Heart failure is the end stage of all kinds of heart disease, and with the aging of our population and the increase in the incidence of cardiovascular disease, the incidence of heart failure has a significant increasing trend. In recent years, due to the in-depth study of the role of sympathetic nervous system and renin-angiotensin-aldosterone system in the occurrence and development of heart failure, drugs such as β-blockers and ACE-I have become the basis of heart failure treatment. On the other hand, in-depth study of myocardial energy metabolism in heart failure can also provide us with new ideas for heart failure treatment. I. Characteristics of normal myocardial energy metabolism Myocardial contraction and diastole require energy, and the heart can convert the chemical energy stored in fatty acids and glucose into the mechanical energy of the interaction between actin and myosin in the myocardial fibers. This conversion process consists of three parts: (1) utilization of energy-producing substrates such as fatty acids and glucose; (2) oxidative phosphorylation in the respiratory chain of the mitochondria within the cardiac myocyte to produce energy (ATP); and (3) transport and utilization of this energy. Fatty acids, glucose, lactate, and pyruvate are all substrates that provide energy. Under normal conditions, 60%-90% of the energy required by the myocardium comes from β-oxidation of free fatty acids. Long-chain fatty acids enter the mitochondria for β-oxidation with the aid of carnitine propionyltransferases-1 and -2 (CPT-1 and CPT-2) to produce acetyl-coenzyme A, which enters the tricarboxylic acid cycle to produce ATP to provide energy. The other 10-40% of energy is provided by carbohydrates such as glucose, lactate and pyruvate. Glucose undergoes glycolysis to produce pyruvate, while lactate produces pyruvate under the action of lactate dehydrogenase (LDH), and finally under the action of pyruvate dehydrogenase (PDH), it is converted into acetyl coenzyme A to enter the tricarboxylic acid cycle to provide energy. In terms of oxygen consumption, fatty acid β-oxidation is a much more oxygen-consuming form of energy supply; to provide the same molecule of ATP, fatty acid oxidation consumes 10% more oxygen than glucose oxidation. Under normal conditions, oxygen supply is adequate and does not cause impairment of myocardial energy metabolism. In mitochondria, electrons from the tricarboxylic acid cycle are transferred to oxygen via the respiratory chain complex, creating an electrochemical gradient across the mitochondrial membrane protons that drives ATP synthase, which phosphorylates ADP and produces ATP.The high-energy phosphate bond in ATP binds to creatine to form creatine phosphate.ATP releases a phosphate that turns into ADP.The creatine phosphate can diffuse into myofibrils, where it is creatine kinase catalyzed by creatine kinase, releasing ATP again to be used as energy for myocardial contraction and diastole. Fatty acid metabolism and glucose metabolism normally regulate each other. Enhanced fatty acid oxidative metabolism can inhibit oxidative metabolism of glucose: (1) citric acid produced by fatty acid oxidation can inhibit phosphofructokinase (PFK) activity, and (2) enhanced fatty acid oxidation can increase levels of acetyl-coenzyme A and reduced coenzyme I (NADH), and can inhibit pyruvate dehydrogenase (PDH) activity, which, in turn, can inhibit glucolysis. Conversely, an increase in glucose and lactate, or an increase in insulin levels, can promote acetyl coenzyme A synthesis and stimulate malonyl coenzyme A production, thereby inhibiting fatty acid oxidation. Second, the energy metabolism of ischemic myocardium In mild ischemia, there is no significant change in myocardial energy. In moderate ischemia, glycolysis in myocytes is accelerated, free fatty acid oxidation is enhanced, and the oxidative phosphorylation of glucose is inhibited. In severe ischemia, the oxidation of both free fatty acids and glucose is inhibited, and the small amount of ATP provided by glucolysis becomes the only source of energy to maintain cardiomyocyte survival. Therefore, in moderate to severe ischemia, the oxidative phosphorylation of glucose is mismatched with anaerobic glycolysis, and at this time, enhanced oxidation of free fatty acids will exacerbate myocardial hypoxia and intracellular acidosis, which may exacerbate myocardial cell injury or lead to myocardial cell death. Third, myocardial energy metabolism in heart failure The main pathological changes in heart failure are myocardial remodeling and myocardial fibrosis. Myocardial remodeling reduces the number of capillaries per unit weight of myocardium and increases the oxygen diffusion distance, resulting in relative hypoxia. In addition, the activity of ATPase in the myocardium can be reduced by 20-40% in heart failure, which impairs myocardial energy utilization and weakens myocardial contractility. In the early stages of heart failure, glucose utilization increases, while free fatty acid utilization may be unchanged or only mildly increased. In severe heart failure, free fatty acid utilization decreases significantly. Also, glucose utilization decreases because insulin resistance can be present in severe heart failure. There may also be mitochondrial structural abnormalities in heart failure, with impaired oxidative phosphorylation processes and reduced or decreased activity of the electron transport chain complex and ATP production in the mitochondria. In severe heart failure, ATP levels in the myocardium may be reduced by 30-40%, and creatine phosphate levels may be reduced by 30-70%, along with reduced creatine transporter function. The reduction of high-energy phosphate compounds and the reduced activity of the creatine kinase system can lead to a decrease in the energy transferred to myofibrils, which ultimately leads to a decrease in the contractile reserve of the myocardium. Fourth, improve myocardial energy metabolism may be a new idea of heart failure treatment 1, ACE-I is the cornerstone of the current treatment of heart failure, its mechanism of action is through the inhibition of heart failure patients in vivo excessive renin – angiotensin – aldosterone system activity, inhibition of myocardial remodeling, so as to block the pathophysiological process of the occurrence and development of heart failure. However, from the point of view of energy metabolism, ACE-I can also directly or indirectly improve the energy metabolism process of the myocardium, improve the mitochondrial function of cardiomyocytes, and increase the level of myocardial high-energy phosphate compounds. 2, β-blocker is one of the main drugs for the treatment of chronic heart failure, which can not only improve the clinical symptoms of patients with heart failure, but also improve the prognosis of patients with heart failure and reduce the mortality rate of heart failure. From the point of view of energy metabolism, there is an elevation of free fatty acids in heart failure and a negative correlation with the creatine phosphokinase/ATP ratio, which is a sign of myocardial energy shortage in heart failure. β-blockers can reduce myocardial oxygen consumption. On the other hand, it can inhibit catecholamine-mediated lipolysis and the release of free fatty acids, reducing the oxidation of fatty acids that consume more oxygen and thus alleviating myocardial hypoxia. β-blockers can also decrease insulin sensitivity, increase myocardial uptake of lactate, and allow the myocardium to utilize more glucose for energy metabolism. these effects of β-blockers improve, to some extent, myocardial energy metabolism. These effects of β-blockers improve myocardial energy metabolism to a certain extent. For heart failure caused by myocardial ischemia, because fatty acid oxidation is a more oxygen-consuming metabolic process, under hypoxic conditions, excessive fatty acid oxidation can exacerbate myocardial hypoxia and can cause intracellular acidosis. Therefore, appropriate inhibition of fatty acid oxidation so that myocardial energy supply is shifted more to the less oxygen-consuming glucose oxidation may help to alleviate myocardial ischemia, improve myocardial energy supply, and reduce intracellular acidosis. Trimetazidine may optimize myocardial energy metabolism by inhibiting β-oxidation of fatty acids. studies such as the TRIMPOL-I and TRIMPOL-II studies, and the Cochrane meta-study, have demonstrated that in addition to increasing exercise capacity in stable angina pectoris, it may also improve cardiac function in patients. It has also been reported in foreign and domestic countries that the use of regular dose trimetazidine for one week before PCI, followed by a loading dose of trimetazidine 60 mg 30 minutes before surgery, significantly reduced intraoperative angina pectoris and intraoperative ischemic myocardial injury during PCI in the trimetazidine group compared with the placebo group. In addition, postoperative cardiac function can be significantly improved. Similar drugs to trimetazidine are ranolazine, which can also inhibit fatty acid beta oxidation and optimize myocardial energy metabolism.