Current Trends and Possibilities of Providing Medical Palliative Care in Chronic Heart Failure.

Chronic heart failure (CHF) is an important healthcare problem because of high prevalence, morbidity and mortality rates. Treatment resistant symptoms, need for communication and support, unite patients with CHF and oncological diseases but despite that CHF patients rarely receive specialized palliative care (SPC). This review is devoted to the need and possible ways of providing SPC to patients with CHF and their families. We discuss here variants of CHF course in terminal phase, the term end of life appropriate care, various specialists' concepts of SPC delivering to CHF patients in accordance with their preferences.

[Specific Features of Pharmacotherapy of Patients With Chronic Heart Failure and Preserved Left Ventricular Ejection Fraction].

The review is devoted to pharmacotherapy of chronic heart failure (CHF) with preserved left ventricular ejection fraction. In this review we discuss data of meta-analyzes of randomized clinical trials and observational studies, as well as the indications for use of inhibitors of the renin-angiotensin-aldosterone system, ß-blockers, and antagonists of mineralocorticoid receptors in these patients in current clinical guidelines. New approaches to therapy of CHF from the perspective of influence on myocardial fibrosis are considered in this review.

Bendopnea: Association With Echocardiographic Features and Clinical Outcomes in Elderly Patients With Chronic Heart Failure.

AIM: to assess the prevalence of bendopnea and association of this symptom with clinical, laboratory and echocardiographic features, clinical outcomes during 2 years of follow-up in ambulatory elderly patients with chronic heart failure (CHF). MATERIALS AND METHODS: We conducted an open, prospective, non-randomized study of 80 ambulatory patients aged ≥60 years admitted with heart failure II-IV NYHA class CHF. Baseline survey included physical examination, estimation of Charlson comorbidity index, echocardiography and laboratory tests. Bendopnea was considered when shortness of breath occurred within 30 sec of sitting on a chair and bending forward. Mean follow-up was 26.6±11.0 months. RESULTS: Bendopnea was present in 38.8 % patients. All these patients complained of shortness of breath during physical exertion and 45.2 % of them had orthopnea.  Bendopnea was associated with the male gender (odds ratio [OR] 11.8, 95 % confidence interval [CI] 4.04-34.8, p<0.001), severity of the clinical status (ШОКС [shocks] scale score)  (OR 1.78, 95 % CI 1.29-2.38, p<0.001), Charlson comorbidity index (OR 1.29, 95 % CI 1.07-1.52, p=0.007), coronary heart disease (OR 26.6, 95 % CI 3.34-21.3, p=0.002), history of myocardial infarction (OR 13.9, 95 % CI 4.2-46.6, p<0.001), left ventricular (LV) aneurysm (OR 13.3, 95 % CI 2.69-65.9, p=0.002), increased indexed LV end-systolic diameter (OR 8.2, 95 % CI 1.9-34.1, p=0.004), left atrial size (OR 4.3, 95 % CI 1,4-12.5, p=0.008), indexed LV end-systolic volume (OR 1.32, 95 % CI 1.07-1.64, p=0.010), pulmonary artery systolic pressure (OR 1.26, 95 % 1.03-1.45, p=0.002), high levels of NT-proBNP (OR 1.0, 95 % CI 1.0-1.002, p=0.055), creatinine (OR 1.04, 95 % CI 1.02-1.07, p=0.001), uric acid (OR 1.006, 95 % CI 1.002-1.011, p=0.004); hospitalizations (OR 7.61, 95 % 2.04-28.4, p=0.003), and patient's mortality (OR 5.63, 95 % CI 1.94-16.4, p=0.001). Multifactorial analysis confirmed association of bendopnea with severity of clinical status (OR 1.70, 95 % CI 1.04-2.8, p=0.033), increased left atrial size (OR 5.67, 95 % CI 2.75-21.32, p=0.029) and Charlson comorbidity index (OR 1.17, 95 % CI 1.04-2.80, p=0.050). During follow-up 51.6 and 12.2 % of patients died among those with and without bendopnea, respectively (OR 4.22, 95 % CI 1.85-9.9, p<0.001). CONCLUSION: Bendopnea is associated with an adverse hemodynamic profile and prognosis, what allows to consider this symptom as a reliable marker of CHF severity.

[Evaluation of inflammatory and endothelial dysfunction's biomarkers in patients with hypertension at achieving the target blood pressure.]

The target organs damage in hypertension is mainly realized through an endothelial dysfunction. The present study investigated the inflammatory and endothelial dysfunction's biomarkers in patients with hypertension before and after the achieving the target level of blood pressure. We've performed clinical and laboratory study of 44 patients (17 men, 27 women, mean age 58.59 ± 10.57 years) with the hypertension stage II, degrees2-3, high and very high risk of cardiovascular complications, not reaching the target level of blood pressure at the previous therapy. All patients received standardized therapy with a fixed combination of amlodipine / indapamide / perindopril in an individually selected dosage. The duration of the follow-up was 6 months. The levels of pro-inflammatory interleukin-6 (IL-6), anti-inflammatory interleukin-10 (IL-10), vascular cell adhesion molecule-1 (sVCAM-1) and vasculoendothelial growth factor (VEGF) were measured. All patients achieved the target blood pressure level at the end of the study (systolic blood pressure was 125.1 ± 6.9 mm Hg, diastolic - 82.2 ± 5 mm Hg, p < 0.001). After 6 months, there was no significant dynamics of inflammatory biomarkers. The level of sVCAM-1, as an indicator of endothelial dysfunction, decreased (898.67 ± 433.5 ng / ml vs. 1063.5 ± 442.4 ng / ml at the start of treatment, p < 0.001). Thus, it is possible to use vascular cell adhesion molecule-1 as a biomarker of endothelial dysfunction in patients with hypertension. Adequate therapy of hypertension with achievement of target blood pressure levels improves vascular endothelial function, significantly reducing sVCAM-1 expression.

[Study of cytokine profile in men with hypertension.]

Gender differences in the risk factors' influence on the development of cardiovascular diseases determine the study of the pathogenetic causes of these features. Inflammatory is one of the mechanisms for the participation of risk factors in the development of hypertension. The aim of the study was to investigate the relationship between inflammatory biomarkers with hypertension and cardiovascular risk factors in men. The study included 60 men with hypertension who were divided into groups depending on the risk of cardiovascular events: 30 men with low risk and 30 men with high risk. 86 hypertensive patients with risk factors such as obesity, impaired glucose metabolism, impaired lipid metabolism also were examined. Biochemical parameters and a wide range of cytokines: IL-4, IL - 8, IL-10, IL-12, IL-17, IL-18, TGF-ß, TNF-α, IFN-γ were estimated. The obtained results were compared with echocardiographic (EchoCG), ambulatory blood pressure monitoring (ABPM), duplex scanning of the carotid arteries. A direct correlation between the risk factors and target organs' damage - left ventricular hypertrophy, increased intima-media complex thickness, was revealed. The dependence of cytokine profile from risk of cardiovascular events in men was also revealed. We studied the contribution of individual risk factors in men in the development of hypertension and the severity of inflammation. More significant changes in the cytokine profile observed in patients with concomitant hyperglycemia, obesity and dyslipidemia. A correlation between cytokine profile and duration of hypertension also revealed. Correlation analysis revealed the relationship between ABPM parameters and levels of interleukins, HS-CRP, and fibrinogen. Biomarkers of inflammation associated with the severity of visceral obesity, with a BMI. Analysis of results also showed the relationship between hyperinsulinemia or insulin resistance and inflammatory biomarkers. The relationship of inflammation with lipid metabolism in hypertensive men was more significant than with the other studied risk factors.

[Study of heat shock protein gene 70 (HSP70) expression and its polymorphous marker (+ 1267A> G) in women under exposure to a long-term stress.]

There was studied the HSP70 gene and its polymorphic marker + 1267A> G (rs754888705) in the HSP70 gene expression in32 women under long-term stress, which was caused by inpatient treatment of their oncologic child. A control group included 25 women without long-term stress factors. There was studied a correlation between the expression level of the HSP70 gene in women and their high blood pressure (BP) episodes. The average duration of stress in the group of children's mothers was 7.3 (2.5-11.5) months. Anxiety level according to HADS in the main group was significantly increased and amounted to 8.7 (7-10) points, in the control group 5 (2-7) points. Depression level in the main group was significantly higher and amounted to 7.7 (7-9) points, in the control group 3.3 (1-5) points. Comparison of the HSP70 gene expression level in blood of young women of the main study group with expression level of this gene in the control group showed a statistically significant predominance of HSP70 gene expression in the main group. The episodes of high BP in women who were under stress conditions did not influence the expression level of the HSP70 gene. Analysis of the alleles of the polymorphic marker frequency in the gene HSP70-2 1267A> G (rs754888705) in the main and control groups showed a statistically significant predominance of allele A in the group of mothers under stress, and predominance of the allele G in the control group. Comparative analysis of the polymorphic marker genotype frequencies in the gene HSP70-2 1267A> G (rs754888705) showed that the AA genotype is significantly more frequent in mothers with episodes of BP increase compared to women without it. An increased level of the HSP70 gene expression in peripheral blood leukocytes in mothers with a life-threatening disease of their child indicates the damaging effect of long-lasting psychoemotional stress at the cellular level and activation of the protective reaction mediated by HSP70. Studying of the genotype AA characteristics of the polymorphic marker A1267G (rs754888705) of the HSP70-2 gene in women under long-lasting stress will let us evaluate the role of genetic factors in hypertensive reactions development.

[Medication Adherence of Elderly Patients With Chronic Heart Failure].

The review is devoted to the problem of medication adherence in elderly patients with chronic heart failure. We consider here specificity of approach to management of elderly outpatients, groups of factors associated with medication adherence, and possible ways to improvement of compliance to treatment in patients from the senior age group with heart failure.

[Risk of Cardiovascular Complications and Geriatric Syndromes Among Elderly Women].

AIM: to assess the prevalence of some geriatric syndromes and their association with high risk of cardiovascular complications (RCVC) among elderly women. MATERIAL AND METHODS: We examined 72 women aged 69-77 years with cardiovascular diseases. Examination included laboratory and echocardiography assessment, dual-energy X-ray absorptiometry, 6-min walk test, assessment of psycho-emotional status using Mini-mental State Examination (MMSE) questionnaire. Frailty was defined as three or more of the following: weight loss, low physical activity levels, MMSE less or equal 23 points, weakness (chair stand test>10 sec), history of multiple falls. Follow up was 7.3 (5.5-7.8) months. RESULTS: High CVR was found in 70.8% women: in 59.1% women aged 65-74 years and in 89.3% - aged more or equal 75 years, =0.006. Osteoporosis (OP) was found in 51.3% women aged 65-74 and in 90.5% - aged more or equal 75 years, =0.024; MMSE was 27 (24-28) vs 24 (20-26) points, respectively, =0.008. The geriatric syndrome of frailty was found in 13.6% women aged 65-74 and in 64.3% - aged more or equal 75 years. Frailty was associated with high CVR (odds ratio [R] 7.2, 95% confidence interval [CI] 1.5-34.2, =0.013), chronic kidney disease (CKD, R 18.9, 95%CI 5.2-20.2, <0.001), P (R 4.5, 95%CI 1.3-15.8, =0.019), history of myocardial infarction (MI, R 6.8, 95%CI 2.2-20.8, =0.001), greater age (R 6.0, 95%CI 2.1-17.5, =0.001). CONCLUSION: High CVR was prevalent among greater age women what could be explained by prevalence of chronic heart failure, atrial fibrillation, CKD. Prevalence of frailty was 13.6 and 64.3% among women aged 65-74 and more or equal 75years, respectively. It was significantly associated with high CVR, OP, PMI, CKD.

[Inflammatory reactions in patients suffering from coronary artery disease with concomitant obesity and type 2 diabetes mellitus].

Of late, inflammatory reactions have been considered to play an important part in the development of atherosclerosis. Acute-phase inflammatory reaction, being initially a protective response directed within the homeostasis system towards lesion repair, may by itself due to various factors favor the development of pathological processes. Considering the role played by inflammation in the development of atherosclerosis, and inflammatory activity in obesity and diabetes mellitus (DM), a range of common and interrelated elements of these processes may be marked out. These are acute phase proteins and cytokines. Insulinoresistance, being the common precursor of obesity and DM, plays the key role in vascular lesion. The use of cytokine activity index seems to be a promising method of revealing patients with high risk of atherosclerosis.

[The stress-modulating effects of laser therapy in IHD patients]. / Stress-moduliruiushchie éffekty lazeroterapii u bol'nykh IBS.

Dependence of the response to helium-neon laser therapy (LT) on initial level and changes of blood plasma hydrocortisone (HC), testosterone (T), diene conjugates (DC) concentration, general antioxidant activity (AOA) of blood plasma, TxB and 6-keto-PGF were estimated in 147 patients with ischemic heart disease and stable angina. The response to LT was observed in patients with high levels of HC, T, AOA and 6-keto-PGF1 alpha. A significant increase of DC was noted in these patients too. The minimal level of HC. T and AOA was recorded in patients with negative clinical effect. The treatment only aggravated HC, T and AOA deficiency and raised DC and TxB level. The findings suggest that the effect of LT is based on modulation of nonspecific adaptive mechanisms.

[Clinical and prognostic value of monitoring the acute phase protein levels in patients with myocardial infarction]. / KLiniko-prognosticheskaia znachimost' monitorirovaniia belkov ostroi fazy u bol'nykh infarktom miokarda.

The value of evaluating the protein levels at the acute stage was examined to define the clinical course and prognosis of myocardial infarction. The time course of hospital myocardial infarction was studied in 117 patients. The Manchini radial immunodiffusion with reference monospecific antisera was employed to determine individual proteins during the acute stage (orosomucoid, C-reactive protein, alpha 1-antitrypsin, C3 complement, ceruloplasmin). The level of circulating immune complexes was measured by polyethylene glycol precipitation. There was a close correlation between the circulating immune complex levels and some acute phase parameters, suggesting the relationship between immune and inflammatory processes. The changes in the magnitude of some acute phase parameters and circulating immune complexes were found to be significant in predicting the development of complications and the fatal outcome of the disease.

[Changes in the superoxide dismutase activity during stimulation of polymorphonuclear leukocytes of peripheral blood]. / Izmenenie aktivnosti superoksiddismutazy v protsesse stimuliatsii polimorfnoiadernykh leikotsitov perifericheskoi krovi.

The functional activity of the peripheral blood polymorphonuclear leukocytes (PML) was investigated by using the method of latex-stimulated luminol-dependent chemiluminescence (CL). The CL-intensity of PML taken from patients with acute myocardial infarction (MI) was found to be 20 times higher than that of normal individuals (NI). The change in activity of endogenous antioxidative enzyme systems may account for alteration of PML CL-parameters. It was established that the initial superoxide dismutase (SOD) activity of unstimulated PML from patients with MI exceeds that of NI, and that rapid increase in intercellular SOD activity (within 30 sec.) occurs in the process of PML stimulation. It was suggested that the change of SOD activity during PML stimulation was the result in the enzyme partial proteolysis in the cells. The positive correlation between initial level of SOD activity and CL-intensity of PML was observed. The investigation of the above parameters in MI dynamic showed a gradual normalization of PML CL-response and insignificant decrease in intracellular SOD activity in case of a favourable cause of the disease. Increased SOD activity in PMLs may be one of the factors contributing to a decrease in PML functional activity in the disease dynamic.

[Characteristics of immune complexes in myocardial infarct]. / Osobennosti immunokompleksnogo protsessa pri infarkte miokarda.

Nonspecific circulating immune complexes (CIC), different in size and stability, are detectable in the blood sera of patients with myocardial infarction; changed concentration of these complexes appears to be a reflection of the defense response of the body, aimed at homeostasis maintenance. No relationship between cardiac glycosides and CIC levels was revealed in patients with myocardial infarction. A reduction of the level of 'large' CICs by days 21-30 of the condition was observed in the patients treated with anticoagulants from the first day of the disease. A low CIC level in the acute period of the disease is a prognostically unfavorable sign in respect of the outcome of the condition.

[Effects of low-intensity laser irradiation on the functional activity of leukocytes and blood antioxidant system in acute myocardial infarction]. / Vliianie nizkointensivnogo lazernogo izlucheniia na funktsional'nuiu aktivnost' leikotsitov i antioksidantnuiu sistemu plazmy krovi pri ostrom infarkte miokarda.

Activation of lipid peroxidation and inadequate antioxidant activity essentially contribute to the pathogenesis of acute myocardial infarction, this fact dictating the necessity of correcting these processes. High efficacy of of He-Ne laser therapy was demonstrated in the treatment of 92 patients with myocardial infarction in the acute and subacute periods. This treatment modality corrected lipid peroxidation parameters, which fact manifested by reduction of leukocytic functional activity and elevation of blood plasma antioxidant characteristics.

[Informative value of immunologic indicators at different periods of acute myocardial infarction]. / Informativnos't immunologicheskikh pokazatelei v razlichnye sroki ostrogo infarkta miokarda.

To elucidate the mechanisms responsible for reorganization in the immune system in patients in the acute period of myocardial parameters for immune status were examined in 40 patients with acute myocardial infarction. The findings were processed by statistic methods of factor analysis. The value of factor exercise with the same parameters varied with the period of the disease. On the first day of myocardial infarction, immune complex concentrations were found to be mostly affected by this process. On day 7, chemiluminescence underwent changes, so did circulating antibody titers on day 30. Evidently, it is advisable to bear in mind the aforementioned relationships while studying the effect of immune responses on the course and prognosis of myocardial infarction.