Aim     To assess the association of polymorphic variants of candidate genes, including two miR-375 microRNA target genes (PRKCA and CDC42) and AGTR1, PAI1, IL10, IFNG, and TGFB1 genes involved in the pathogenesis of atherosclerosis as the major cause of myocardial infarction (MI), with the age of the first MI in groups of patients of different sexes.

Material and methods            Genotyping of DNA samples from peripheral blood of 548 ethnic Russian patients with a known age of MI onset was performed using real-time polymerase chain reaction. Differences in the frequencies of carriage of alleles and genotypes of the studied polymorphic variants, as well as their biallelic combinations, were analyzed in groups of patients with an age of MI onset less than and more than the median.

Results            In men, an association was found between the age of first MI and carriage of the AGTR1 rs5186*C / C (p=0.016; odds ratio, OR, 2.58; 95% confidence interval, CI: 1.13-5.89) and PRKCA rs887797*A / A (p=0.033; OR, 2.03; 95% CI: 1.01-4.11) genotypes, as well as combinations of AGTR1 rs5186*C / C + PRKCA rs1010544*A (p=0.0064; OR, 3.27; 95% CI: 1.32-8.07), AGTR1 rs5186*A + PRKCA rs887797*G (p=0.0021; OR, 0.42; 95 % CI: 0.24-0.75) and AGTR1 rs5186*A / A + CDC42 rs12038474*A (p=0.005; OR, 0.47; 95 % CI: 0.27-0.82). In women, only combinations of PRKCA rs1010544*A + IL10 rs1800896*A / A (p=0.032; OR, 1.94; 95% CI: 1.01-3.74) and PRKCA rs1010544*G + IFNG rs2430561*T / T (p=0.026; OR, 0.20; 95% CI: 0.044-0.96) were associated with the age at first MI.

Conclusion      A number of polymorphic variants of the genome associated with the age at first MI was identified. For the first time, it was shown that the set of such variants differs in men and women.

Aim     To study the activation sequence of compensatory mechanisms during the development of diastolic dysfunction.

Material and methods            The study was performed on rats with stress cardiomyopathy induced by high doses of isoproterenol (120 mg/kg twice a day). Heart function was studied 3-5 and 8-10 days after the injection by echocardiography and left ventricular (LV) catheterization. The content, isoform composition of the sarcomeric protein connectin (titin) and its mRNA content were also measured.

Results            The early period was characterized by the presence of systolic dysfunction evident as a decrease in the minute volume due to impaired myocardial  LV contractility, and slower LV filling and relaxation. Compensatory changes at this stage were manifested as increases in the left atrial volume and diastolic pause duration due to reduced contraction rate and arterial elasticity. The content of the more compliant N2BA connectin isoform and its mRNA was increased. These changes facilitated increases in LV filling and ejection. In the second period, diastolic dysfunction developed, when the minute volume, contraction rate and LV contractility became normal, although the left atrial pressure remained elevated, and the aortic diameter and LV wall thickness increased. The increased content of the N2BA isoform remained, and this was associated with stable slowing of LV relaxation.

Conclusion      The study showed that in the initial period, compensation is achieved by urgent mobilization of the circulatory system, while the improvement in myocardial contractility is secondary.

Aim     To assess the effect of annual seasonal flu vaccination for 3 years on the risk of acute respiratory infection (ARI) and cardiovascular events (CVE) in cardiological patients followed up using two analytical methods.

Material and methods            This prospective comparative study included 817 patients in October 2012. CVE, other chronic non-communicable diseases, and ARI recorded from October 2012 through November 2015 were analyzed. Vaccinated and unvaccinated patients were compared using survival curves and a self-controlled case series method for paired 6-month periods. Differences were considered statistically significant at p<0.05.

Results            The analysis included 813 patients (mean age, 63.3±11.6 years; 40.5% men; in the 2012/13-2013/14-2014/15 season, 45-44-41% of patients, respectively, were vaccinated; 1, 2, and 3 vaccinations were received by 60, 57, and 285 patients, respectively; 413 were unvaccinated). Compared to unvaccinated patients, the patients vaccinated three times developed the first ARI later (p<0.0001); the relative risk of developing cardiovascular complications (CVC) was 0.88 (95% confidence interval: 0.65-1.10). Among vaccinated patients, there were fewer patients with ARI (p<0.001) and cardiovascular diseases (p=0.02) not only in summer compared to winter, but also in summer, ARI developed in 41.2% fewer patients than in unvaccinated (p=0.002).

Conclusion      The use of two analytical methods allowed us to identify additionally both non-specific and persistent specific effects of three-year flu immunization in cardiological patients in summer, which needs to be confirmed in randomized placebo-controlled studies.

Aim     To evaluate the efficacy and safety of a single sublingual dose of captopril in patients with poor control of arterial hypertension (AH) despite continuous use of long-acting angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). The safety of a single additional dose of a short-acting ACE inhibitor to relieve elevations of blood pressure (BP) in AH patients on ACE inhibitors or ARBs has not been adequately studied.

Material and methods            This was a multicenter, prospective, randomized, double-blind, placebo-controlled pharmacodynamic study. The study included men and women aged 18 to 65 years with an established diagnosis of AH and ineffective treatment, despite regular use of constant doses of antihypertensive drugs for at least 3 weeks before inclusion in the study, who have not missed doses during the previous 3 days. Patients were randomly assigned to a sublingual Capoten 25 mg group (captopril group) or a placebo group at a 1:1 ratio. If the effect was insufficient after 30 min, an additional dose of the study drug (Capoten 25 mg or the respective placebo) was administered in each group.

Results            The study included 114 patients (57 patients in each group). At baseline, systolic BP (SBP) and diastolic BP (DBP) before the administration of the study drug did not differ significantly between the groups. At one hour after study drug dosing in the captopril group and the placebo group, mean decrease in SBP was 22.0 ± 10.7 and 11.8 ± 11.9 mm Hg, respectively (p < 0.001). At one hour after captopril dosing, the mean decrease in DBP was 14.1±8.3 and 7.5±5.8 mm Hg, respectively (p<0.001). The need for a second dose in the captopril group and the placebo group was 12.3 and 75.4%, respectively.

Conclusion      The study confirmed the efficacy and safety of captopril compared to placebo in patients with a marked increase in BP in the absence of damage to target organs, which supports the validity of using captopril as a first-line drug in such clinical situations.

Aim    To analyze the biomechanics of the thoracic aorta (TA) in degenerative calcific aortic stenosis (AS) using segmental ultrasound assessment of the aortic wall deformation.
Material and methods        A total of 109 patients with severe AS and 11 healthy volunteers were evaluated. 2D speckle-tracking transesophageal echocardiography was performed in all patients. We calculated the global peak systolic circumferential strain (GCS, %), GCS normalized to pulse arterial pressure (GCS/PAP), and β2 stiffness index (SI) of the aortic wall at 4 levels of the TA: sinuses of Valsalva (SV), sinotubular junction (STJ), mid-ascending aorta (AA), and descending aorta (DA).
Results In patients with aortic stenosis, GCS and GCS/PAP in all TA segments were statistically significantly lower than in healthy volunteers (SV: 3.1 [1.3; 4.4] and 3.8 [1.5; 5.9]; 12.2 [9.9; 13.4] and 20.2 [17; 28.6], p<0.001; at STJ level: 4.5 [2.4; 6.5] and 5.7 [3.3; 8.7]; 8.4 [5.6; 10] and 14.7 [10.9; 18.6], p<0.001; at AA level: 3.1 [0.8; 4.7] and 3.9 [1.4; 6.4]; 8.6 [7.6; 11.7] and 18.0 [12.1; 20.2], p<0.001; DA: 3.9 [3.1; 6] and 5.6 [3.6; 8.4]; 10.4 [7; 11.2] and 17.2 [14.1; 21.5], p<0.001, respectively). Furthermore, the SI in AS patients was statistically significantly increased to 19.1 [12.9; 26.5] and 4.8 [3.6; 5.3], p<0.001 in SV; 13.4 [10.1; 19.9] and 6.7 [5.6; 8.3], p<0.001 at STJ level; 17.8 [13.4; 26.9] and 5.6 [4.6; 8.1], p<0.001 at AA; 17.2 [11.1; 25.3] and 5.6 [4.6; 7.4], p<0.001 at DA, respectively. 69 (63.3%) AS patients had multidirectional GCS of the aortic wall in the aortic root and the TA ascending and descending sections. Patients with AS showed a uniform decrease in GCS and GCS/PAD and an increase in the SI and diameters in all TA segments from the aortic annulus to the descending section. In all AA segments, GCS, GCS/PAD and SI did not differ between AS patients with bicuspid aortic valve (AV) (n=47) and tricuspid AV (n=62) (p>0.05). An inverse correlation was found between the mean transaortic pressure gradient and GCS and GCS/PAD in the SV (r=-0.33; p<0.01, and r=-0.26; p<0.01, respectively) and in the AA (r=-0.23; p<0.05 and r=–0.21; p<0.05, respectively).
Conclusion    Severe AS is associated with non-adaptive remodeling of the TA, reduced and multidirectional deformation along the circumference of the aortic wall in the aortic root, and the TA ascending and descending segments, which is closely related to disorders of transaortic hemodynamics.

Objective To explore the clinical application value of right ventricular (RV) myocardial global longitudinal strain
(RVGLS) in assessing changes in RV function in patients with pulmonary embolism.
Material and methods Patients with pulmonary embolism who were treated successfully in our hospital from January 2022 to
December 2023 were enrolled in this study. Included were 34 pulmonary embolism patients without pulmonary hypertension (Group B), 31 with pulmonary hypertension (Group C), and 35 healthy volunteers, matched by gender and age (Group A). Clinical data and RV function-related variables of these groups were compared.
Results Compared with pre-treatment values of Group A, the following variables of Groups B and C had higher pre-treatment values (p<0.05): RV end-diastolic diameter (RVEDD), RV to left ventricular diameter ratio (RV / LV), RV work index (RIMP), main pulmonary artery diameter (MPA), pulmonary artery systolic pressure (PASP), RVGLS, RV free wall longitudinal strain (RVFWLS),
The following variables had lower values (p<0.05): RV area change fraction (RVFAC), RV ejection fraction (RVEF), RV short-axis shortening rate (RVFS), tricuspid annular peak systolic velocity (S’), tricuspid annular systolic excursion (TAPSE). After therapy, significant differences were observed in the aforementioned indicators between Group C (with pulmonary hypertension) and Group A (healthy controls), with Group C showing persistently elevated RVEDD, RV / LV ratio, RIMP, MPA, PASP, RVGLS, and RVFWLS, alongside reduced RVFAC, RVEF, RVFS, S’, and TAPSE compared to Group A (all p<0.05). Compared to pre-treatment values in Group B (without pulmonary hypertension), pre-treatment Group C demonstrated significantly higher RVEDD, RV / LV ratio, RIMP, MPA, PASP, RVGLS, and RVFWLS, and significantly lower RVFAC, RVEF, RVFS, S’, and TAPSE (all p<0.05). Post-treatment comparisons between Groups B and C revealed that these differences remained significant (all p<0.05). ROC curve analysis revealed that RVGLS> 20.59 % is the best cutoff value for predicting the occurrence of pulmonary embolism, and RVGLS> –17.42 % is the best cutoff value for predicting the occurrence of pulmonary hypertension in patients with
pulmonary embolism. The results of multivariable logistic regression model analysis showed that RVGLS>–20.59 % is independently related to the occurrence of pulmonary embolism, and RVGLS>–17.42 % is independently related to pulmonary embolism complicated by pulmonary hypertension (p<0.05). In Groups A and B, RVGLS was negatively correlated with RVFAC, RVEF, and TAPSE (p<0.05 for all) and positively correlated with RIMP and PASP (p<0.05 for all). In Groups B and C, RVGLS was negatively correlated with RVFAC and RVEF in patients with pulmonary embolism before and after treatment (for all <0.05) and positively correlated with RIMP and PASP (p<0.05 for all).
Conclusion RVGLS can be applied to evaluate the RV function of patients with pulmonary embolism. RVGLS>–20.59 % is independently related to pulmonary embolism, and there is a significant correlation between RVGLS and RVVFAC, RVEF, RIMP, and PASP in patients with pulmonary embolism before and after treatment.

Aim Atrial fibrillation (AF) and heart failure (HF) are prevalent cardiovascular conditions. The estimated glomerular filtration rate (eGFR) is a crucial marker for assessing kidney function and has demonstrated prognostic significance in various cardiovascular diseases. However, its specific impact on patients with both AF and HF remains unclear.
Material and methods This retrospective cohort study utilized data from the MIMIC–IV database, focusing on a subset of ICU patients diagnosed with both atrial fibrillation (AF) and heart failure (HF). Patients were categorized based on eGFR levels, and the association between eGFR and all-cause ICU mortality, as well as 28‑day post-discharge mortality, was analyzed using the Cox proportional hazards model.
Results Analysis revealed significant differences (p<0.001) in age, ICU length of stay, and prevalence of chronic diseases across different eGFR groups. As eGFR increased, the risk of death (HR) significantly decreased. The group with the lowest eGFR (first quartile, Q1) had the highest mortality risk, whereas the highest eGFR group (Q4) showed a protective effect (HR=1.14, P=0.019). There was a significant non-linear relationship between eGFR and all-cause mortality (p<0.001). Lower eGFR levels substantially increased mortality risk, highlighting eGFR as a key prognostic indicator for AF patients with HF. Survival probability and mortality risk varied significantly among different eGFR levels (HR=0.54, 95 % CI: 0.48– 0.60, p<0.001). These findings underscore the importance of monitoring and intervening in renal function.
Conclusion Lower eGFR levels are independently linked to higher all-cause mortality in patients with AF and HF.

Background Severe aortic stenosis (AS) is a life-threatening condition that necessitates prompt intervention, even in high-risk patients with contraindications to surgical aortic valve replacement (SAVR). Transcatheter aortic valve replacement (TAVR) has become a transformative treatment, utilizing various access routes, including transfemoral (TF), transapical, and other, alternative pathways. The selection of the access route significantly impacts procedural safety and outcomes. The purpose of this study is to compare the safety profiles of different TAVR access routes in high-risk patients with severe AS.
Material and methods Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a comprehensive literature search was performed in PubMed and Cochrane Library databases to identify studies that evaluated the safety outcomes of TAVR via various access routes in high-risk patients. Key endpoints analyzed were procedural complications, 30‑day mortality, cardiac electrophysiological abnormalities, stroke incidence, and vascular complications. Meta-analysis utilizing RevMan 5.3 was performed, employing fixed or random effects models based on heterogeneity.
Results Seven studies encompassing 2,351 patients were included in the analysis. The pooled analysis revealed that the non-TF access routes were associated with a significantly higher risk ratio (RR) for procedural complications [RR=1.76; 95 % confidence interval (CI): 1.63–1.89, p<0.00001] compared to the TF approach. No statistically significant difference in 30‑day mortality was observed among the access routes [OR=0.79; 95 % CI: 0.60–1.05, p=0.11]. However, alternative routes had increased odds of
cardiac electrophysiological abnormalities [OR=1.44; 95 % CI: 1.12–1.84, p=0.004]. There was no significant difference in stroke incidence between access routes [OR=1.16; 95 % CI: 0.75–1.79, p=0.51], but vascular complications were significantly more frequent with non-femoral routes [OR=1.70; 95 % CI: 1.29–2.24, p=0.0001].
Conclusion This meta-analysis underscores the critical role of access route selection in the safety of TAVR. While the TF approach remains the gold standard due to its lower complication rates, alternative routes are indispensable for anatomically or clinically challenging cases. Refinements in procedural techniques, patient selection, and advanced imaging are essential to optimizing outcomes across all access routes. Further large-scale studies are warranted to validate these findings and enhance clinical decision-making.

Pulmonary embolism (PE) is a complex emergency condition, the diagnosis and treatment of which still have many unresolved issues and "gray areas". Current clinical guidelines for the management of patients with PE are partly outdated and do not take into account a number of modern data. In this review, the authors identified unresolved issues and provided the latest data on the assessment of pre-test probability, risk stratification, diagnosis and treatment of acute PE, particularly in patients with intermediate-high and high risk of death. The issues of reperfusion catheter techniques and intensive care are addressed individually. The requirement for specialized PE centers of expert level and their prospects are discussed