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

Abstract

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.

Meta-analysis of trimetazidine treatment for cardiomyopathy

“…TMZ initially used as an anti-ischaemic or ‘cytoprotective’ agent through regulating a metabolic pathway of switching cardiac metabolism from FFA to glucose oxidation, increasing glucose utilization, improving the rate of ATP production, optimizing energy, thereby reducing myocardial damage, and achieving purpose of myocardial protection [ 22 ]. FFA inhibitors could be used as metabolic modulators to protect the ischaemic myocardium, the effects of TMZ on cardiomyopathy were previously evaluated primarily for patients with ischemic heart failure [ 23 ]. TMZ could improve heart functions, which has been confirmed by clinical studies [ 24 ].…”

Os efeitos da trimetazidina na variabilidade da frequência cardíaca (VFC) em pacientes com insuficiência cardíaca

“…Trimetazidine affects myocardial substrate use by inhibiting oxidative phosphorylation and by shifting energy production from free fatty acids (FFA) to glucose oxidation 27 . The beneficial effect of this agent has been attributed to preservation of phosphocreatine and adenosine triphosphate (ATP) intracellular levels and reduction of cell acidosis, calcium overload and free radical-induced injury caused by ischemia [26][27][28][29][30][31][32] . In heart failure, similar to what happens during acute myocardial ischemia, glucose and lactate oxidation are decreased and fatty acid oxidation is increased, increasing the oxygen requirement per ATP molecule produced.…”