Myocardial Energy Research Articles

Risk prediction model for major adverse cardiovascular events (MACE) during hospitalization in patients with coronary heart disease based on myocardial energy metabolic substrate.

The early attack of coronary heart disease (CHD) is very hidden, and clinical symptoms generally do not appear until cardiovascular events occur. Therefore, an innovative method is needed to judge the risk of cardiovascular events and guide clinical decision conveniently and sensitively. The purpose of this study is to find out the risk factors related to MACE during hospitalization. In order to develop and verify the prediction model of energy metabolism substrates, and establish a nomogram to predict the incidence of MACE during hospitalization and evaluate their performance. The data were collected from the medical record data of Guang'anmen Hospital. This review study was collected the comprehensive clinical data of 5,935 adult patients hospitalized in the cardiovascular department from 2016 to 2021. The outcome index was the MACE during hospitalization. According to the occurrence of MACE during hospitalization, these data were divided into MACE group (n = 2,603) and non-MACE group (n = 425). Logistic regression was used to screen risk factors, and establish the nomogram to predict the risk of MACE during hospitalization. Calibration curve, C index and decision curve were used to evaluate the prediction model, and drawn ROC curve to find the best boundary value of risk factors. The logistic regression model was used to establish a risk model. Univariate logistic regression model was mainly used to screen the factors significantly related to MACE during hospitalization in the training set (each variable is put into the model in turn). According to the factors with statistical significance in univariate logistic regression, five cardiac energy metabolism risk factors, including age, albumin(ALB), free fatty acid(FFA), glucose(GLU) and apolipoprotein A1(ApoA1), were finally input into the multivariate logistic regression model as the risk model, and their nomogram were drawn. The sample size of the training set was 2,120, the sample size of the validation set was 908. The C index of the training set is 0.655 [0.621,0.689], and the C index of the validation set was 0.674 [0.623,0.724]. The calibration curve and clinical decision curve show that the model performs well. The ROC curve was used to establish the best boundary value of the five risk factors, which could quantitatively present the changes of cardiac energy metabolism substrate, and finally achieved prediction of MACE during hospitalization conveniently and sensitively. Age, albumin, free fatty acid, glucose and apolipoprotein A1 are independent factors of CHD in MACE during hospitalization. The nomogram based on the above factors of myocardial energy metabolism substrate provides prognosis prediction accurately.

Evaluating the effect of PD-1 inhibitors on left ventricular function in lung cancer with noninvasive myocardial work.

The treatment of advanced lung cancer has been revolutionized by immune checkpoint inhibitors (ICIs) in recent years, largely driven by programmed cell death-1 (PD-1) inhibitors. However, patients with lung cancer who are treated with PD-1 inhibitors are prone to immune-related adverse events (irAEs), especially cardiac adverse events. Noninvasive myocardial work is a novel technique used to assess left ventricular (LV) function, which can effectively predict myocardial damage. Here, noninvasive myocardial work was used to evaluate changes in LV systolic function during PD-1 inhibitor therapy and to assess ICIs-related cardiotoxicity. From September 2020 to June 2021, 52 patients with advanced lung cancer in the Second Affiliated Hospital of Nanchang University were prospectively enrolled. In total, 52 patients underwent PD-1 inhibitor therapy. The cardiac markers, noninvasive LV myocardial work, and conventional echocardiographic parameters were measured at pretherapy (T0) and posttreatment after the first (T1), second (T2), third (T3), and fourth (T4) cycles. Following this, the trends of the above parameters were analyzed using analysis of variance with repeated measures and the Friedman nonparametric test. Furthermore, the relationships between disease characteristics (tumor type, treatment regimen, cardiovascular risk factors, cardiovascular drugs, and irAEs) and noninvasive LV myocardial work parameters were assessed. Throughout the follow-up, the cardiac markers and conventional echocardiographic parameters showed no significant changes. Based on the normal reference ranges, patients with PD-1 inhibitor therapy had increased values of LV global waste work (GWW) and decreased global work efficiency (GWE) that began at T2. Compared with T0, GWW increased from T1 to T4 (42%, 76%, 87%, and 87%, respectively), while global longitudinal strain (GLS), global work index (GWI), and global constructive work (GCW) decreased in varying degrees (P<0.001). Most of the disease characteristics had no effect on the LV myocardial work parameters; however, the numbers of irAEs were closely associated with GLS (P=0.034), GWW (P<0.001), and GWE (P<0.001). Patients with 2 or more irAEs had higher values of GWW and lower GLS and GWE. Noninvasive myocardial work can accurately reflect myocardial function and energy utilization in patients with lung cancer who are undergoing PD-1 inhibitor treatment and may thus benefit the management of patients with ICIs-related cardiotoxicity.

Dependence of cardiomyocyte force, velocity, and power generation on ATP concentration

Theoretical analysis and computer modeling of myocardial energy metabolism under physiological and heart failure conditions predicts that cytoplasmic ATP and ADP levels both fall roughly in proportion to reductions in total adenine nucleotide pool observed in heart failure. Assessing sub-maximal force and velocity in loaded myocardial muscle at MgATP levels in the range of 2 to 8 mM, Beard et al. ( Biophys. J. 2022. 121: 3213–3223) observed effects of MgATP on myocardial power generation that suggest that although maximal force and velocity are not substantially sensitive to differences in [MgATP] that occur in the normal versus failing myocardium, maximal power generation, which occurs at submaximal force and velocity, is sensitive to [MgATP]. Previously developed computational models are not able to reproduce the observed dependence on MgATP. The goals of the present study are to construct and analyze a computational model of muscle dynamics to analyze data on the dependence of maximal force, velocity, and power generation on [MgATP] in order to determine a potential mechanism to explain the MgATP-dependent phenomena. Model development and identification was guided by dynamic measurements on permeabilized mouse trabecular fibers. The data include force-velocity relation and time constant of tension development. The mathematical model used to simulate cardiomyocyte crossbridge mechanics was based on the previous crossbridge and calcium models from Tewari et al. (J Mol Cell Cardiol, 2016. 96: 11-25) and Campbell et al. (Biophys J, 2018. 115: 543-553). The developed model includes strain- and metabolite-dependent transition between attachment states, and ATP-dependent destabilization of the super-relaxed (SRX) myosin state. Model-based analysis of force and velocity dyanmics is consistent with the hypothesis that ATP assocition with the myosin protein influence the kinetics and thermodynamics of transitions between the SRX and disorded (DRX) states. Funding: Department of Veterans Affairs Merit Review Award I01BX000740 (A.J.B.) and National Heart, Lung, and Blood Institute grant R01 HL154624 (A.J.B., D.A.B.) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The role of (18F)-fluoro-D-glucose positron emission tomography/computed tomography in the surveillance of abnormal myocardial energy metabolism and cardiac dysfunction in a rat model of cardiopulmonary resuscitation.

To investigate the feasibility and usefulness of 2-deoxy-2-(18F)-fluoro-D-glucose positron emission tomography/computed tomography [(18F)-FDG PET/CT] as a novel examination in the surveillance of abnormal myocardial energy metabolism and cardiac dysfunction after cardiopulmonary resuscitation (CPR). Thirteen male Sprague-Dawley rats were randomly divided into a sham group (n = 4), CPR group (n = 4), and trimetazidine (TMZ) + CPR group (n = 5). The expression levels of the myocardial injury marker cardiac troponin I (CTNI) in serum were tested at 6 hours after CPR or TMZ + CPR. The ejection fraction and fraction shortening were evaluated by echocardiography. (18F)-FDG PET/CT was used to measure the FDG uptake and the standardized uptake value (SUV) after CPR or TMZ + CPR for 6 hours. The intermediary carbohydrate metabolites of glycolysis including phosphoenolpyruvate, 3-phospho-D-glycerate, and the lactate/pyruvate ratio were detected through the multiple reaction monitoring approach. Simultaneously, the authors also tested the expression levels of the total adenosine triphosphate (ATP) and the key intermediate products of glucose ovidation as alpha ketoglutarate, citrate, and succinate in the myocardium. The authors found that the aerobic oxidation of glucose was reduced, and the anaerobic glycolysis was significantly enhanced in the myocardium in the early stage of CPR. Meanwhile, the myocardial injury marker CTNI was upregulated considerably (P = 0.014, P = 0.021), and the left ventricular function of the animal heart also markedly deteriorated with the downregulation of ATP after CPR. In contrast, myocardial injury and cardiac function were greatly improved with the increase of ATP in the CPR + TMZ group. In addition, aerobic glucose oxidation metabolites were significantly increased (P < 0.05) and anaerobic glycolysis metabolites were significantly decreased (P < 0.05) after CPR in the myocardium. Surprisingly, (18F)-FDG PET/CT could track the above changes by detecting the FDG uptake value and the SUV. Glucose metabolism is an essential factor for myocardial self-repair after CPR. (18F) FDG PET/CT, as a non-invasive technology, can monitor myocardial energy metabolism and cardiac function by tracking changes in glucose metabolism after CPR.

Targeting Mitochondrial Metabolism to Save the Failing Heart.

Despite considerable progress in treating cardiac disorders, the prevalence of heart failure (HF) keeps growing, making it a global medical and economic burden. HF is characterized by profound metabolic remodeling, which mostly occurs in the mitochondria. Although it is well established that the failing heart is energy-deficient, the role of mitochondria in the pathophysiology of HF extends beyond the energetic aspects. Changes in substrate oxidation, tricarboxylic acid cycle and the respiratory chain have emerged as key players in regulating myocardial energy homeostasis, Ca2+ handling, oxidative stress and inflammation. This work aims to highlight metabolic alterations in the mitochondria and their far-reaching effects on the pathophysiology of HF. Based on this knowledge, we will also discuss potential metabolic approaches to improve cardiac function.

Mesaconine alleviates doxorubicin-triggered cardiotoxicity and heart failure by activating PINK1-dependent cardiac mitophagy.

Aberrant mitophagy has been identified as a driver for energy metabolism disorder in most cardiac pathological processes. However, finding effective targeted agents and uncovering their precise modulatory mechanisms remain unconquered. Fuzi, the lateral roots of Aconitum carmichaelii, shows unique efficacy in reviving Yang for resuscitation, which has been widely used in clinics. As a main cardiotonic component of Fuzi, mesaconine has been proven effective in various cardiomyopathy models. Here, we aimed to define a previously unrevealed cardioprotective mechanism of mesaconine-mediated restoration of obstructive mitophagy. The functional implications of mesaconine were evaluated in doxorubicin (DOX)-induced heart failure models. DOX-treated mice showed characteristic cardiac dysfunction, ectopic myocardial energy disorder, and impaired mitophagy in cardiomyocytes, which could be remarkably reversed by mesaconine. The cardioprotective effect of mesaconine was primarily attributed to its ability to promote the restoration of mitophagy in cardiomyocytes, as evidenced by elevated expression of PINK1, a key mediator of mitophagy induction. Silencing PINK1 or deactivating mitophagy could completely abolish the protective effects of mesaconine. Together, our findings suggest that the cardioprotective effects of mesaconine appear to be dependent on the activation of PINK1-induced mitophagy and that mesaconine may constitute a promising therapeutic agent for the treatment of heart failure.

Influence of Isolated Resistance Exercise on Cardiac Remodeling, Myocardial Oxidative Stress, and Metabolism in Infarcted Rats.

Exercise is an important therapeutic strategy for preventing and treating myocardial infarction (MI)-induced cardiac remodeling and heart failure. However, the myocardial effects of resistance exercise on infarcted hearts are not completely established. In this study, we investigated the effects of resistance exercise on structural, functional, and molecular cardiac alterations in infarcted rats. Three months after MI induction or simulated surgery, Wistar rats were assigned into three groups: Sham (n = 14); MI (n = 9); and exercised MI (MI-Ex, n = 13). Exercised rats performed, 3 times a week for 12 weeks, four climbs on a ladder with progressive loads. Cardiac structure and left ventricle (LV) function were analyzed by echocardiogram. Myocyte diameters were evaluated in hematoxylin- and eosin-stained histological sections as the smallest distance between borders drawn across the nucleus. Myocardial energy metabolism, lipid hydroperoxide, malondialdehyde, protein carbonylation, and antioxidant enzyme activities were evaluated by spectrophotometry. Gene expressions of NADPH oxidase subunits were evaluated by RT-PCR. Statistical analyses were performed using ANOVA and Tukey or Kruskal-Wallis and Dunn's test. Mortality did not differ between the MI-Ex and MI groups. MI had dilated left atrium and LV, with LV systolic dysfunction. Exercise increased the maximum load-carrying capacity, with no changes in cardiac structure or LV function. Myocyte diameters were lower in MI than in Sham and MI-Ex. Lactate dehydrogenase and creatine kinase activity were lower in MI than in Sham. Citrate synthase and catalase activity were lower in MI and MI-Ex than in Sham. Lipid hydroperoxide concentration was lower in MI-Ex than in MI. Nox2 and p22phox gene expressions were higher in MI-Ex than in Sham. Gene expression of Nox4 was higher in MI and MI-Ex than in Sham, and p47phox was lower in MI than in Sham. Late resistance exercise was safe in infarcted rats. Resistance exercise improved maximum load-carrying capacity, reduced myocardial oxidative stress, and preserved myocardial metabolism, with no changes in cardiac structure or left ventricle function in infarcted rats.

Early detection of myocardial ischemia in resting ECG: analysis by HHT

BackgroundExercise electrocardiography (ECG) is a noninvasive test aiming at producing ischemic changes. However, resting ECG cannot be adopted in diagnosing myocardial ischemia till ST-segment depressions. Therefore, this study aimed to detect myocardial energy defects in resting ECG using the Hilbert–Huang transformation (HHT) in patients with angina pectoris.MethodsElectrocardiographic recordings of positive exercise ECG by performing coronary imaging test (n = 26) and negative exercise ECG (n = 47) were collected. Based on the coronary stenoses severity, patients were divided into three categories: normal, < 50%, and ≥ 50%. During the resting phase of the exercise ECG, all 10-s ECG signals are decomposed by HHT. The RT intensity index, composed of the power spectral density of the P, QRS, and T components, is used to estimate the myocardial energy defect.ResultsAfter analyzing the resting ECG using HHT, the RT intensity index was significantly higher in patients with positive exercise ECG (27.96%) than in those with negative exercise ECG (22.30%) (p < 0.001). In patients with positive exercise ECG, the RT intensity index was gradually increasing with the severity of coronary stenoses: 25.25% (normal, n = 4), 27.14% (stenoses < 50%, n = 14), and 30.75% (stenoses ≥ 50%, n = 8). The RT intensity index of different coronary stenoses was significantly higher in patients with negative exercise ECG, except for the normal coronary imaging test.ConclusionsPatients with coronary stenoses had a higher RT index at the resting stage of exercise ECG. Resting ECG analyzed using HHT could be a method for the early detection of myocardial ischemia.

Emerging Roles of SIRT5 in Metabolism, Cancer, and SARS-CoV-2 Infection.

Sirtuin 5 (SIRT5) is a predominantly mitochondrial enzyme catalyzing the removal of glutaryl, succinyl, malonyl, and acetyl groups from lysine residues through a NAD+-dependent deacylase mechanism. SIRT5 is an important regulator of cellular homeostasis and modulates the activity of proteins involved in different metabolic pathways such as glycolysis, tricarboxylic acid (TCA) cycle, fatty acid oxidation, electron transport chain, generation of ketone bodies, nitrogenous waste management, and reactive oxygen species (ROS) detoxification. SIRT5 controls a wide range of aspects of myocardial energy metabolism and plays critical roles in heart physiology and stress responses. Moreover, SIRT5 has a protective function in the context of neurodegenerative diseases, while it acts as a context-dependent tumor promoter or suppressor. In addition, current research has demonstrated that SIRT5 is implicated in the SARS-CoV-2 infection, although opposing conclusions have been drawn in different studies. Here, we review the current knowledge on SIRT5 molecular actions under both healthy and diseased settings, as well as its functional effects on metabolic targets. Finally, we revise the potential of SIRT5 as a therapeutic target and provide an overview of the currently reported SIRT5 modulators, which include both activators and inhibitors.

Caloric restriction increases the resistance of aged heart to myocardial ischemia/reperfusion injury via modulating AMPK–SIRT1–PGC1a energy metabolism pathway

A large number of data suggest that caloric restriction (CR) has a protective effect on myocardial ischemia/reperfusion injury (I/R) in the elderly. However, the mechanism is still unclear. In this study, we created the I/R model in vivo by ligating the mice left coronary artery for 45 min followed by reperfusion. C57BL/6J wild-type mice were randomly divided into a young group fed ad libitum (y-AL), aged fed ad libitum (a-AL) and aged calorie restriction group (a-CR, 70% diet restriction), and fed for 6 weeks. The area of myocardial infarction was measured by Evan’s blue-TTC staining, plasma cholesterol content quantified by ELISA, fatty acids and glucose measured by Langendorff working system, as well as protein expression of AMPK/SIRT1/PGC1a signaling pathway related factors in myocardial tissue detected by immunoblotting. Our results showed that CR significantly reduced infarct size in elderly mice after I/R injury, promoted glycolysis regardless of I/R injury, and restored myocardial glucose uptake in elderly mice. Compared with a-AL group, CR significantly promoted the expression of p-AMPK, SIRT1, p-PGC1a, and SOD2, but decreased PPARγ expression in aged mice. In conclusion, our results suggest that CR protects elderly mice from I/R injury by altering myocardial substrate energy metabolism via the AMPK/SIRT1/PGC1a pathway.

Therapeutic Use and Molecular Aspects of Ivabradine in Cardiac Remodeling: A Review.

Cardiac remodeling can cause ventricular dysfunction and progress to heart failure, a cardiovascular disease that claims many lives globally. Ivabradine, a funny channel (If) inhibitor, is used in patients with chronic heart failure as an adjunct to other heart failure medications. This review aims to gather updated information regarding the therapeutic use and mechanism of action of ivabradine in heart failure. The drug reduces elevated resting heart rate, which is linked to increased morbidity and mortality in patients with heart failure. Its use is associated with improved cardiac function, structure, and quality of life in the patients. Ivabradine exerts several pleiotropic effects, including an antiremodeling property, which are independent of its principal heart-rate-reducing effects. Its suppressive effects on cardiac remodeling have been demonstrated in animal models of cardiac remodeling and heart failure. It reduces myocardial fibrosis, apoptosis, inflammation, and oxidative stress as well as increases autophagy in the animals. It also modulates myocardial calcium homeostasis, neurohumoral systems, and energy metabolism. However, its role in improving heart failure remains unclear. Therefore, elucidating its molecular mechanisms is imperative and would aid in the design of future studies.

UPLC-Q-TOF-MS metabolomic study on improvement of acute myocardial ischemia in rats by Dalbergia cochinchinensis heartwood

This paper aimed to study the effect of Dalbergia cochinchinensis heartwood on plasma endogenous metabolites in rats with ligation of the left anterior descending coronary artery, and to analyze the mechanism of D. cochinchinensis heartwood in improving acute myocardial ischemic injury. The stability and consistency of the components in the D. cochinchinensis heartwood were verified by the establishment of fingerprint, and 30 male SD rats were randomly divided into a sham group, a model group, and a D. cochinchinensis heartwood(6 g·kg~(-1)) group, with 10 rats in each group. The sham group only opened the chest without ligation, while the other groups established the model of ligation. Ten days after administration, the hearts were taken for hematoxylin-eosin(HE) staining, and the content of heart injury indexes in the plasma creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH), energy metabolism-related index glucose(Glu) content, and vascular endothelial function index nitric oxide(NO) was determined. The endogenous metabolites were detected by ultra-high-performance liquid chromatography-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS). The results showed that the D. cochinchinensis heartwood reduced the content of CK-MB and LDH in the plasma of rats to relieve myocardial injury, reduced the content of Glu in the plasma, improved myocardial energy metabolism, increased the content of NO, cured the vascular endothelial injury, and promoted vasodilation. D. cochinchinensis heartwood improved the increase of intercellular space, myocardial inflammatory cell infiltration, and myofilament rupture caused by ligation of the left anterior descending coronary artery. The metabolomic study showed that the content of 26 metabolites in the plasma of rats in the model group increased significantly, while the content of 27 metabolites decreased significantly. Twenty metabolites were significantly adjusted after the administration of D. cochinchinensis heartwood. D. cochinchinensis heartwood can significantly adjust the metabolic abnormality in rats with ligation of the left anterior descending coronary artery, and its mechanism may be related to the regulation of cardiac energy metabolism, NO production, and inflammation. The results provide a corresponding basis for further explaining the effect of D. cochinchinensis on the acute myocardial injury.

Clozapine-induced Myocarditis: Pathophysiologic Mechanisms and Implications for Therapeutic Approaches.

Clozapine, a superior treatment for treatment-resistant schizophrenia can cause potentially life-threatening myocarditis and dilated cardiomyopathy. While the occurrence of this condition is well known, its molecular mechanisms are unclear and may be multifactorial. Putative mechanisms warrant an in-depth review not only from the perspective of toxicity but also for understanding the molecular mechanisms of the adverse cardiac effects of clozapine and the development of novel therapeutic approaches. Clozapine-induced cardiac toxicity encompasses a diverse set of pathways, including (i) immune modulation and proinflammatory processes encompassing an IgEmediated (type I hypersensitivity) response and perhaps a cytokine release syndrome (ii) catecholaminergic activation (iii) induction of free radicals and oxidative stress (iv) activation of cardiomyocyte cell death pathways, including apoptosis, ischemia through impairment in coronary blood flow via changes in endothelial production of NO and vasoconstriction induced by norepinephrine as well as other factors released from cardiac mast cells. (v) In addition, an extensive examination of the effects of clozapine on non-cardiac cellular proteins demonstrates that clozapine can impair enzymes involved in cellular metabolism, such as pyruvate kinase, mitochondrial malate dehydrogenase, and other proteins, including α-enolase, triosephosphate isomerase and cofilin, which might explain clozapine-induced reductions in myocardial energy generation for cell viability as well as contractile function. Pharmacologic antagonism of these cellular protein effects may lead to the development of strategies to antagonize the cardiac damage induced by clozapine.

Cardiac positron emission tomography in prediction of the clinical course of chronic thromboembolic pulmonary hypertension: prospective cohort study

INTRODUCTION: During the development of CTEPH maladaptive mechanisms in the right ventricle are accompanied by disturbances in myocardial energy metabolism and perfusion. These changes can be assessed visually and quantitatively using the molecular imaging method — PET with [18F]-FDG and [13N]-NH3.OBJECTIVE: Using cardiac PET/CT investigate the relationship between perfusion and metabolism of the right ventricular myocardium and the results of other instrumental examination methods in patients with CTEPH of different severity, as well as to calculate the threshold PET values to determine the group of patients with an unfavorable clinical course of the disease.MATERIALS AND METHODS: The study included 36 patients with a verified diagnosis of CTEPH, who were examined using a standard diagnostic protocol. Patients underwent cardiac PET/CT examinations with two radiopharmaceuticals: with [18F]-FDG to study the metabolism of the ventricular myocardium and with [13N]-NH3 to assess cardiac perfusion. For each radiopharmaceutical semi-quantitative accumulation indices (SUV) and the ratio of the levels of radiopharmaceutical uptake in the right and left ventricles (SUV RV/SUV LV) were obtained. Statistics: Shapiro-Wilk test, Student’s t-test, and Mann-Whitney U-test, Pearson correlation analysis, linear regression analysis, ROC analysis.RESULTS: The level of [18F]-FDG accumulation in the right ventricular myocardium is higher in patients with a high functional class of PH than in groups I, II (p&lt;0.01). All indicators of SUV RV/SUV LV for [18F]-FDG demonstrate a direct linear relation-ship with the level of mean PAP (r=0.691, p&lt;0.0001), PVR (r=0.715, p&lt;0.0001), right ventricular size (r=0.658, p&lt;0.0001), PASP (r=0.581, p&lt;0.001) and inverse linear relationship with the functional parameters of the right ventricle CI (r=–0.555, p=0.001), CO (r=–0.488, p=0.005), TAPSE (r=–0.552, p&lt;0.001), TAVS (r=–0.537, p&lt;0.001), and SvO2 (r=–0.666, p&lt;0.0001). A correlation was found between the accumulation of [13N]-NH3 and the main hemodynamic parameters used to assess the severity of the disease (СI, SvO2). The threshold values of [18F]-FDG and [13N]-NH3 accumulation indices have been obtained, which with high sensitivity (69.2–83.3%), specificity (68.4–94.7%) and diagnostic accuracy (0.73–0.83) make it possible to identify patients with a low cardiac index and an unfavorable prognosis.DISCUSSION: The obtained results confirm the presence of glucose hypermetabolism in right ventricular cardiomyocytes in the development of pulmonary hypertension and the association of these metabolic changes with the severity of PH. A significant correlation was demonstrated between the accumulation of both radiopharmaceuticals in the heart and the results of other examination methods characterizing the severity of disease and the prognosis of patients with CTEPH. Using a non-invasive PET/CT procedure, threshold values of PET parameters were obtained, which in the future can be used to identify patients with an unfavorable clinical prognosis.CONCLUSION: Cardiac PET/CT with [18F]-FDG and [13N]-NH3 is a promising non-invasive imaging technique that can be used to study metabolic and perfusion changes in the right ventricular myocardium in CTEPH, as well as to identify patients with a high risk of adverse events.

Ferric derisomaltose therapy and heart failure: implications and molecular insights.

Iron is essential to the production of myocardial energy and proteins critical for cardiovascular function. Nearly 50% of patients with heart failure with reduced ejection fraction (HFrEF) meet current criteria for iron deficiency, and there has been considerable interest in intravenous repletion of iron stores as a therapeutic strategy to improve HFrEF outcomes. However, the data on intravenous iron therapy in HFrEF have been mixed.

Targeting Energy Protection as a Novel Strategy to Disclose Di’ao Xinxuekang against the Cardiotoxicity Caused by Doxorubicin

Doxorubicin (DOX) can induce myocardial energy metabolism disorder and further worsen heart failure. "Energy protection" is proposed as a new cardiac protection strategy. Previous studies have found that Di'ao Xinxuekang (DXXK) can improve doxorubicin-induced cardiotoxicity in mice by inhibiting ferroptosis. However, there are very few studies associating DXXK and energy protection. This study aims to explore the "energy protection" effect of DXXK on cardiotoxicity induced by DOX. A DOX-induced cardiotoxicity model established in rats and H9c2 cells are used to analyze the therapeutic effects of DXXK on serum indexes, cardiac function indexes and cardiac histopathology. The metabonomic methods were used to explore the potential mechanism of DXXK in treating DOX-induced cardiotoxicity. In addition, we also observed the mitochondrial- and autophagy-related indicators of myocardial cells and the mRNA expression level of the core target regulating energy-metabolism-related pathways. Our results indicated that DXXK can improve cardiac function, reduce myocardial enzymes and alleviate the histological damage of heart tissue caused by DOX. In addition, DXXK can improve mitochondrial damage induced by DOX and inhibit excessive autophagy. Metabonomics analysis showed that DOX can significantly affects the pathways related to energy metabolism of myocardial cells, which are involved in the therapeutic mechanism of DXXK. In conclusion, DXXK can treat DOX-induced cardiotoxicity through the AMPK-mediated energy protection pathway.

Myocardial work and energy loss of left ventricle obtained by pressure-strain loop and vector flow mapping: a new perspective on idiopathic left bundle branch block

To date, no research has been conducted on the electrical activity and mechanical dyssynchrony of idiopathic left bundle branch block (iLBBB) with normal left ventricular ejection fraction (LVEF). This study sought to assess the left ventricular summation of energy loss (EL-SUM) and average energy loss (EL-AVE) using vector flow mapping as well as myocardial work using pressure-strain loop (PSL) in patients with iLBBB and normal LVEF. We prospectively recruited 35 patients with iLBBB and 35 control participants with normal LVEF. Echocardiography was performed. Conventional echocardiographic parameters, myocardial work, and energy loss (i.e., the EL-SUM and EL-AVE) were calculated. In relation to global myocardial work, compared to the control participants, the iLBBB patients showed decreased global longitudinal strain (GLS; -15.32%±2.58% vs. -18.27%±2.12%; P=0.001), a decreased global work index (GWI; 1,428.24±338.18 vs. 1,964.87±264.16 mmHg%; P<0.001), decreased global work efficiency (GWE) (84.48±5.19 vs. 91.73±5.31 mmHg%; P<0.001), and significantly increased global waste work (GWW; 341.60±132.62 vs. 161.80±106.81 mmHg%; P<0.001). In relation to the regional index, the iLBBB patients had a significantly reduced basal anteroseptal segment (879.15±370.50 vs. 1,746.38±154.44 mmHg%; P<0.001), basal inferoseptal segment (1,111.42±389.04 vs. 1,677.25±223.10 mmHg%; P<0.001), mid-anteroseptal segment (1,097.54±394.83 vs. 1,815.06±291.22 mmHg%; P<0.001), mid-inferoseptal segment (1,012.54±353.33 vs. 1,880.88±254.39 mmHg%; P<0.001), apical anterior segment (1,592.42±366.64 vs. 1,910.00±170.27 mmHg%; P=0.001), apical lateral segment (1,481.62±342.95 vs. 1,817.19±227.55 mmHg%; P=0.001), apical septal segment (1,437.65±428.22 vs. 1,852.25±275.19 mmHg%; P=0.001), and apex (1,542.62±342.89 vs. 1,907.06±197.94 mmHg%; P<0.001). The iLBBB patients had increased EL-AVE and EL-SUM during the late-diastole, isovolumic-systole, and rapid-ejection periods [EL-AVE in T2: 28.3 (8.7, 49.0) vs. 6.8 (5.4, 9.4) J/(s·m3); P=0.029]; [EL-AVE in T3: 24.7 (13.0, 46.8) vs. 7.2 (5.4, 10.8) J/(s·m3), P<0.001]; [EL-AVE in T4: 18.3 (12.0, 27.6) vs. 7.7 (4.1, 11.6) J/(s·m3), P=0.002]; [EL-SUM in T2: 8.3 (2.2, 14.5) vs. 2.1 (1.6, 3.2) J/(s·m), P=0.049]; [EL-SUM in T3: 7.6 (4.0, 14.5) vs. 2.2 (1.7, 3.3) J/(s·m), P<0.001]; [EL-SUM in T4: 5.3 (3.6, 9.7) vs. 2.2 (1.4, 3.0) J/(s·m), P=0.004]. The GWI and GWE were reduced in patients with iLBBB, especially in the septum and apex. The EL-SUM and EL-AVE were higher in patients with iLBBB during the late-diastole, isovolumic-systole, and rapid-ejection periods. EL and PSL reflect the LV hemodynamics of patients with iLBBB.

Pyruvate Dehydrogenase Complex and Glucose Oxidation as a Therapeutic Target in Diabetic Heart Disease.

Diabetic cardiomyopathy was originally described as the presence of ventricular dysfunction in the absence of coronary artery disease and/or hypertension. It is characterized by diastolic dysfunction and is more prevalent in people with diabetes than originally realized, leading to the suggestion in the field that it simply be referred to as diabetic heart disease. While there are currently no approved therapies for diabetic heart disease, a multitude of studies clearly demonstrate that it is characterized by several disturbances in myocardial energy metabolism. One of the most prominent changes in myocardial energy metabolism in diabetes is a robust impairment in glucose oxidation. Herein we will describe the mechanisms responsible for the diabetes-induced decline in myocardial glucose oxidation, and the pharmacological approaches that have been pursued to correct this metabolic disorder. With surmounting evidence that stimulating myocardial glucose oxidation can alleviate diastolic dysfunction and other pathologies associated with diabetic heart disease, this may also represent a novel strategy for decreasing the prevalence of heart failure with preserved ejection fraction in the diabetic population.

Advances in extracardiac mechanisms for heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a syndrome with highly heterogeneous clinical symptoms, and its incidence has been increasing in recent years. Compared with heart failure with reduced ejection fraction (HFrEF), HFpEF has a worse prognosis. Traditional therapies targeting the internal mechanisms of the heart show limited or inefficacy on HFpEF, and new therapeutic targets for HFpEF are expected to be found by focusing on the extracardiac mechanisms. Recent studies have shown that cardiopulmonary pathophysiological interaction exacerbates the progression of HFpEF. Hypertension, systemic vascular injury, and inflammatory response lead to coronary microvascular dysfunction, myocardial hypertrophy, and coronary microvascular remodeling. Acute kidney injury affects myocardial energy production, induces oxidative stress and catabolism of myocardial protein, which leads to myocardial dysfunction. Liver fibrosis mediates heart injury by abnormal protein deposition and inflammatory factors production. Skeletal muscle interacts with the sympathetic nervous system by metabolic signals. It also produces muscle factors, jointly affecting cardiac function. Metabolic syndrome, gut microbiota dysbiosis, immune system diseases, and iron deficiency promote the occurrence and development of HFpEF through metabolic changes, oxidative stress, and inflammatory responses. Therefore, the research on the extracardiac mechanisms of HFpEF has certain implications for model construction, mechanism research, and treatment strategy formulation.

Особливості серцевої недостатності у пацієнтів, які перенесли коронавірусну інфекцію

An analysis of primary and secondary myocardial lesions under the conditions of transmission of the COVID-19 infection, causative factors and consequences of the progression of the pathological condition was carried out. Some possibilities of protection against infection and its consequences are noted. Among the first problems with the spread of SARS-CoV-2 in patients with heart failure is the need to distinguish viral lung disease from acute edema. Particular attention is paid to disorders of immune regulation and inflammation, which can exacerbate the imbalance between oxygen supply and myocardial energy needs. At the same time, the importance of troponin I, natriuretic peptide type B and C-reactive protein and creatinine, hypokalemia are highlighted. The central role is played by angiotensin-converting enzyme 2, the suppression of which enhances the local inflammatory response and fibrosis. Progression of infection is associated with stress cardiomyopathy and acute decompensation of chronic heart failure. They note the possibility of reducing infection, protecting the heart from systolic dysfunction, and correcting stress-induced biological reactions of the body, in particular, by the action of low temperatures.