New directions in the treatment of heart failure: targeting free fatty acid oxidation.

The possibility of modifying cardiac metabolism by switching the fuel used by the myocardium could become increasingly important. Inhibitors of free fatty acid (FFA) oxidation could have an important role in therapeutic strategy for patients with heart failure, and shifting the energy substrate preference away from FFA metabolism and toward glucose metabolism may be an effective adjunctive treatment. Additionally, abnormalities of glucose homeostasis in patients with heart failure contribute to the progression of the primary disease. If not adequately treated, these abnormalities can contribute to the occurrence of complications, including severe left ventricular dysfunction. Apart from meticulous metabolic control of frank diabetes, special attention should be paid to insulin resistance, a distinct clinical entity. The observed combined beneficial effects of FFA inhibitors on left ventricular function and glucose metabolism represent an additional advantage of these drugs, especially when abnormalities of myocardial and glucose metabolism coexist.