Myocardial fatty acid metabolism and cardiac performance in heart failure

Abstract

It is well established that cardiac metabolism is abnormal in heart failure (HF). Experimental studies suggest that in severe HF, cardiac metabolism reverts to a more fetal-like substrate use characterized by enhanced glucose and downregulated free fatty acid (FFA) metabolism. Correspondingly, in humans, when FFA levels are similar, myocardial glucose metabolism is increased, and FFA metabolism is decreased. However, depression of left ventricular function and insulin resistance induces a shift back to greater FFA uptake and oxidation by increasing circulating FFA availability. Myocardial insulin resistance may further impair myocardial glucose uptake and lead to an energy depletion state. Experimental and preliminary clinical studies suggest that metabolic modulators enhancing myocardial glucose oxidation may improve cardiac function in patients with chronic HF. However, it has been found that acute FFA deprivation is harmful to the cardiac performance. Optimizing myocardial energy metabolism may serve as an additional approach for managing HF, but further studies are warranted.

Lipid Use and Misuse by the Heart

“…Patients with heart failure show a profound switch from FAO to preferential use of glucose as a substrate for ATP generation through glycolysis 4–10 and utilization of alternative sources of energy including lactate, ketone bodies and amino acids. 11, 12 Further, flux through anaerobic glycolysis is increased. 8, 13 Altogether, these changes in metabolic pathways and usage of substrates for energy provision leads to a chronically altered state with decreased ATP production and energy depletion of the failing myocardium.…”

Application of Solid Phase Microextraction for Quantitation of Polyunsaturated Fatty Acids in Biological Fluids

“…[65][66][67] From a metabolic point of view, the cardiovascular response to increased metabolic demands after cardiac sur--gery may lead to enhanced glucose and down regulated free fatty acid (FFA) metabolism; yet the heart can use several substrates, among which free fatty acids (FFAs) and glucose are the major sources. 65 Having known this fact, the rea--son behind fatty acid elevation right after com--mencing bypass could be clearly explained. The alteration in metabolic profile of ALA and its me--tabolites was already reported and discussed in the studied group of patients and current tar--geted analysis confirms previous findings.…”

Metabolic Syndrome Is Associated With More Pronounced Impairment of Left Ventricle Geometry and Function in Patients With Calcific Aortic Stenosis

“…3) Obesity and MetS are associated with impaired coronary microvascular function, which may, in turn, negatively impact myocardial perfusion and function (31). 4) In cardiac hypertrophic remodeling induced by pressure overload, there is a shift in myocardial substrate oxidation from free fatty acids (FFAs) toward carbohydrates (9,(32)(33)(34). Although initially beneficial, a sustained decline in FFA oxidation due to hemodynamic overload may cause an inappropriate accumulation of lipids in the hypertrophied myocardium resulting in cellular toxicity (i.e., lipotoxicity phenomenon), contractile dysfunction, and eventually heart failure (35).…”