Aim    Optimal combination therapy for chronic heart failure (CHF) currently implies the mandatory use of at least four classes of drugs: renin-angiotensin-aldosterone (RAAS) system inhibitors or angiotensin receptor blocker neprilysin inhibitors (ARNI); beta-adrenoblockers (BAB); mineralocorticoid receptor antagonists; and sodium-glucose cotransporter 2 inhibitors. Furthermore, many of these drugs are able to decrease blood pressure even to hypotension and alleviate tachycardia. This study focused on the relationship of 24-h blood pressure (BP) and heart rate (HR) with the prognosis for CHF patients with sinus rhythm and left ventricular ejection fraction (LV EF) <50 % as well as on suggesting possible variants of safe therapy for CHF depending on the combination of studied factors.
Material and methods    Effects of clinical data, echocardiographic parameters, 24-h BP, and heart rhythm (data from 24-h BP and ECG monitors) on the prognosis of 155 patients with clinically pronounced CHF, LV EF <50 %, and sinus rhythm who were followed up for 5 years after discharge from the hospital.
Results    The one-factor analysis showed that the prognosis of CHF patients was statistically significantly influenced by the more severe functional class (FC) III CHF compared to FC II, reduced LV EF (<35 %), a lower 24-h systolic BP (SBP) (<103 mm Hg), the absence of hypotensive episodes in daytime, a low variability of nighttime BP (<7.5 mm Hg), a higher 24-h HR (>71 bpm vs. <60 bpm), the absence of therapy with RAAS inhibitors + BAB, and a lower body weight index. The multi-factor analysis showed that more severe CHF FC, lower LV EF, and the absence of RAAS inhibitors + BAB therapy retained the influence on the prognosis. After eliminating the influencing factor of drug therapy, also a low SBP variability significantly influenced the prognosis. An additional analysis determined the following four groups of CHF patients with reduced heart systolic function according to mean 24-h HR and SBP: the largest group (38.1 % of all patients) with controlled HR (≤69 bpm), preserved SBP (>103 mm Hg), and the lowest death rate of 15.3 %; the group with increased HR (>69 bpm) but preserved SBP (30.3 % of all patients) where the death rate was 44.7 %, which was significantly higher than in the first group; the group with normal HR (≤69 bpm) but reduced SBP (≤103 mm Hg) (16.1 % of patients) where the death rate was 40 %, which was comparable with the second group and significantly worse than in the first group; and the group with both increased HR (>69 bpm) and reduced SBP (≤103 mm Hg) (15.5 % of patients), which resulted in the maximal risk of death (70.8 % of patients with CHF and LV EF <50 %), which was significantly higher than in the three other groups.
Conclusion    Low SBP (including 24-h SBP with reduced variability in day- and nighttime) in combination with high HR (including by data of Holter monitoring), low LV EF, more severe clinical course of CHF, and the absence of an adequate treatment with neurohormonal modulators (RAAS inhibitors and BAB) significantly increased the risk of death. Isolating four types of FC II-III CHF with sinus rhythm and EF <50% based on the combination of HR and BP identifies patients with an unfavorable prognosis, which will help developing differentiated therapeutic approaches taking into account clinical features.

Aim      To evaluate the predictive value of indexes of left ventricular mechanical dyssynchrony (MD) as determined by data of electrocardiogram (ECG)-gated myocardial perfusion scintigraphy (ECG-MPS) for prediction of the efficacy of resynchronization therapy (RT) in patients with chronic heart failure (CHF).

Material and methods  This prospective study included 32 patients with nonischemic CHF and standard indications for RT. All patients underwent complete clinical an instrumental examination, including 24-h ECG monitoring and echocardiography (EchoCG). In order to evaluate the left ventricular (LV) myocardial perfusion, contractile function, and MD, myocardial perfusion scintigraphy was performed for all patients at rest prior to RT. In addition to the perfusion defect size at rest and hemodynamic parameters, LV MD was determined. The following indexes were used for analysis of dyssynchronization: phase standard deviation (PSD), phase histogram bandwidth (HBW), and phase histogram asymmetry and steepness. The treatment efficacy was evaluated by the clinical status of patients (clinical condition evaluation scale for CHF patient) and EchoCG at 6 months following RT. The criteria for a positive response to RT were an increase in LV ejection fraction (EF) by 5% and/or a decrease in the LV end-diastolic volume by 15% compared to preoperative values.

Results According to ECG-MPS findings, all patients had scintigraphic signs of severe CHF with dilated LV cavity (end-diastolic volume, EDV 246 [217; 269] ml) and also of pronounced mechanical and electrical dyssynchrony. The values of mechanical dyssynchrony were PSD 53 [41; 61], HBW 176 [136; 202], asymmetry 1.62 [1.21; 1.89], and steepness 2.81 [1.21; 3.49]. The QRS duration was 165 [155; 175] msec. Furthermore, the LV perfusion was moderately impaired (perfusion defect size 4 [3; 10] %). Mean follow-up duration after implantation of the resynchronizing device was 6±1.7 mos. According to the selected criteria, 20 (63 %) patients were considered as responders and 12 (37 %) patients as non-responders. Before implantation of the cardiac synchronizing device, responders and non-responders differed only in LV MD (PSD 44 [35; 54] vs. 63 [58; 72]; p=0.0001); HBW 158 [118; 179] vs. 205 [199; 249]; p=0.0001; asymmetry 1.77 [1.62; 2.02] vs. 1.21 [0.93; 1.31]; p=0.0001; steepness 3.03 [2.60; 3.58] vs. 1.21 [0.19; 1.46]; p=0.0001), respectively. A one-factor logistic regression analysis showed that MD values were statistically significant predictors of a positive response to RT. A multi-factor logistic analysis of phase histogram steepness (odds ratio, OR 1.196; 95 % confidence interval, CI 1.04–1.37) and PSD (OR 0.67; 95 % CI 0.47–0.97) were identified as independent predictors for the response to RT. According to results of the ROC analysis, a PSD <55 and a phase histogram steepness >1.54 may predict the effectiveness of RT (AUC= 0.92; р=0.0001).

Conclusion      LV MD parameters determined with ECG-MPS allow predicting the effectiveness of RT in patients with nonischemic CHF. In this patient group, high values of standard deviation and low values of phase histogram steepness were independent predictors for the absence of response to RT after 6 mos. of follow-up.

Aim      Improvement of quality of life is one of the most important goals for the treatment of patients with chronic heart failure (CHF). This study searched for ways to increase the efficiency of CHF treatment based on parameters of quality of life in CHF patients during and after the treatment with exogenous phosphocreatine (EP).

Material and methods  The effect of a single course of EP treatment on quality of life of patients with functional class (FC) II-IV CHF with reduced or mid-range left ventricular ejection fraction was studied as a part of the all-Russia prospective observational study BYHEART. The presence of FC II-IV CHF and a left ventricular ejection fraction <50 % were confirmed by results of 6-min walk test (6MWT) and findings of echocardiography after stabilization of the background therapy.

Results An interim data analysis showed that the course of EP treatment was associated with a significant improvement of quality-of-life indexes as determined by the Minnesota Living with Heart Failure Questionnaire (LHFQ) total score. These indexes significantly increased and remained at a satisfactory level for 6 mos. following completion of the treatment course. Also, the treatment significantly beneficially influenced the clinical condition of patients (heart failure severity scale), results of 6MWT, and the increase in left ventricular ejection fraction.

Conclusion      The conclusions based on results of the interim analysis should be confirmed by results of the completed study. Complete results are planned to be published in 2022.

Aim      To create a three-dimensional mathematical model of coronary flow in patients with ischemic heart disease based on findings of computed tomography angiography (CTA) with subsequent calculation of the fractional flow reserve (FFRCTA) and comparison of estimated FFRCTA with FFR reference values measured by coronary angiography (CAG).

Material and methods  The study included 10 patients with borderline stenosis (50–75 %) as determined by CTA performed with a 640‑slice CT-scanner. Based on CTA findings, three-dimensional mathematical models were constructed for further calculation of FFRCTA. Later, an invasive measurement of FFR (FFRINV) was performed for all patients. FFR values <0.8 indicated the hemodynamic significance of stenosis.

Results FFRCTA and FFRINV values differed insignificantly in most cases (n=9) and exceeded 5% in only one case. The regression analysis showed a close correlation between estimated and invasively measured FFR values.

Conclusion      Preliminary results showed a good consistency of calculated and measured FFR values. Therefore, further development of the method for mathematical modeling of three-dimensional blood flow by CTA findings is promising. Noninvasive evaluation of FFR is particularly relevant for analysis of hemodynamic significance of borderline (50–75 %) coronary stenoses.

Aim      To study the effect of residual coronary injury after a percutaneous coronary intervention (PCI), as evaluated with the SYNTAX scale (residual SYNTAX score, RSS), on the mid-term prognosis for patients with non-ST elevation acute myocardial infarction (NSTEMI) and also to determine threshold RSS values for patients at high and low risk of adverse cardiac events.

Material and methods  A single-center, retrospective study was performed. From 421 patients with NSTEMI after PCI with stenting, 169 patients were selected who originally had multivessel coronary disease and who had undergone a repeated inpatient examination, including mid-term (11.7±3.0 mos.) coronary angiography. The endpoints were recurrent clinical manifestations of angina, repeat revascularization (RR), unstable angina (UA), recurrent acute myocardial infarction (AMI), cardiac death, and also a composite endpoint (major adverse cardiac events, MACE) that included UA, recurrent AMI, and cardiac death. After revealing a significant direct correlation between RSS and the probability of recurrent AMI, UA, MACE, or RR (p <0.05) using the ROC analysis, we have established threshold RSS values that divided patients into groups with high and low risk of the cardiac events listed above.

Results For a significantly high risk of recurrent AMI (area under the curve, AUC 0.79±0.05; 95 % confidence interval, CI 0.68–0.89; р=0.048), the threshold RSS score was 8 (sensitivity 100 %, specificity 70.9 %). For UA and MACE, the RSS scores were both 3 (AUC 0.68±0.5; 95 % CI 0.58–0.79; p=0.005 and AUC 0.71±0.05; 95 % CI 0.61–0.8; p=0.001, respectively). The probability of UA during the observation period with RSS >3 was 4.07 times higher and that of MACE was 5.23 times higher than with RSS<3 (95 % CI 1.44–11.49; р=0.01 and 95 % CI 1.88–14.53; р=0.001, respectively).

Conclusion      The study demonstrated a significant, direct correlation between the RSS and the risk of adverse cardiac events in patients with NSTEMI during one year of observation. Specific threshold values were obtained, which may help in choosing both the extent of revascularization and the tactics for postoperative management of patients.

Aim    To study the role of blood concentration of growth differentiation factor 15 (GDF-15) as a predictor of left atrial/left atrial appendage (LA/LAA) thrombosis in patients with nonvalvular atrial fibrillation (AF).
Material and methods    538 patients with nonvalvular AF were admitted to the Tyumen Cardiology Research Center in 2019–2020 for radiofrequency ablation and elective cardioversion. According to findings of transesophageal echocardiography (EcoCG), 42 (7.8%) of these patients had LA/LAA thrombosis and 79 (14.7%) of them had the effect of spontaneous echo contrast (SEC). This comparative, cross-sectional, cohort study included at the initial stage 158 successively hospitalized patients with nonvalvular AF: group 1 (with LA/LAA thrombosis, n=42) and group 2 (without LA/LAA thrombosis and without SEC, n=116). To eliminate significant differences in age between the groups, an additional inclusion criterium was introduced, age from 45 to 75 years. Finally, 144 patients were included into the study: group 1 (with LA/LAA thrombosis, n=42, mean age 60.9±7.2 years) and group 2 (without LA/LAA thrombosis and without SEC, n=116, mean age 59.5±6.0 years). 93 (91%) patients in group 1 and 40 (95%) patients in group 2 had arterial hypertension (p=0.4168); 53 (52%) and 29 (^(%), respectively, had ischemic heart disease (p=0.0611). The groups did not differ in sex, profile of major cardiovascular diseases, or frequency and range of oral anticoagulant treatment. General clinical evaluation, EchoCG, and laboratory tests, including measurements of blood concentrations of GDF-15 and NT-proBNP, were performed.
Results    In the group with LA/LAA thrombosis, 1) persistent AF prevailed whereas paroxysmal AF was more frequently observed in patients without thrombosis; 2) a tendency toward more pronounced chronic heart failure was observed; 3) tendencies toward a high median CHA2DS2‑VASc score and toward a greater proportion of patients with scores ≥3 were observed. According to EchoCG findings, group 1 had higher values of sizes and volumes of both atria and the right ventricle, left ventricular (LV) end-systolic volume and size, pulmonary artery systolic blood pressure, and LV myocardial mass index. LV ejection fraction (EF) was in the normal range in both groups but it was significantly lower for patients with LA/LAA thrombosis, 59.1±5.1 and 64.0±7.3, respectively (p=0.00006). Concentrations of GDF-15 (p=0.00025) and NT-proBNP were significantly higher in group 1 than in group 2 (p=0.000001). After determining the threshold values for both biomarkers using the ROC analysis, two independent predictors of LA/LAA thrombosis were obtained by the stepwise multiple regression analysis: GDF-15 >935.0 pg/ml (OR=4.132, 95 % CI 1.305–13.084) and LV EF (OR=0.859, 95 % CI 0.776–0.951). The ROC analysis assessed the model quality as good: AUC=0.776 (p<0.001), sensitivity 78.3 %, specificity 78.3 %.
Conclusion    For patients with nonvalvular AF, both increased GDF-15 (>935.0 pg/ml) and LV EF are independent predictors for LA/LAA thrombosis.

Aim    The aim of this study was to investigate the short-term effect of the COVID-19 pandemic on the management of warfarin therapy used for atrial fibrillation (AF) and prosthetic valve disease.
Material and methods    The study included 139 Atrial fibrillation (AF) patients and 173 prosthetic valve patients (PVP) who were using warfarin. The time in therapeutic range (TTR), International Normalized Ratio (INR) averages, the numbers of INR tests, and the non-adherence to INR monitoring (NIM) were compared for the pre-covid period (PCP) and the COVID-19 period (CP). Also, adherence to warfarin therapy was evaluated with a questionnaire.
Results    For all patients, the INR values were higher in the CP (2.47 vs 2.60, p<0.001), and the NIM percentage was higher (19.2 % vs 71.5 %, p<0.001) in the CP. The number of INR tests was lower during the CP (p<0.001).The percentage of patients with TTR≥70 % was lower during the CP (41.7 % vs 33 % p=0.017). Subgroup analysis showed that for PVP, TTR values and the percentage of patients with TTR ≥70 % were similar in both the PCP and CP periods. The questionnaire showed that for 94.1 % of respondents, the major cause of NIM in the CP was the COVID-19 pandemic. However, during the CP, adherence to warfarin medication was high (95.5 %).
Conclusion    Lower TTR during the COVID-19 pandemic can increase bleeding and thromboembolic cases.Therefore, patients taking warfarin should be followed more closely, and more practical ways should be considered for INR testing.

Aim    Mortality prediction is very important for more effective treatment of patients with acute coronary syndrome. Hematological and lipid parameters have been used for this purpose, as this approach is non-invasive and cost effective. In this study, our aim was to evaluate which parameter predicts mortality most accurately.
Material and Methods    Data of 554 patients with at least one total coronary artery occlusion were collected retrospectively. Receiver operating characteristic curves were used to determine the optimal cut-off points of Neu / HDL, Neu / Lym, Mono / HDL, Trig / HDL, HDL / LDL, Plt / Lym and Lym / HDL according to long-term cardiovascular survival. Median follow-up time was 520 days, and 30 patients died.
Results    The mean age was 60.96±0.50 yrs. The area under the curve (AUC) for Neu / HDL was 0.830 (p<0.001, 95 % confidence interval [CI]: 0.753 to 0.908). The cut-off point was 0.269, with a sensitivity of 74.2 % and a specificity of 74.2 %. The AUC for Neu / Lym was 0.688 (p<0.001, 95 % CI: 0.586 to 0.790). The cut-off point was 5.322, with a sensitivity of 67.7 % and a specificity of 67.1 %. The Neu / HDL (hazard ratio, HR [confidence interval, CI]: 0.202 [0.075–0.545], p=0.002) and Neu / Lym (0.306 [0.120–0.777], p=0.013) were associated with increased risk of death according to multivariate Cox regression analysis.
Conclusions    Neu / HDL offers a better long-term mortality prediction than Neu / Lym, Mono / HDL, Trig / HDL, HDL / LDL, Plt / Lym, or Lym / HDL after treatment of total coronary artery occlusion.

Arterial hypertension (AH) is one of the most important risk factors for development of myocardial infarction, chronic heart failure, stroke, cognitive disorders and dementia, and chronic kidney disease. Currently, special attention is paid to increased blood pressure variability (BPV) as a new risk factor for development of cardiovascular and cerebrovascular complications. The available evidence-based body of clinical studies demonstrates the importance of reducing not only the blood pressure itself but also the increased BPV to provide significant improvement of the prognosis and limits the risk of complications. This notion has been validated in consensus documents on the management of patients with AH. Among antihypertensive drugs, the fixed-dose combination (FC) amlodipine/perindopril has demonstrated a unique capability for reducing all types of BPV (visit-to-visit, day-to-day, during 24 h). According to current clinical guidelines, this combination belongs to first-line FCs indicated for most patients with AH. A distinctive feature of the FC amlodipine/perindopril is numerous data from real-life clinical practice, which support both its high antihypertensive efficacy and the ability to decrease high BPV. Therefore, the FC amlodipine/perindopril can be recommended for a broad range of AH patients to achieve BP control and to improve the prognosis.

This review addresses morphological changes in coronary arteries following stenting, which result from damage to the vascular wall. These changes include 1) formation of a thrombus in the site of intimal injury; 2) inflammation; 3) proliferation and migration of smooth muscle cells; 4) formation of extracellular matrix. Each of these pathological processes has specific morpho-biological features. The review shows the role of von Willebrand factor in development of early thrombosis after intimal injury, which provokes activation of the inflammatory response followed by proliferation of smooth muscle cell that synthetize the extracellular matrix. These cellular and intercellular changes are based on overexpression of TGF-β1 protein, which facilitates modulation of various types of smooth muscle cells, including contractile and secretory ones. Issues of fine regulation of cellular and intercellular interactions by apoptosis, activation of mTOR signaling molecules, and microRNA are still understudied. Dynamic changes in drug-coated stents during development of neoatherosclerosis and late thrombosis remain not elucidated. Current reports show that initial mechanisms triggering pathological regenerative and hyperplastic processes that result in coronary restenosis in the area of implanted stents may form early (first hours or days) after stenting. Most studies were performed on experimental rather than on autopsy material, which does not allow fully unbiased interpretation of obtained data. Studying dynamics of morphological and molecular changes in coronary arteries after stenting, including on autopsy material, will allow one to express an opinion on the risk of postoperative thrombosis and restenosis.

The article focuses on ultrasound diagnosis of cardiac tumors (CT). In recent time, the frequency of detecting cardiac neoplasm has been growing. Correct diagnosis at an early stage of the process would allow timely treatment. Before the introduction of two-dimensional echocardiography (EchoCG), life-time diagnosis of CT was very rare. This article describes major echocardiographic criteria for most common benign, malignant, and metastatic CTs. The article is illustrated with original echocardiographic images.