Decreased myocardial free fatty acid uptake in patients with idiopathic dilated cardiomyopathy: evidence of relationship with insulin resistance and left ventricular dysfunction |
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| Authors: | Tuunanen Helena Engblom Erik Naum Alexandru Scheinin Mika Någren Kjell Airaksinen Juhani Nuutila Pirjo Iozzo Patricia Ukkonen Heikki Knuuti Juhani |
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| Institution: | 1. Division of Cardiology, Department of Internal Medicine, St Louis Veterans Administration Medical Center, St Louis, MO;2. Washington University School of Medicine, St Louis, MO;3. Department of Biostatistics, College of Public Health and Social Justice, St Louis University, St Louis, MO;4. Department of Epidemiology, College of Public Health and Social Justice, St Louis University, St Louis, MO;5. Department of Internal Medicine, Washington University School of Medicine, St Louis, MO;6. Division of Cardiology, Department of Internal Medicine, St Louis University School of Medicine, St Louis, MO;1. Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, The Key Laboratory of Remodeling-related Cardiovascular Disease, Ministry of Education, Beijing 100029, China;2. Department of Cardiology, the People''s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, China;3. Department of Ultrasound, the People''s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, China;4. Department of Endocrinology, the People''s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, China;5. Department of Cardiology, China–Japan Friendship Hospital of Ministry of Health, Beijing 100029, China;1. Section of Endocrinology, VA Boston Healthcare System, Harvard Medical School;2. Division of Endocrinology Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School;3. Department of Medicine, Boston Medical Center, Boston University School of Medicine;4. Normative Aging Study, VA Boston Healthcare System and Boston University Schools of Public Health and Medicine;5. Normative Aging Study, VA Boston Healthcare System and Boston University School of Medicine |
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| Abstract: | BackgroundResults on myocardial substrate metabolism in the failing heart have been contradictory. Insulin resistance, a common comorbidity in heart failure patients, and medical therapy may modify myocardial metabolism in complex fashions. Therefore, we characterized myocardial oxidative and free fatty acid (FFA) metabolism in patients with idiopathic dilated cardiomyopathy (IDCM) and investigated the contributions of insulin resistance and β-blocker therapy.Methods and ResultsNineteen patients with IDCM (age 58 ± 8 years, ejection fraction 33 ± 8.8%) and 15 healthy controls underwent examination of myocardial blood perfusion, oxidative and FFA metabolism using positron emission tomography and 15O]H2O, 11C]acetate and 11C]palmitate, respectively. Echocardiography was used to assess myocardial function, work, and efficiency of forward work. Insulin resistance was calculated using the homeostasis model assessment index (HOMA index) and the degree of β-blockade was estimated with a β-adrenoceptor occupancy test. IDCM patients were characterized by decreased cardiac efficiency (35 ± 2 versus 57 ± 12 mm Hg·L·g?1, P < .0001) and reduced myocardial FFA uptake (5.5 ± 2.0 versus 6.4 ± 1.2 μmol·100 g?1·min?1, P < .05), but the FFA β-oxidation rate constant was not changed. In the patients, myocardial FFA uptake was inversely associated with left ventricular (LV) ejection fraction (r = ?0.63, P < .01), indicating that further depression of LV function induces an opposite switch to greater FFA uptake. The FFA β-oxidation rate constant correlated positively with the HOMA index (r = 0.53, P < .05). In patients on β-1 selective β-blockers, β-1 adrenoceptor occupancy correlated inversely with LV work, oxidative metabolism, and FFA uptake; similar relationships were not found in patients on nonselective β-blocker.ConclusionsMyocardial FFA metabolism is reduced in patients with IDCM. However, when LV function is further depressed and insulin resistance manifested, myocardial FFA uptake and oxidation are, in turn, upregulated. These findings may partly explain the discrepancies between previous studies about cardiac metabolism in heart failure. |
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