| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2006;114:2130-2137.)
© 2006 American Heart Association, Inc.
Heart Failure |
From the Turku PET-Centre (H.T., A.N., K.N., P.N., P.I., H.U., J.K.) and the Department of Medicine, Turku University Central Hospital (E.E., K.E.J.A., P.N., H.U.), Turku, Finland; the Hatter Heart Research Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa (L.H.O.); the Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark (B.H.); and the Institute of Clinical Physiology, National Research Council, Pisa, Italy (P.I.).
Correspondence to Dr Juhani Knuuti, Turku PET Centre, PO BOX 52, FIN-20521 Turku, Finland. E-mail juhani.knuuti{at}utu.fi
Received June 11, 2006; revision received August 11, 2006; accepted August 16, 2006.
Background Metabolic modulators that enhance myocardial glucose metabolism by inhibiting free fatty acid (FFA) metabolism may improve cardiac function in heart failure patients. We studied the effect of acute FFA withdrawal on cardiac function in patients with heart failure caused by idiopathic dilated cardiomyopathy (IDCM).
Methods and Results Eighteen fasting nondiabetic patients with IDCM (14 men, 4 women, aged 58.8±8.0 years, ejection fraction 33±8.8%) and 8 matched healthy controls underwent examination of myocardial perfusion and oxidative and FFA metabolism, before and after acute reduction of serum FFA concentrations by acipimox, an inhibitor of lipolysis. Metabolism was monitored by positron emission tomography and [15O]H2O, [11C]acetate, and [11C]palmitate. Left ventricular function and myocardial work were echocardiographically measured, and efficiency of forward work was calculated. Acipimox decreased myocardial FFA uptake by >80% in both groups. Ratepressure product and myocardial perfusion remained unchanged, whereas stroke volume decreased similarly in both groups. In the healthy controls, reduced cardiac work was accompanied by decreased oxidative metabolism (from 0.071±0.019 to 0.055±0.016 min1, P<0.01). In IDCM patients, cardiac work fell, whereas oxidative metabolism remained unchanged and efficiency fell (from 35.4±12.6 to 31.6±13.3 mm Hg · L · g1, P<0.05).
Conclusions Acutely decreased serum FFA depresses cardiac work. In healthy hearts, this is accompanied by parallel decrease in oxidative metabolism, and myocardial efficiency is preserved. In failing hearts, FFA depletion did not downregulate oxidative metabolism, and myocardial efficiency deteriorated. Thus, failing hearts are unexpectedly more dependent than healthy hearts on FFA availability. We propose that both glucose and fatty acid oxidation are required for optimal function of the failing heart.
This article has been cited by other articles:
![]() |
C. J. Zuurbier, F. J. Hoek, J. van Dijk, N. G. Abeling, J. C. M. Meijers, J. H. M. Levels, E. de Jonge, B. A. de Mol, and H. B. Van Wezel Perioperative hyperinsulinaemic normoglycaemic clamp causes hypolipidaemia after coronary artery surgery Br. J. Anaesth., April 1, 2008; 100(4): 442 - 450. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. D. Evans and Y. Niu Hypolipidaemic effects of high-dose insulin therapy Br. J. Anaesth., April 1, 2008; 100(4): 429 - 433. [Full Text] [PDF] |
||||
![]() |
R. Gelinas, F. Labarthe, B. Bouchard, J. Mc Duff, G. Charron, M. E. Young, and C. Des Rosiers Alterations in carbohydrate metabolism and its regulation in PPAR{alpha} null mouse hearts Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1571 - H1580. [Abstract] [Full Text] [PDF] |
||||
![]() |
J Knuuti and F M Bengel Positron emission tomography and molecular imaging Heart, March 1, 2008; 94(3): 360 - 367. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. M. Witteles and M. B. Fowler Insulin-Resistant Cardiomyopathy: Clinical Evidence, Mechanisms, and Treatment Options J. Am. Coll. Cardiol., January 15, 2008; 51(2): 93 - 102. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Neglia, A. De Caterina, P. Marraccini, A. Natali, M. Ciardetti, C. Vecoli, A. Gastaldelli, D. Ciociaro, P. Pellegrini, R. Testa, et al. Impaired myocardial metabolic reserve and substrate selection flexibility during stress in patients with idiopathic dilated cardiomyopathy Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3270 - H3278. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. A. Cooper, A. Whaley-Connell, J. Habibi, Y. Wei, G. Lastra, C. Manrique, S. Stas, and J. R. Sowers Renin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin resistance Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2009 - H2023. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. D. Abel Glucose for the Aging Heart? Circulation, August 21, 2007; 116(8): 884 - 887. [Full Text] [PDF] |
||||
![]() |
H. Ashrafian, M. P. Frenneaux, and L. H. Opie Metabolic Mechanisms in Heart Failure Circulation, July 24, 2007; 116(4): 434 - 448. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Oh, J.-H. Chung, S.-M. Kang, S. W. Smith, D. Niederseer, C. Thaler, J. Niebauer, P. Korantzopoulos, J. A. Goudevenos, P. Knaapen, et al. The Failing Heart N. Engl. J. Med., June 14, 2007; 356(24): 2544 - 2546. [Full Text] [PDF] |
||||
![]() |
H. Wiggers, M. Halbirk, and H. Norrelund Letter by Wiggers et al Regarding Article by Tuunanen et al, "Free Fatty Acid Depletion Acutely Decreases Cardiac Work and Efficiency in Cardiomyopathic Heart Failure" Circulation, May 29, 2007; 115(21): e545 - e545. [Full Text] [PDF] |
||||
![]() |
G. Fragasso, A. Palloshi, and G. Perseghin Letter by Fragasso et al Regarding Article by Tuunanen et al, "Free Fatty Acid Depletion Acutely Decreases Cardiac Work and Efficiency in Cardiomyopathic Heart Failure" Circulation, May 29, 2007; 115(21): e546 - e546. [Full Text] [PDF] |
||||
![]() |
H. Tuunanen, A. Naum, K. Nagren, P. Nuutila, P. Iozzo, H. Ukkonen, J. Knuuti, E. Engblom, K.E. J. Airaksinen, B. Hesse, et al. Response to Letters Regarding Article, "Free Fatty Acid Depletion Acutely Decreases Cardiac Work and Efficiency in Cardiomyopathic Heart Failure" Circulation, May 29, 2007; 115(21): e547 - e547. [Full Text] [PDF] |
||||
![]() |
H. Taegtmeyer and K. Ballal No Low-Fat Diet for the Failing Heart? Circulation, November 14, 2006; 114(20): 2092 - 2093. [Full Text] [PDF] |
||||
|
Circulation Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search Copyright © 2006 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited. |