Under normal conditions, 60-90% of the energy required by the myocardium comes from beta-oxidation of free fatty acids. Long-chain fatty acids enter the mitochondria for beta-oxidation with the help of carnitine propionyltransferase-1 and -2 (CPT-1 and CPT-2) to produce acetyl coenzyme A, which enters the tricarboxylic acid cycle to produce ATP for energy. Another 10-40% of energy is provided by carbohydrates such as glucose, lactate and pyruvate. Glucose undergoes glycolysis to produce pyruvate, while lactate is converted to pyruvate by the action of lactate dehydrogenase (LDH) and finally to acetyl coenzyme A by the action of pyruvate dehydrogenase (PDH), which enters the tricarboxylic acid cycle to provide energy. In terms of oxygen consumption, fatty acid β-oxidation is a more oxygen-intensive form of energy supply, providing one molecule of ATP as well, 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 generated by the tricarboxylic acid cycle are transferred to oxygen via the respiratory chain complex, producing an electrochemical gradient across the mitochondrial membrane proton that drives ATP synthase, which phosphorylates ADP to produce ATP. the high-energy phosphate bond in ATP binds to creatine to form creatine phosphate. after ATP releases a phosphate, it becomes ADP. creatine phosphate can diffuse into myofibrils, which, under creatine kinase catalyzed by creatine kinase, releasing ATP, which is used as energy for myocardial contraction and diastole. I. Under normal conditions, fatty acid metabolism and glucose metabolism can be regulated by each other. Enhanced oxidative fatty acid metabolism can inhibit oxidative glucose metabolism: (1) citric acid produced by fatty acid oxidation can inhibit phosphofructokinase (PFK) activity, and (2) enhanced fatty acid oxidation can increase acetyl coenzyme A and reduced coenzyme I (NADH) levels and inhibit pyruvate dehydrogenase (PDH) activity, which in turn can inhibit glucose enzymes. Conversely, increased glucose and lactate, or increased insulin levels, can promote acetyl coenzyme A synthesis and stimulate malonyl coenzyme A production, which can inhibit fatty acid oxidation. Second, the energy metabolism of ischemic myocardium In mild ischemia, there is no significant change in the energy of myocardium. In moderate ischemia, glycolysis of cardiomyocytes is accelerated, while the oxidation of free fatty acids 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 gluconeogenesis becomes the only source to maintain the survival of cardiomyocytes. Therefore, in moderate to severe ischemia, the oxidative phosphorylation of glucose and anaerobic glycolysis are mismatched, and the enhanced oxidation of free fatty acids at this time will aggravate myocardial hypoxia and intracellular acidosis, which may aggravate myocardial cell injury or lead to myocardial cell death. Myocardial energy metabolism in heart failure The main pathological changes in heart failure are myocardial remodeling and myocardial fibrosis. Myocardial remodeling decreases the number of capillaries per unit weight of myocardium, increases the oxygen dispersion distance, and results in relative myocardial hypoxia. In addition, the activity of ATPase in the myocardium can be reduced by 20%-40% in heart failure, resulting in impaired myocardial energy utilization and reduced myocardial contractility. In early heart failure, glucose utilization increases, while free fatty acid utilization may be unchanged or only mildly increased. In severe heart failure, the utilization of free fatty acids is significantly reduced. Also, glucose utilization is reduced because insulin resistance may be present in severe heart failure. In heart failure there may also be structural abnormalities of the mitochondria, impaired oxidative phosphorylation processes, reduced or decreased electron transport chain complex activity and ATP production in the mitochondria. In severe heart failure, myocardial ATP levels may be reduced by 30-40% and creatine phosphate levels may be reduced by 30-70%, along with a reduction in creatine transporter function. The decrease in high-energy phosphate compounds and the reduced activity of the creatine kinase system can lead to a decrease in energy transport to the myogenic fibers and ultimately to a decrease in myocardial contractile reserve. Fourth, improving myocardial energy metabolism may be a new idea in the treatment of heart failure. 1, ACE-I is the cornerstone of the current treatment of heart failure, and its mechanism of action is to inhibit myocardial remodeling by suppressing the excessive renin-angiotensin-aldosterone system activity in heart failure patients, thus blocking the pathophysiological process of heart failure occurrence and development. However, from the perspective of energy metabolism, ACE-I can also directly or indirectly improve the energy metabolic process of myocardium, improve the mitochondrial function of cardiac myocytes, and increase the level of myocardial high-energy phosphate compounds. 2, β-blockers are one of the main drugs for the treatment of chronic heart failure, which can not only improve the clinical symptoms of heart failure patients, but also improve the prognosis of heart failure patients and reduce the mortality rate of heart failure. From the perspective of energy metabolism, there is an elevation of free fatty acids in heart failure and a negative correlation with 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 inhibits catecholamine-mediated lipolysis and free fatty acid release, reducing the oxidation of fatty acids that consume more oxygen, thus reducing myocardial hypoxia. β-blockers also reduce insulin sensitivity, increase myocardial uptake of lactate, and increase myocardial use of glucose for energy metabolism. these effects of β-blockers improve myocardial energy metabolism. These effects of β-blockers improve myocardial energy metabolism to some extent. 3. For heart failure caused by myocardial ischemia, since fatty acid oxidation is a more oxygen-consuming metabolic process, under hypoxic conditions, excessive fatty acid oxidation can aggravate myocardial hypoxia and can cause intracellular acidosis. Therefore, appropriate inhibition of fatty acid oxidation to shift more myocardial energy supply to less oxygen-consuming glucose oxidation may help to relieve myocardial ischemia, improve myocardial energy supply, and reduce intracellular acidosis. Trimetazidine may optimize myocardial energy metabolism by inhibiting beta-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, it may also improve cardiac function in patients. Foreign and domestic studies have also reported that a conventional dose of trimetazidine for one week before PCI, followed by a loading dose of trimetazidine 60 mg 30 minutes before the procedure, significantly reduced intraoperative angina and intraoperative ischemic myocardial injury in the trimetazidine group compared with the placebo group. In addition, post-procedure cardiac function could be significantly improved. Drugs similar to trimetazidine include ranolazine, which can also inhibit β-oxidation of fatty acids and optimize the energy metabolism of myocardium. Other drugs to improve myocardial energy metabolism: (1) Levocaine: Levocaine is an essential cofactor of fatty acid metabolism, which can help transfer the accumulated acetyl coenzyme A to mitochondria, and promote the change of myocardial energy metabolism from mainly anaerobic glycolysis to mainly fatty acid oxidation, so that the intracellular energy metabolism can be restored to normal. At the same time, lecaconitine can reduce the accumulation of free fatty acids and long-chain lipid acyl lecaconitine and other harmful substances in cardiomyocytes, and reduce the damage of cardiomyocytes. Levocarnitine is suitable for dilated cardiomyopathy heart failure. (2) Coenzyme Q10: Coenzyme Q10 acts as a carrier of electron transfer and plays a role in the oxidative phosphorylation process of myocardial mitochondria, participating in the synthesis of ATP. (3) Creatine phosphate: a major functional substance in myocardial metabolism, exogenously provided phosphocreatine can act at multiple sites of myocardial energy metabolism (transport, storage and distribution of energy) to provide energy. (4) Fructose phosphate (FDP): Fructose phosphate is an intermediate product of glycolysis, providing a reaction substrate for exogenous glycolysis under various hypoxic conditions, and to some extent, increasing the production of small amounts of ATP. (5) cAMP-dependent positive inotropic drugs (cyclophosphoglycoside glucosamine, milrinone, dobutamine, etc.): these drugs can exogenously provide ATP, directly or indirectly activate a series of protein kinases, promote calcium inward flow, and enhance phosphorylation. These drugs can improve symptoms in patients with heart failure, but they can only be applied short-term. Long-term application of these drugs has been shown to increase mortality in patients. (6) Carnitine propionyltransferase-1 (CPT-1) inhibitors: Etmoxir and Methylpalmoxir belong to this class of drugs, whose effect is to reduce the beta-oxidation of fatty acids by inhibiting CPT-1 and reducing the entry of free fatty acids into mitochondria. (7) Traditional Chinese medicine: Ginseng and Astragalus injection. Ginsenosides in Ginseng and Mai injection can improve myocardial energy metabolism and increase myocardial contractility by inhibiting the activity of Na-K-ATPase in the cardiomyocyte membrane. Macrocephalus can stabilize the myocardial cell membrane, reduce mitochondrial swelling and the release of lactate dehydrogenase and phosphocreatine kinase, accelerate protein synthesis for DNA replication in damaged myocardial cells, facilitate injury repair, and increase the energy reserve of ischemic myocardium. It has also been demonstrated that Astragalus can improve the energy metabolism of the myocardium and thus be used in the treatment of heart failure. There is an obvious impairment of myocardial energy metabolism in heart failure, so modulating its myocardial energy metabolism according to the different conditions of patients may be a new target for heart failure treatment. Currently, drugs targeting various aspects of myocardial energy metabolism are effective in improving the symptoms of heart failure, but evidence-based evidence needs to be accumulated on whether other drugs to improve myocardial metabolism, except for ACE-I and β-blockers, can improve the prognosis of patients.