myocardial substrate use from increased free fatty acid (FFA) oxidation to increased glucose oxidation.
Methods and ResultsWe
studied the effect of carvedilol therapy on myocardial FFA and glucose
use in 9 patients with stable New York Heart Association functional
class III ischemic cardiomyopathy (left
ventricular ejection fraction
35%) using myocardial
positron emission tomography studies and resting echocardiograms before
and 3 months after carvedilol treatment. Myocardial uptake of the novel
long chain fatty acid metabolic tracer 14(R,
S)-[18F]fluoro-6-thia-heptadecanoic acid
([18F]-FTHA) was used to determine
myocardial FFA use, and
[18F]fluoro-2-deoxy-glucose
([18F]-FDG) was used to determine
myocardial glucose use. After carvedilol treatment, the mean
myocardial uptake rate for [18F]-FTHA
decreased (from 20.4±8.6 to 9.7±2.3 mL · 100
g1 · min1;
P<0.005), mean fatty acid use
decreased (from 19.3±7.0 to 8.2±1.8 µmoL · 100
g1 · min1;
P<0.005), the mean myocardial
uptake rate for [18F]-FDG was unchanged
(from 1.4±0.4 to 2.4±0.8 mL · 100 g1
· min1;
P=0.14), and mean glucose use
was unchanged (from 11.1±3.1 to 18.7±6.0 µmoL · 100
g1 · min1;
P=0.12). Serum FFA and glucose
concentrations were unchanged, and mean left ventricular
ejection fraction improved (from 26±2% to 37±4%;
P<0.05).
ConclusionsCarvedilol treatment in patients with heart failure results in a 57% decrease in myocardial FFA use without a significant change in glucose use. These metabolic changes could contribute to the observed improvements in energy efficiency seen in patients with heart failure.
Key Words: fatty acids glucose metabolism heart failure
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