doi: 10.1161/CIRCULATIONAHA.107.691329
(Circulation. 2007;115:e547.)
© 2007 American Heart Association, Inc.
Correspondence |
Response to Letters Regarding Article, "Free Fatty Acid Depletion Acutely Decreases Cardiac Work and Efficiency in Cardiomyopathic Heart Failure"
Turku PET Centre, Turku, Finland
Department of Medicine, Turku University Central Hospital, Turku, Finland
Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
Hatter Heart Research Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa
We appreciate the opportunity of answering the points raised in the Letters to the Editor by Fragasso et al and Wiggers et al. Unfortunately, our results have been misinterpreted.
The main purpose of our study was not to study the effect of acipimox on cardiac contractile function but to compare the responses in patients with heart failure with those in healthy volunteers.1 Therefore, a placebo group was not necessary. Our initial hypothesis was "that acute FFA depletion would result in an increased myocardial efficiency of forward work in patients with heart failure." Although in both groups cardiac function was slightly depressed by acipimox, only in the healthy volunteers did changes in oxidative metabolism parallel the changes in cardiac function. In contrast, in patients with heart failure, oxidative metabolism was not downregulated so that myocardial efficiency deteriorated further. Therefore, we considered our results unexpected and contrary to our hypothesis.
We do not understand the comment by Wiggers et al that our results were not in agreement with our previous study by Mäki et al2 because we do not see any link between the 2 studies. In the study by Mäki et al,2 the effect of insulin on the glucose uptake in hibernating myocardium was investigated.
Furthermore, we do not agree with Fragasso et al that a metabolic situation similar to our study could be mimicked by administration of food that increases insulin (not so with acipimox). Neither do we know of any evidence that reduced insulin and glucose concentrations after acipimox prevent an increase in cardiac glucose uptake. In contrast, in our previous studies,3–5 after administration of acipimox, serum insulin and glucose concentrations remain at the fasting levels, whereas myocardial glucose uptake increases 6-fold in fasting volunteers.
However, we do agree with Fragasso et al that just reducing free fatty acid availability by acipimox may not be sufficient to optimize cardiac metabolism. Actually, that was also our conclusion.1 In regard to the effects of direct cellular free fatty acid oxidation inhibitors such as trimetazidine, further studies are needed to understand their effects on myocardial metabolism in heart failure.
In summary, our study clearly documents that switching substrate metabolism acutely by nicotinic acid derivatives does not improve myocardial efficiency and is not an option for the treatment of patients with dilated cardiomyopathy. Further studies are needed to fully understand the potential of metabolic modulation in the treatment of heart failure.
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Acknowledgments |
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Disclosures
None.
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References |
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 Top References |
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1. Tuunanen H, Engblom E, Naum A, Nagren K, Hesse B, Airaksinen KE, Nuutila P, Iozzo P, Ukkonen H, Opie LH, Knuuti J. Free fatty acid depletion acutely decreases cardiac work and efficiency in cardiomyopathic heart failure. Circulation. 2006; 114: 2130–2137.
2. Mäki M, Luotolahti M, Nuutila P, Iida H, Voipio-Pulkki L-M, Ruotsalainen U, Haaparanta M, Solin O, Hartiala J, Härkönen R, Knuuti J. Glucose uptake in the chronically dysfunctioning but viable myocardium. Circulation. 1996; 93: 1658–1666.
3. Knuuti MJ, Maki M, Yki-Jarvinen H, Voipio-Pulkki LM, Harkonen R, Haaparanta M, Nuutila P. The effect of insulin and FFA on myocardial glucose uptake. J Mol Cell Cardiol. 1995; 27: 1359–1367.[CrossRef][Medline] [Order article via Infotrieve]
4. Knuuti MJ, Yki-Järvinen H, Voipio-Pulkki L-M, Mäki M, MD, Ruotsalainen U, Härkönen R, Teräs M, Haaparanta M, Bergman J, Hartiala J, Wegelius U, Nuutila P. Enhancement of myocardial 18-FDG uptake by nicotinic acid derivative. J Nucl Med. 1994; 35: 989–98.
5. Nuutila P, Knuuti MJ, Ruotsalainen U, Teräs M, Voipio-Pulkki L-M, Haaparanta M, Solin O, Wegelius U, Yki-Järvinen H. Effect of antilipolysis on heart and skeletal muscle glucose uptake in overnight fasted humans. Am J Physiol. 1994; 267: E941–E946.[Medline] [Order article via Infotrieve]
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