Progression Of Chronic Heart Failure Research Articles

Exploring the pathways of drug repurposing and Panax ginseng treatment mechanisms in chronic heart failure: a disease module analysis perspective.

Chronic Heart Failure (CHF) is a significant global public health issue, with high mortality and morbidity rates and associated costs. Disease modules, which are collections of disease-related genes, offer an effective approach to understanding diseases from a biological network perspective. We employed the multi-Steiner tree algorithm within the NeDRex platform to extract CHF disease modules, and subsequently utilized the Trustrank algorithm to rank potential drugs for repurposing. The constructed disease module was then used to investigate the mechanism by which Panax ginseng ameliorates CHF. The active constituents of Panax ginseng were identified through a comprehensive review of the TCMSP database and relevant literature. The Swiss target prediction database was utilized to determine the action targets of these components. These targets were then cross-referenced with the CHF disease module in the STRING database to establish protein-protein interaction (PPI) relationships. Potential action pathways were uncovered through Gene Ontology (GO) and KEGG pathway enrichment analyses on the DAVID platform. Molecular docking, the determination of the interaction of biological macromolecules with their ligands, and visualization were conducted using Autodock Vina, PLIP, and PyMOL, respectively. The findings suggest that drugs such as dasatinib and mitoxantrone, which have low docking scores with key disease proteins and are reported in the literature as effective against CHF, could be promising. Key components of Panax ginseng, including ginsenoside rh4 and ginsenoside rg5, may exert their effects by targeting key proteins such as AKT1, TNF, NFKB1, among others, thereby influencing the PI3K-Akt and calcium signaling pathways. In conclusion, drugs like dasatinib and midostaurin may be suitable for CHF treatment, and Panax ginseng could potentially mitigate the progression of CHF through a multi-component-multi-target-multi-pathway approach. Disease module analysis emerges as an effective strategy for exploring drug repurposing and the mechanisms of traditional Chinese medicine in disease treatment.

#909 Role of cystatin C in the development and progression of chronic heart failure in patients with diabetes

Abstract Background and Aims It has been known that cystatin C is a marker for early prediction of renal function. In recent years, studies have shown that cystatin C plays an important role in predicting new or worsening cardiovascular diseases. The aim of our study was to investigate the role of cystatin C in the development and progression of chronic heart failure (CHF) in patients with diabetes. Method A total of 499 patients with DT1 and DT2, aged 34 to 84 years (60 [60; 72]), were examined. All patients underwent standard clinical and laboratory examination, with an assessment of the levels of the natriuretic peptides (BNP and NTproBNP) in baseline plasma samples. Renal function was assessed based on the levels of serum creatinine and cystatin C. Patients were divided into quartiles according to cystatin C levels: Q1 <0.78 mg/l, Q2 0.78-0.92 mg/l, Q3 0.93-1.38 mg/l, Q4 >1.38 mg/l. Results Significant differences in the levels of BNP and NTproBNP were observed in patients with diabetes with cystine C levels ≥0.93 mg/l (32.20 [19.85; 69.35] pg/ml and 104.25 [57.70; 210.08] ng/l, respectively). There were significant correlations between cystatin C and the levels of BNP (r = 0.56, p < 0.05) and NTproBNP (r = 0.58, p < 0.05). Logistic regression analysis showed the prognostic value of cystatin C, and not creatinine, as a predictor of heart failure in patients with diabetes and GFR>60 ml/min/1.73 m2 (1 mg/l increase of cystatin C was associated with 7.085 times increase in CHF odds). ROC analysis revealed that the level of cystatin C ≥0.96 mg/l with a sensitivity of 84% and specificity of 75% predicted increased BNP and NTproBNP in patients with diabetes (ROC AUC = 0.844). Conclusion Cystatin C level could be used as a predictive indicator of CHF in patients with diabetes and GFR>60 ml/min/1.73 m2.

СВЯЗЬ ЦИРКУЛИРУЮЩИХ УРОВНЕЙ АМИНОКИСЛОТ С РАЗВЕТВЛЕННОЙ ЦЕПЬЮ У ПАЦИЕНТОВ С ХРОНИЧЕСКОЙ СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТЬЮ С НАЛИЧИЕМ НАРУШЕНИЙ УГЛЕВОДНОГО ОБМЕНА

The importance of the problem of chronic heart failure (CHF) is hard to overestimate: this syndrome is diagnosed in millions of patients around the world and its prevalence continues to grow. The proportion of patients suffering from carbohydrate metabolism disorders (CMD) is also steadily increasing. The close connection between carbohydrate metabolism disorders and the progression of CHF allowed such patients to be classified into a separate phenotype cluster - the “metabolic phenotype of CHF”. The pathophysiology of the “metabolic phenotype of CHF” is based on significant metabolic disorders, which determines the characteristic features of the metabolome of this cohort of patients. Therefore, the purpose of this work is to compare and evaluate the relationship between metabolites that occupy one of the most important places in the metabolic processes of the body - the levels of branched chain amino acids (BCAA) and the phenotypic characteristics of patients with CHF. The study included 218 patients: 133 patients of the main group suffering from CHF and having CMD; comparison group - 85 patients with CHF without CMD. The groups were comparable by gender (p=0,324) and age (p=0,936). The levels of BCAAs - leucine, isoleucine, valine - in the blood plasma of patients were assessed by high-performance liquid chromatography combined with mass spectrometry (HPLC-MS). Based on the results of the analysis, the following data were obtained: plasma levels of valine and leucine in patients with CHF and CMD were higher (p=0,022 and p<0,001, respectively) than in patients with CHF and normal carbohydrate metabolism. A direct relationship between the level of leucine + isoleucine and the concentration of glucose (r=0,3, p<0,001) and an inverse relationship between the plasma concentration of valine and the level of N-terminal propeptide of natriuretic hormone (NTproBNP) (r=-0,388, p<0,001) were found. It has been established that a high level of tissue insulin resistance in patients is associated with increased concentrations of BCAA. The results indicate the important role of BCAA in the pathogenesis of the “metabolic phenotype of CHF,” which requires further research in this direction.

Out of hospital sudden cardiac arrest as a prognostic factor for in-hospital mortality in patients admitted with cardiogenic shock

Abstract Funding Acknowledgements None. Background The mortality in cardiogenic shock (CS) is still high despite new comprehensive therapies. Cardiac arrest (CA) frequently complicates CS which can have an unfavourable effect on the course after admission. Purpose The study aimed to analyse the clinical characteristics and prognosis of patients admitted with CS after out-of-hospital cardiac arrest (OHCA) compared to the group without OHCA. Methods The studied group consisted of a total of 80 patients with an average age of 62 ± 13 years (81 % male) admitted to tertiary hospital with CS in the period 2021-2022. The severity of the shock according to the Society for Cardiac Angiography and Interventions (SCAI) SHOCK classification among the whole population was from C to E: 7 (9%), 38 (48%), and 35 (43%), respectively. The cohort was divided into 2 subgroups: the OHCA group consisted of 23 individuals (29%) and the without OHCA (non-OHCA group) consisted of 57 individuals. Results The groups did not differ in terms of demographic parameters and comorbidities. There were no differences in baseline heart rate 95 [50;114] vs. 91 [77;105] beats per minute and mean artery pressure 75 [70;97] vs. 82 [70;97] mmHg for OHCA vs. non-OHCA, respectively, all p> 0.05. Patients from OHCA group had higher baseline creatinine level 1.65 [1.35;1.88] vs. 1.37 [1.08; 1.65] mg/dL, p=0.019, white blood cell count 12 [9;16] vs. 17 [12;23] × 109/L, p=0.015 and lower pH from blood gas analysis 7.0 [6.9;7.2] vs. 7.3 [7.2;7.4], p<0.001). In the OHCA group, 90% of cases of CS were caused by acute coronary syndrome (ACS), while in the group without OHCA, 76% were due to ACS and 20 % due to the progression of chronic heart failure, p=0.032. Mechanical Circulatory Support (MCS) was used in almost every patient (98% non-OHCA vs. 95% OHCA), however, the OHCA group was more often treated with V-A ECMO 14 (64%) vs. 16 (28%) in the non-OHCA, p=0.004. The overall number of in-hospital deaths was 57 (71%). The OHCA group had significantly higher in-hospital mortality 22 (96%) compared to the non-OHCA patients 35 (61%), p=0.002. Conclusion Patients experiencing CS complicated by OHCA have more often ischaemic ethology of shock, have a greater degree of organ damage and a lower pH in blood gas analysis at admission, and have extremely high in-hospital mortality rates when compared with patients facing CS but without prior OHCA, which underscores the urgent need for improved prevention methods, interventions, and public awareness.

The severity of chronic heart failure and the parameters of daily blood pressure profile in patients with coronary heart disease

Aim: Although the prevalence of coronary heart disease (CHD) and hypertension which are the most common causes of the development and progression of chronic heart failure (CHF) is high, 24-hour ambulatory blood pressure (BP) monitoring (ABPM) in patients with CHF is not mandatory to be performed. The growing number of evidence suggests that excessive decrease in BP which clearly reflects increased BP variability (BPV) affects the survival of patients with heart failure (HF). The objective of the study was to investigate the relationship between the parameters specific to CHF severity and features of daily BP profiles in patients with ischemic CHF and hypertension. Methods: Ninety patients with functional class II–IV of CHF and CHD (the main group) and 50 non-CHF patients with hypertension (the comparative group) were examined. The transthoracic echocardiography (TTE) [atrial end-systolic dimension (ESD), ventricular end-diastolic dimension (EDD), left ventricular mass index (LVMI), and left ventricular ejection fraction (LVEF)] and 24-hour ABPM (BPV parameters and proportions of hypotensive episodes) were performed. The relationships between the abovementioned parameters were evaluated using the univariate correlation analysis and stepwise multiple linear regression. Results: Higher functional class of CHF is found to be associated with a higher incidence of daytime systolic BP (SBP) decline and nighttime SBP and diastolic BP (DBP) variability while higher LVEF is related to the hypotensive episodes regardless of CHF. Conclusions: It appears that the larger trials involving CHF patients with reduced LVEF should be conducted to clarify the obtained results.

PATHOGENIC MECHANISMS OF HEART FAILURE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Highlights The review presents up-to-date data on the contribution of type 2 diabetes mellitus to the development and progression of heart failure. The review highlights the key mechanisms of the pathogenesis of heart failure associated with changes in the energy metabolism of cardiomyocytes. AbstractType 2 diabetes mellitus is one of the main risk factors that significantly worsen the prognosis of heart failure and increases the probability of fatal cardiovascular events. The development of heart failure in diabetic patients involves a great number of risk factors for the rapid progression of atherosclerosis, as well as numerous combinations of neurohumoral, molecular and histological changes not associated with atherogenesis, which interconnection results in cardiovascular complications and heart failure decompensation. This review discusses the key mechanisms underlying development of heart failure in type 2 diabetes mellitus, in particular, special attention is paid to cardiomyocyte energy metabolism, cardiomyocyte death, and the significance of epigenetic factors in progression of chronic heart failure.

Role of PPAR-related genes in chronic heart failure: evidence from large populations

BackgroundThe role of PPAR signaling and its associated genes in the pathogenesis and progression of chronic heart failure (CHF) remains elusive.MethodsWe accessed the gene expression profile and relevant baseline information of CHF samples from the Gene Expression Omnibus (GEO) database, specifically from the GSE57338 project.ResultsFrom GSE57338 project, we derived the expression value of 126 PPAR-related genes. A protein-protein interaction network was then established to illustrate potential protein interactions. ClueGO analysis results revealed that these genes predominantly participate in functions such as export across plasma membrane, regulation of lipid metabolic process, fatty acid metabolism, circulatory system vascular processes, alcohol metabolism, triglyceride metabolism and regulation of lipid localization and response to nutrient. Using the cytohubba plug-in in Cytoscape, we pinpointed ACADM, PPARG and CPT2 as potential central molecules in HF pathogenesis and progression. Subsequent Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis delved into the potential biological role of these three genes in CHF. Immune infiltration analysis suggested that the infiltration level of neutrophils and M2 macrophages might be notably influenced by these genes, thereby playing a role in the CHF mechanism.ConclusionsOur research provides a comprehensive insight into the significance of PPAR associated genes in CHF development. Notably, the genes ACADM, PPARG and CPT2 emerged as potential targets for clinical interventions.

The role of canagliflozin in the prevention of stroke and chronic kidney disease in patients with type 2 diabetes mellitus: an expert council resolution

Over the past 10 years of studying the complications of type 2 diabetes mellitus (DM) and ways to deal with them, significant progress has been made in one of the most important areas of treatment — the prevention of cardiovascular and renal complications. Thus, when using inhibitors of type 2 sodium-glucose cotransporter, a significant reduction in the risks of cardiovascular mortality and progression of chronic heart failure, which occupy the main place in the structure of mortality in this cohort of patients, as well as a positive effect on diabetic nephropathy, one of the most common complications of type 2 diabetes, has been proven. However, there are other complications that significantly affect the duration and quality of life of patients. In particular, these include stroke, which occupies the 2nd-3rd place in the frequency of death of people with type 2 diabetes, and albuminuria, a frequent manifestation of diabetic kidney disease, which is associated with an increased risk of cardiovascular complications (including stroke) and chronic renal failure. Recent studies indicate the important role of sodium-glucose cotransporter type 1 in the development of these complications. Canagliflozin has the highest affinity for these transporters among iSGLT-2 registered in the Russian Federation. This article aims to evaluate the mechanisms of action of canagliflozin and its possible role in the prevention of stroke and albuminuria.

Right Ventricular Dysfunction and Exercise Impairment in Patients with Heart Failure, Insulin Resistance, and Diabetes Mellitus: Insights from the T.O.S.CA. Registry (Cardiovascular Diabetology 2022).

Insulin resistance (IR) and type 2 diabetes mellitus (T2D) are known to affect the progression of chronic heart failure (CHF), but little evidence exists about the impact of IR and T2D on right ventricular dysfunction and exercise tolerance. Insights from the T.O.S.C.A. Registry: Echocardiographic hallmarks and cardiopulmonary exercise test (CPET) results were evaluated at baseline and after an average time of 36 months. T2D patients exhibited a greater intraventricular septum (IVS) thickness (11 ± 2 mm, 10 ± 2 mm, 10 ± 2 mm, in T2D, IR, and EU, respectively; p<.05) and LV wall thickness (0.34 ± 0.1, 0.32 ± 0.1, and 0.32 ± 0.1, in T2D, IR, and EU, respectively; p<.05). Moreover, T2D patients exhibited worse LV filling dynamics with larger left atrial volume index compared to IR and EU. Right ventricle dysfunction, expressed as a lower TAPSE/PASP ratio, was found in T2D [0.52(0.32-0.72)] than in EU and IR [0.60(0.30-0.90); p<.05]. T2D patients showed a significantly lower VO2 max peak when compared to IR and EU patients (15.8 ± 3.8 vs. 16.5 ± 4.3 vs. 18.4 ± 4.3 ml/Kg/min; p<.003), with an inverse relationship between the HOMAIR classes and VO2 max. Right ventricle structure and function deteriorated more rapidly in T2D, as suggested by more relevant deterioration in TAPSE/PASP ratio (-10% in EU patients, -14% in IR patients, -21% in T2D; p<.05). The study findings suggest that the right ventricle structure, function, and cardiopulmonary performance deteriorate with IR and, more evidently, due to chronic exposure to hyperglycemia in T2D. Impaired exercise tolerance, poor cardiorespiratory fitness, diastolic dysfunction, and left atrial enlargement predispose patients to poor quality of life, suboptimal adherence to physical activity, and an overall increase in the risk of all-cause and cardiovascular mortality. In addition, chronic hyperglycemia accelerates the progression of these alterations, especially in patients with poor glycemic control over time. Highly selective and even more non-selective sodium glucose transporter type 2 inhibitors and glucagon-like peptide 1 receptor agonists should be considered as the first-line therapy for improving CV outcomes in T2D and CHF. Further studies are needed to understand the role of these molecules in treating pre-clinical conditions, such as IR and metabolic syndrome.

Molecular Hydrogen Reduces the Degree of Endothelial Alteration under Conditions of Chronic Heart Failure.

We studied the effect of molecular hydrogen H2 on the content of circulating endothelial cells and the macrohistological structure of the heart in rats with simulated chronic heart failure. Inhalation with 2% H2 was carried out repeatedly (40 min per day for 5 consecutive days) or once (40 min). Molecular hydrogen inhalations in both regimens caused a decrease in the number of circulating endothelial cells; the most pronounced effect was observed after repeated inhalations on day 14 after chronic heart failure modeling. The decrease in the count of circulating endothelial cells under the action of H2 was accompanied by recovery of the myocardial structure and a decrease in its weight. Molecular hydrogen in chronic heart failure limited the damage to endothelial cells and improved the structure of rat myocardium, which allows us to consider H2 inhalations as the means reducing the progression of chronic heart failure.

Chronic vagus nerve stimulation in patients with heart failure: challenge or failed translation?

Autonomic imbalance between the sympathetic and parasympathetic nervous systems contributes to the progression of chronic heart failure (HF). Preclinical studies have demonstrated that various neuromodulation strategies may exert beneficial cardioprotective effects in preclinical models of HF. Based on these encouraging experimental data, vagus nerve stimulation (VNS) has been assessed in patients with HF with a reduced ejection fraction. Nevertheless, the main trials conducted thus far have yielded conflicting findings, questioning the clinical efficacy of VNS in this context. This review will therefore focus on the role of the autonomic nervous system in HF pathophysiology and VNS therapy, highlighting the potential reasons behind the discrepancy between preclinical and clinical studies.

Polymorphism of coagulation factor genes in patients with type 2 diabetes mellitus and chronic heart failure with retained ejection fraction

BACKGROUND. Patients with type 2 diabetes mellitus (DM2) have disorders of cellular and plasma hemostasis independent of the level of glycemia, increased platelet activation, combined with microvascular angiopathy. The study of the role of genetic markers of hemostasis disorders in the formation and progression of chronic heart failure (CHF) in patients with type 2 diabetes will allow for prevention, possibly optimize treatment and improve prognosis.AIM. To reveal polymorphisms of genes of the hemostasis system in patients with type 2 diabetes mellitus and chronic heart failure with preserved ejection fraction.MATERIALS AND METHODS. The frequency of coagulation factor genetic polymorphisms was studied in patients with CHF-pEF and DM2 (52 people), CHF with reduced ejection fraction (CHF-rEF) and DM2 (49) and healthy volunteers (66), mean age 69.9±10.1 years old. DNA was isolated from venous blood according to the method of the manufacturer. Genetic polymorphisms were determined by real-time polymerase chain reaction.RESULTS. The frequencies of polymorphisms rs1799963 and rs6025 of the genes of blood coagulation factors F2 (prothrombin) and F5 (factor V of blood coagulation) in all three groups were insignificant and comparable in magnitude. In patients with CHF and DM2, the frequencies of the rs6046 polymorphism of the factor F7 gene in the heterozygous form were slightly higher (by 2.6 and 1.7 times, respectively) than in the control group, but the result was not statistically significant. The CHF-pEF and CHF-rEF groups differ in the frequencies of F13 (rs5985) and fibrinogen (rs1800790) genetic polymorphisms, but are more common in patients with CHF-rEF and DM2.CONCLUSION. Based on the results of the study, it follows that the groups of CHF-pEF and CHF-rEF differ significantly in the frequencies of polymorphisms of the studied genes, both among themselves and with the control group. The highest frequency of polymorphisms of genes, the products of which are involved in the coagulation and cellular components of hemostasis, is observed in the group of patients with DM2 and CHF-rEF.

HDAC3 Impairs Cardiac Function in Chronic Heart Failure Rats via Mediating MicroRNA-26b-3p to Target High Mobility Group AT-Hook 2.

Histone deacetylase 3 (HDAC3) has been studied in chronic heart failure (CHF), while the regulatory mechanism of HDAC3 on the development of CHF in regulating microRNA (miR)-26b-3p/high mobility group AT-hook 2 (HMGA2) axis has not been extensively investigated. This study aimed to probe the effects of HDAC3, miR-26b-3p and HMGA2 on CHF. CHF rat models were established using aortic coarctation. HDAC3, miR-26b-3p and HMGA2 levels in CHF rats were examined. Thereafter, the CHF rats were injected with relative oligonucleotides and plasmids of HDAC3, miR-26b-3p and HMGA2 to detect the cardiac function, inflammatory reaction, myocardial tissue pathological changes, and cardiomyocyte apoptosis. The binding relationship between miR-26b-3p and HMGA2 and the interaction between HDAC3 and miR-26b-3p were validated. HDAC3 and HMGA2 were elevated, while miR-26b-3p was decreased in CHF rats. The reduced HDAC3 or HMGA2 or enriched miR-26b-3p attenuated cardiac dysfunction, inflammatory reaction, myocardial tissue pathological changes and cardiomyocyte apoptosis in CHF rats, while the reduction of miR-26b-3p exerted the opposite effects. Furthermore, the inhibition of the miR-26b-3p or elevation of HMGA2 reversed the effect of reduced HDAC3 on mitigating CHF progression. Mechanically, miR-26b-3p targeted HMGA2 and HDAC3 bound to miR-26-3p. Downregulation of HDAC3 relieves cardiac function in CHF rats via mediating miR-26b-3p/HMGA2 axis. This study provides novel theory references and a distinct direction for the therapy strategies of CHF.

Efficiency and safety of Vortioxetine in the treatment of depressive disorders in cardiac patients

Importance of the problem. Diseases of the cardiovascular system are in the first place among the causes of death and disability in most industrialized countries, which is undoubtedly an urgent medical and social problem and causes significant economic damage. The prevalence of depressive disorders in modern society, according to WHO estimates, is quite high, and the causes of depressive disorders and methods for their correction in patients with various somatic diseases have been the subject of study by specialists around the world for many decades. The comorbidity of depressive disorders with cardiac pathology is beyond doubt, and the bidirectional relationship of these disorders significantly aggravates the condition of patients, worsens their quality of life and reduces adherence to treatment. The most important conditions for the use of antidepressants in cardiology practice are good tolerability, absence of toxic effect, minimal interaction with other drugs, and relative safety in case of overdose. Vortioxetine, being a modern multimodal antidepressant, demonstrates not only a sufficiently high antidepressant and anti-anxiety activity, but also has a procognitive effect, as well as minimal side effects and undesirable cross-interactions with other drugs, which is confirmed by international randomized placebo-controlled trials. The aim of this work was to evaluate the efficacy and safety of Vortioxetine in the treatment of concomitant depressive disorders in patients with coronary heart disease (CHD), angina pectoris 2-3 functional class (FC) (I 20.8 according to ICD-10), receiving complex therapy for the main (cardiological) diseases at the inpatient and outpatient stages of therapy. Materials and methods. The study included patients with a diagnosis of coronary artery disease, angina pectoris FC 2-3, hypertension 2-3, aged 45 to 66 years (mean age 57.1±1.1 years), receiving complex therapy for the underlying cardiac disease and Vortioxetine at a dose of 10-15 mg/day. within 8 weeks. Anxiety and depressive manifestations were assessed on the HADS scale, the level of cognitive impairment on the PDQ questionnaire, social functioning on the SF-36 questionnaire, the general clinical impression on the CGI-C scale, and the main indicators of the functioning of the cardiovascular system upon admission to the hospital, after 4 weeks of hospitalization. treatment and another 4 weeks after discharge during the period of outpatient observation.The result of the combined therapy of patients with cardiac pathology and concomitant depressive disorder (basic therapy for CVD and Vortioxetine) was not only an improvement in the cardiovascular system (decrease in heart rate, blood pressure, the frequency of anginal pain, an increase in exercise tolerance), but also the relief of depressive manifestations, which contributed to an increase in the adherence of cardiological patients to the implementation of medical recommendations, and, in turn, led to a decrease in the level of end points—mortality, hospitalization rates, progression of chronic heart failure and disability. Conclusions. Appointment of Vortioxetine to cardiac patients with concomitant depressive disorder of moderate severity is quite effective not only in terms of relief of painful manifestations of the CVS, but also leads to a reduction in anxiety-depressive disorders and an improvement in cognitive and social functioning. The good tolerability of the drug makes it possible to recommend it for the treatment of depressive disorders in cardiological patients in a hospital setting and in outpatient practice.

THE COURSE OF CHRONIC HEART FAILURE IN PERSONS WITH POST-INFARCTION CARDIOSCLEROSIS WITH ARTERIAL HYPERTENSION AND TYPE 2 DIABETES MELLITUS AND OBESITY ACCORDING TO A NUMBER OF MET

Objective: To investigate the effect of lipid metabolism, biomarkers of fractalkin and clusterin inflammation on the development and progression of chronic heart failure (CHF) in patients with post-infarction cardiosclerosis, type 2 diabetes and obesity. Design and method: A retrospective analysis of a comprehensive examination of 67 patients with postinfarction cardiosclerosis with concomitant type 2 diabetes and obesity. All patients were divided into 3 groups depending on the functional class (FC) of CHF: 1 group (n = 22) - patients with CHF II FC; Group 2 (n = 23) - patients with CHF III FC; Group 3 (n = 22) - patients with CHF IV FC. All patients were examined clinically, they underwent instrumental, biochemical and hormonal examinations. Results: With the progression of CHF from FC II to FC III there is a deterioration of lipid metabolism: a significant increase in cholesterol levels by 5.5%, TG – by 15.7%, LDL cholesterol – by 74.4%, VLDL cholesterol – by 15.9%, reduction of HDL cholesterol by 27.6% (p&lt;0,05). An analysis of the fractal equation showing that ailing on CHF is advised by FC; and the level of clusterine - on the contrary decreases. Classical changes in patients with postinfarction cardiosclerosis with CHF and concomitant type 2 diabetes mellitus and obesity, which are the formation of atherogenic lipid metabolism disorders associated with body weight, as well as changes in the latest indicators such as fractalkin and clusterin, indicating the role of these molecules in the progression of CHF. Conclusions: Due to the progression of chronic heart failure in patients with postinfarction cardiosclerosis and AH concomitant type 2 diabetes and obesity, an increase in all fractions of lipoproteins at stage III functional class was diagnosed, and then their decrease, which may indicate a deterioration in this category of patients, due to the progression of metabolic shifts, stagnation, dysfunction of the main parenchymal organs. Increased circulatory levels of fractalkin and decreased clusterin content in patients with postinfarction cardiosclerosis with concomitant type 2 diabetes mellitus and obesity is accompanied by an increase in the functional class of chronic heart failure.

Sacubitril/valsartan as a component of therapy for chronic heart failure

Chronic heart failure is in the vast majority of cases the outcome of many cardiovascular diseases. Despite significant achievements in the early diagnosis and treatment of cardiological pathology, the prevalence of chronic heart failure is steadily increasing, increasing the material costs of the healthcare system. Experts explain this aspect by the aging of the population of the developed countries of the world due to an increase in life expectancy. The presented review highlights the possibilities of using sacubitril/valsartan in clinical practice in order to inhibit the progression of chronic heart failure.

CHARACTERISTICS OF HEART RHYTHM DISORDERS ACCORDING TO THE DATA OF HOLTER ECG MONITORING IN PATIENTS WITH HEART FAILURE AND ATRIAL FIBRILLATION

Chronic heart failure (CHF) is one of the most significant medical, economic and social problems of the 21st century and remains the main cause of morbidity and mortality worldwide.The purpose. To study the indicators of Holter ECG monitoring, the dynamics of ischemic changes, heart rate, indicators of heart rhythm variability and blood pressure in patients with heart failure and atrial fibrillation.Material and methods. 150 patients aged 45-65 were examined. All patients were divided into groups: Group I – patients with HF with sinus rhythm or atrial fibrillation (AF) (permanent or persistent form), (n=75). Group II – patients without HF with AF, (n=75). Group III – control group: 36 practically healthy people. All patients underwent a clinical examination, ECG, echocardiography (ECHOKG), Holter ECG monitoring (HM ECG) and daily BP monitoring (DMAT).Research results. The analysis of the ECG of the examined patients indicates the presence of heart rhythm disorders, which is an important risk factor and progression of CHF. The results of XM ECG indicate the presence of ventricular arrhythmias of various gradations along with AF. There was a probable difference in the direction of an increase in the number of ventricular extrasystoles (VAS), both single and, most importantly, extrasystoles of high gradations, in patients with CHF and AF compared with healthy subjects. In addition, the number of SHEs in patients with CHF and AF was likely lower than in patients with CHF with sinus rhythm. Indicators of maximum heart rate, ST segment depression and QT interval dispersion in patients with CHF and AF were significantly higher (p&lt;0.05) than similar parameters in patients without CHF with AF.Conclusions: Ventricular heart rhythm disturbances were detected in the examined patients, which is a predictor of an unfavorable prognosis in patients with chronic heart failure. There was a probable difference in the direction of increased levels of maximum heart rate, maximum depression, ST segment elevation, dispersion of the QT interval, QTc, an increase in the total duration of episodes of myocardial ischemia, in patients with chronic heart failure and atrial fibrillation in comparison with healthy subjects.

Acute kidney injury in patients with myocardial infarction and percutaneous coronary interventions: laboratory markers and the influence on the frequency of recurrent cardiovascular events

Highlights. Biomarkers of acute kidney injury and their effect on the frequency of recurrent coronary events in patients with myocardial infarction after percutaneous coronary interventions.Aim. To study biomarkers of acute kidney injury (AKI) and prognosis, as well as the frequency of recurrent cardiovascular events in patients with myocardial infarction and percutaneous coronary interventions.Methods. 166 patients with myocardial infarction and performed percutaneous coronary interventions were studied, divided into 2 groups: with acute kidney injury (n = 91) and without it (n = 50), the control group consisted of 25 people. All patients underwent standard general clinical and biochemical blood tests to assess the level of C-reactive protein, markers of myocardial necrosis, natriuretic peptide (NTproBNP), microalbuminuria (MAU). In both groups, the glomerular filtration rate (GFR) was calculated using the CKD-EPI formula. An increase in serum creatinine by 26.5 mmol/L or more during the first 3 days from the value at admission was the reason for the study of the level of Kidney Injury Molecule-1 (KIM-1) and interleukin 18 (IL-18) in urine on the 3rd and 14th days from hospitalization. All patients underwent coronary angiography and stenting of the infarct-dependent artery. 6 months and 1 year after discharge for this acute coronary event, repeated examinations of patients were performed to assess the frequency of repeated cardiovascular events and kidney function.Results. It was revealed that the creatinine level in the examined patients did not differ statistically significantly at admission, but there was a decrease in the filtration function of the kidneys in patients with AKI. On the third day of hospitalization, there was an increase in creatinine levels in the first group of patients with a decrease in GFR. The level of the KIM-1 and IL-18 molecules on the 3rd day of hospitalization in the first group was higher than the corresponding indicator of the comparison group. Also, patients with AKI showed a significant increase in the level of NTproBNP and MAU in the early period of kidney damage. When studying correlations, it was revealed that the level of MAU in the group with AKI is interrelated with the indicator of C-reactive protein and creatinine on the 3rd day of hospitalization. Also, a positive statistically significant correlation was found between the level of the KIM-1 molecule, IL-18, creatinine level on the 3rd day of hospitalization, NTproBNP and the level of MAU. During the follow-up of patients 6 months and a year after discharge, unstable angina pectoris, myocardial infarction, as well as progression of chronic heart failure were more often detected in the group with AKI. A persistent decrease in kidney function after a year was observed in most patients of the first group.Conclusion. The data obtained indicate the influence of acute kidney injury on the progression of renal dysfunction and the frequency of recurrent cardiovascular events, which is confirmed by the obtained associative relationships of the level of the KIM-1 molecule, creatinine and GFR with the prognosis of cardiovascular disease.

ВЛИЯНИЕ ГЕНА ФАКТОРА, ИНДУЦИРУЕМОГО ГИПОКСИЕЙ, НА ТЕЧЕНИЕ АНТРАЦИКЛИН-ИНДУЦИРОВАННОЙ ХРОНИЧЕСКОЙ СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТИ

Relevance. Chronic heart failure (CHF) is a serious complication in the treatment of tumor diseases due to the cardiotoxic effect of anticancer drugs, especially anthracyclines. Despite an ever-increasing understanding of the molecular basis of anthracycline-induced cardiotoxicity, the precise mechanisms of action remain unknown, limiting the ability to effectively prevent this complication of polychemotherapy (PCT). Aim. To evaluate the effect of polymorphism (rs11549465) of the hypoxia-inducible factor subunit 1 alpha (HIF1α) gene on the course of anthracycline-induced CHF. Materials and methods. The study included 114 women with CHF that developed 12 months after the end of breast cancer chemotherapy using anthracycline drugs. All patients received therapy with carvedilol and enalapril. The control group (n = 70) consisted of women who received doxorubicin as part of chemotherapy, but they did not develop CHF 12 months after completion of PCT. The HIF1α gene polymorphism (rs11549465) was assessed using polymerase chain reaction. The course of CHF was monitored at baseline, after 12 and 24 months. Results. No significant differences were found in the frequencies of the studied polymorphism of the HIF1α gene in the groups of patients with CHF and the control group. Consequently, HIF1α gene polymorphisms are not associated with an increased risk of developing cardiac dysfunction after tumor therapy with anthracycline antibiotics. However, it was found that in women with progression of CHF after chemotherapy with anthracyclines, the frequency of occurrence of the CT genotype was statistically significantly higher than that in the group of women without progression of this pathology after 24 months of prospective observation (68.5 and 23.3%, respectively, p = 0.009). Consequently, the presence of the CT genotype of the HIF1α gene (rs11549465) (OR = 2.93; p = 0.009) is associated with an unfavorable course of CHF after anthracycline chemotherapy. Conclusion. The results obtained may indicate a genetically determined predisposition to the progression of anthracycline-induced CHF. The presence of the CT genotype of the HIF1α gene (rs11549465) is associated with an unfavorable course of CHF after anthracycline chemotherapy, which can be realized through changes in the activity of HIF1α and, accordingly, the sensitivity of cardiomyocytes to hypoxia.

Clinical features of asthenic disorders in chronic heart failure

The aim of the study is to study the clinical features of asthenic disorders in chronic heart failure (CHF) considering the reaction to the disease. 62 inpatients with CHF II-IV functional class (FC) according to NYHA were examined. Research methods included somatic, psychopathological and pathopsychological examination using psychometric scales. According to a pathopsychological study using the Multidimensional Fatigue Inventory (MFI-20), asthenic disorders were discovered in all examined patients, realized mainly by «general fatigue» (75.8%) and «physical fatigue» (72.6%), more rarely «mental fatigue» was observed (32.2%). Correlations of «general fatigue» with the age of patients were revealed (p=0.018). There was a relationship between the severity of asthenic disorders and the severity of CHF, as evidenced by the correlation between «general fatigue» and reduced ejection fraction (EF) of the left ventricle (p=0.005), as well as «physical fatigue» and FC according to NYHA (p=0.022). The negative impact of all components of the dimensions of asthenic disorders on the quality of life was determined (p<0.05). According to the concept of the formation of different perceptions of the manifestations of a somatic disease, two types of reactions to asthenic disorders were identified: 1. Dissociative reactions, manifested by a discrepancy between the severity of CHF and a subjective assessment of the condition with an underestimation of the asthenic symptoms denial of its influence on the usual lifestyle and associated with an unfavorable course of CHF and 2. Adaptive reactions, realized by a harmonious perception of asthenia, awareness of the need to change lifestyle considering the presence of CHF symptoms. In accordance with the results, the described clinical features of asthenic disorders allow to distinguish asthenia in CHF and other pathology, and the identified types of reactions can contribute to the timely verification of asthenia, prevention of further progression of CHF, and the development of appropriate treatment approaches.