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.

[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.

[Soluble guanylate cyclase: restoration of the NO-sGC-cGMP signaling pathway activity. A new opportunity in the treatment of heart failure].

Studying the key mechanisms of cardiovascular diseases has opened new possibilities for the pharmacological impact on the pathophysiological mechanisms of heart failure (HF). The signaling pathway, nitric oxide - soluble guanylate cyclase - cyclic guanosine monophosphate (NJ-sGC-cGMP), provides normal functioning of the cardiovascular system in healthy people and serves as a potential target for medicines in HF with reduced ejection fraction (HFrEF). In HFrEF progression, the sGC activity decreases due to endothelial dysfunction and oxidative stress. The increased synthesis of cGMP resulting from sGC stimulation can restrict myocardial fibrosis, reduce stiffness of the vascular wall and induce vasodilation; in this process, the mechanism of action of sGC stimulators does not overlap with other therapeutic targets. According to the results of the international randomized clinical study VICTORIA, the use of the sGC stimulator, vericiguat, in patients with HF, ejection fraction <45%, and a recent episode of decompensation in their history reduced the risk of repeated hospitalization and cardiovascular death. Also, this treatment was characterized by a favorable safety profile when added to standard therapy.

[Prospects for use of Vericiguat in HFrEF: Implications of VICTORIA Trial Results. Advisory Board Summary].

In September 2021, an online meeting of the Council of Experts was held. The proposed focus of discussion was publishing the results of an international prospective, randomized, double-blind, placebo-controlled study VICTORIA. The objective of the VICTORIA study was evaluation of the efficacy and safety of supplementing a standard therapy with vericiguat at a target dose of 10 mg twice a day as compared to placebo for prevention of cardiovascular death and hospitalization for heart failure (HF) in patients with clinical manifestations of chronic HF and left ventricular ejection fraction <45% who have recently had an episode of decompensated HF. The aim of the meeting was interpretation of the VICTORIA study results on efficacy and safety of vericiguat for a potential use in a Russian population of patients after a recent episode of decompensated chronic HF with reduced ejection fraction.

[The impact of BMI on the course of the acute SARS-COV-2 infection and the risks that emerge during the first year after the hospital discharge. Subanalysis evidence of the AKTIV and AKTIV 2 registries].

BACKGROUND: There is enough evidence of the negative impact of excess weight on the formation and progression of res piratory pathology. Given the continuing SARS-CoV-2 pandemic, it is relevant to determine the relationship between body mass index (BMI) and the clinical features of the novel coronavirus infection (NCI). AIM: To study the effect of BMI on the course of the acute SARS-COV-2 infection and the post-covid period. MATERIALS AND METHODS: AKTIV and AKTIV 2 are multicenter non-interventional real-world registers. The АКТИВ registry (n=6396) includes non-overlapping outpatient and inpatient arms with 6 visits in each. The АКТИВ 2 registry (n=2968) collected  the  data  of  hospitalized  patients  and  included  3  visits.  All  subjects  were  divided  into  3  groups:  not  overweight  (n=2139), overweight (n=2931) and obese (n=2666). RESULTS: A higher BMI was significantly associated with a more severe course of the infection in the form of acute kidney injury (p=0.018), cytokine storm (p<0.001), serum C-reactive protein over 100 mg/l (p<0.001), and the need for targeted therapy (p<0.001) in the hospitalized patients. Obesity increased the odds of myocarditis by 1,84 times (95% confidence interval [CI]: 1,13-3,00) and the need for anticytokine therapy by 1,7 times (95% CI: 1,30-2,30).The  patients  with  the  1st  and  2nd  degree  obesity,  undergoing  the  inpatient  treatment,  tended  to  have  a  higher  probability  of  a  mortality  rate.  While  in  case  of  morbid  obesity  patients  this  tendency  is  the  most  significant  (odds  ratio  -  1,78; 95% CI: 1,13-2,70). At the same time, the patients whose chronical diseases first appeared after the convalescence period, and those who had certain complaints missing before SARS-CoV-2 infection, more often had BMI of more than 30 kg/m2 (p<0,001).Additionally, the odds of death increased by 2,23 times (95% CI: 1,05-4,72) within 3 months after recovery in obese people over the age of 60 yearsCONCLUSION.  Overweight  and/or  obesity  is  a  significant  risk  factor  for severe  course  of  the  new  coronavirus  infection  and  the associated cardiovascular and kidney damage Overweight people and patients with the 1st and 2nd degree obesity tend to have a high risk of death of SARS-CoV-2 infection in both acute and post-covid periods. On top of that, in case of morbid obesity patients this tendency is statistically significant. Normalization of body weight is a strategic objective of modern medicine and can contribute to prevention of respiratory conditions, severe course and complications of the new coronavirus infection.

Comparative analysis of tryptophan and downstream metabolites of the kynurenine and serotonin pathways in patients with arterial hypertension and coronary artery disease.

Aim    To compare serum concentrations of tryptophane (Trp) and its metabolites in subjects with no cardiovascular disease (CVD) and patients with СVD, including arterial hypertension (AH) and ischemic heart disease (IHD).Material and methods    This study included 131 participants; 58 participants (11 of them with documented peripheral atherosclerosis) were included into the AH group, 46 participants were included into the IHD group, and 27 participants with no signs of CVD were included into the control group. Plasma concentrations of Trp and its metabolites were measured by high-performance liquid chromatography in combination with a triple quadrupole analyzer.Results    Comparison of the three study groups revealed significant differences in concentrations of Trp (р=0.029), kynurenine (p<0.001), kynurenine/Trp ratio (p<0.001), quinolinic acid (р=0.007), kynurenic acid (р=0.003), serotonin (p<0.001), and 5­hydroxyindoleacetic acid (5­HIAA) (р=0.011). When the AH group was subdivided into subgroups without and with documented peripheral atherosclerosis, the intergroup differences remained for concentrations of kynurenine, kynurenine/Trp ratio, quinolinic acid, kynurenic acid, serotonin, and 5­HIAA. Also, correlations were found between concentrations of Trp metabolites and laboratory and instrumental data, primarily inflammatory markers. Conclusion    Analysis of serum concentrations of Trp and its metabolites in CVD patients showed increases in kynurenine, kynurenine/Trp ratio, quinolinic acid, kynurenic acid, and 5­HIAA along with decreases in concentrations of Trp and serotonin in the groups of AH, AH with documented peripheral atherosclerosis, and IHD.

The Prognostic Value of Neuregulin-1ß in Heart Failure Patients With Preserved Ejection Fraction.

Aim      To determine the neuregulin-1ß concentration in patients with chronic heart failure with preserved ejection fraction (HFpEF) and the association of this biomarker with the functional status of patients, echocardiographic parameters of the structural and functional condition of the heart, and the risk of unfavorable outcome.Material and methods  This observational, prospective study included 47 patients with HFpEF; 32 (68%) of them were females. Mean age was 70 [66-77] years, EF was 57 [56; 58] %. The group of healthy volunteers consisted of 40 people; 32 (55 %) of them were females; mean age was 56 [53-61] years. For all patients, the functional status was evaluated (6-min walk test, 6MWT); standard echocardiography (EchoCG) was performed; and concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and neuregulin-1ß were measured. The follow-up period was two years. Cases of cardiovascular (CV) death and hospitalizations for decompensated chronic heart failure (CHF) were recorded.Results Median concentration of neuregulin-1ß was 0.969 [0.348; 1.932] ng/ml in the HFpEF group, which was significantly higher than 0.379 [0.195; 0.861] ng/ml in the group of healthy volunteers (р=0.003). Significant correlations between the neuregulin-1ß concentration and the distance walked in 6MWT or with EchoCG parameters of left ventricular diastolic function were not found. Mean observation time was 456 [244; 730] days. 21 outcomes were observed, including 2 CV deaths and 19 hospitalizations for CHF. Patients with high concentrations of neuregulin-1ß (≥Me) had a greater frequency of hospitalizations for CHF (Log-rank, p=0.046) and a higher risk of this outcome (risk ratio, 1.30; 95 % confidence interval, 1.01-1.66; p=0.037).Conclusion      Patients with HFpEF had increased concentrations of neuregulin-1ß. High levels of neuregulin-1ß were associated with a higher risk of hospitalization for decompensated CHF.

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.

[Clinical case of the cardiovascular system involvement in a patient with Charcot-Marie-Tooth disease].

Hereditary motor and sensory type 1A neuropathy (known as Charcot-Marie-Tooth disease) is a disease of peripheral nerves characterized by symptoms of progressive polyneuropathy with preferential damage of distal extremity muscles. Damage to the cardiovascular system is extremely rare and heterogenous in this pathology. This disease is not included in the list of indications for interventional antiarrhythmic aid. We could not find in available literature a clinical description of the development of sinus node dysfunction associated with this pathology. The present clinical report presents a case of detection and successful treatment of a damage to the cardiovascular system that manifested itself as sinus node dysfunction/sick sinus syndrome in the tachy-brady variant. A combination treatment approach using radiofrequency catheter ablation, implantation of a permanent pacemaker, and antiarrhythmic therapy associated with drug and non-drug treatment of motor sensory neuropathy resulted in recovery and long-term maintenance of sinus rhythm as well as in beneficial changes in the patient's neurological status.

Epidemiology of atrial fibrillation in a representative sample of the European part of the Russian Federation. Analysis of EPOCH-CHF study.

Aim    To study true prevalence of atrial fibrillation (AF) in a representative sample from the European part of the Russian Federation; to describe characteristics of patients with AF; and to provide the frequency of anticoagulant treatment.Material and methods    Cross-sectional data of the EPOCH epidemiological study (2017) were used. Data were collected in 8 constituent entities of the Russian Federation; the sample size was 11 453 people. The sample included all respondents who had given their consent for participation and were older than 10 years. Statistical tests were performed in the R system for statistical data analysis.Results    The prevalence of AF in the representative sample from the European part of the Russian Federation was 2.04 %. The AF prevalence increased with age and reached a maximum value of 9.6% in the age group of 80 to 89 years. The AF prevalence among females was 1.5 times higher than among men. With age standardization, the AF prevalence was 18.95 and 21.33 per 1,000 people for men and women, respectively. The AF prevalence increased in the presence of concurrent cardiovascular diseases (CVDs) or diabetes mellitus as well as with an increased number of comorbidities in the same person and reached 70.3 and 60.0 % in patients with 4 and 5 comorbidities, respectively. Patients with AF had a greater number of comorbidities and higher CHA2DS2VASc scores (5.0 vs. 2.0, p<0.001) compared to patients with CVDs without AF. Only 22.6 % of patients with CVD and AF took anticoagulants. Only 23.9% of patients with absolute indications for the anticoagulant treatment received anticoagulants.Conclusion    The AF prevalence in the European part of the Russian Federation was 2.04 %; it increased with age and in patients with concurrent CVDs or diabetes mellitus. Most of AF patients (93.2 %) required a mandatory treatment with oral anticoagulants.

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.

[Mobile health technologies in cardiology].

Digital medicine is becoming an essential part of the healthcare system. The intense development of mobile technologies, the global coverage of mobile networks, and the growing attachment in the society to mobile devices have prompted the creation of mobile healthcare (mHealth). At present, mobile healthcare technologies have been tested in various cardiovascular diseases. Among the main tasks set for telemedicine, it is necessary to note improvements of general medical care, monitoring of patients' condition, accuracy of clinical diagnoses, timely correction of therapy, and improvement of emergency care. Clinical studies are performed in parallel with active work in the field of informational technologies to provide safety of data storage and intellectual processing. Finally, despite the broad public support for the development of this area of medicine, the search continues for methods to improve patients' compliance with the prescribed therapy. This article presents current information about the use of mHealth in cardiology, study results, prospects of mobile healthcare, and major difficulties in implementing projects in this area.

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.

The Effect of COVID-19 on Long-Term Cardiac Function in Patients With Chronic Heart Failure.

Aim      To evaluate functional changes in the heart in the long-term following COVID-19 in patients with chronic heart failure (CHF).Material and methods  Case reports of 54 patients aged 69.1±9.7 years who had COVID-19 from January 2021 through January 2022 and had been previously diagnosed with NYHA functional class II-III CHF were studied. Two comparison groups were isolated: HF with LV EF >50 % (n=39) and <50 % (n=15). Echocardiography was used to evaluate changes in LV EF and pulmonary artery systolic pressure (PASP) 5-6 months following COVID-19.Results In all CHF patients after COVID-19 at 5.8 months on average, LV EF decreased (median difference, 2.5 %; 95 % confidence interval (CI): 6.99×10-5- 4.99) and PASP increased (median difference, 8 mm Hg; 95 % CI: 4.5-12.9). In the HF group with LV EF <50 %, the decrease in EF was greater than in the group with LV EF >50 % (6.9 and 0.7 %, respectively; p=0.037); furthermore, the CHF phenotype did not influence the change in PASP (p=0.4). The one-factor regression analysis showed that the dynamics of LV EF decrease was significantly influenced by the baseline decrease in LV EF, whereas the change in PASP was influenced by the dynamics of LV EF decrease, presence of dyslipidemia, and statin treatment. Furthermore, the multifactorial analysis showed that prognostically significant factors for long-term changes in LV EF following COVID-19 were male gender (odds ratio (OR), 5.92; 95 % CI: 1.31-26.75; p=0.014), LV EF at baseline <50 % (OR, 0.88; 95 % CI: 0.8-0.96; p<0.001); changes in PASP depended on the presence of dyslipidemia (OR, 0.08; 95 % CI: 0.01-0.84; p=0.018).Conclusion      This study showed that COVID-19 in the long term can influence the course of CHF; in this process, HF patients with EF <50 % have progression of systolic dysfunction and PASP, whereas patients with EF >50 % have an isolated increase in PASP.

[Focus ultrasound for cardiology practice. Russian consensus document].

This document is a consensus document of Russian Specialists in Heart Failure, Russian Society of Cardiology, Russian Association of Specialists in Ultrasound Diagnostics in Medicine and Russian Society for the Prevention of Noncommunicable Diseases. In the document a definition of focus ultrasound is stated and discussed when it can be used in cardiology practice in Russian Federation.

Mitral valve replacement and implantation of an extracardial mesh frame in patients with severe heart failure: results of a clinical study and a description of a clinical case 18 years after surgery.

Aim    Dilated cardiomyopathy (DCMP) is a major cause for severe heart failure. Development of a combination (drug and surgery) treatment of this disease is relevant. This prospective observational study was aimed at evaluating short- and long-term results of extracardiac mesh implantation in DCMP patients with heart failure resistant to the optimum drug therapy.Material and methods    The extracardiac mesh ACOR-1 was implanted in 15 patients with DCMP. All meshes were produced individually for each patient and made of Gelweave (great Britain) vascular graft strips. The mesh size corresponded to the heart diastolic size, which was measured after achieving a maximum possible clinical improvement for the patient. Long-term results were followed for up to 4 years. Mean age of patients was 43.1±10.8 years (from 28 to 62 years). One patient was followed up for 18 years. Data of that patient were presented as a clinical case report.Results    From October, 2003 through October, 2007, 15 DCMP patients received mesh implants. Cases of in-hospital death were absent. In 3 mos. after the surgery, left ventricular volumes decreased (end-diastolic volume decreased from 251.7±80.7 to 229.0±61.3 ml; end-systolic volume decreased from 182.3±73.6 to 167.7±46.2 ml), and the left ventricular pump function improved (ejection fraction increased from 25.2±6.0 to 27.1±5.1 %; cardiac index increased from 2.0±0.5 to 2.4±0.7 ml /min /m2). The functional state of patients improved by one NYHA class, from 3.7±0.3 to 2.8±0.6. In some cases, the left ventricular size and the systolic function completely normalized. There were no episodes of circulatory decompensation in the long term after surgery. Actuarial survival for the observation period was 100%.Conclusion    Implantation of extracardiac mesh prevented progression of heart dilatation and, in combination with drug therapy, it may represent an effective method for treatment of DCMP.

[Biomarkers in Heart Failure: Current and Future].

Heart failure (HF) is the ending of practically all cardiovascular diseases and the reason for hospitalization of 49% of patients in a cardiological hospital. Available instrumental diagnostic methods and biomarkers not always allow verification of HF, particularly in patients with preserved left ventricular ejection fraction. Prediction of chronic HF in patients with risk factors faces great difficulties. Currently, natriuretic peptides (NUP) are widely used for the diagnosis, prognosis and management of patients with HF and are included in clinical guidelines for diagnosis and treatment of HF. Following multiple studies, the understanding of NUP significance has changed. This resulted in a need for new biomarkers to improve the insight into the process of HF and to personalize the treatment by better individual phenotyping. In addition, current technologies, such as transcriptomic, proteomic and metabolomic analyses, provide identification of new biomarkers and better understanding of features of the HF pathogenesis. The aim of this study was to discuss recent reports on NUP and novel, most promising biomarkers in respect of their possible use in clinical practice.