Heart Failure Of Ischemic Origin Research Articles

Clinical markers of cognitive impairment in patients with chronic heart failure of ischemic origin during out-patient regular follow-up: a cross-sectional study

Background: Cognitive impairment (CI) is present in 25–50% of chronic heart failure (CHF) patients. Doctors who monitor patients with cardiovascular disorders do not have clearly set criteria for their referral to a neurologist in case of suspected CI. Therefore, CHF patients do not receive treatment for CI on time.
 Aim: To identify significant clinical markers of CI in patients with CHF of ischemic origin.
 Materials and methods: This cross-sectional cohort study included 134 patients with CHF of ischemic origin (mean age 63.36 ± 10.63 years; men, 76.12%), who were regularly monitored in a municipal polyclinic. All patients were tested for CI with the Montreal Cognitive Assessment Scale (MoCA); basic hemodynamic parameters, lipid profile, brain natriuretic peptide (NT-proBNP) were assessed, and triglyceride-glucose index (TyG) and body mass index (BMI) were calculated. Cardio-ankle vascular index (CAVI) was measured, echocardiography and a 6-minute walk test (SMWТ) were performed and past history of CHF, arterial hypertension (AH) and diabetes mellitus (DM) was collected.
 Results: CI (MoCA score ≤ 25) was detected in 85 (63.43%) outpatients with CHF of ischemic origin; the group without CI (MoCA score 26) included 49 (36.67%) patients. There were significant correlations between MoCA and CAVI scores (partial correlation coefficient, r = -0.802, p 0.001; adjusted squared multiple correlation coefficient (adj. R2) = 0.881, p 0.001), MoCA and TyG (r = -0.357, p = 0.029; adj. R2 = 0.363, p 0.001), MoCA and SMWТ (r = -0.211, p = 0.037; adj. R2 = 0.696, p 0.001). The multivariate test for significance of planned comparisons between CAVI and MoCA scores (Wilks' lambda) was 0.005 (F = 4.74; p 0.001).
 Conclusion: CAVI, TyG and SMWТ values are the clinical markers of CI in patients with CHF of ischemic origin. There is a direct association between increased CAVI and the presence of CI, regardless of age, lipid metabolism parameters, structural and functional heart parameters, CHF duration, AH and DM. Identification of these markers could be an indication for an in-depth assessment of CHF patients by a neurologist.

The features of heart failure of ischemic origin in patients with concomitant atrial fibrillation and diabetes mellitus

The features of heart failure of ischemic origin in patients with concomitant atrial fibrillation and diabetes mellitus

ERYTHROPOIETIN SYNTESIS IN PATIENTS WITH CHRONIC HEART FAILURE DEPENDING ON COMORBID PATHOLOGY

Introduction. Decreased production of erythropoietin by the kidneys plays crucial role in the development of anemia in patients with chronic heart failure, especially on the background of comorbid diabetes mellitus type 2. In diabetic patients due to early damage of the kidney vessels and following erythropoietin deficiency anemia develops much earlier than clinically significant decrease of glomerular filtration rate.
 The aim of the study was to find out possible dependence of changes in the erythropoietinsynthesizing function of the kidneys on the degree of severity of anemic hypoxia in elderly and senile patients with chronic heart failure, including those with comorbid type 2 diabetes mellitus.
 Materials and methods. 120 patients with chronic heart failure of ischemic origin, type 2 diabetes mellitus and mild and moderate anemia were examined. Control group comprised 12 people with chronic heart failure without comorbid pathology. The examined groups were comparable in terms of gender and age, differing in the presence of comorbid diabetes mellitus and degree of severity of anemic syndrome. The level of erythropoietin in blood serum was determined by standard enzymelinked immunosorbent assay.
 Results. Type 2 diabetes mellitus in patients with chronic heart failure results in a significant decrease in erythropoietin production by 25 % compared to the control group (p<0,05). Comorbid to heart failure anemia leads to an increase in the level of erythropoietin by 74,4 % (р<0,05), and in the case of chronic heart failure and type 2 diabetes mellitus on the background of concomitant anemia – only by 39,5 % (р<0,05). As the severity of anemia in patients with chronic heart failure without diabetes progresses, the severity of the compensatory response of the kidneys to chronic anemic hypoxia is significantly higher than in patients with heart failure and comorbid type 2 diabetes.
 Conclusions. Diabetic nephropathy in patients with chronic heart failure and comorbid anemia leads to a significant deterioration of the erythropoietin-synthesizing function of the kidneys, complicating the course of both main and comorbid diseases.

Role of radionuclide assessment of global and regional mechanical dyssynchrony of the heart in prognosis of cardiac resynchronization therapy in patients with heart failure

Aim. To determine the prognostic significance of cardiac regional mechanical dyssynchrony (MD), assessed by radionuclide equilibrium ventriculography (REVG) in candidates for cardiac resynchronization therapy (CRT).Material and methods. The study included 65 patients with indications for CRT according to current guidelines. Prior to CRT, all patients underwent REVG to assess cardiac contractile function and MD. According to the phase analysis, indicators of global and regional cardiac MD were evaluated: phase standard deviation (PSD), histogram band width (HBW), entropy, and interventricular dyssynchrony. The regional assessment included an evaluation of phase histograms obtained from the analysis of the contraction of certain walls: left ventricular (LV) anterior, lateral, posterior wall, right ventricular (RV) free wall, and the interventricular septum. To evaluate the effectiveness of treatment 6 months after CRT, all patients underwent echocardiography, on the basis of which patients were divided into groups of responders and non-responders.Results. REVG revealed significant differences in the initial regional MD values between the groups of responders and non-responders: in responders, MD values of RV free wall (PSD: 39 (28-67) vs 28 (20-50), p=0,03) and LV anterior wall (PSD: 28,5 (16-40) vs 14 (11-24), p=0,0005) were higher, and the LV lateral wall was lower (PSD: 10 (7-14) vs 15 (9-26), p=0,007) than in non-responders. Multivariate logistic regression found following independent predictors of a positive response to CRT: heart failure of ischemic origin, LV HBW, RV free wall PSD, anterior wall PSD, LV lateral wall HBW (p<0,001). The sensitivity and specificity of the model was 93% and 91%, respectively.Conclusion. Regional MD scintigraphy parameters increase the predictive value of REVG in CRT candidates. The most informative in this regard are the PSD of RV free wall and LV anterior wall, as well as the HBW of LV lateral wall.

Beta-adrenoreactivity of erythrocyte membranes and expression of beta1-adrenergic receptors of cardiomyocytes in patients with heart failure with different left ventricular ejection fraction

Introduction. More and more studies demonstrate the importance of determining the beta-adrenergic reactivity of erythrocyte membranes (beta-ARM) for predicting the severity of cardiovascular diseases, including chronic heart failure. But the presence of general patterns between the change in beta-ARM and the expression of beta1adrenergic receptors on the membranes of cardiomyocytes, depending on the left ventricular ejection fraction (LVEF) remains questionable.Aim: To evaluate beta-ARM and expression of beta1-adrenergic receptors of cardiomyocytes in groups of patients with heart failure with preserved (≥ 50%) and reduced (< 50%) LV EF.Materials and methods. The study included 100 patients with chronic heart failure of ischemic origin. Groups of 79 patients with LVEF ≥ 50% and 21 patients with LVEF < 50% were formed. The levels of epinephrine and norepinephrine in blood plasma and the expression of beta1-adrenergic receptors in myocardial samples were assessed using enzyme immunoassay. Beta-ARM was determined in whole blood by assessing the inhibition of hemolysis of erythrocytes placed in a hypoosmotic medium in the presence of a selective beta-blocker.Results. In the group with LV EF < 50%, beta-ARM was increased (p = 0.037), amounting to 31.9% (23.2; 40.1), compared with the group with LVEF ≥ 50%, where beta-ARM was 21.4% (15.0; 31.7). At the same time, in patients with LV EF < 50%, the expression of beta1-AR on cardiomyocyte membranes was significantly lower than in the other group (p = 0.037): 2.7 (2.1; 3.0) ng/mg and 3.1 (2.4; 3.9) ng/mg total protein, respectively. However, plasma levels of epinephrine and noradrenaline were comparable in the study groups.Conclusion. Patients with heart failure with LVEF < 50% were characterized by increased beta-ARM and reduced expression of beta1-AR on cardiomyocyte membranes compared with the group with LVEF ≥ 50% with comparable levels of circulating catecholamines.

The assessment of the depressive states severity and their relationship with concomitant type 2 diabetes and obesity in patients with chronic heart failure of ischemic origin

The aim is to assess the prevalence and expressiveness of depressive disorders in patients with chronic heart failure (CHF) of the ischemic origin, depending on the presence of concomitant type 2 diabetes mellitus (T2DM), obesity and their combined course, as well as to assess the influence of existing metabolic disorders on the development of depression in individuals of this cohort. Materials and methods. The study included 154 patients with CHF of ischemic origin. Group 1 included patients with CHF with coronary heart disease (CHD), T2DM and obesity (n = 42). The second group consisted of patients with CHF on the background of CHD with concomitant T2DM (n = 46), and the third group – with concomitant obesity (n = 36). The comparison group was formed from patients who had signs of CHF of ischemic origin without metabolic disorders (n = 30). The Beck Depression Inventory (BDI) was used to assess the presence and nature of depressive disorders. Results. In patients with isolated CHF of ischemic origin, depression was found in 60 % of cases, according to BDI. In the second group depression was manifested in 80.6 % of cases, and in the third group – in 91.3 % of cases. 95.2 % of patients of the first group had depressive disorders. The average value of scores in patients of the first group significantly exceeded that of the patients of the fourth group by almost two times. Comparing the scores of patients of the second and third groups with the fourth group determined their increase by 57 % and 36 %, respectively. It was established that in patients with CHF of ischemic origin against the background of the combined course of T2DM, mild depression was found in 1/3 of patients, a quarter of patients had manifestations of moderate depression, 9.5 % of patients had severe depression and 4.8 % of people in this group had symptoms of mild depression. Conclusions. The presence of type 2 diabetes mellitus is associated with the development of depression in patients with chronic heart failure of ischemic origin. The combined course of type 2 diabetes mellitus and obesity is a risk factor for the development of depression and its progression to a marked/severe form.

Prognostic significance of NT-proBNP and sST2 biomarkers in patients with post-myocardial infarction heart failure after a coronavirus infection

Aim. To determine the prognostic significance of N-terminal pro-brain natriuretic peptide (NT-proBNP) and soluble ST2 (sST2) in patients with post-myocardial infarction heart failure after a coronavirus disease 2019 (COVID-19)Material and methods. Three following groups were formed: in patients of group I (main), who underwent inpatient treatment for COVID-19, the cause of heart failure (HF) was prior Q-wave myocardial infarction; in patients of group II (comparison) without COVID-19, the cause of HF was prior Q-wave myocardial infarction; Group III (comparison) — patients with HF of ischemic origin without postinfarction cardiosclerosis and COVID-19. Statistical processing was carried out using the software package IBM SPSS Statistics Version 26.0.Results. The patients of all three groups included in the present study were comparable. After 6 months in group I, HF course worsening was recorded. In patients of groups I and II, an increase in NYHA HF class from 2 to 3 and 4 was recorded, in contrast to patients of group III, among whom the number of patients with class 3 HF decreased by 25% due to compensation to class 2. Patients of the studied groups, who had elevated serum levels of NT-proBNP and sST2, had more pronounced structural and functional myocardial disorders than patients with normal levels of these biomarkers. Using analysis of adverse cardiovascular events, such as recurrent myocardial infarction, cerebrovascular accident, hospitalization due to coronary artery disease, decompensated HF, which required hospitalization, a predictive model was developed using a neural network. There were following most important factors of the developed model: age, level of NT-proBNP and sST2, lung involvement according to computed tomography.Conclusion. Modern biomarkers NT-proBNP and sST2 have sufficient predictive value to determine the risk of adverse events in HF.

Modern possibilities of correction of broncho-obstructive syndrome in chronic heart failure of ischemic origin in combination with chronic obstructive pulmonary disease: simple randomized parallel group study

AIM: To evaluate the efficacy and safety of complex basic therapy for chronic heart failure (CHF) of ischemic origin in combination with chronic obstructive pulmonary disease (COPD) with the inclusion of prolonged bronchodilators.
 MATERIALS AND METHODS: The study included 67 patients (50 men and 17 women) with CHF IIIII functional class (FC) with left ventricular ejection fraction (LVEF) of 45% in combination with moderate-to-severe COPD (GOLD). The patients were divided into three groups: group 1 (n=30) received formoterol as part of therapy, group 2 (n=19) received aclidinium, and group 3 (n=18) received a fixed combination of aclidinum and formoterol. The basic therapy for CHF included nebivolol, losartan, eplerenone, diuretics, low-dose glucocorticosteroids, nitrates, and cardiac glycosides (if necessary). The clinical condition of patients, intracardiac hemodynamics, was indicated using echocardiography, a 6-min walking test (6MWT), bifunctional 24-h monitoring of blood pressure and heart rate, and spirometry. Quality of life was assessed using the Minnesota Living with Heart Failure Questionnaire, St. Georges Respiratory Questionnaire, and Modified Medical Research Council dyspnea scale.
 RESULTS: After 6 months of therapy, the clinical and instrumental parameters and quality of life improved in all groups. At the end of the observation period, the average FC of CHF and dyspnea severity decreased by 17.5, 18.2, 20.1 20.5, 24.2, and 28.1%, respectively. The increase in exercise tolerance was 22.1, 22.6, and 29.2%. An improvement in intracardiac hemodynamics was noted. The LVEF increased by 17.1, 20.5, and 24.6%, and the myocardial mass index decreased by 8.7, 14.2, and 17.4%. The total peripheral vascular resistance, degree of pulmonary hypertension, and duration and frequency of painless myocardial ischemia significantly decreased. The best results were obtained in group 3 using nebivolol, reninangiotensinaldosterone system antagonists, and a combination of long-acting bronchodilators. Therapy was well tolerated by all study groups, with no serious adverse side effects.
 CONCLUSION: The inclusion of nebivolol and losartan in basic therapy, while taking long-acting bronchodilators, improves the clinical and functional states of patients and quality of life, and slows down disease progression. When used in a fixed combination, the use of aclidinium and formoterol improves spirometry to a greater extent.

NESFATIN-1 ACTIVITY IN THE BLOOD SERUM IN PATIENTS WITH CHRONIC HEART FAILURE OF ISCHEMIC ORIGIN AGAINST THE BACKGROUND OF TYPE 2 DIABETES MELLITUS AND OBESITY.

The aim: To study the nesfatin-1 activity in the blood serum of patients with chronic heart failure (CHF) of ischemic origin against the background of such metabolic disorders as type 2 diabetes mellitus (T2DM) and obesity. Materials and methods: 154 patients with CHF were examined, and divided into 4 groups, according to the presence of metabolic disorders. Group 1 included patients with CHF on the background of coronary heart disease (CHD) and T2DM and obesity (n=42). The second group consisted of patients with heart failure on the background of CHD with concomitant T2DM (n=46), the third group - with concomitant obesity (n=36), the fourth group was formed from patients with signs of heart failure of ischemic origin without metabolic disorders (n=30). The control group (CG) included 30 practically healthy persons of comparable age. Results: The mean level of serum nesfatin-1 was 1.64±0.27 ng/mL in the СHF group, 0.342±0.19 ng/mL in the CHF + T2DM + obesity group, 1.06±0.36 ng/ mL in the obese + CHF group, 0.96±0.27 ng/mL in the CHF + T2DM group and 2.98±0.38 ng/mL in the CG. Significant correlation was found between the serum nesfatin-1 level and BMI (r=-0.34, p<0.05), HOMA (r=-0.54, p<0.05), insulin (r=-0.41, p<0.05). No significant correlation was found between the serum nesfatin-1 level and blood glucose level (r=0.13, p=0.65). Conclusions: Thus, nesfatin-1 may play a significant role in the pathogenesis of both weight-related abnormalities and type 2 diabetes mellitus in patients with chronic heart failure of ischemic origin.

Baroreflex sensitivity but not microvolt T-wave alternans can predict major adverse cardiac events in ischemic heart failure.

Major adverse cardiovascular events (MACE) constitutes the main cause of morbidity and mortality in ischemic heart failure (HF) patients. The prognostic value of the autonomic nervous system parameters and microvolt T-wave alternans (MTWA) in this issue has not been identified to date. The aim herein, was to assess the usefulness of the abovementioned parameters in the prediction of MACE in HF patients with left ventricular systolic dysfunction of ischemic origin. Baroreflex sensitivity (BRS), heart rate variability (HRV), MTWA and other well-known clinical parameters were analyzed in 188 ischemic HF outpatients with left ventricular ejection fraction (LVEF) ≤ 50%. During 34 (14-71) months of follow-up, 56 (30%) endpoints were noted. Univariate Cox analyses revealed BRS (but not HRV), MTWA, age, New York Heart Association functional class III, LVEF, implantable cardioverter-defibrillator presence, use of diuretics and antiarrhythmic drugs, diabetes, and kidney insufficiency were defined as significant predictors of MACE. Pre-specified cut-off values for MACE occurrence for the aforementioned continuous parameters (age, LVEF, and BRS) were: ≥ 72 years, ≤ 33%, and ≤ 3 ms/mmHg, respectively. In a multivariate Cox analysis only BRS (HR 2.97, 95% CI 1.35-6.36, p < 0.006), and LVEF (HR 1.98, 95% CI 0.61-4.52, p < 0.038) maintained statistical significance in the prediction of MACE. Baroreflex sensitivity and LVEF are independent of other well-known clinical parameters in the prediction of MACE in patients with HF of ischemic origin and LVEF up to 50%. BRS ≤ 3 ms/mmHg and LVEF ≤ 33% identified individuals with the highest probability of MACE during the follow-up period.

Insulin-like Growth Factor-1 and Myocardial Remodeling in Patients with Chronic Heart Failure of Ischemic Origin

Aim. To study the presence and nature of correlations between the level of Insulin-like growth factor-1 (IGF-1) and structural and functional parameters of the heart in the development of myocardial remodeling and fibrosis in patients with chronic heart failure (CHF) of ischemic origin.Material and methods. The study included 120 men with class II-IV CHF who have history of myocardial infarction, which are divided into 3 groups depending on the CHF class. The control group included 25 healthy men. Assessment of left ventricular (LV) structural-functional state was carried out by echocardiography. Investigation of IGF-1 and N-terminal precursor indices of cerebral natriuretic peptide (NT-pro BNP) was performed by enzyme immunoassay.Results. Patients with class II CHF were hyperexpression of IGF-1, with class III CHF were registered low-normal level, with class IV CHF was established a deficiency of IGF-1. The most significant structural-geometric rearrangement of LV and significant deficit of IGF-1 recorded in patients with class IV CHF (95,6±7,02 ng/ml with class IV CHF versus 178,3±11,36 ng/ml and 124,3±9,14 ng/ml with class II and III CHF; р&lt;0,05). In patients of class III-IV CHF, correlation relationships between IGF-1 level and echocardiographic parameters (LV myocardial mass index are established: r=-0,59, p=0,05; end systolic volume index: r=-0,55, p=0,05; value of LV ejection fraction: r=0,61, p=0,05). Significant negative correlation are established in patients with class III-IV CHF between IGF-1 level and NT-pro BNP levels (r=-0,51; р=0,05).Conclusion. The intensity of myocardial remodeling and fibrosis processes in patients with a progressive course of CHF is related to deficit of IGF-1 and is associated with a high level of activity of natriuretic peptides.

THE SOLUBLE ST2 BLOOD LEVEL IN PATIENTS WITH DEPRESSIVE DISORDERS AND ISCHEMIC HEART FAILURE SYNDROME

&#x0D; Mental disorders are among the leading causes of the global health-related burden. This burden was high across the entire lifespan, for both sexes, and across many locations. Heart failure (HF) persists as an increasing global epidemic; indeed, its estimated prevalence is currently more than 37.7 million people worldwide. ST2 (growth stimulation expressed gene 2) is a member of the interleukin (IL)-1 receptor family. Recent studies revealed that elevated levels of sST2 were associated with adverse outcomes in patients with acute dyspnoea, acute coronary syndromes, and HF. The purpose of this study: to evaluate the relationship between ST2 levels in the blood of patients with heart failure and depression. Material and methods: there were examined 129 patients with depression of varying severity together with the syndrome of HF of ischemic genesis, FC II-IV (NYHA). Depressive disorders were screened using the Hospital Anxiety and Depression Scale, which showed 8 or more points to indicate depressive episodes. The severity of depressive disorders was determined using the Hamilton scale. Transthoracic echocardiography was performed; the plasma content of soluble ST2 (sST2) and the titers of the N-terminal fragment of the brain natriuretic peptide (NT-proBNP) in the blood were determined by ELISA. Statistical analysis was performed using the standard software package "Statistica for Windows 12.0" (StatSoft, Tulsa, OK, USA).Results: The average age of the examined patients was (67.21 ± 11.73) years; among them - 41 women (31.8%). It was noted that the levels of soluble ST2 and NT-pro-BNP in the blood of patients with depressive disorders and HF of ischemic origin increased with decreasing LV EF. According to the Hamilton questionnaire, the majority of patients with HF suffered from depressive disorders of moderate intensity - 96 (74.4%) people. Univariate correlation analysis showed a direct relationship between soluble ST2 levels in the blood of the examined patients and the severity of depressive symptoms (rs = 0.33; p = 0.041); blood content of NT-pro-BNP (rs = 0.51; p = 0.015); resting heart rate (rs = 0.31; p = 0.011) and feedback from LV EF (rs = -0.39; p = 0.043).Conclusion. Patients with depressive disorders and concomitant heart failure of ischemic origin more often showed elevated levels of soluble ST2 molecule in the blood, which depend on the intensity of depression and impaired myocardial contractile function.

Levels of angiogenesis markers in patients with different heart failure phenotypes

Aim. To assess the relationship between the levels of angiogenesis markers and various heart failure (HF) phenotypes in patients with class II-IV HF of ischemic origin.Material and methods. This cross-sectional cohort study was based on the clinical departments of the National Medical Research Center for Therapy and Preventive Medicine. The study involved 180 patients aged 30-85 years with class II-IV HF of ischemic origin as follows with (n=90) and without (n=90) metabolic syndrome (MS). All patients included in the study signed an informed consent to personal data processing, participation in a clinical trial and consent to blood biobanking. All patients were divided into three groups: HF with reduced ejection fraction (HFrEF) — left ventricular (LV) EF &lt;40%, HF with mildly reduced EF (HFmrEF) — LVEF from 40 to 49%, HF with preserved EF (HFpEF) — LVEF &gt;49%. In addition to the standard paraclinical investigations, angiogenesis markers were analyzed with the determination of transforming growth factor β (TGF-β), vascular endothelial growth factor A (VEGF-A), pentraxin-3 (PTX-3). Statistical analysis was performed using Microsoft Office Excel, STATISTICA 10.0 software packages (Statsoft, USA).Results. Transthoracic echocardiography determined that 74 (41,1%) patients had LVEF &lt;50%, while 71 (39,4%) — &lt;40%. For the group of patients with HFpEF, there was an association with an increase in TGF-β ≥7,2 ng/ml (p=0,011). The threshold level of PTX-3 ≥55 ng/ml is associated with the development of HFpEF (p=0,001). For the HFmrEF phenotype, the threshold values of VEGF-A, TGF-β and PTX-3 were determined, which did not reach the significance level. However, an upward trend in VEGF-A &gt;200 ng/ml was noted (p=0,052). In HFrEF patients, a threshold value of VEGF-A &gt;195 ng/ml (p=0,001) associated with reduced LVEF was determined.Conclusion. Thus, the present work showed the relevance of using PTX-3, VEGF-A and TGF-β as additional markers for assessing the HF course. So, patients with HFpEF had increased levels of PTX-3 and TGF-β, while patients with HFmrEF and HFrEF — increased VEGF-A values. Determination of the level of these angiogenesis markers should be used to improve the efficiency of diagnosis and treatment of patients with various class II-IV HF phenotypes.

Is there the phenotype of chronic heart failure with “intermediate” left ventricular ejection fraction? Additional echocardiographic criteria for left ventricular systolic dysfunction in patients with chronic heart failure of ischemic origin with ejection fraction in the “gray area”

Patients with chronic heart failure (CHF) with left ventricular ejection fraction (LV EF) in the range of 40–55 % form a separate group with “intermediate” or “moderately reduced” LV EF. Since there are a number of additional criteria in echocardiography other than EF for determining LV systolic function (TEI, MAPSE, systolic velocity of the fibrous ring of the mitral valve (S’), E/e’, dP/dt mitral regurgitation, etc.), their use may be helpful in the final identification of systolic dysfunction in CHF patients with LV EF within the “gray area”. The aim of the work – to find out the possibility of using ultrasound parameters of LV systolic function as additional diagnostic criteria for systolic dysfunction and to develop an algorithm for its diagnosis in CHF patients with LV EF within the “gray zone” (40–55 %). Materials and methods. The study included 79 patients (men – n = 49; women – n = 30) with CHF of ischemic origin with LV EF from 40 % to 55 % (main group) who were divided into two subgroups: the first subgroup (n = 40) – patients with LV EF within the “gray area 45–55 %”, the second subgroup (n = 39) – patients with LV EF less than 45 %. The comparison group – 90 patients with coronary heart disease without signs of CHF (men – n = 40, 44.5 %; women – n = 50, 55.5 %). The patient groups were age-, sex-, height-, weight-, body surface area-matched. Doppler echocardiographic examination was performed on the device Esaote MyLab Eight (Italy). Results. According to our results, 90 % (71/79) of CHF patients with reduced LV EF had mitral regurgitation. Additional examination of the systolic index dP/dT of less than 1200 mm Hg/s on the flow of mitral regurgitation allowed to classify CHF patients from the “gray area” (LV EF 40–55 %) to the CHF phenotype with reduced LV EF, and that was almost half of patients – 50.6 % (40/79). Cut off points were established for Myocardial Performance Index TEI of the LV &gt;0.56 r. u., the right ventricle &gt;0.51 r. u., decrease in systolic dP/dT ≤1000 mm Hg/s, systolic velocity of the medial (S med ≤7 cm/s) and the lateral (S lat ≤7 cm/s) fibrous ring of the mitral valve, the amplitude of the medial (MAPSE med ≤11.7 mm) and the lateral (MAPSE lat ≤11.1 mm) fibrous ring of the mitral valve. Conclusions. The cohort of CHF patients with “intermediate” LV EF is a heterogeneous group, which includes patients according to one formal criterion – LV EF in the range of 40–55 %. LV EF is a surrogate marker, insufficient for the final determination of the CHF phenotype. Additional criteria for systolic dysfunction include ventricular TEI, dP/dT mitral regurgitation, systolic velocity (S), and amplitude (MAPSE) of the medial and lateral fibrous ring of the mitral valve. In the presence of two or more additional ultrasound criteria for systolic LV dysfunction, CHF patients with LV EF within 40–55 % should be considered as patients with reduced LV EF.

The relationship between systolic function and serum NGAL levels in patients with chronic heart failure of ischemic origin

Neutrophil gelatinase-associated lipocalin (NGAL) is considered one of the most informative biomarkers of chronic kidney disease (CKD). NGAL can also serve as a biomarker of cardiovascular disease and heart failure (HF). However, the relationship between systolic function and serum NGAL concentrations in patients with chronic HF (CHF) of ischemic origin remains insufficiently studied. The aim. To study the influence of tubulo-interstitial injury marker NGAL on systolic function in patients with CHF of ischemic origin. Materials and methods. The study included 51 patients with CHF, stage II AB, NYHA II-IV FC. Doppler echocardiographic examination was performed on the device Esaote MyLab Eight (Italy) according to standard methods. NGAL levels were analyzed using an ELISA kit (E-EL-H0096, Elabscience, USA). Depending to the concentration of serum NGAL, the patients were divided into 2 subgroups. In the first group (n = 37), the NGAL level was higher than 168 ng/ml, in the second (n = 14) – less than 168 ng/ml. Results. The mean serum NGAL concentration in the first subgroup was 192 (183; 200) ng/ml, in the second subgroup – 154 (134; 160) ng/ml. The patients with CHF of ischemic origin with tubulo-interstitial injury (according to the serum concentration of NGAL) did not differ significantly from the patients with CHF of ischemic origin without tubulo-interstitial injury in age (P = 0.950), height (P = 0.983), weight (P = 0.681), body surface area (P = 0.975). Most of left ventricular systolic function indicators showed a downward tendency (S 6.90 ± 2.85 cm/s vs. 7.67 ± 2.83 cm/s (P = 0.536); S lat 7.33 ± 2.08 cm/s vs. 11.00 ± 4.00 cm/s (P = 0.467); TEI LV 0.56 ± 0.26 c.u. vs. 0.49 ± 0.14 c.u. (P = 0.747)) in the patients with CHF of ischemic origin with elevated serum levels of NGAL compared to similar indicators in the patients with CHF of ischemic origin without tubulo-interstitial injury. The index of LVEF was significantly lower in the patients with CHF with elevated serum NGAL compared to that in the patients with CHF with normal serum NGAL (50.43 ± 17.85 % vs. 63.29 ± 13.24 % (P = 0.021)). Conclusions. Serum NGAL was not only the sensitive marker of tubulo-interstitial injury in patients with CHF of ischemic origin, but also appeared to be a predictor of changes in systolic heart function.

Full spectrum of clonal haematopoiesis-driver mutations in chronic heart failure and their associations with mortality.

AimsSomatic mutations in haematopoietic stem cells can lead to the clonal expansion of mutated blood cells, known as clonal haematopoiesis (CH). Mutations in the most prevalent driver genes DNMT3A and TET2 with a variant allele frequency (VAF) ≥ 2% have been associated with atherosclerosis and chronic heart failure of ischemic origin (CHF). However, the effects of mutations in other driver genes for CH with low VAF (<2%) on CHF are still unknown.Methods and resultsTherefore, we analysed mononuclear bone marrow and blood cells from 399 CHF patients by deep error‐corrected targeted sequencing of 56 genes and associated mutations with the long‐term mortality in these patients (3.95 years median follow‐up). We detected 1113 mutations with a VAF ≥ 0.5% in 347 of 399 patients, and only 13% had no detectable CH. Despite a high prevalence of mutations in the most frequently mutated genes DNMT3A (165 patients) and TET2 (107 patients), mutations in CBL, CEBPA, EZH2, GNB1, PHF6, SMC1A, and SRSF2 were associated with increased death compared with the average death rate of all patients. To avoid confounding effects, we excluded patients with DNMT3A‐related, TET2‐related, and other clonal haematopoiesis of indeterminate potential (CHIP)‐related mutations with a VAF ≥ 2% for further analyses. Kaplan–Meier survival analyses revealed a significantly higher mortality in patients with mutations in either of the seven genes (53 patients), combined as the CH‐risk gene set for CHF. Baseline patient characteristics showed no significant differences in any parameter including patient age, confounding diseases, severity of CHF, or blood cell parameters except for a reduced number of platelets in patients with mutations in the risk gene set in comparison with patients without. However, carrying a mutation in any of the risk genes remained significant after multivariate cox regression analysis (hazard ratio, 3.1; 95% confidence interval, 1.8–5.4; P < 0.001), whereas platelet numbers did not.ConclusionsSomatic mutations with low VAF in a distinct set of genes, namely, in CBL, CEBPA, EZH2, GNB1, PHF6, SMC1A, and SRSF2, are significantly associated with mortality in CHF, independently of the most prevalent CHIP‐mutations in DNMT3A and TET2. Mutations in these genes are prevalent in young CHF patients and comprise an independent risk factor for the outcome of CHF, potentially providing a novel tool for risk assessment in CHF.

Adherence to ESC cardiac resynchronization therapy guidelines: findings from the ESC CRT Survey II

Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with heart failure (HF) and electrical dyssynchrony. The European Society of Cardiology (ESC) Guidelines provide evidence-based recommendations indicating optimal patient selection for CRT implantation in both the 2013 European Heart Rhythm Association (EHRA) and the 2016 Heart Failure Association (HFA) Guidelines. We assessed the adherence to guidelines and identified factors associated with guideline adherence. In 2016, the HFA and EHRA conducted the CRT Survey II in 42 ESC countries. The data collected were sufficient to evaluate adherence to guidelines in 8021 patients. Of these, 67% had a Class I guideline indication for CRT implantation, which was significantly correlated with female gender (1.70, P < 0.0001), age <75 years (1.55, P < 0.0001), non-ischaemic HF aetiology (1.22, P < 0.0001), and elective admission (1.87, P < 0.0001). A further 26% of implants had a Class IIa indication, 5% IIb and only 2% a contraindication to CRT-a Class III indication. Patients implanted under Level IIa indications were much more likely to have more comorbidities than patients implanted under Level I indications. However, there were large variations in guideline adherence between ESC countries. Implanters in ESC member states demonstrate a high degree of adherence to ESC guidelines with 98% of implants having a documented Class I, IIa or IIb indication. Cardiac resynchronization therapy implantation without a Class I indication was more likely in men, patients age ≥75 years, with HF of ischaemic origin and in patients admitted to hospital acutely.

Platelet aggregation in patients with heart failure of ischemic origin depends on blood levels of iron and bilirubin

Platelet aggregation in patients with heart failure of ischemic origin depends on blood levels of iron and bilirubin

Influence of diuretic therapy on the features of heart rhythm variability changes in chronic heart failure patients

Цель. Изучить сравнительное влияние фуросемида и торасемида на показатели вариабельности ритма сердца у пациентов с хронической сердечной недостаточностью ишемического генеза.&#x0D; Методы. В исследование вошли 48 пациентов (29 мужчин и 19 женщин) с ишемической болезнью сердца, осложнённой хронической сердечной недостаточностью II-IV функциональных классов по NYHA. Все пациенты были рандомизированы на две группы: первая группа (25 человек) в качестве диуретической терапии получала фуросемид, вторая (23 человека) - торасемид. Всем больным проводили клиническое обследование, включающее оценку жалоб и данных объективного состояния, лабораторные и инструментальные исследования (электрокардиографию, эхокардиографию, тест 6-минутной ходьбы, 24-часовое мониторирование электрокардиограммы по Холтеру) до начала диуретической терапии и через 30 дней после неё.&#x0D; Результаты. На фоне проведённой 1-месячной диуретической терапии зарегистрирована позитивная динамика клинических параметров в обеих основных группах пациентов, получающих лечение как фуросемидом, так и торасемидом. На фоне лечения фуросемидом отмечено ухудшение параметров вариабельности ритма сердца. Терапия торасемидом привела к значительному улучшению показателей вегетативной регуляции сердечной деятельности.&#x0D; Вывод. Мочегонная терапия фуросемидом характеризуется изменениями временных и спектральных параметров вегетативной регуляции сердечного ритма в сторону усиления симпатических и ослабления парасимпатических влияний; диуретическая терапия торасемидом сопровождается значительным улучшением показателей вариабельности ритма сердца, ослаблением симпатических и усилением парасимпатических влияний на ритм сердца, что обеспечивает дополнительную кардиопротекцию при лечении пациентов с хронической сердечной недостаточностью ишемического генеза.

Therapeutic correction of anemia in patients with chronic heart failure of ischemic origin with iron’s drugs in combination with quercetin

The aim of the study was to evaluate the effectiveness of anemia's correction in patients with chronic heart failure of ischemic genesis with iron's drugs in comparison with their combination with quercetin based clinical, cardiohemodynamic characteristic, indicators of erythropoiesis and cytokines. Materials and methods. Tere were examinated 120 patients with chronic heart failure due to iscemic heart disease and anemia. Chronic heart failure FC II diagnosed in 49 pations, III FK – 42 and FC IV – 29. Patients with CHF and anemia were divided in 2 groups. 1 group recieved standart therapy and iron’s drugs, the 2 group was additionally assigned quercetin. Hemoglobin, serum iron, erythropoetin and ferritin levels were evaluated. Results. After the therapy, the level of erythrocytes, hemoglobin, hematocrit, serum iron in the first group increased by 5.3, 20.3, 12.8, 40.2 %, respectively, in the II group – by 9.2, 25.6, 14.2 and 62.4 % respectively. The level of erythropoietin before the onset of therapy in both groups significantly exceeded the control indices. After treatment it significantly decreased in the I group by 20.4 %, in II – by 28.2 %. A significant increase of the level of tumor necrosis factor-α, interleukin-1β was determined in both groups of patients with chronic heart failure and anemia, In first group level of tumor necrosis factor -α significantly decreased by 14.2 %, interleukin-1β – on 6.5 %, in II group – by 26.6 % and 28.1 % respectively after the treatment. In the first group the end-diastolic diameter was significantly decreased by 7.7 %, the end-diastolic volume by 9.5 %, the end-systolic diameter by 7.9 %, the end systolic volume by 7.5 %, the ejection fraction increased by 14.4 % and indicators of a 6-minute walk test by 19.4 %, quality of life parameters by 24.2 %, in II group the end diastolic diameter decreased by 11.3 %, the end diastolic volume by 10.2 %, the end systolic diam, eter by 9.4 %, the end systolic volume by 13.6 %, the ejection fraction increased by 18.3 %, the distance of 6-minute walk test improved by 34.0 % the quality of life parameters by 32.9 %. Conclusions. It has been detected, that anemia’s correction in patients with CHF, who received combination of standart treatment with iron’s drugs accompanied by an increase in the level of erythrocytes, hemoglobin, iron, and decreased level in the initially increased levels of erythropoetin, ferritin, tumor necrosis factor-α, interleykin-1β. Favorable changes in erythropoiesis were accompanied by a positive dynamics of the morphofunctional parameters of the myocardium, the distance during the 6-minute walk test and the quality of life indicators. Quercetin, included in the scheme of therapy of patients with chronic heart faiulure and anemic syndrome, potentiated hematopoietic and hemodynamic effects of therapy.