Postinfarction Chronic Heart Failure Research Articles

Body Surface Potential Mapping during Atrial Depolarization in Rats with Post-Infarction Chronic Heart Failure against the Background of Fabomotizole Therapy.

Cardiac remodeling in rats with post-infarction chronic heart failure caused by anterior transmural myocardial infarction leads to an atypical location of areas of positive and negative cardioelectric potentials on the body surface before the onset of the PII-wave on the ECG in the limb leads, which is a sign of increased heterogeneity of atrial depolarization associated with the appearance of additional excitation focus in the left atrium. A course of therapy with fabomotizole leads to a decrease in the heterogeneity of atrial depolarization at the initial stages of the formation of the cardioelectric field of the atria on the body surface before the onset of the PII-wave, thereby producing an antiarrhythmic effect.

МАТЕМАТИЧЕСКИЕ МОДЕЛИ И ЧИСЛЕННЫЕ МЕТОДЫ В КАРДИОЛОГИИ: СОБСТВЕННЫЙ ОПЫТ

Вackground. In the era of digital transformation in medicine, which is radically changing the way patient information is stored, processed and used, medical professionals need new tools and approaches that can efficiently process and interpret data for fast and accurate decision making. These methods also enable the creation of personalized treatment approaches, taking into account individual patient characteristics and risks. In this article, the authors share their own experience in applying numerical methods in cardiology. Purpose of the study. To develop methods of effective risk assessment of cardiovascular outcomes in different categories of patients. Characteristics of patients and methods of the study. Three variants of outcome prediction were included in the study. The 1st - assessment of the total risk of one-year cardiovascular outcomes after myocardial infarction with ST-segment elevation, the 2nd - assessment of the risk of postinfarction chronic heart failure, the 3rd – assessment of the risk of progressive course of atherosclerosis. Statistical analysis methods included the free cross-platform visual programming system Orange, the SPSS 22.0 package, and the C programming language console. Results and Conclusion. The conducted study has shown that the application of different approaches: regression analysis, machine learning, Excel programming capabilities, C programming language and console interface allows to develop models of cardiovascular outcomes prediction with high accuracy.

Correlation of the Left Ventricular Systolic Dysfunction and Ventricular Depolarization in a Post-Infarction Model of Chronic Heart Failure.

The body surface potential mapping of the heart during the period of ventricular depolarization and the inotropic function of the ventricles were studied in rats under conditions of a translational model of post-infarction chronic heart failure developed by us. We revealed a statistically significant (p<0.001) correlation between the left-ventricular ejection fraction and the values of the maximum positive and negative extrema of the cardioelectric field on the body surface of rats with post-infarction chronic heart failure caused by anterior transmural myocardial infarction. The calculated linear regression equations have high predictive efficiency, which makes it possible to use the amplitude characteristics of the heart cardioelectric field as a marker of the development of chronic heart failure.

Efficacy of Empagliflozin in the Treatment of Experimental Myocardial Infarction

Introduction. With the emergence of empagliflozin in the pharmaceutical market, there has been an increase in publications on the primary and secondary pharmacodynamics of the drug, and the list of potential indications for the use of this sodium-glucose co-transporter inhibitor is increasing. Hypotheses about pharmacological effects and mechanisms of their implementation are tested both in large-scale clinical studies and in animal experiments.Aim. The purpose of this work was to study the effectiveness of empagliflozin by echocardiographic, histological and molecular biological analyses at the three most significant points of the dynamic transition from acute myocardial infarction to post-infarction chronic heart failure in laboratory male rats.Materials and methods. The experiment was performed on 60 male outbred rats. Myocardial infarction was modeled in narcotic animals by permanent ligation of the left coronary artery. Based on echocardiographic (EchoCG) study data, animals were randomized to two groups: control infarction: untreated pathology group treated with placebo and pathology group treated with empagliflozin 1 mg/kg per os intragastric daily from the first day of the experiment. At 10, 20 and 30 days after the operation, the animals were also subjected to EchoCG testing, and a group of 10 animals from each group were euthanized for histological examination and molecular analysis.Results and discussion. Empagliflozin use in animals after myocardial infarction modeling contributed to a significant increase in myocardial performance on days 10, 20 and 30, reaching a maximum on day 20 (47.58 ± 1.87 %). The drug promotes long-term preservation of the area of damage to the heart muscle with early formation of mature connective tissue, and also increases myocardial resistance to hypoxia by increasing the amount of HIF-1.Conclusion. Based on the studies carried out, it can be concluded that it is possible to use the sodium-glucose cotransporter type 2 empagliflozin in the formation of post-infarction chronic heart failure in the conditions of normoglycemia.

Phosphoproteomic and proteomic profiling in post-infarction chronic heart failure.

Background: Post-infarction chronic heart failure is the most common type of heart failure. Patients with chronic heart failure show elevated morbidity and mortality with limited evidence-based therapies. Phosphoproteomic and proteomic analysis can provide insights regarding molecular mechanisms underlying post-infarction chronic heart failure and explore new therapeutic approaches. Methods and results: Global quantitative phosphoproteomic and proteomic analysis of left ventricular tissues from post-infarction chronic heart failure rats were performed. A total of 33 differentially expressed phosphorylated proteins (DPPs) and 129 differentially expressed proteins were identified. Bioinformatic analysis indicated that DPPs were enriched mostly in nucleocytoplasmic transport and mRNA surveillance pathway. Bclaf1 Ser658 was identified after construction of Protein-Protein Interaction Network and intersection with Thanatos Apoptosis Database. Predicted Upstream Kinases of DPPs based on kinase-substrate enrichment analysis (KSEA) app showed 13 kinases enhanced in heart failure. Proteomic analysis showed marked changes in protein expression related to cardiac contractility and metabolism. Conclusion: The present study marked phosphoproteomics and proteomics changes in post-infarction chronic heart failure. Bclaf1 Ser658 might play a critical role in apoptosis in heart failure. PRKAA1, PRKACA, and PAK1 might serve as potential therapeutic targets for post-infarction chronic heart failure.

Features of post-infarction chronic heart failure in patients with a new coronavirus infection COVID-19

Background. The coronavirus pandemic has caused a rapid increase in the number of cases and high deaths worldwide. A new coronavirus infection in the presence of an initial cardiac pathology can provoke decompensation of chronic heart failure.&#x0D; Aim. To study the clinical features of postinfarction chronic heart failure occurring against the background of a new coronavirus infection.&#x0D; Material and methods. The study included 80 patients with decompensated chronic heart failure. Three groups have been formed. In patients of the first group (n=40), who underwent inpatient treatment for a new coronavirus infection, the cause of chronic heart failure was a previous Q-myocardial infarction. In patients of the second group (n=20), who did not tolerate COVID-19 earlier and at the time of the current hospitalization, the cause of chronic heart failure was a previous Q-myocardial infarction. The third group (n=20) consisted of patients with chronic heart failure of ischemic etiology without postinfarction cardiosclerosis, not previously and at the time of examination infected with the SARS-Cov-2 virus. Statistical analysis was carried out using the IBM SPSS Statistics V26 program. The KolmogorovSmirnov, KruskalWallis, and Pearson 2 tests were used.&#x0D; Results. Symptoms of left and right ventricular heart failure were equally common in all groups. Patients of the studied groups had a history of paroxysmal and permanent forms of atrial fibrillation, while the latter variant was more common in patients of the first group with chronic heart failure with postinfarction cardiosclerosis and coronavirus infection. According to echocardiography, the most pronounced structural and functional changes in the myocardium were also found in patients of the first group with postinfarction heart failure and a new coronavirus infection. Thus, statistically significant differences related to the size of the left atrium, end diastolic volume and end systolic volume of the left ventricle, systolic pressure in the pulmonary artery. An increase in the end systolic volume of the left ventricle by 94.6% was registered in the first group compared with the third group of patients (p=0.001). Systolic pressure in the pulmonary artery in the first group was 14.2% higher than the normal values (p 0.001), while in patients of the second and third groups this indicator was within the normal range.&#x0D; Conclusion. In patients with postinfarction cardiosclerosis suffering from a new coronavirus infection, symptoms of chronic heart failure are more pronounced, characterized by a significant decrease in exercise tolerance; cardiac arrhythmias are more often recorded, and structural and functional changes in the myocardium are of a maladaptive nature.

Transcatheter targeted myocardial restoration using hydrogel-based cell-free compound: Toward an adoptable clinical protocol

BackgroundThere is a need for a targeted, comprehensive, minimally invasive myocardial restoration treatment aimed at patients with chronic postinfarction heart failure that can provide a sustained effect and be conveniently adopted with transcatheter techniques. Here we evaluated the effectiveness of a platelet-rich plasma hydrogel-based, cell-free therapeutic compound delivered with the aid of a 3-dimensional electromechanical mapping and catheter-based technique (NOGA) in a porcine translational model. MethodsWe assessed the feasibility of targeted, minimally invasive transcatheter NOGA-guided injections of the therapeutic compound in myocardial infarction (MI) survivors at 8 weeks post-MI. ResultsAnimals undergoing NOGA-guided hydrogel injections at 8 weeks post-MI demonstrated a significant improvement of the selected left ventricular parameters at a 12-week follow-up. Compared to nonintervention, the hydrogel-based therapy provided significant improvements in end-diastolic volume (−11.0% ± 11.1% vs 6.3% ± 15.2%; P = .008) and ejection fraction (−9.1% ± 16% vs 12.7% ± 18.6%; P = .009). In the slice closest to the apex, significant differences in scar area were observed; the treatment group demonstrated a smaller mean scar area in the infarcted zone compared with the control group (47.1% ± 7.0% vs 59% ± 8.2%; P = .013) and a smaller mean scar area in the border zone compared with the saline group (31.4% ± 8.3% vs 42.6% ± 9.0%; P = .016). ConclusionsThe study implies a translational potential of the hydrogel-based therapy and should trigger clinical trials focused on establishing a restoration therapy that can be integrated into a clinical protocol.

Intraventricular pressure gradient: A novel tool to assess the post-infarction chronic congestive heart failure.

Congestive heart failure (CHF), the leading cause of death, is deemed a grave sequel of myocardial infarction (MI). The employment of left ventricular end-diastolic pressure (LVEDP), as a primary indication of CHF, becomes restricted owing to the potential impairment of heart function and caused injury to the aortic valve during its measurement. Echocardiography is the standard technique to detect cardiac dysfunction. However, it exhibits a low capacity to predict the progression of CHF post chronic MI. Being extremely sensitive, noninvasive, and preload-independent, intraventricular pressure gradient (IVPG) was lately introduced to evaluate cardiac function, specifically during cardiomyopathy. Yet, the utility of its use to assess the CHF progression after chronic MI was not investigated. Herein, in the current research, we aimed to study the efficacy of a novel echocardiographic-derived index as IVPG in the assessment of cardiac function in a chronic MI rat model with CHF. Fifty healthy male rats were involved, and MI was surgically induced in 35 of them. Six months post-surgery, all animals were examined using transthoracic conventional and color M-mode echocardiography (CMME) for IVPG. Animals were euthanized the following day after hemodynamics recording. Gross pathological and histological evaluations were performed. J-tree cluster analysis was conducted relying on ten echocardiographic parameters suggestive of CHF. Animals were merged into two main clusters: CHF+ (MI/HF + group, n = 22) and CHF– (n = 28) that was joined from Sham (n = 15), and MI/HF– (n = 13) groups. MI/HF+ group showed the most severe echocardiographic, hemodynamic, anatomic, and histologic alterations. There was no significant change in the total IVPG among various groups. However, the basal IVPG was significantly increased in MI/HF+ group compared to the other groups. The remaining IVPG measures were considerably increased in the MI/HF+ group than in the Sham one. The segmental IVPG measures were significantly correlated with the anatomical, histological, echocardiographic, and hemodynamic findings except for the heart rate. Moreover, they were significant predictors of CHF following a long-standing MI. Conclusively, IVPG obtained from CMME is a substantially promising noninvasive tool with a high ability to detect and predict the progression of CHF following chronic MI compared to conventional echocardiography.

Current approaches to risk assessment of chronic heart failure after myocardial infarction

In the last decade, there has been an increase in the number of survivors of myocardial infarction (MI). However, the risk of developing chronic heart failure (CHF) remains high in this category of patients. Population aging and comorbidity further contribute to adverse outcomes. Optimization of approaches to identify predictors of postinfarction CHF is an important clinical task of modern medicine.The aim of the investigation is to develop a method to assess the risk of CHF development after MI.Material and Methods. The present analysis included 186 patients who underwent MI from January 2019 to January 2020: 86 patients with signs of CHF above functional class (FC) 2 (NYHA) (mean age 64.3 years) and 100 patients without signs of CHF or with CHF 1 (NYHA) (mean age 62.6 years) by day 30 of MI. A mathematical model of CHF risk after MI was built by factor and correlation analysis methods.Results. A method for assessing CHF risk after a previous MI was developed. The proposed formula is programmed in Excel table processor and includes 5 indicators: presence of atrial fibrillation, Killip class of acute heart failure, triglycerides level, ST-segment elevation of electrocardiogram, left ventricular ejection fraction less than 45 %. The authors’ approach allows long-term personalized monitoring, taking into account the ranked contribution of each factor in a particular patient; it is characterized by high sensitivity, specificity, and accuracy.Conclusion. The present study investigated the factors of formation of postinfarct chronic heart failure syndrome. An original mathematical formula for CHF risk estimation, including routine indices of MI patients, has been proposed. The approach allows personalized management of selected cohorts of patients – with increased and standard risk of postinfarction CHF.

Intraventricular pressure gradient: a promising tool to predict the post-infarction chronic congestive heart failure in rats

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction: Congestive heart failure (CHF), the main reason for morbidity and mortality, is considered a serious consequence of myocardial infarction (MI). The use of left ventricular end-diastolic pressure (LVEDP) as a chief indicator of CHF becomes limited because of the possible impairment of cardiac function and induced aortic valve damage during its recording. Echocardiography is the gold standard approach to diagnose structural myocardial dysfunction. However, its ability to predict chronic CHF following MI is still limited. Recently, intraventricular pressure gradient (IVPG) was presented as a non-invasive, highly sensitive preload-independent diastolic function parameter to assess cardiac function, especially during cardiomyopathy. However, there have not been any investigations demonstrating the feasibility of IVPG in the evaluation of post-infarction chronic CHF. Purpose This study aimed to investigate the utility of IVPG to assess the heart function in a rat model with chronic CHF following MI with evaluating its capacity to predict these changes. Methods Fifty male rats were included. MI was induced via ligation of the left anterior descending artery (LAD) at the level of the atrioventricular junction (MI animals, n = 35). Sham animals were subjected to the same left thoracotomy procedure without LAD ligation (Sham animals, n = 15). Transthoracic conventional echocardiography and colour M-mode echocardiography (CMME) for IVPG were performed in all animals 6 months post-surgery. The next day, animals were anesthetized, ventilated, and euthanized after the recording of hemodynamics. The heart weight, and lung and liver wet-to-dry weight ratios were recorded. J-tree cluster-analysis was performed based on ten echocardiographic variables indicative of CHF. Results Based on the cluster analysis, animals were joined into two clusters; CHF+ (n = 22) and named MI/HF+, and CHF- (n = 28) that was joined from sham (n = 15), and MI/HF- (n = 13). MI/HF+ presented the most severe anatomical and echocardiographic changes indicative of CHF with significant reduction of all IVPG indices and impairment of the hemodynamics. The IVPG indices were significantly (P&amp;lt; 0.0001) correlated with the anatomical and echocardiographic findings, LVDP, LVEDP, HR, -dP/dtmin, and Tau. Meanwhile, LVSP was only significantly correlated with apical IVPG (R = 0.677, P = 0.022). dP/dtmax was significantly correlated with total IVPG, basal IVPG, and apical IVPG (R = 0.797, P = 0.017, R = 0.724, P = 0.003, and R = 0.652, P = 0.026 ; respectively). Moreover, total, basal, mid-to-apical, mid-, and apical IVPG were significant (P&amp;lt; 0.0001) predictors of chronic CHF following MI. Conclusion Compared to the structural, and functional indices of conventional echocardiography, IVPG derived from CMME could provide a substantial non-invasive tool to diagnose and predict CHF after long-term MI.

Choice of Tactics for Experimental Therapy of Chronic Heart Failure with ALM-802 Compound.

The cardioprotective activity of ALM-802 compound was demonstrated in model experiments simulating postinfarction chronic heart failure in rats forming in 90 days after anterior transmural myocardial infarction. ALM-802 decreased the left ventricle and improved its inotropic function (p=0.038). This effect was observed in case of systematic administration of ALM-802 over 28 days (starting from day 91 after infarction modeling). This is apparently the minimum time for the cardioprotective effect of ALM-802 to prevent or treat the resulting heart failure, because short-term systematic therapy (15 days) produced no positive effect.

Studies of Molecular Mechanisms Underlying Cardioprotective Action of the ALM-802 Compound.

The mechanisms underlying cardioprotective activity of compound ALM-802 were studied in experiments on rats with chronic post-infarction heart failure. Real-time PCR showed that compound ALM-802 (daily intraperitoneal injections in a dose of 2 mg/kg for 28 days starting from day 91 after myocardial infarction modeling) restored the expression of genes encoding β1- (p=0.00001) and β2-adrenoreceptors (p=0.01) and type 2 ryanodine receptors (p=0.008) in the myocardium that was reduced in control animals. These effects can serve as the basis for the ability of the compound to reduce the intensity of remodeling and increase the inotropic function of the left heart ventricle shown earlier in this model.

Confirmation of validity of the developed translational model of chronic heart failure in rats

The exprimants based on our translational model of chronic post-infarction heart failure within the use of echocardiography showed that in animals after 90 days after the reproduction of the myocardial infarction compared to the sham operated animals there is a significant increase in the endsystolic and end-diastolic sizes of the left ventricle (respectively, from 2.49 ± 0.09 to 3.91 ± 0.17 mm, p = 0.0002, and from 3.56 ± 0.12 to 5.20 ± 0.19 mm, p = 0.0002) and the decrease of its inotropic function that indicates a simulated pathology. 5 days after the echocardiographic study, the animals' exercise tolerance was assessed in the treadmill-run to failure test. It is proved in rats that 90 days after the coronary artery litigation the tolerance of physical activity decreases sharply – the value of the distance covered by them is 109.21 ± 11.61 m, which is 2.5 times less than the distance covered by sham operated animals ( p = 0.003) and 5.3 times less than the distance covered by intact rats ( p = 0.0001), – which is pathognomonic for chronic heart failure and complements the data of previously conducted morpho-histological, biochemical and molecular studies, indicating that the present model reproduces the main clinical and diagnostic signs of the simulated pathology.

The influence of myocardoprotection on the course of postinfarction chronic heart failure

Objective. To study the effect of Thiotriazoline in patients with post-infarction chronic heart failure (CHF).&#x0D; Materials and methods. We examined 46 patients with ischemic heart disease (IHD) who had undergone myocardial infarction. The average age was 50.8±3.2 years; men – 32 (70 %), women – 14 (30 %). All patients were examined in the form of anamnesis and examination, general clinical and biochemical studies, electrocardiography. The assessment of CHF manifestations in patients of both groups was carried out according to the New York classification based on the results of the 6-minute walk test. The distribution into two groups was carried out according to the following parameters: the 1st group included 26 (56.5 %) patients (men – 19 [73.1 %], women – 7 [26.9 %]), who, along with basic therapy, received Thiotriazoline at a dose of 8.0 intravenously jet for 10 days; the 2nd (control) group included 22 (43.5 %) patients (men – 14 [63.6 %], women – 8 [36.4 %]) who received standard therapy (β-blockers, angiotensin-converting enzyme inhibitors, calcium antagonists, nitrates). Distribution by class of CHF at the time of inclusion in the study was observed in 1st group in 21 (80.7 %) patients: I functional class (FC) – 2 (9.5 %), II FC – 11 (52.4 %), III FC – 6 (28.6 %) and IV FC – 2 (9.5 %). In 2nd group – (77.3 %) patients: I FC – 3 (17.6 %), II FC – 6 (35.3 %), III FC – 7 (41.2 %) and IV FC – 1 (5.9 %) patients. According to the Minnesota questionnaire in group 1, the quality of life indicators (average value in points) were 71.1±1.8 points (p&lt;0.05). The 2nd group had 67.9±1.9 points (p&lt;0.05).&#x0D; Results and discussion. Positive hemodynamics and assessment of CHF manifestations by FC served as a clear statement of improvement in the quality of life. In the group receiving Thiotriazoline, the number of patients with II FC increased from 11 (42.3 %) to 14 (54 %), I FC – from 2 (9.5 %) to 6 (23 %) compared to the initial data due to patients from III FC and IV FC. The number of patients with III FC decreased to 2 (7.8 %) and IV FC – to 1 (3.8 %), and in the control group there was a slight negative dynamic (III FC – to 2 (9.5 %) and IV FC – without changes). The quality of life according to the Minnesota questionnaire indicated a positive trend. In group 1, the quality of life indicators improved from 71.1±1.8 to 53.3±0.6 points (p&lt;0.01); in group 2 – from 67.9±1.9 to 63.3±1.9 points (p&lt;0.05).&#x0D; Conclusions. Thiotriazoline is a cytoprotector of the highest class, in particular, a myocardoprotector, which, when used (from 10 days in a hospital and then up to 1 month), improves the metabolism of the heart muscle, stabilizing intracellular mechanisms. Thiotriazoline is indicated for all patients with IHD who have suffered a myocardial infarction in the early stages of CHF.

Выбор тактики экспериментальной терапии хронической сердечной недостаточности соединением АЛМ-802

The cardioprotective activity of ALM-802 compound was demonstrated in model experiments simulating postinfarction chronic heart failure in rats forming in 90 days after anterior transmural myocardial infarction. ALM-802 decreased the left ventricle and improved its inotropic function (p=0.038). This effect was observed in case of systematic administration of ALM-802 over 28 days (starting from day 91 after infarction modeling). This is apparently the minimum time for the cardioprotective effect of ALM-802 to prevent or treat the resulting heart failure, because short-term systematic therapy (15 days) produced no positive effect.

Endothelial function, systemic inflammation and cardiac hemodynamics in different age patients with post infarction chronic heart failure.

Endothelial function, systemic inflammation and cardiac hemodynamics in different age patients with post infarction chronic heart failure.

Effect of Tivorel on the level of matrix metalloproteinases-2 and 9, galectin-3, final glycation products and functional state of the endothelium in patients with postinfarction chronic heart failure with preserved ejection fraction

The objective: to evaluate the effect of Tivor-L (20 mg levocarnitine + 42 mg arginine hydrochloride, Yuriya-Pharm) on AGEs, galectin-3, MMP-2,9 serum level, cardiac haemodynamics and endothelial function in patients with post infarction HFpEF.Materials and methods. All individuals (35) included aged 40 to 80 years, 23 (66%) males and 12 (34%) females were diagnosed with (HFpEF) according to ESC guidelines (2016). First (1-st ) group (n=15) pts with postinfarction HFpEF treated with Tivor-L in addition to standard treatment for Chronic heart failure (CHF). Second (2nd) group (n=20) – pts with postinfarction HFpEF with standard treatment for CHF without Tivor-L. All the patients included in 1st group got Tivor-L intravenously daily for 10 days in addition to the conventional therapy. General biochemical blood analysis, complete blood count and glomerular filtration rate, MMP-2, MMP-9, galectin-3 and AGEs serum levels were determined before and after treatment.Results. Mean galectin-3 level in 1st was decreased by 16.4 % on the whole (p&lt;0,05), in compare with standard therapy – no significant changes (p&gt;0,05). significant decreasing of MMP-2, MMP-9 levels on 41% and 78,5% in 1st group (p&lt;0,05). The FMD level was significantly higher in 1st group than in standard therapy group (p&lt;0,05). Endothelial function normalizing was achieved in 10 (66%) of 1st group patients.Conclusion. Most of the pts with postinfarction HFpEF have increased AGEs serum level, and endothelial dysfunction. There were a significant decrease in galectin-3 and MMP-2, MMP-9 serum levels after adding of Tivor-L to the conventional treatment for chronic heart failure.

Endothelial function, systemic inflammation and cardiac hemodynamics in different age patients with post infarction chronic heart failure.

Heart failure (HF) is a major cause of morbidity and mortality. After myocardial infarction, physiological and anatomical ventricular changes occur, There is also an inflammatory reaction with release of cytokines, growth factors and reactive oxygen species production, which contributes to perpetuate ventricular dysfunction. The study was designed to evaluate the level of inflammatory markers (white blood cells and C-reactive protein), endothelial function and cardiac hemodynamic in different age patients with post infarction heart failure. We divided 45 patients with HF with preserved ejection fraction (HFpEF) with mean age 67,5 [65,5; 71,7] years into two main groups. 1st group: 25 patients with HFpEF and history of myocardial infarction. 2nd group: 20 patients with HFpEF and stable angina (without myocardial infarction in anamnesis). Standard laboratory blood tests for erythrocyte sedimentation rate, C-reactive protein, haematological parameters, lipid profile, glucose, renal and liver function tests, echocardiographic examination, endothelial function estimation were performed. Patients with a history of myocardial infarction had significantly higher levels of left ventricle end diastolic volume, left ventricle end systolic dimension (p&lt;0.05). There was estimated direct correlation between LVEDV, LVESD and age - R=0.68 (p&lt;0.05), R=0.52 (p&lt;0.05). Further analysis of cardiac hemodynamics depending on age revealed significant differences between LVEDV indices in patients with myocardial infarction. A significantly higher level of leukocytes was found in patients with HFpEF with a history of myocardial infarction in both groups (p&lt;0.05). A direct correlation between the leukocyte count and age in patients with HFpEF-R = 0.48 (p&lt; 0.05) was also found. Patients with HFpEF with a history of myocardial infarction had a significantly higher level of CRP, including in the age aspect (p&lt;0.05). A direct correlation between CRP level and age was established in patients with HFpEF - R=0.46 (p&lt;0.05). It was revealed that in the older age groups with myocardial infarction the signs of endothelial dysfunction were significantly more frequent (p&lt;0.05). Reverse correlations were established between the level of endothelium dependent vasodilatation (ESVD) and CRP (R=-0.48, p&lt;0.05), triglycerides (R=-0.45, p&lt;0.05), diastolic blood pressure (R=-0.54, p&lt;0.05). Conclusion: high level of inflammation markers, endothelial dysfunction and changes in cardiac hemodynamics were recorded more often in elderly patients with post infarction heart failure.

Role of KATP Channels in Beneficial Effects of Exercise in Ischemic Heart Failure.

Exercise training reduces pathological remodeling and improves cardiac function in ischemic heart failure; however, causal mechanisms underlying the cardiac benefits of exercise are poorly understood. Because opening of adenosine triphosphate (ATP)-sensitive K ⁺(KATP) channels protects the heart during myocardial stress, we hypothesized that such a mechanism is responsible for some of the cardiac benefits induced by exercise in postinfarction chronic heart failure (CHF). Left ventricular myocytes were isolated from three groups of rats: Sham, CHF Tr (4 wk after myocardial infarction, rats underwent 8 wk of aerobic interval training 5 d·wk⁻¹) and CHF Sed (rats sedentary for 12 wk after infarction). Cardiomyocyte survival after oxidative stress exposure (200 μM H2O2) and calcium handling (cells loaded with Fura-2 AM and electrically paced at 1 Hz) were assessed in the presence of KATP channel inhibitor glibenclamide. Expression of KATP subunits (SUR2A and Kir6.2) was evaluated using immunoblotting. Exercise improved cardiac function in CHF Tr animals. Cardiomyocytes from CHF Sed rats were more susceptible to oxidative stress-induced cell death than CHF Tr and Sham cardiomyocytes, with glibenclamide completely abolishing the protective effect of exercise. Glibenclamide did not affect cardiomyocyte survival in Sham or CHF Sed rats. In addition, exercise increased the systolic Ca²⁺ transient amplitude and improved diastolic Ca²⁺ removal in CHF Tr cardiomyocytes (compared with CHF Sed); both were significantly attenuated by glibenclamide. Exercise resulted in increased expression of KATP channel subunits in CHF Tr hearts, with more pronounced and significant effect on SUR2A. Our data suggest that KATP channel upregulation induced by chronic exercise likely mediates some of exercise-induced beneficial effects on cardiac function in postischemic heart failure.

Improved outcome with repeated intracoronary injection of bone marrow-derived cells within a registry: rationale for the randomized outcome trial REPEAT.

Regenerative therapies have evolved as a promising new option in the treatment of post-infarction heart failure. A major limitation of intracoronary application of autologous bone marrow-derived mononuclear cells (BM-MNCs) is that homing of the applied cells is profoundly reduced in patients with post-infarction heart failure compared with patients with acute myocardial infarction. However, early pilot and also randomized controlled trials have demonstrated significant improvements in overall cardiac function. The aim of the present analysis was to quantify a potential mortality risk reduction and reduced hospitalization in order to provide data for a prospective outcome trial. The results of an ongoing single-centre registry including 297 post-infarction heart failure patients suggest that repeated intracoronary application of autologous bone marrow-derived cells is associated with a significant better 2-year survival compared with a single BM-MNC application (2-year survival 93.6 vs. 84.0%, P = 0.03). Likewise, mortality is significantly lower at 2-year follow-up compared with the mortality estimated by the use of the Seattle Heart Failure Model (SHFM) in patients receiving repeated BM-MNC application (observed mortality 6.4%, predicted mortality 16.2%, P = 0.02). Although the trend persisted at 3-year follow-up, the mortality reduction was no longer statistically significant between single and repeated treatment (mortality 21.9 vs. 13.7%, P = 0.06). Repeated intracoronary administration of BM-MNC appears to be associated with improved clinical outcome compared with single treatment at 2 years. This registry provides the rationale for the design of the multicentre randomized, controlled, open-label REPEAT trial, which prospectively compares the effects of single vs. repeated intracoronary application of autologous BM-MNC on total and SHFM-predicted mortality in patients with chronic post-infarction heart failure.