Assessment of the Level of Matrix Metalloproteinases, VEGF and MicroRNA-34a in Patients With Non-obstructive and Obstructive Lesions of the Coronary Arteries.

AIM: To assess the levels of matrix metalloproteinases (MMP), vascular endothelial growth factor (VEGF), and miRNA-34a expression in patients with ischemic heart disease (IHD) and obstructive and nonobstructive coronary artery (CA) disease. MATERIAL AND METHODS: This cross-sectional observational study included 64 patients with IHD (diagnosis verified by coronary angiography or multislice computed tomography coronary angiography), of which 33 (51.6%) were men aged 64.9±8.1 years. 20 patients had nonobstructive CA disease (stenosis <50%), and 44 had hemodynamically significant stenoses. The control group consisted of 30 healthy volunteers. MMP-1, -9, -13, and -14, miRNA-34a, and VEGF were measured in all patients. RESULTS: The concentration of MMP-1 was significantly higher in patients with ischemia and nonobstructive CA disease (INOCAD) (p=0.016), and the concentration of MMP-9 was the highest in the group with obstructive CA disease (p<0.001). The concentrations of MMP-13 and MMP-14 did not differ significantly between the groups. The highest VEGF concentrations were observed in the INOCAD group (p<0.001). The expression of miRNA-34a significantly differed between the IHD groups with different types of CA disease and controls (p <0.001). Patients with hemodynamically significant stenosis showed moderate relationships between the concentrations of MMP-14 and VEGF (ρ=0.418; p=0.024), as well as between VEGF and miRNA-34a (ρ=0.425; p=0.022). Patients with INOCAD had a significant negative correlation between the concentrations of MMP-13 and VEGF (ρ= -0.659; p=0.003). Correlation analysis showed in all IHD patients a moderate relationship of the concentrations of MMP-1 and MMP-14 with VEGF (ρ=0.449; p=0.002 and p=0.341; p=0.019, respectively). According to ROC analysis, a MMP-9 concentration above 4.83 ng/ml can be a predictor for the presence of hemodynamically significant CA obstruction in IHD patients; a VEGF concentration higher than 27.23 pg/ml suggests the absence of hemodynamically significant CA stenosis. CONCLUSION: IHD patients with INOCAD had the greatest increase in MMP-1, whereas patients with obstructive CA disease had the highest level of MMP-9. According to our data, concentrations of MMP-9 and VEGF can be used to predict the degree of CA obstruction. The expression of miRNA-34a was significantly higher in IHD patients with INOCAD and CA obstruction than in the control group, which suggested a miRNA-34a contribution to the development and progression of coronary atherosclerosis. In the future, it may be possible to use this miRNA as a diagnostic marker for IHD.

The EXCEL Study: Long-term Observation of the Effectiveness of Drug and Non-drug Rehabilitation in Patients with Ischemic Heart Failure.

AIM: To study the long-term effect of enhanced external counterpulsation (EECP) therapy on exercise tolerance, quality of life (QoL), and indicators of the structural and functional state of the cardiovascular system in patients with stable ischemic heart disease (IHD) complicated by chronic heart failure (CHF). MATERIAL AND METHODS: This open randomized EXCEL study included 120 patients with verified IHD complicated by NYHA II-III functional class CHF with reduced or mid-range left ventricular (LV) ejection fraction. Patients were randomized into group 1 (n=40), optimal drug therapy (ODT) and EECP (35 hours, 2 courses per year); group 2 (n=40), ODT and EECP (35 hours, 1 course per year); and group 3 (control; n=40), ODT and placebo counterpulsation (35 h, 1 course per year). All patients underwent a 6-minute walk test (6MWT), evaluation of clinical status, QoL with the MLHFQ and SF-36 questionnaires, structural and functional state of large blood vessels and microvasculature, measurement of brain natriuretic peptide precursor (NT-proBNP), and echocardiography at baseline and after 12 months. RESULTS: In groups 1 and 2 after 12 months, the 6MWT distance increased statistically significantly (44.5 and 24.9%, respectively) and the following indexes improved: QoL (SF-36, MLHFQ), the condition of large blood vessels (phase shift, radial augmentation index, central aortic systolic pressure (CASP)) and microvasculature (occlusion index, percentage of perfused capillaries, percentage of capillary recovery), and the LV systolic function (from 40.6±7.5 to 47.5±10.2% and from 41.3± 6.8 to 43.9±10.3%, respectively). The proportion of patients with a >20% increase in the 6MWT at 12 months was 97.5, 72.5, and 7.7%, respectively. A statistically significant decrease in NT-proBNP was observed in all groups. In group 3, the incidence of hospitalizations for CHF and the risk of the composite endpoint were significantly higher. CONCLUSION: For the 12-month study period, the effects of EECP in patients with IHD complicated by CHF included improvements in exercise tolerance, QoL, vascular and cardiac functional parameters, and a decrease in the incidence of adverse outcomes.

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.

Endothelial dysfunction and inflammation in patients with non-obstructive coronary arteries.

Aim To determine levels of markers for endothelial dysfunction and inflammation, endothelin-1, E-selectin, and tumor necrosis factor α (TNF-α) in patients with ischemic heart disease (IHD) and non-obstructive and obstructive coronary artery (CA) disease.Material and methods This study included 32 patients with verified IHD and non-obstructive (main group, n=19) and obstructive (comparison group, n=13) CA disease. Endothelial dysfunction was diagnosed by photoplethysmography and videocapillaroscopy. Serum concentrations of endothelin-1, E-selectin, and TNF- α were measured in all patients.Results Patients with non-obstructive CA disease showed a tendency towards more pronounced endothelial dysfunction (alternative stiffness index, 7.8 m /s [6.35; 9.08]; reflection index, 36.95 % [23.4; 52.65]; capillary density following reactive hyperemia, 54.33 cap /mm2 [48.92; 75.83]; capillary density following venous occlusion, 74.33 cap /mm2 [67.83; 93.00]) compared to the comparison group (alternative stiffness index, 9.05 m/s [7.08; 10.58]; reflection index, 28.25 % [23.35; 53.75]; capillary density following reactive hyperemia, 66.83 cap /mm2 [50.83; 78.67]; capillary density following venous occlusion, 87.0 cap /mm2 [77.58; 78.67]), although statistically significant differences were not found. Concentration of endothelin-1 was significantly higher in the IHD group with non-obstructive CA disease (0.45 ng/ml [0.28;0.65]) compared to patients with CA atherosclerotic stenosis (0.35 ng/ml [0.25; 0.38], p=0.035). Concentrations of E-selectin did not significantly differ between the groups (main group, 21.1 ng/ml [18.45; 35.03]; comparison group, 28.55 ng/ml [19.08; 35.01], p=0.29). In both groups, concentrations of TNF-α did not exceed the lower threshold of sensitivity (<2.3 pg/ml).Conclusion Endothelial dysfunction and increased endothelin-1 in patients with non-obstructive CA disease along with inflammation may additionally contribute to the pathogenesis of IHD in the absence of hemodynamically significant CA stenoses. Too low level of TNFα in both groups prevented us from using it as a diagnostic marker. Further study is needed that would include a greater number of patients and a search for alternative markers.

[Assessment of the structural and functional state of blood vessels in patients with hypertrophic cardiomyopathy].

Aim      To evaluate the structural and functional condition of the vasculature using fingertip photoplethysmography and computerized videocapillaroscopy in patients with hypertrophic cardiomyopathy (HCMP).Material and methods  The study included patients with HCMP (n=48; 28 (57 %) men; age, 54.3±13.6 years) and healthy volunteers (control group, n=33, 15 (45 %) men; age, 58.2±8.8 years). Standard laboratory and instrumental examination (blood count and biochemistry, electrocardiography, echocardiography, Holter electrocardiogram monitoring) were performed for all HCMP patients. The condition of vascular wall at various levels of the vasculature was evaluated by fingertip photoplethysmography (apparatus Angioscan-01) and computerized nail-fold videocapillaroscopy (apparatus Capillaroscan-01). The photoplethysmography study analyzed structural parameters, including the arterial wall stiffness index (aSI) of large blood vessels and the resistance index (RI) of small muscular arteries. Endothelial dysfunction was evaluated by the occlusion index (OI) and phase shift (PS). The capillaroscopy study assessed structural parameters, including the resting capillary density (rCD) and the capillary density following venous occlusion (voCD), and functional parameters, including the percentage of perfused capillaries (PPC), the percentage of restored capillaries (PRC), and the capillary density after the reactive hyperemia test (rhCD).Results The study showed increases in aSI (8.8 [6.8; 12.2] and RI (32.5 [17.4; 47.9] in the HCMP group. The OI was significantly lower in the HCMP group (1.3 [1.1; 1.5]) than in the control group (1.8 [1.5; 2.7], р<0.001). Also, PS values were significantly decreased in the HCMP group (4.4 [2.3; 8.6]) compared to the control group (8.4 [5.1; 12.1]. p=0.018). Disorders of structural and functional capillary indexes were observed in HCMP patients compared to the control group; rCD and voCD were decreased in the HCMP group (60 [52.6; 68] and 88 [75; 90], respectively) compared to the control group (75.8 [60; 87] and 90 [73; 101]), however, no intergroup difference reached a statistical significance. The rhCD, PPC, and PRC values were decreased in the HCMP group (66.3 [55; 72], 86.7 [70.9; 104.2] and 1.7 [-6.95; 20.3], respectively) compared to the control group (86 [68.6; 100], 103 [96; 114] and 18.4 [8.1; 27.4], respectively); PPC and PRC values were significantly different (р<0.005 and p<0.004, respectively).Conclusion      In patients with HCMP, fingertip photoplethysmography and computerized videocapillaroscopy showed increased wall stiffness in both large blood vessels and microvasculature, pronounced endothelial dysfunction, and decreases in capillary density and percentage of restored capillaries following respective tests.

[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.

[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.

[Treatment and secondary prevention of venous thromboembolism in cancer patients].

Oncological patients are a high-risk group for venous thromboembolic complications. These complications significantly impair the outcome of antitumor treatment and take a leading place in the structure of mortality. Treatment of venous thromboembolic complications in oncological patients is a serious challenge. When selecting an anticoagulant, the physician should consider its efficacy and safety and possible drug interactions. Based on results of multiple studies presented in this article, physicians will be able to choose an optimum therapeutic tactics and secondary prevention of thromboembolic complications for this group of patients.

[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.

[Vasoprotective Effects of Prolonged Therapy With Perindopril A in Patients with Hypertension Including Concomitant Type 2 Diabetes Mellitus].

Objective Investigate the dynamics of morphological and functional markers of vascular remodeling in patients with arterial hypertension (AH), including those with concomitant type 2 diabetes mellitus (DM2), during 12-month administration of perindopril A.Material and Methods The study included patients with grade I-II AH, with and without DM2 (30 and 32 patients, respectively), who underwent outpatient correction of initially ineffective antihypertensive therapy and administration of perindopril A, 10 mg/day. Morphological and functional parameters of vascular remodeling were evaluated in all patients at baseline and at 12 months using photoplethysmography. Stiffness index (SI) and phase shift (PS) were measured in large vessels. Reflection index (RI) and occlusion index (OI) were measured in microvessels. Computed nailfold videocapillaroscopy was used to determine capillary density (CD) at rest (CDr), CD during venous occlusion test (CDvo), and CD during reactive hyperemia test (CDrh). Data are medians [interquartile range].Results After 12-month administration of perindopril A, the morphological and functional parameters of vascular remodeling in AH patients without DM2 significantly improved at all vascular levels. SI decreased to 9.25 [7.8; 10.93 ] m/s and PS increased to 7.4 [5.6; 9.05] ms. In microvasculature, a statistically significant reduction was observed in RI, 31 [27; 36.5]%, and an increase was observed in OI, which characterizes endothelium function, 1.75 [1.68; 1.9]. Capillary CDr significantly increased to 40.5 [34.93; 46] cap/mm2, as did CDvo and CDrh. At the same time, in the group of patients with AH and DM2, a significant improvement was observed for the large vessels. SI decreased to 9.8 [9.08; 10.58] m/s, and PS increased to 6.95 [5.13; 10.08]. The RI index, reflecting the structural condition of arterioles, significantly decreased to 34 [25.9; 45.53]%, and the OI index, characterizing endothelial function, did not change significantly, 1.4 [1.3; 1.6]. Capillary CDr significantly increased to 31.55 [27.68; 34.7 ] cap/mm2; however, CDvo and CDrh did not change significantly. Renal function improved in both groups.Conclusion Both groups demonstrated improvement of morphological parameters at all levels of the arterial bed. However, patients with AH and concomitant DM2 showed no improvement of the endothelial function of arterioles and capillaries compared to improvement in AH patients without DM2. This reflected the more severe endothelial dysfunction present in AH patients with DM2.

[Circulating Neuregulin-1 and Chronic Heart Failure with Preserved Ejection].

Chronic heart failure (CHF) with preserved ejection fraction (CHFpEF) is an unsolved, socially relevant challenge since it is associated with a high level of morbidity and mortality. Early markers for this pathology are unavailable, and therapeutic approaches are undeveloped. This necessitates extensive studying the mechanisms of CHFpEF to identify therapeutic targets. According to current notions, systemic inflammation and endothelial dysfunction play an important role in the pathogenesis of CHFpEF. These processes induce the development of myocardial fibrosis and impairment of cardiomyocyte relaxation, thereby resulting in diastolic dysfunction and increased left ventricular (LV) filling pressure. Neuregulin-1 (NRG-1) is a paracrine growth factor and a natural agonist of ErbB receptor family synthesized in the endothelium of coronary microvessels. The NRG-1 / ErbB4 system of the heart is activated at early stages of CHFpEF to enhance the cardiomyocyte resistance to oxidative stress. Preclinical and clinical (phases II and III) studies have shown that the recombinant NRG-1 therapy results in improvement of myocardial contractility and in LV reverse remodeling. Results of recent studies suggest possible anti-inflammatory and antifibrotic effects of NRG-1, which warrants studying the activity of this system in patients with CHFpEF.

[Anticoagulant Therapy in Elderly Patients With Atrial Fibrillation].

Is this paper discuss problems of selection of anticoagulant therapy in elderly patients with atrial fibrillation, use of unreasonably low doses of anticoagulants, their risks and adherence to therapy is discussed in the paper.

[Tactics of Selection of Anticoagulant Therapy in Patients With Atrial Fibrillation and Ischemic Heart Disease].

In the clinical practice a physician quite often is at a loss due to "freedom of choice" granted by availability of direct oral anticoagulants (DOAC). If a patient with nonvalvular atrial fibrillation (AF) has indications for therapy with anticoagulants which DOAC should be preferred? What are benefits for a patient with ischemic heart disease and AF when definite NOAC is chosen and what are risks inherent of this choice? Answers to such questions are given in this paper.

[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.

[Modern approaches to the problem of hypertrophic cardiomyopathy].

This review presents modern data about a hereditary disease of myocardium - hypertrophic cardiomyopathy. The main features of its epidemiology, pathophysiological changes in intracardiac hemodynamics, formation of main clinical symptoms of the disease and variants of its clinical course are considered in terms of modern concepts. Much attention is given to characteristics of the variants of the disease and understanding of the formation of its clinical picture of each of them for the choice of the strategy for the management of these patients.

[Matrix metalloproteinases and hypertrophic cardiomyopathy].

Prognosis of patients with hypertrophic cardiomyopathy (HCMP) to a great extent is determined by clinical variant of the disease. As the system of matrix metalloproteinases (MMPs) plays an important role in development and progression of the processes of fibroformation and tissue remodeling polymorphisms of modifier genes regulating its components can influence clinical course of HCMP. Among possible markers of prognostication of the course of cardiovascular diseases the role of MMPs and their tissue inhibitors has been discussed. With the aim of studying effects of MMPs on the course of HCMP we conducted this investigation in which we included 58 patients and a group of healthy volunteers (control group) with comparable sex and age. In all participants (n=112) we determined polymorphism of MMP-3 - rs3025058 and markers of fibroformation (MMP-3, TIMP-1, TIMP-2, and collagen IV). We found that unfavorable allele variant MMP-3 1171 was associated with hypertrophy of interventricular septum. We also established that levels of TIMP-1 in the group of patients with HCMP were significantly lowered in comparison with those in control group. Concentration of marker MMP-3 was elevated in the group of patients with variant "atrial fibrillation" compared with groups of stable course and progressing course. We revealed medium degree reverse correlation between MMP-3 marker and thickness of left ventricular posterior wall and direct correlation of this parameter with coefficient of asymmetry. Polymorphism MMP-3 - 1171 produced an impact on the level of TIMP-1 marker. The data obtained by us confirm effect of the system of MMPs on formation of hypertrophic remodeling of the heart in HCMP.

[Renin-angiotensin-aldosterone system in hypertrophic cardiomyopathy].

Keeping in mind an important role of renin-angiotensin aldosterone system (RAS) in developing of cardiac remodeling and fibrosis, genetic polymorphisms coding its components could have influence with clinical variants of the course. Biomarkers could appear predictors of adverse. To examine the contribution of the RAS to developing of different hypertrophic cardiomyopathy (HCM) clinical variants of the course we studied 58 patients with HCM and controls comparable by age and gender. All patients were genotyped of gene polymorphisms CMA1 A(-1903)G rs1800875, AGTM235T rs699, AGTR1 A1166C rs5186, CYP11B2-344 T/C rs1799998. Angiotensin-converting enzyme (ACE) and angiotensin II (AII) levels were measured in 40 patients with HCM and 39 controls. We found out that AII were significantly decreased in patients with HCM than in healthy controls. The positive correlation between AII and left ventricle posterior wall (LVPW) were detected. Severity of heart hypertrophy were associated with pejorative genotype of AGT M235T polymorphism and CMA1 A(-1903) polymorphism. Significant association between the AG genotype of CMA1 A(-1903) polymorphism and angina class II-III and ventricular extrasystole of high gradation was observed. Our data not only support the hypothesis that RAAS polymorphisms may influence phenotype, but also allow for create new approaches to possible predicting adverse outcomes.

[Hypertrophic cardiomyopathy -- modern state of the problem. Issues of epidemiology and nomenclature, genetics and pathophysiology, variants of course and differential diagnosis].

The problem of the study of hypertrophic cardiomyopathy (HCM) has preserved its actuality because of high prevalence (1:500), risk of sudden cardiac death (SCD) in individuals of young able-bodied age. Subject of great interest appear problems of search for additional clinical, instrumental and genetic markers, environmental factors which are capable to influence formation of a clinical variant of HCM course, risk of SCD, and prognosis of HCM. Important problem requiring further study appears to be molecular genetic characteristic of the disease. Integrated nomenclature of various forms and variants of course of HCM is essential for elaboration of tactics of management of patients and assessment of results of multicenter trials.

[Contemporary trends of genetic analysis in hypertrophic cardiomyopathy].

Subject of great interest of contemporary scientific community is a search for additional genetic and environmental factors which are capable to influence formation of a clinical variant of the course of hypertrophic cardiomyopathy (HCMP). It has been shown by many works that besides mutations in genes of sarcomere proteins clinical course of HCMP is also affected by modifier genes of the cardiovascular system such as association of polymorphisms RAAS, sympathoadrenal system, NO-synthase, endothelin system, and system of blood coagulation. Attempts have been made to study effects of these polymorphisms on formation of clinical variant of HCMP course and to search for associations with development of unfavorable variants.