Konstantin Yurievich Nikolaev

Calcific aortic valve stenosis and atherosclerotic coronary artery disease not only share common risk factors but also exert synergistic effects on the left ventricular (LV) myocardium. Hemodynamically significant coronary artery disease is detected in 60–70 % of patients with severe aortic stenosis, and concomitant LV hypertrophy, by increasing myocardial susceptibility to ischemia, accelerates the development of subendocardial replacement fibrosis—an independent predictor of adverse prognosis after valve replacement. This review presents an analysis of current evidence on structural and functional LV remodeling in patients with severe aortic stenosis following transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR). Data on the population prevalence of aortic stenosis are systematized, and the mechanisms of myocardial morphofunctional remodeling are detailed, with a central focus on myocyte hypertrophy, interstitial fibrosis, and neurohormonal dysregulation. The dynamics of LV reverse structural remodeling achieved with the two alternative strategies for correcting aortic stenosis are examined using echocardiography and cardiac magnetic resonance imaging. It is shown that TAVI is associated with earlier and more pronounced reverse remodeling within the first 6 months after the intervention, whereas SAVR is characterized by gradual yet sustained improvement in LV morphofunctional parameters. The molecular basis of cardiomyocyte hypertrophy regression and interstitial fibrosis reversal is analyzed in detail, and the correlation between cardiac structural remodeling and clinical outcomes and long-term prognosis is discussed. The review also systematizes findings obtained by national research groups investigating this problem. In parallel, predictors capable of limiting or, conversely, potentiating the completeness of reverse myocardial structural recovery are analyzed. Future research horizons are outlined, with particular emphasis placed on the implementation of proteomic and genomic techniques, which pave the way toward personalized selection of the valve replacement strategy.

Machine learning (ML) models integrating genetic and clinical data show promise for personalizing antiplatelet therapy after myocardial infarction (MI). This study aimed to develop an ML model using clinical features and CYP2C19 genotype to predict long-term major adverse cardiac events (MACEs) and guide P2Y12 inhibitor selection. In a prospective observational study of 218 patients with MI undergoing percutaneous coronary intervention, with up to 9-year follow-up for MACEs, we trained and evaluated multiple models incorporating clinical, genetic, and angiographic variables. Uplift modeling principles were applied to assess treatment heterogeneity, and feature importance was analyzed using Shapley Additive Explanations (SHAP). The optimal model (CatBoost with SHAP-based feature selection) achieved an area under the receiver operating characteristic curve of 0.721. Discrimination remained stable under bootstrap resampling and across both infarction presentations. Key prognostic predictors included age, comorbidity index, number of significant coronary lesions, P2Y12 inhibitor type, stent type, and CYP2C19 loss-of-function/gain-of-function variants. Notably, CYP2C19 variants were significant MACE predictors, while drug-eluting stents and ticagrelor were associated with lower predicted long-term risk. These findings suggest that an ML framework incorporating CYP2C19 genotype can stratify long-term MACE risk. This data-driven approach points to the prognostic utility of genetic testing and supports the potential role of ticagrelor, particularly in genetically defined high-risk patients with MI, for optimizing secondary prevention.

Surfactant protein D (SP-D), traditionally considered in the literature as a marker of acute and chronic bronchopulmonary diseases, is also associated with cardiometabolic disorders. Both from the standpoint of molecular mechanisms of action and in terms of the few available clinical studies, the cardiometabolic effects of SP-D remain poorly understood. At the same time, given the relevance of atherosclerosis and metabolic disorders, scientific interest in SP-D remains high. SP-D indirectly promotes the secretion of tumor necrosis factor (TNF-α) and interferon gamma (IFN-γ), exerting a proinflammatory effect, and by binding to lipids, affects atherogenesis. The purpose of the literature review was to systematize modern knowledge about SP-D as a promising marker of cardiometabolic disorders. The article highlights the results of recent studies that allow us to clarify and supplement the already known mechanisms of action of SP-D, as well as to determine the role of SP-D in atherogenesis and metabolic disorders. The search for relevant information on the topic of the article was performed in the search engines PubMed, Google Scholar, and in the scientific electronic library eLibrary.ru. The search depth was 35 years: from 1990 to 2025. Full-text original scientific articles, open-access literature reviews in English and Russian were selected that corresponded to the stated topic. The following tags were used for the search in English and in Russian: «SP-D», «Surfactant protein D» including in combination with the following tags «Atherosclerosis», «Atherosclerotic plaque», «Coronary artery disease», «Peripheral artery disease», «Dyslipidemia», «Metabolic Disorders», «Hypertension», «Diabetes», «Obesity». A total of 40 foreign and domestic publications were subjected to critical analysis. A literature review demonstrated the potential role of SP-D as a cardiometabolic marker and a marker of cardiovascular prognosis in patients with coronary heart disease (CHD), chronic obstructive pulmonary disease (COPD), diabetes mellitus type 2 (T2DM), obesity, peripheral artery disease (PAD) and in hemodialysis patients.

Aim of the study was to evaluate the effect of ticagrelor treatment in combination with high-dose statins on the relative risk of ischemic cardiovascular events during long-term follow-up in patients with myocardial infarction (MI) carrying different genotypes of rs2305948 VEGFR2. Material and methods. The study included 218 patients with acute MI, including 23 % women , average age 58 [52; 64] years. After the initial examination and preparation in the hospital emergency department, patients underwent coronary angiography followed by percutaneous coronary intervention or coronary artery bypass grafting. Two groups were identified for further observation in accordance with the therapy mode: 1 – individuals who received treatment with ticagrelor (12 months) and high-dose statins (≥ 12 months) after MI (n = 48, 22 %), 2 – individuals who took other drug combinations of statins in low or high doses in combination with various platelet P2Y12 receptor inhibitors – clopidogrel or ticagrelor (n = 170, 78 %). All 218 patients underwent genotyping (C/C, C/T, T/T) rs2305948 VEGFR2 using real-time polymerase chain reaction. The duration of outpatient observation of these patients was 9 years (2015–2024) after MI. Results. It was established that in the first group, in 48 individuals, along with 6 (13 %) identified heterozygous (C/T) genotypes of rs2305948 VEGFR2, 42 (87 %) cases with the homozygous genotype C/C were also identified, and in the second group, in 170 individuals, along with 70 (41 %) heterozygous C/T and homozygous T/T genotypes, 100 (59 %) cases with the homozygous genotype C/C rs2305948 VEGFR2 were identified (χ2 = 13.56, p < 0.001). In patients with MI in the first group, who received treatment with ticagrelor in combination with high-dose statins, there was a lower incidence of cardiovascular death (p = 0.024), recurrent acute coronary syndrome (p = 0.011), repeat myocardial revascularization (p = 0.025) and a combined end point (CEP) (p < 0.001) than among patients in group 2 who received other drug combinations of statins in high or low doses and P2Y12 platelet inhibitors. In a multivariate analysis using binary logistic regression, the Charlson comorbidity index increased the relative risk of CEP by 2.2 times (p < 0.001), the C/T and T/T rs2305948 VEGFR2 genotypes increased by 2.1 times (p = 0.023), and baseline three-vessel coronary disease increased by 2.3 times (p = 0.001). At the same time, treatment with ticagrelor in combination with high-dose statins reduced the risk of CEP by 72 % (p = 0.005), achieving low-density lipoprotein cholesterol level less than 1.4 mmol/l within 3 years after MI by 54 % (p = 0.044), and the use of drug-eluting stents by 45 % (trend, p = 0.093). Conclusions. In long-term follow-up (9 years) in patients with MI, the relative risk of ischemic cardiovascular events is directly determined by the C/T and T/T rs2305948 VEGFR2 genotypes, severe comorbidity, and baseline three-vessel coronary disease. The relative risk of ischemic events is inversely determined by treatment with ticagrelor in combination with high-dose statins and achievement of target low-density lipoprotein cholesterol level after MI.

The aim of the study was to analyze the associations of rs2305948 KDR (VEGFR2) genotypes, the state of collateral coronary blood flow, as well as the intensity of statin therapy with the development of structural and functional remodeling of the left ventricle and the onset of ischemic cardiovascular events during long-term observation in patients with myocardial infarction (MI). Material and methods. The prospective observational study included 51 patients with acute MI with ST-segment elevation. All patients underwent coronary angiography and angioplasty with stenting of the coronary arteries, as well as echocardiography and laboratory diagnostics with biomarker assessment at the hospital stage and over time (36 months). Also, the rs2305948 genotypes of the KDR (VEGFR2) gene were determined using real-time polymerase chain reaction. Two groups were allocated for further observation: 1 – with poor coronary collaterals (n = 25), 2 – with good coronary collaterals (n = 26). The duration of outpatient observation and treatment of both groups of patients with registration of ischemic cardiovascular events after MI was 108 months. Results and discussion. In group 1, compared with group 2, there was a higher incidence of severe left ventricular structural and functional remodeling (LVSFR) over 36 months (p = 0.0380), the combined end point (CEP) over 108 months (p = 0.0001), carriage of genotypes C/T and T/T rs2305948 KDR (VEGFR2) (p = 0.0002), as well as the size of the acute and past MI zone (according to the value of the LV local contractility impairment index) (p = 0.0107 and p = 0.0443, respectively); at the post-infarction stage – all echocardiographic parameters of LVSFR (p < 0.05). According to the logistic regression analysis, the development of LVSFR was directly affected by hypertension (p = 0.037) and inversely by the presence of good coronary collaterals in the MI zone (p = 0.024); the onset of CEP was directly determined by the comorbidity index (p = 0.041) and inversely by the presence of good coronary collaterals (p < 0.0001), as well as long-term treatment with high doses of statins (p = 0.043). Conclusions. The development of LVSFR and the onset of CEP are associated with the rs2305948 genotypes of KDR (VEGFR2), the status of coronary collaterals, the size of the MI zone, as well as long-term use of high-dose statin therapy in post-infarction patients.

The aim of the study is to evaluate cardiac fatty acid binding protein as a prognostic biomarker for the occurrence of severe post-infarction structural and functional remodeling of the left ventricular myocardium and heart failure with clinical manifestations in patients with acute myocardial infarction during long-term follow-up. Material and methods. The study included 95 patients with acute myocardial infarction and ST-segment elevation (mean age 56.8 ± 9.8 years). Upon admission to the emergency room, all patients underwent clinical and laboratory studies to determine cardiac fatty acid binding protein (cFABP) and high-sensitivity troponin T (hs-TnT). At the end of the long-term follow-up (Me = 36 months), the patients were examined for clinically evident heart failure (NYHA functional class II and higher), high-sensitivity C-reactive protein (hsCRP) was determined in the blood, and echocardiography was performed. According to the echocardiography data, the presence and severity of structural and functional remodeling of the left ventricle myocardium (SFR LV) were established. Results. It was determined that the presence of clinically evident heart failure is directly associated with age, the Charlton comorbidity index, cFABP ≥10 ng/ml upon admission to the hospital and has a direct tendency to be associated with hs-TnT upon admission to the hospital. The presence of severe structural and functional remodeling of the left ventricle myocardium is directly associated with age, obesity, creatinine, cFABP ≥ 10 ng/ml and hs-TnT upon admission to hospital, and there is also a direct tendency towards an association with age. It was revealed that hs-TnT upon admission to hospital is directly associated with hsCRP ≥ 2 mg/l at the end of long-term followup. Conclusions. the presence of cFABP ≥ 10 ng/ml in the blood of patients with acute myocardial infarction upon admission to hospital is associated with an increase in the probability of developing clinically evident heart failure during long-term follow-up by 4.27 times, and severe structural and functional remodeling of the left ventricle myocardium is 3.07 times more likely, which is due to the size of the infarction lesion and the subsequent development of myocardial fibrosis.

Aim. To evaluate clinical associations and predictive value of lipoprotein transport and metabolism markers determined in a collection of serum samples from patients with myocardial infarction (MI).Material and methods. Collection of blood samples from 88 patients with the acute MI was created in the Biobank of Yugra laboratory for subsequent biochemical assessment of serum levels of lipoprotein transport and metabolism markers. All patients were included in a clinical prospective study for 48 months with registration of medical events and remote tomographic assessment of coronary artery (CA) involvement upon follow-up completion.Results. Direct associations were established between proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and low-density lipoprotein cholesterol levels, coronary atherosclerosis, Global Registry of Acute Coronary Events (GRACE) 2.0 risk score, and the risk of recurrent acute coronary syndrome. Lipoprotein (a) levels >50 mg/dl were detected in 28,4% of patients with MI and were associated with prior medical events, coronary and non-coronary artery atherosclerosis, comorbidity, recurrent coronary lesions, and the risk of major cardiac events at the end of follow-up. A relationship was established between a high (5,14) triglyceride-glucose index and comorbidity, recurrent coronary lesions, and the death risk at the end of follow-up.Conclusion. The Biobank of Yugra laboratory is an effective base for laboratory research. Lipoprotein transport and metabolism markers are associated with clinical factors, comorbidity, vascular atherosclerosis and a negative prognosis in patients with MI.

HighlightsThe complex role of the brain natriuretic peptide in the pathogenesis of arterial hypertension, as well as the successful use of the N-terminal fragment of the prohormone brain-type natriuretic peptide as a biomarker of cardiovascular diseases determine the relevance of this work. Aim. To study the association between brain natriuretic peptide levels (NT-proBNP) and markers of the severity of resistant arterial hypertension.Methods. The study included 40 patients with diagnosed resistant arterial hypertension (RAH) and 30 patients with AH. All patients underwent clinical examination and measurement of NT-proBNP levels before and after receiving standard antihypertensive therapy.Results. Before receiving standardized antihypertensive therapy (AHT), NT-proBNP levels in the group of patients with RAH and in the group of patients with non-resistant hypertension did not differ significantly (p = 0.48), but systolic BP was statistically significantly higher (p = 0.039) in the group of patients with RAH. RAH revealed a direct association between NT-proBNP and sodium (r = 0,38; p = 0.01), as well as a direct association between NT-proBNP and body mass index (r = 0,32; p = 0.02). Factor analysis revealed a relationship between NT-proBNP and age (p < 0.01), as well as a direct relationship between NT-proBNP and potassium (r = 0,29; p = 0.04). After receiving standardized AHT, NT-proBNP levels decreased in the RAH group and in the non-resistant AH group (p = 0.03; p = 0.0001), but the decrease was less pronounced in the RAH group. NT-proBNP levels after standardized AHT in the RAH group were higher (p < 0.0001) compared to the non-resistant AH group, and relatively high NT-proBNP levels were directly associated with the presence of RAH (p = 0.0025).Conclusion. The results of the study indicate the presence of an association between NT-proBNP levels and resistant arterial hypertension. Supposedly, this association determines the uncontrolled course of resistant arterial hypertension – desensitization of receptors that regulate vascular tone, lipid metabolism disorders and natriuresis dysfunction.

   Aim. To evaluate the associations of VEGFR2 rs2305948 polymorphism with the occurrence of cardiovascular events during long-term follow-up in patients with myocardial infarction.   Material and methods. The study included 218 patients with acute infarction (MI), mean age 57.7 ± 9.9 years (M ± SD). After clinical examination and preparation, patients urgently underwent coronary angiography followed by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). All patients underwent determination of the rs2305948 VEGFR2 allelic variant by polymerase chain reaction. The duration of long-term follow-up of these patients was 9 years (from 2015 to 2024).   Results. It was determined that during long-term follow-up, patients with rs2305948 VEGFR (C/T and T/T), in contrast to patients with rs2305948 VEGFR (C/C), were more likely to experience cardiovascular death, recurrent acute coronary syndrome (ACS), recurrent revascularization and a combined end point (cardiovascular death, recurrent ACS, coronary stent/bypass thrombosis, acute ischemic cerebrovascular accident, repeated myocardial revascularization). Using multivariate analysis, it was determined that the occurrence of cardiovascular death during long-term follow-up is directly influenced by the Charlton comorbidity index (p < 0.001) and rs2305948 VEGFR2 (C/T and T/T) (p = 0.030). The onset of a combined endpoint is directly determined by the Charlton comorbidity index (p = 0.014) and rs2305948 VEGFR2 (C/T and T/T) (p = 0.034) and vice versa by subsequent outpatient treatment with high doses of statins (p < 0.001).   Conclusions. The presence of rs2305948 VEGFR (C/T and T/T) in patients with MI increases the likelihood of cardiovascular death by 2.82 times and the combined endpoint by 2.10 times during long-term follow-up (9 years).

Aim. To evaluate the efficacy of P2Y₁₂ receptor inhibitors (clopidogrel and ticagrelor) in patients with myocardial infarction (MI) living in the northern region of Russia (Khanty-Mansi Autonomous Okrug — Yugra), depending on the carriage of various CYP2C19 allelic variants.Material and methods. This prospective observational study included 218 patients with acute MI who underwent percutaneous coronary intervention (PCI). The patients also underwent determination of allelic variants of the CYP2C19 gene. Patient were divided into groups receiving clopidogrel (n=164, 75%) and ticagrelor (n=54, 25%). Using biostatistical analysis methods, a comparison of clinical and genetic characteristics was performed, as well as an assessment of the risk of ischemic events between the groups in the long-term (108 months, 9 years) post-infarction period.Results. Reduced (*1/*2, *2/*2, *1/*3) and increased (*1/*17, *17/*17) metabolizer CYP2C19 genotypes, as well as severe comorbidity, are reliable independent predictors of composite outcome (cardiovascular death, recurrent acute coronary syndrome, coronary stent/bypass thrombosis, myocardial revascularization, acute ischemic cerebrovascular accident) during a long-term (9 years) follow-up. The advantages of ticagrelor over clopidogrel in terms of the effect on the incidence of ischemic events in the long-term period were established without a significant difference for bleeding both in the general cohort of patients and among carriers of CYP2C19 allelic variants (*1/*2, *2/*2, *1/*3) and (*1/*17,*17/*17) in patients with MI.Conclusion. Ticagrelor is significantly more effective than clopidogrel in reducing the risk of ischemic events in the general cohort of patients, as well as in carriers of reduced (*1/*2, *2/*2, *1/*3) and increased (*1/*17, *17/*17) metabolizer CYP2C19 genotypes during 9-year follow-up after the index MI.