[Cardiac Dysfunction and Arterial Hypertension as Manifestations of Cardiovasculotoxicity of iVEGF-Containing Chemotherapy. Clinical Case].

Significant advances in timely diagnosis and modern antitumor therapy have led to a considerable increase in the survival rate of cancer patients. On the other hand, the incidence of cardiovascular (CV) diseases and their complications is increasingly growing, including due to side effects of anticancer drugs. CV complications are the most common cause of non-oncological death of cancer patients. The development of polychemotherapy-induced arterial hypertension (AH) is closely associated with the use of certain groups of drugs, for example, inhibitors of vascular endothelial growth factor (iVEGF). Such AH is generally dose-dependent and reversible after interruption or termination of treatment. However, systemic AH, regardless of its genesis, is one of the key risk factors for many CV events (myocardial infarction, stroke, heart failure, arrhythmias) and kidney disease. Therefore, thorough blood pressure monitoring and its timely and adequate correction if needed are indicated when using certain groups of chemotherapy drugs. This article describes a clinical follow-up of a patient with induced AH associated with the iVEGF antitumor therapy for advanced uterine cancer with a rapid development of left ventricular myocardial dysfunction.

[Assessment of systemic inflammation activity, myocardial structure and functional features, their relationship in patients with multiple myeloma, receiving bortezomib therapy].

AIM: To study the dynamics of calculated indices [neutrophil-lymphocyte ratio (NLR); systemic inflammation index (SIV)] and biomarkers of systemic inflammation [interleukin-1ß (IL-1ß); high-sensitivity C-reactive protein (hsCRP)], parameters of the structure-and-function state of the myocardium and intracardiac hemodynamics, and their relationship in patients newly diagnosed with multiple myeloma (MM) at the onset of the disease and after 6 courses of chemotherapy (CT) containing the proteasome inhibitor bortezomib. MATERIAL AND METHODS: This prospective study included 30 patients aged 63.8±10.0 years diagnosed with MM; 17 (56.7 %) of them were men. The following tests were performed for all patients: measurement of IL-1ß and hsCRP, calculation of the inflammation indexes NLR and SIV, transthoracic echocardiography before and after 6 courses of bortezomib-containing CT. At the time of study completion, 9 patients dropped out due to reasons not related to cardiovascular complications of CT. RESULTS: The antitumor therapy was associated with increases of immune-inflammation indexes: NLR increased from 1.54 [1.02; 1.83] to 2.9 [1.9; 4.35] (p=0.009) and SIV increased from 402.95 [230.5; 534.0] to 1102.2 [453.1; 1307.9] (р=0.014). IL-1ß increased from 5.15 [4.05; 5.77] to 6.22 [5.66; 6.52] pg/ml remaining within the reference range (p=0.142) whereas hsCRP decreased from 1.02 [0.02; 2.71] to 0.02 [0.02; 0.82] IU/l (p=0.138). Statistically significant changes in parameters of heart remodeling and clinical picture of cardiovascular complications were not observed. A correlation analysis showed significant inverse correlations of hsCRP with left ventricular ejection fraction (LV EF) (r= -0.557; p=0.003), the number of plasma cells (PC) with LV EF (r= -0.443; p=0.023), and a direct correlation of the number of PC with hsCRP (r=0.433; p=0.022). CONCLUSION: During the study, the accepted criteria for cardiotoxicity of bortezomib-containing chemotherapy in patients with MM, were not met. The identified correlations between the level of markers for acute inflammation, indexes of intracardiac hemodynamics, and the immediate MM substrate may indicate the role of chronic low-intensity inflammation in the pathogenesis of myocardial remodeling in patients with MM. This necessitates further studies on larger samples of patients to assess the prognostic significance.

Cardio-oncology today: digest of the first European clinical guidelines (2022).

Over the past few decades, due to the extensive implementation of cancer screening programs, up-to-date early diagnostic methods, and effective combinations of antitumor therapy, it has become possible to significantly improve survival of cancer patients. At the same time, despite the effective treatment of malignancies, most patient face adverse and often life-threatening effects of specific treatment on the heart and blood vessels. All this resulted in active development of a new field in cardiology, cardio-oncology. In recent years, based on the experience of leading experts, data from large studies, and meta-analyses, both international and Russian Consensuses, conciliation documents, have been formed and published. These documents regulate principal methodological approaches to management and control of the cardiovascular conditions in cancer patients. Finally, 2022 was marked by issuing the first official European Guidelines on Cardio-Oncology in the history of medicine. This article highlights the most relevant, in our opinion, positions of these guidelines as well as controversial and unresolved issues.

Relationship Between Markers of the Acute Phase of Inflammation, Parameters of Blood Lipid Composition and Intracardiac Hemodynamics During Chemotherapy in Patients With Multiple Myeloma.

Aim      To evaluate in a pilot study time-related changes in the clinical state, indexes of the acute phase of inflammation, parameters of blood lipid profile, intracardiac hemodynamics, and disorders of cardiac rhythm/conduction in patients who are not candidates for autologous hemopoietic stem cell transplantation, during three bortezomib-containing chemotherapy courses (VCD) followed by a correlation analysis.Material and methods  This pilot study included 20 patients diagnosed with myeloma, who were not candidates for autologous hemopoietic stem cell transplantation and who had undergone three courses of VCD chemotherapy (bortezomib, cyclophosphamide and dexamethasone). In addition to mandatory examinations, measurement of blood lipid profile, transthoracic echocardiography (EchoCG), and 24-h Holter electrocardiogram (ECG) monitoring were performed for all participants before and after a specific therapy.Results Following three bortezomib-containing courses of chemotherapy, patients of the study group had significant increases in the neutrophil-lymphocyte ratio (NLR) (1.6±0.2 and 2.5±0.4; р=0.05), cholesterol concentration (4.8±1.1 and 5.6±1.1 mmol/l, р=0.05), and low-density lipoprotein concentration (2.8±0.4 and 3.5±0.8 mmol/l, р=0.02). In comparing the changes in parameters of intracardiac hemodynamics, criteria for genuine cardiotoxicity were not met, however, a tendency to emergence/progression of myocardial diastolic dysfunction was noted. No clinically significant disorders of cardiac rhythm/conduction were observed. The correlation analysis performed prior to the start of chemotherapy, showed significant strong, direct correlations between the C-protein concentration and left atrial (LA) volume (r=0.793; p=0.006), right atrial (RA) volume (r=0.857; p=0.002), left ventricular (LV) end-diastolic dimension (EDD) (r=0.589; p=0.043), and LV end-diastolic volume (EDV) (r=0.726; p=0.017). Following the specific treatment, significant, medium-power and strong correlations were found between NLR and EDV (r= -0.673; p=0.033), NLR and end systolic volume (ESV) (r= -0.710; p=0.021), respectively. Significant direct correlations were found between the bortezomib dose per one injection and the serum concentration of triglycerides following the treatment (r=0.78; p=0.05); a single bortezomib dose and parameters of intracardiac hemodynamics: LA (r=0.71; p=0.026), RA (r=0.74; p=0.014), EDD (r=0.837; p=0.003), EDV (r=0.749; p=0.013), ESV (r=0.553; p=0.049).Conclusion      For the first time, a comprehensive evaluation was performed in patients with multiple myeloma, including the dynamics of blood lipid profile, intracardiac hemodynamics and disorders of cardiac rhythm/conduction during bortezomib-containing antitumor therapy, with an analysis of correlation with levels of acute inflammation phase markers. Although in the observation window for genuine cardiotoxicity, clinically significant cardiovascular complications were not detected, the found correlations may evidence a potential role of systemic inflammation activity in myocardial remodeling in the studied patient cohort.

Characteristic of cardiovascular status and intracardiac hemodynamics in patients with multiple myeloma before the start of antitumor therapy.

AIM: assessment of risk factors, cardiovascular status and intracardiac hemodynamics in patients with multiple myeloma before the start of specific antitumor therapy. Materials and methods: The study included 2 equal groups of patients: the first group - 25 patients with a newly diagnosed diagnosis of multiple myeloma (MM), the comparison group - 25 patients with proven cardiovascular diseases (CVD) (hypertension (HD) and coronary heart disease (CHD)). All patients included in the study underwent standard laboratory diagnostics, instrumental research methods (ECG, Echo-KG, 24-hour Holter monitoring); proven CVD risk factors were also evaluated. Results: When comparing the two groups, it was reliably shown that the state of CVD in patients with MM is comparable to that in patients with proven CVD. In patients from the main group, were revealed significant positive correlations of average strength between indicators of systemic inflammation, the lipid spectrum and intracardiac hemodynamics: between the levels of CRP and triglycerides (r=0,415, p<0,05); between the values of CRP and LDL (r=0,345, p=0,09); CRP and LA volume (r=0,434, p<0,05); CRP and final diastolic volume (r=0,30, p<0,05). At the beginning, a high risk of developing CV- events in patients with MM may be due to cardiac remodeling associated with the activity of systemic inflammation. CONCLUSION: in view the use of potentially cardiovasculartoxicity drugs for the treatment of multiple myeloma, the assessment of the CV status and consultation with a cardiologist/cardiologist with the selection of the necessary therapy should be obligatory step before starting specific treatment.

To study the dynamics of serum levels of vascular remodeling in patients with hypertension, including in combination with type 2 diabetes mellitus during 12­month therapy with perindopril A.

Aim      To study the dynamics of serum markers for vascular remodeling in patients with arterial hypertension (AH), including AH associated with type 2 diabetes mellitus (DM2) during the 12-month treatment with the angiotensin-converting enzyme (ACE) inhibitor, perindopril A.Material and methods  The study included patients with grade 1-2 AH with or without type 2 DM (30 and 32, respectively). Perindopril A 10 mg/day was administered for the outpatient correction of previous, ineffective antihypertensive therapy. The following biomarkers were measured for all patients at baseline and at 12 months: matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), E-selectin, endothelin 1, transforming growth factor ß-1 (TGF-ß1), and von Willebrand factor (WF). Laboratory tests were performed with enzyme immunoassay.Results After 12 months of the perindopril A (perindopril arginine) 10 mg/day treatment, both groups achieved the goal blood pressure. Evaluation of biomarker dynamics during the perindopril A treatment showed significant decreases in MMP-9, TIMP-1, and endothelin 1 in the AH group; then the level of TIMP-1 returned to normal values (р<0.05). In the AH+DM2 group, the MMP-9 concentration was significantly decreased (р<0.05); the other values did not show any significant differences. In both groups, MMP-9 was significantly decreased (28.6 % (р=0.01) in group 1 and 33.2 % (р=0.00) in group 2. Notably, in none of these groups, did this index reach normal values. Also, there were no significant differences in this index between the groups (р=0.66). It should be noted that the decreases in TIMP-1 were significantly different between the groups (р=0.001). Thus, this biomarker did not significantly decrease in patients with AH and DM2 (р=0.26) whereas in group 1 (AH without DM2), the level of TIMP-1 decreased by 39.3 % and reached the normal range (р=0.005).Conclusion      Concentrations of biomarkers were decreased in both groups. However, in the AH group, there were statistically significant decreases in the markers that reflect processes of fibrosis and vasoconstriction. At the same time in the AH+DM2 group, there was no significant dynamics of the biomarkers, which was most likely due to more pronounced damage of blood vessels. However, the decrease in MMP-9 may indicate an alleviation of fibrotic processes in arterial walls. These results allow a conclusion that the long-term treatment with the ACE inhibitor, perindopril A, may reverse remodeling of the vascular changes that are called "early vascular ageing".r aging".

Possible pathway for heart failure with preserved ejection fraction prevention and treatment: the angiotensin-converting enzyme inhibitor effect on endothelial function in comorbid patients.

Aim      To evaluate the effect of perindopril on the endothelial function and levels of endothelial dysfunction markers in groups of patients with heart failure with preserved (HFpEF) and mid-range (intermediate) left ventricular ejection fraction (HFmrEF).Material and methods  40 patients with HFpEF (n=20) and HFmrEF (n=20) were evaluated. At baseline, parameters of the morpho-functional state of large blood vessels and of microvessels were evaluated with photoplethysmography, and levels of E-selectin and endothelin-1 (ET-1) were measured. The patients were prescribed perindopril, and after 12 months of treatment, photoplethysmographic parameters and endothelial dysfunction markers were determined again.Results After 12 months of the perindopril treatment, improvements in the endothelial function of both large blood vessels and microvessels were noted. The phase shift increased from 10.1 to 10.9 ms in the HFpEF group (р=0.001) and from 8.35 to 9.65 ms in the HFmrEF group (р=0.002). Furthermore, the occlusion index increased from 1.45 to 1.75 in patients with HFpEF (р=0.004) and from 1.5 to 1.75 in patients with HFmrEF (р=0.010). The Е-selectin concentration decreased in both groups, from 57.25 to 42.4 ng/ml (р=0.00008) and from 40.5 to 35.7 ng/ml (р=0.010) in patients with HFpEF and HFmrEF, respectively. The ET-1 concentration decreased from pg/ml (р=0.010) in patients with HFpEF whereas in patients with HFmrEF, there was no significant change in the ET-1 concentration after 12 months of the perindopril treatment.Conclusion      At 12 months, the endothelial function improved and E-selectin and ET-1 levels decreased in patients with HFpEF and HFmrEF.

[Assessment of the Dynamics of Oxidative Stress Indicators and Early Markers of Myocardial Damage and Dysfunction in Patients with Aggressive Lymphoproliferative Diseases During of Anticancer Therapy].

Aim      To evaluate the dynamics of indexes of oxidative stress and markers of myocardial injury and dysfunction in patients with aggressive type lymphomas during the antitumor therapy.Material and methods  This study included 75 patients with lymphoproliferative diseases of aggressive type. The main group consisted of 53 patients who received one course of antitumor therapy during the study. The comparison group consisted of 22 patients who have not received any specific treatment so far. Troponin I (TnI), high-sensitivity troponin (hsTnI), heart-type fatty acid binding protein (Н-FAВР), N-terminal pro-brain natriuretic peptide (NT-prоBNP), superoxide dismutase (SOD), and myeloperoxidase (MPO) were measured in patients of both groups at baseline, and in the main group, they were measured at 4 hours after administration of antitumor agents and on completion of the course. Functional status of the cardiovascular system was evaluated by electrocardiography in all patients at baseline and after the course of antitumor treatment and by echocardiography.Results The chemotherapy was associated with increased levels of NT-prоBNP, SOD, and MPO (30.670±15.367 vs. 52.309±25.718 pmo l/l; 1.61±0.135 vs. 1.74±0.193 U/ml; and 507.54±91.51 vs. 742.3±49.01 ng/ml, respectively). The study results indicated activation of oxidative stress on the background of the administered antitumor therapy, progressive myocardial dysfunction, and increased frequency of arrhythmic episodes.Conclusion      The study results allowed identifying NT-prоBNP, MPO, and SOD as important indexes for determining a patient group at high risk of cardiotoxicity during the antitumor treatment.

[Positive Effects of Perindopril on Microvascular Vessels in Patients With Chronic Heart Failure].

Aim      To evaluate the effect of 12-month perindopril treatment on structure and function of microvasculature (MV) in patients with chronic heart failure with preserved (HFpEF) and intermediate (HFiEF) left ventricular ejection fraction.Material and methods  30 patients with HFpEF and HFiEF were evaluated. Perindopril at a maximum tolerated dose was administered to all patients for 12 months. Changes in MV structure and function were assessed with photoplethysmography and capillaroscopy prior to the treatment onset and at 12 months, i.e., after completion of the perindopril treatment.Results The 12-month perindopril treatment was associated with improvement of the endothelial function evident as increases in the occlusion index (OI) and the phase shift (PS). OI increased from 1.45 [1.3; 1.6] to 1.8 [1.6; 2.2] (p=0.00004). PS increased from 7.1 ms [4.8; 10.2] to 9.2 ms [6.7; 13.2] (p=0.0003). Stiffness of muscular large blood vessels was decreased. Arterial stiffness index (aSI) decreased from 8.8 [6.6; 11.0] to 7.45 [6.5; 9.4] m /s (р=0.01). The perindopril treatment was associated with increased density of the capillary network at rest (р=0.008) and in tests with venous occlusion (р=0.003) and reactive hyperemia (р=0.0003).Conclusion      The study showed an improvement of endothelial function associated with the 12-month perindopril therapy in patients with HFpEF and HFiEF.

[Vasculotoxicity of Chemotherapy: Assessment оf Endothelial Dysfunction Biomarkers' Levels in Gastric Cancer Patients].

Aim To evaluate dynamics of biomarkers for endothelial dysfunction (ED), including endothelin-1 (ET-1) and von Willebrand factor (VWF) in patients with stomach cancer (adenocarcinoma) before and after polychemotherapy (PCT); to compare these results with respective values in healthy volunteers and patients with cardiovascular diseases (CVD); to study correlations of the ED biomarkers with indexes of instrumental evaluation of endothelial dysfunction.Material and methods The study included 75 participants, including 25 healthy volunteers (control group), 25 patients with documented CVDs (arterial hypertension + ischemic heart disease), and 25 patients of the main group with histologically documented stage II-IV stomach cancer (adenocarcinoma) who received different courses of PCT with platinum-based agents (oxaliplatin, cisplatin) and fluoropyrimidines (5 fluorouracil, capecitabin). Laboratory measurement of ED biomarkers, computerized nailfold video capillaroscopy (CNVC), and finger laser photoplethysmography (PPG) (methods for noninvasive evaluation of vascular wall and ED), electrocardiography, 24-h ECG Holter monitoring, and echocardiography (EchoCG) were performed for all patients of the main group prior to PCT and within one months after the last course completion. This evaluation was performed once for healthy volunteers and patients of the CVD group upon inclusion into the study.Results In the main group, ET-1 levels were non-significantly lower than normal and did not change during the courses of antitumor treatment (0.95 [0.6; 1.4] and 0.94 [0.7; 1.4] pg /ml (р<0.9) before and after PCT, respectively). Statistically significant differences were found between the control group and oncological patients after the treatment (р<0.04). Levels of VWF remained within the normal range in all examined participants and did not significantly differ between study groups, including oncological patients before and after the specific treatment (р>0.05 for all comparisons). The correlation analysis detected significant correlations of ET-1 levels with functional disorders of microcirculation, ET-1 with the occlusion index (rs=0.56; p=0.005), ЕТ-1 with percentage of capillary restoration (PCR, rs= -0.72; p=0.018) and with the incidence rate of supraventricular extrasystole (rs=0.48; p=0.032).Conclusion The dynamics of ED biomarkers was studied for the first time in patients with stomach cancer receiving a specific antitumor therapy. Although no significant changes in ЕТ-1 and VWF were observed during the PCT (probably due to exhaustion of the endothelial system and a small patient sample), these indexes can be considered as early vasculotoxicity markers due to the presence of significant correlations with indexes of impaired endothelial function according to the results of instrumental evaluation.

[Metabolomic profiling in patients with metabolic syndrome].

OBJECTIVE: To identify biomarkers, which are most specific for patients with metabolic syndrome (MS) using metabolomic profiling. MATERIALS AND METHODS: Metabolomic profiling of patients with MS and comparison of their profile with the profile of volunteers was performed using high-performance liquid chromatography-mass-spectrometry. RESULTS: The metabolomic profile of MS patients differed in several amino acids, including choline, cysteine, and serine and in the acylcarnitine group (р<0.05 for all comparisons). CONCLUSION: The metabolites most specific for MS patients were identified. Increased concentrations of a combination of amino acids and carnitines can be considered as possible additional risk factors for cardiovascular diseases.

[The effect of chemotherapy on endothelial function and microcirculation in patients with gastric cancer].

OBJECTIVE: To evaluate and study the dynamics of endothelial dysfunction instrumental indicators, vascular wall stiffness and microcirculation state in patients with gastric cancer (adenocarcinoma) before and after chemotherapy; compare it with the results obtained from healthy volunteers and patients with cardio-vascular diseases. MATERIALS AND METHODS: The study included 65 people: 25 healthy volunteers, 15 patients with known cardio-vascular diseases (CVD) and 25 patients with histologically confirmed gastric cancer (adenocarcinoma) stage 2-4 who underwent surgical treatment followed by chemotherapy according to the FOLFOX, XELOX, and XP regimes. For non-invasive assessment of the vascular wall's state of large vessels and microcirculation, all patients in the main group underwent computer nailfold capillaroscopy and finger photoplethysmography before chemotherapy and within a month after the completion of the last course. For healthy volunteers and patients with CVD, the above studies were performed once during the examination. RESULTS: The data obtained indicate a significant increase in the reflection index of small muscle arteries (RI) and the stiffness index of large conducting arteries (aSI) during chemotherapy. In cancer patients, even before the treatment, endothelial dysfunction was detected, which significantly worsened after treatment (occlusion index (IO) before and after chemotherapy 1.7 (1.38; 1.9) vs. 1.3 (1.2; 1.5), p<0.0002, respectively). Significant differences in the compared indices in cancer patients and CVD group were revealed only after chemotherapy. Significant structural and functional disorders of capillaries were noted in the studied groups, which also worsened during chemotherapy in the main group (density of the capillary network at rest 43.23cap/mm2 vs. 42.19cap/mm2, p <0.01, respectively; density of the capillary network after the reactive hyperemia test 46.77cap/mm2 vs. 44.11cap/mm2, p<0,02, respectively). CONCLUSION: In this study, for the first time, the dynamics of endothelial dysfunction indicators, vascular wall stiffness and microcirculation state in patients with gastric cancer were studied, and a reliable increasing of these changes was proved during chemotherapy. The results indicate the need for a further search for accurate and effective methods of identifying early signs of close and distant vasculotoxicity, the development of individual prevention programs in order to significantly reduce the risk of cardiovascular events during and after chemotherapy.

[Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow].

Aim      To study changes in markers for myocardial direct injury and dysfunction and endothelial dysfunction (ED) indexes in patients with indolent lymphoma during the antitumor treatment.Material and methods  Current antitumor therapy for lymphoma is often associated with cardio- and vasculotoxicity, studying of which is a relevant scientific direction. Markers for myocardial direct injury and dysfunction and ED indexes were studied in patients with indolent lymphomas receiving polychemotherapy (PCT). The study included 77 patients with newly diagnosed indolent type lymphoma. The main group (n=52): mean age, 63.4±2.8 years, 15 (28.8 %) men who had received one course of PCT. The comparison group (n=25): mean age, 61.8±3.7 years, 8 (32 %) men who had not received PCT. Troponin I (TnI), high-sensitivity troponin I (hs-сTnI), heart-type fatty acid binding protein (h-FAВР), and N-terminal pro-B-type natriuretic peptide (NT-prоBNP) were measured in patients of both groups. ED was evaluated by measuring the level of vascular cell adhesion molecule (VCAM) and by assessing the structure and function condition of small blood vessels using photoplethysmography. In both groups, the study parameters were determined at the start of the study (T1) and following the PCT course in the main group; if the PCT schedule included anthracycline antibiotics, the second point (T2) was assessed at 6 h following the drug administration.Results In both groups, the level of NT-proBNP was increased. This increase was significantly more pronounced in the comparison group (49.896±23.228 vs 20.877±8.534 pmol/l, respectively, p=0.011) whereas a tendency to its increase was observed after the PCT course. Before the start of the treatment, laboratory and instrumental signs of ED were noticed: the level of VCAM was 4951±1297 and 3225±757 ng/ml in the comparison group and the main group, respectively (р=0.246); reflection index was <1.8 in 23 (44.2%) patients of the main group and in 16 (64%) patients of the comparison group (р=0.098). During the PTC course, the endothelial function significantly improved; the level of VCAM decreased by 748 ng/ml (p=0.016), which was associated with significant decreases in erythrocyte sedimentation rate by 2.71 mm/h (р=0.027) and lactate dehydrogenase level by 62.38 U/l (р=0.026). Statistically significant decreases in other inflammatory markers (alpha-2-globulin, fibrinogen, C-reactive protein, neutrophil count) were not observed.Conclusion      The level of NT-proBNP showed the highest sensitivity in assessing the cardiotoxic effect of PCT. The dynamics of VCAM level suggested a possible role of the disease itself in the development of ED in this patient group.

[The Use of Selective Inhibitor of If-Channels Ivabradine in Patients with Ischemic Heart Disease, Heart Failure with High Heart Rate].

Ischemic heart disease (IHD) and chronic heart failure (CHF) belong to leading causes of death among patients with cardiovascular diseases (CVD). Modern medical approaches to the treatment of patients with CHF do not always provide a significant improvement in the quality of life, a decrease in the frequency of CHF exacerbations and hospitalizations, and an improvement of the long-term prognosis. According to the neurohumoral theory of IHD and CHF development, the blockade of the sympathoadrenal system with ß-adrenoblockers (ß-AB) is pathogenetically substantiated, and preparations of this group are recommended as one of the main classes of drugs for the treatment of patients with CHF. However, selection of heart rhythm slowing therapy in patients with CHF of ischemic genesis is often difficult due to the development of undesirable side effects of ß-AB, intolerance and/or due to the presence of contraindications for their use. Randomized studies have shown that prescribing a combination of ß-AB and If-channel blocker ivabradine for heart rate (HR) reduction or solely ivabradine when use of ß-AB is impossible in complex CHF therapy, improves the left ventricle (LV) diastolic function, reducing mortality from CHF decompensation. However, the prognostic significance of the use of ivabradine in patients with CHF with preserved left ventricular ejection fraction of ischemic genesis with heart rate higher than 70 beats/min receiving maximum tolerated doses of ß-AB remains not fully investigated.

[Comorbidity of Chronic Obstructive Pulmonary Disease and Cardiovascular Diseases: Place of Therapy with Modern ß-Adrenoblockers].

Chronic obstructive pulmonary disease (COPD) is the fourth largest cause of worldwide mortality.  Presence of comorbidities is registered in 96% of COPD patients. The most important of these are cardiovascular diseases (coronary artery disease, arterial hypertension, chronic heart failure), which contribute to COPD patients' mortality in every third case. COPD and cardiovascular diseases have common risk factors and pathogenesis mechanisms. Cardioselective beta-blockers reduce morbidity risk and frequency of COPD exacerbation, are effective and safe in treatment of COPD patients.

[The Role of Endothelial Dysfunction in the Development of Cardiotoxic Action of Cytostatics in Patients with Lymphoproliferative Diseases].

Understanding mechanisms of chemotherapy cardiotoxicity is an important problem due to the lack of clear understanding of its occurrence. Development of endothelial dysfunction is considered to be one of possible ways in implementation of these side effects. The analysis of endothelin-1 and e-selectin levels in 26  patients with lymphoproliferative diseases before and after the completion of the treatment program was been performed. The results of the study showed normal values of E-selectin level and increased level of endothelin-1 in the whole group of patients before treatment. After completion of chemotherapy program, in the whole group, there was a decrease of these two markers. However, values of level of endothelin-1 with vasoconstrictor effect remained high even after the end of therapy. It is imp ortant that at detailed analysis the dynamics of investigated markers in patients of older age group (median age 64 years) was associated with worsening of endothelial dysfunction.

[Metabolomic Profiling of Patients With Cardiovascular Diseases].

Cardiovascular diseases (CVD) are the main cause of death worldwide. A broad study of the pathogenetic mechanisms of the CVD onset and progression has led to understanding of the importance of endothelial dysfunction (ED) in these processes. During recent years intensive work has been conducted in the direction of searching for markers of ED. Metabolomics is an intensively advancing approach to early diagnostics of diseases. Metabolomic analysis based on mass spectrometry allows to study complete metabolic profiles and their deviations resulting from changes in expression of genes and RNA, protein activity, or environmental factors. Metabolomic analysis has already demonstrated significant results in the solving of different scientific and clinical problems. It appears to be a promising method for detecting early biomarkers of CVD. Various aspects of application of metabolomic profiling in the field of cardiovascular diseases are discussed in this article.

[Hypertrophic Cardiomyopathy and Ischemic Heart Disease. Variants of Combination Pathology].

The issues of epidemiology and pathophysiology of hypertrophic cardiomyopathy (HCMP), as well as the search for its additional clinical-instrumental and genetic markers, environmental factors capable to influence the formation of its clinical variant and prognosis are subjects of great interest to the modern scientific community. Besides genetic markers of main neurohumoral systems, and morphofunctional parameters of intracardiac hemodynamics clinical course of the disease is influenced by a complex of concomitant pathology including ischemic heart disease (IHD), joining of which is possible in 10% of cases. IHD substantially aggravates course of HCMP and hampers selection of medical therapy. It should be noted that prognosis of primary hypertrophies is affected by episodes of ischemia of complex genesis and addition of IHD significantly increases risk of sudden death in these patients.