Inhibition of free fatty acids metabolism as a therapeutic target in patients with heart failure

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Abstract

Recent studies have evidenced that alterations of cardiac metabolism can be present in several cardiac syndromes. In heart failure, wasting of subcutaneous fat and skeletal muscle is relatively common and suggests an increased utilisation of non-carbohydrate substrates for energy production. In fact, fasting blood ketone bodies as well as fat oxidation during exercise have been shown to be increased in patients with heart failure. This metabolic shift determines a reduction of myocardial oxygen consumption efficiency. A direct approach to manipulate cardiac energy metabolism consists in modifying substrate utilisation by the heart. To date, the most effective metabolic treatments include several pharmacological agents that directly inhibit fatty acid oxidation. Clinical studies have shown that these agents can substantially increase the ischaemic threshold in patients with effort angina. However, the results of current research is also supporting the concept that shifting the energy substrate preference away from fatty acid metabolism and towards glucose metabolism could be an effective adjunctive treatment in patients with heart failure, in terms of left ventricular function and glucose metabolism improvement. In fact, these agents have also been shown to improve overall glucose metabolism in diabetic patients with left ventricular dysfunction. In this paper, the recent literature on the beneficial therapeutic effects of modulation of cardiac metabolic substrates utilisation in patients with heart failure is reviewed and discussed.

Original languageEnglish
Pages (from-to)603-610
Number of pages8
JournalInternational Journal of Clinical Practice
Volume61
Issue number4
DOIs
Publication statusPublished - Apr 2007

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Nonesterified Fatty Acids
Heart Failure
Glucose
Fatty Acids
Therapeutics
Ketone Bodies
Subcutaneous Fat
Left Ventricular Dysfunction
Therapeutic Uses
Left Ventricular Function
Oxygen Consumption
Energy Metabolism
Fasting
Skeletal Muscle
Fats
Inhibition (Psychology)
Pharmacology
Exercise
Efficiency
Research

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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abstract = "Recent studies have evidenced that alterations of cardiac metabolism can be present in several cardiac syndromes. In heart failure, wasting of subcutaneous fat and skeletal muscle is relatively common and suggests an increased utilisation of non-carbohydrate substrates for energy production. In fact, fasting blood ketone bodies as well as fat oxidation during exercise have been shown to be increased in patients with heart failure. This metabolic shift determines a reduction of myocardial oxygen consumption efficiency. A direct approach to manipulate cardiac energy metabolism consists in modifying substrate utilisation by the heart. To date, the most effective metabolic treatments include several pharmacological agents that directly inhibit fatty acid oxidation. Clinical studies have shown that these agents can substantially increase the ischaemic threshold in patients with effort angina. However, the results of current research is also supporting the concept that shifting the energy substrate preference away from fatty acid metabolism and towards glucose metabolism could be an effective adjunctive treatment in patients with heart failure, in terms of left ventricular function and glucose metabolism improvement. In fact, these agents have also been shown to improve overall glucose metabolism in diabetic patients with left ventricular dysfunction. In this paper, the recent literature on the beneficial therapeutic effects of modulation of cardiac metabolic substrates utilisation in patients with heart failure is reviewed and discussed.",
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