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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Trimetazidine, a metabolic modulator, has cardiac and extracardiac benefits in idiopathic dilated cardiomyopathy
Circulation, Volume 118, No. 12, Year 2008
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Description
Background - The anti-ischemic agent trimetazidine improves ejection fraction in heart failure that is hypothetically linked to inhibitory effects on cardiac free fatty acid (FFA) oxidation. However, FFA oxidation remains unmeasured in humans. We investigated the effects of trimetazidine on cardiac perfusion, efficiency of work, and FFA oxidation in idiopathic dilated cardiomyopathy. Methods and Results - Nineteen nondiabetic patients with idiopathic dilated cardiomyopathy on standard medication were randomized to single-blind trimetazidine (n=12) or placebo (n=7) for 3 months. Myocardial perfusion, FFA, and total oxidative metabolism were measured using positron emission tomography with [15O]H2O, [11C] acetate, and [11C]palmitate. Cardiac function was assessed echocardiographically; insulin sensitivity was assessed by the homeostasis model assessment index. Trimetazidine increased ejection fraction from 30.9±8.5% to 34.8±12% (P=0.027 versus placebo). Myocardial FFA uptake was unchanged, and β-oxidation rate constant decreased only 10%. Myocardial perfusion, oxidative metabolism, and work efficiency remained unchanged. Trimetazidine decreased insulin resistance (glucose: 5.9±0.7 versus 5.5±0.6 mmol/L, P=0.047; insulin: 10±6.9 versus 7.6±3.6 mU/L, P=0.031; homeostasis model assessment index: 2.75±2.28 versus 1.89±1.06, P=0.027). The degree of β-blockade and trimetazidine interacted positively on ejection fraction. Plasma high-density lipoprotein concentrations increased 11% (P<0.001). Conclusions - In idiopathic dilated cardiomyopathy with heart failure, trimetazidine increased cardiac function and had both cardiac and extracardiac metabolic effects. Cardiac FFA oxidation modestly decreased and myocardial oxidative rate was unchanged, implying increased oxidation of glucose. Trimetazidine improved whole-body insulin sensitivity and glucose control in these insulin-resistant idiopathic dilated cardiomyopathy patients, thus hypothetically countering the myocardial damage of insulin resistance. Additionally, the trimetazidine-induced increase in ejection fraction was associated with greater β1-adrenoceptor occupancy, suggesting a synergistic mechanism. © 2008 American Heart Association, Inc.
Authors & Co-Authors
Tuunanen, Helena
Finland, Turku
Turun Yliopistollinen Keskussairaala
Engblom, Erik
Finland, Turku
Turun Yliopistollinen Keskussairaala
Naum, Alexandru
Finland, Turku
Turun Yliopistollinen Keskussairaala
Någren, Kjell
Finland, Turku
Turun Yliopistollinen Keskussairaala
Scheinin, Mika
Finland, Turku
Turun Yliopisto
Finland, Turku
Varsinais-suomen Sairaanhoitopiiri
Hesse, Birger
Denmark, Copenhagen
Rigshospitalet
Airaksinen, Juhani K.E.
Finland, Turku
Turun Yliopistollinen Keskussairaala
Nuutila, Pirjo
Finland, Turku
Turun Yliopistollinen Keskussairaala
Iozzo, Patricia
Finland, Turku
Turun Yliopistollinen Keskussairaala
Italy, Pisa
Istituto Di Fisiologia Clinica Del Cnr
Ukkonen, Heikki
Finland, Turku
Turun Yliopistollinen Keskussairaala
Opie, LionelH H.
South Africa, Cape Town
University of Cape Town
Knuuti, Juhani M.
Finland, Turku
Turun Yliopistollinen Keskussairaala
Finland, Turku
Turku Pet Centre
Statistics
Citations: 251
Authors: 12
Affiliations: 7
Identifiers
Doi:
10.1161/CIRCULATIONAHA.108.778019
ISSN:
00097322
Research Areas
Disability
Environmental
Noncommunicable Diseases