МНЕНИЕ ЭКСПЕРТА
It has been proven and widely accepted that comprehensive cardiac rehabilitation that underlies secondary prevention reduces morbidity, disability, and mortality from cardiovascular diseases and their complications, improves quality of life, and minimizes economic losses to the healthcare system and the state as a whole. Unfortunately, despite the recognized benefits of cardiac rehabilitation, it remains underutilized or inadequately utilized. In addition to the common barriers to participation in rehabilitation that occur in most countries, the Russian Federation faces a number of limiting factors related to discrepancies between current regulations and clinical guidelines on cardiac rehabilitation, which critically impacts the rehabilitation of cardiac patients. To address this issue, it would be appropriate to separate cardiac rehabilitation from the "medical rehabilitation of patients with somatic diseases." This situation requires cardiologists to create a consensus document on cardiac rehabilitation, which should address organizational issues, routing, a description of cardiac rehabilitation programs with proven effectiveness, and criteria of the rehabilitation effectiveness specific to cardiac patients. Therefore, this should be a document aimed at reducing mortality, complications, disability, and increasing the life expectancy of cardiac patients, which is the primary goal of healthcare.
RESEARCH ARTICLES
Aim To study the quantitative characteristics of cardiomyocyte mitochondrial ultrastructure using electron microscopy data of patients with chronic heart failure (CHF) and to analyze the association of these characteristics with CHF clinical parameters and severity.
Material and methods The study analyzed a total of 180 micrographs of right atrial appendage cardiomyocytes from 30 patients with CHF and reduced or mid-range left ventricular ejection fraction (LVEF). Standard laboratory and instrumental tests, including echocardiography, a 6-minute walk test (6MWT), and a cardiorespiratory exercise test, were performed in all patients. Biopsy samples were collected during coronary artery bypass grafting. Electron microscopy was performed with a JEM-1400 transmission electron microscope. The total interfibrillar mitochondrial area (Smtx) was calculated at a magnification of ×5,000. Also, the ratio of the outer membrane length of an individual mitochondrion to the length of its inner membrane at a magnification of ×15,000 was calculated.
Results The Smtx positively correlated with the exercise tolerance (r=0.593; p=0.033), peak oxygen consumption during exercise (r=0.395; p=0.012), and the distance covered in the 6MWT (r=0.483; p=0.002). A negative correlation was found between Smtx and the concentration of N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) (r= -0.472; p=0.017). The ratio of the outer mitochondrial membrane length to the inner membrane length inversely correlated with LVEF (r= -0.593; p=0.033).
Conclusion The total area of cardiomyocyte interfibrillar mitochondria correlated with exercise tolerance, peak oxygen consumption, and NT-proBNP concentration, while the mitochondrial membrane length ratio correlated with left ventricular ejection fraction. This suggests an association between quantitative parameters of mitochondrial ultrastructure and clinical manifestations of CHF.
Aim To evaluate changes in speech signal parameters during treatment in patients with chronic heart failure (CHF) and to optimize a set of speech parameters that can be used for remote monitoring of patients' condition after treatment.
Material and methods Speech signals of 55 patients with CHF during exacerbation and 38 patients of the same group during remission were analyzed using a proprietary technique. The results were compared with speech signal data of 57 apparently healthy individuals. The following acoustic and prosodic parameters were calculated for the three groups using the Praat v 6.4.35 software: mean, minimum, and maximum values of the fundamental tone frequency, its standard deviation, variation range and mean absolute slope, jitters (local, abs, rap, ppq5, ddp), shimmers (local, apq3, apq5, apq11, dda), harmonic-to-noise ratio, and the ratio of the number of voiced frames to the total number of frames.
Results The study compared three groups: patients before treatment (group 1.1), after treatment (group 1.2), and a control group of apparently healthy individuals (group 2). Analysis of speech signal parameters showed that patients before treatment had significantly different from the control values of several parameters, which reflected the frequency and amplitude instability of the voice. After the course of therapy, the Jitter (local) value was significantly decreased (p=0.012), while in group 1.2, the jitter values did not differ from the values in the control group, indicating the normalization of the frequency stability of the voice signal. The Bowley skew index also was significantly increased (p=0.041) and approached the values of the control group (p=0.068). The Shimmer (dda) and Shimmer (apq3) indexes did not show positive dynamics and maintained significant differences from the control values.
Conclusion The study showed that during treatment of patients with CHF, as their condition improved, jitter significantly decreased while the nonparametric pitch asymmetry coefficient increased and approached the control values. Other speech parameters either did not change significantly or did not approach the values in the control group. This finding can be used for remote monitoring of CHF patients after hospital discharge.
Aim To develop of a protein panel to identify patients with progressive chronic heart failure with reduced left ventricular ejection fraction (HFrEF) based on proteomic analysis of blood fractions.
Material and methods The study included 81 patients with HFrEF associated with postinfarction myocardial scarring or dilated cardiomyopathy. Patients were enrolled both in a stable period (n=48) and with signs of decompensated heart failure (n=33). Proteomic chromatography-mass-spectrometric analysis of blood plasma and extracellular vesicles (EVs) was performed in all patients. The analysis identified proteins differentially represented between groups in each blood compartment. The effectiveness of using individual proteins and integrated protein panels based on these proteins to identify patients with progressive HFrEF was assessed.
Results Twelve plasma proteins and one BB fraction protein were detected, the concentration of which significantly differed between the groups with and without decompensated HFrEF. Individual protein concentrations demonstrated approximately the same quality indicators in identifying patients with decompensated HF as the classical HF marker, the N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP). Accordingly, we developed two integrated panels including the concentrations of NT-proBNP and several plasma or BB fraction proteins. The plasma panel included five proteins (APOE, LPA, C7, GPLD1, and TF), and the BB panel included two proteins (APOC4, FGB); the proteins are designated in accordance with their genes in the UniProt database. The plasma protein panel demonstrated the highest efficiency in identifying patients with decompensated HF, with a sensitivity of 78.8% and a specificity of 87.5%.
Conclusion The study resulted in the development of a plasma protein panel that can identify patients with progressive chronic HFrEF. This panel is more effective than previously described or currently used biomarkers. However, further research is needed to implement this protein panel into clinical practice.
Aim To study the pharmacokinetics and prove the bioequivalence of Hyposart I (indapamide 1.5 mg + candesartan 16 mg) modified-release film-coated tablets (OOO AKRIKHIN, Russia) compared to the concomitant drugs Arifon® retard (indapamide) prolonged-release film-coated tablets, 1.5 mg (Servier Laboratories, France) + Atacand® (candesartan) tablets, 16 mg (AstraZeneca AB, Sweden).
Material and methods Two two-period crossover-design bioequivalence studies were conducted. In Study 1, healthy volunteers (n=72) took the drugs once either fasted or after a meal, and in Study 2 (n=24), they took them multiple times in a fasting condition. The dosing interval was 7 days. Analyte concentrations in samples were measured by a validated analytical method of high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). Pharmacokinetic parameters were determined for both drugs in Study 1 and for indapamide only in Study 2.
Results The 90% confidence intervals for the ratios of all Ln-transformed pharmacokinetic parameters (Cmax and AUC0-t of candesartan and indapamide in Study 1; Cmax, ss, AUC(0-τ) ss and Cτ, ss of indapamide in Study 2) were in the range of 80-125%.
Conclusion The study has proved the bioequivalence of Hyposart I (AO AKRIKHIN) to the reference concomitant drugs Atacand® (AstraZeneca AB, Sweden) and Arifon® retard (Servier Laboratories, France).
Aim To evaluate the efficacy and safety of a new 3D navigation-guided technique for transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis (AS) and a high risk of atrioventricular (AV) conduction disorder.
Material and methods The study presents the results of a single-center prospective randomized pilot study. Sixty patients meeting inclusion and exclusion criteria with at least one criterion of a high risk for AV conduction disorder were enrolled in the study. All included patients were randomized 1:1 into two groups. In Group 1, TAVI was performed using a 3D navigation-guided technique, while in Group 2, the classical TAVI technique was used. The primary endpoint was the composite incidence of permanent pacemaker (PP) implantation and new-onset complete left bundle branch block (LBBB) at 6 months.
Results In the early postoperative period, the 3D navigation-guided TAVI group had a lower incidence of new-onset LBBB (10.3% vs. 33.3%; p=0.03), better parameters of intraventricular conduction according to electrophysiology study (EPS) (H-V interval 79.1±13.5 ms vs. 96.0±39.9 ms; p=0.03) and electrocardiography (QRS complex duration 108.0±16.3 ms vs. 119.0±22.6 ms; p=0.04). The incidence of PP implantation during the hospital stage, A-H interval duration, and Wenckebach point in the AV junction according to EPS did not differ significantly between the groups. The incidence of the primary endpoint (PP implantation + new-onset LBBB) during the 6-month follow-up period was 43.3% in the classical technique group and 16.7% in the 3D navigation-guided TAVI group (p=0.02). There were no statistically significant differences between the groups in the incidence of procedural complications or major adverse cardiovascular and cerebrovascular outcomes.
Conclusion This study demonstrated the efficacy and safety of a new 3D navigation-guided TAVI technique in reducing the composite rate of implantation PP and LBBB at 6 months post-procedure, with comparable rates of procedural complications and major adverse cardiac and cerebrovascular events (MACCE) during long-term follow-up. Implementation of these findings into clinical practice will enable personalization and optimization of transcatheter treatment outcomes in patients with severe AS.
Aim To identify predictors of increased N-terminal pro-brain natriuretic peptide (NT-proBNP) in a population of outpatients at a high risk for chronic heart failure (CHF) using methods based on the clinical decision limit (CDL), reference intervals (RI), and age- and sex-adjusted NT-proBNP ratio.
Material and methods Timely diagnosis and initiation of treatment at the early stages of CHF improve the prognosis of patients. Accordingly, a program for supporting patients at a high-risk of CHF by measuring NT-proBNP was implemented in all federal districts (FDs) of the Russian Federation. The analysis included 11,740 patients at high risk of developing CHF, who had a single NT-proBNP measurement in an outpatient setting. The inclusion criteria were age >18 years, symptoms and signs of CHF and/or abnormalities on electrocardiogram and/or the presence of diseases (arterial hypertension and/or any form of ischemic heart disease). The analysis included determining the proportion of patients with NT-proBNP test results above the CDL (NT-proBNP ≥125 pg/ml) and above the RI (97.5th percentile). For additional assessment, the age- and gender-adjusted NT-proBNP ratio was used. The risk of elevated NT-proBNP was assessed based on CDL, RI, and the NT-proBNP ratio.
Results The median age of patients was 66 [58.0; 73.0] years, 55.8% were >65 years, and 59.3% were women. In 43.5% of patients, the NT-proBNP concentration was less than 125 pg/ml. The risk of achieving CDL was 50% higher among men, associated with the patient's age, and increased by 73% in the 45-54 age group, 2.52 times in the 55-64 age group, and 6.62 times in the >65 years age group compared to the 18-44 age group. Living in a city with a population of less than one million people increased the risk of achieving CDL by 17% compared to living in a city with a population of over a million. NT-proBNP values above the RI were achieved by 22% of patients, with the risk being 69% higher among men and 24% higher among patients living in cities with a population of less than one million. Evaluation of the NT-proBNP test results using the RI criterion showed that 44.3% of patients with normal RI values had NT-proBNP values above the CDL (≥125 pg/ml). The NT-proBNP ratio was the lowest in the Ural Federal District and the highest in the Far Eastern Federal District. The risk of an increased NT-proBNP ratio ≥1 was higher among men by 67% (p<0.001), for residents of small towns by 21% (p<0.001), and for residents of the Far Eastern Federal District compared to any other region (p<0.001).
Conclusion Independent risk factors for elevated NT-proBNP when assessed by the RI and NT-proBNP ratio included male gender, residence in cities with a population of less than one million, and residence in the Far Eastern Federal District. Assessing the NT-proBNP test solely based on the CDL, without taking into account physiological changes related to gender and age, carries a risk of overdiagnosis of CHF.
Aim Evaluation of clinical, demographic, laboratory, and instrumental characteristics of patients with acute decompensated heart failure (ADHF) depending on the outcome over the hospitalization period.
Material and methods The prevalence of chronic heart failure (CHF) and ADHF remains extremely high. Hospitalization for ADHF is the most important predictor of death and readmission in the long term, and each subsequent hospitalization significantly increases the risk of death. Research of in-hospital mortality in this group of patients is limited in the Russian literature; however, numerous studies have examined mortality at 30, 60, and more days after discharge. This comprehensive retrospective study included patients aged >18 years who were hospitalized for ADHF in a multidisciplinary hospital from December 1, 2019 through December 1, 2021. Patients were divided into two groups based on their outcomes during their hospital stay. Laboratory, clinical, and instrumental characteristics were assessed with subsequent multivariate data analysis. Statistical analysis was performed using an IBM SPSS Statistics version 24.0 software.
Results During the observation period, 498 patients were included. In-hospital mortality was 8% (n=41). According to the results of binary logistic regression, the need for inotropic drugs (odds ratio (OR) 94.6; 95% confidence interval (CI): 19.8-451; p<0.001), presence of an infectious disease requiring antimicrobial therapy (OR 6.6; 95% CI 1.5-29; p=0.01), an increase in high-sensitivity troponin >99th percentile on admission (OR 6.1; 95% CI: 1.35-28.1; p=0.01), and systolic blood pressure <110 mmHg. (OR 4.2; 95% CI 1.06-16.6; p=0.01) were directly associated with the likelihood of death during the hospital stay. The resulting regression model was statistically significant (p<0.001). Based on the value of the Nigelkirk determination coefficient, the compiled model takes into account 71.1% of the factors that determine the likelihood of death during hospital stay. The sensitivity of the model was 98.6%, the specificity was 74.1%, and the diagnostic efficiency was 96.5%.
Conclusion Thirty percent of hospitalized patients with ADHF without signs of acute coronary syndrome or other focal pathology had elevated high-sensitivity troponin levels >99th percentile upon admission, which was directly associated with the in-hospital mortality. These patients represent a special group with a poor prognosis during their hospital stay, and myocardial injury markers have a high predictive value for assessing clinical outcomes in this patient population.
Objective To evaluate coronary CT angiography (CCTA) combined with Coronary Artery Disease Reporting and Data System (CAD-RADS) grading and with high-risk plaque characteristics for predicting 30 day major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS).
Material and methods A prospective, multicenter cohort study was conducted by enrolling 300 ACS patients admitted to four tertiary hospitals from January 2023 to June 2024. All patients underwent CCTA examination within 24 h of admission. Coronary artery stenosis severity was assessed using CAD-RADS 2.0 criteria, and high-risk plaque characteristics, including low-density plaque, positive remodeling, spotty calcification, and napkin-ring sign, were analyzed. Baseline clinical data were collected, Global Registry of Acute Coronary Events (GRACE) scores were calculated, and the 30 day MACE incidence was evaluated. Logistic regression analysis was used to evaluate risk factors, and receiver operating characteristic (ROC) curves were used to assess diagnostic performance.
Results The incidence of 30 day MACE was 22.7 % (68 / 300 cases). Spearman’s rank correlation analysis demonstrated that MACE incidence showed a significant positive correlation with the CAD-RADS grade (ρ=0.658, p<0.05), increasing from 0 % in CAD-RADS grade 0 to 100 % in CAD-RADS grade 5. Patients in the MACE group were older, had higher prevalence of diabetes and higher GRACE scores (all p<0.05). High-risk plaque characteristics, i.e., low-density plaque, positive remodeling, and napkin-ring sign, were detected more frequently in the MACE group (all p<0.05). Multivariate analysis showed that the GRACE score and positive remodeling were independent predictors of 30 day MACE (both p<0.05). The comprehensive prediction model combining GRACE score, CAD-RADS grading, and high-risk plaque characteristics achieved an area under the ROC curve (AUC) of 0.789, significantly superior to the GRACE score model alone (AUC=0.723, p=0.018), representing a 9.1 % improvement in discriminative ability.
Conclusion A non-invasive imaging examination, CCTA, combined with CAD-RADS grading and high-risk plaque assessment can improve the prediction of 30 day MACE risk in ACS patients beyond traditional risk scores, providing important reference for clinical risk stratification and precision treatment decision-making.
Objective To evaluate the predictive value of novel biomarkers for early detection of renal function injury following percutaneous coronary intervention (PCI) in patients with acute coronary syndrome.
Material and methods A prospective observational study was conducted, enrolling 326 patients with acute coronary syndrome who underwent PCI at Zhangjiakou First Hospital from January to December 2024. Patients were divided into acute kidney injury (AKI) group (n=52) and non-AKI group (n=274) based on whether AKI occurred within 48 h post-PCI. Blood samples were collected at pre-PCI baseline and at 2, 6, 12, and 24 h post-procedure to measure traditional renal markers (serum creatinine, blood urea nitrogen, estimated glomerular filtration rate, Cystatin C) and novel biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule-1 [KIM-1], interleukin-18 [IL-18], tissue inhibitor of metalloproteinases-2 [TIMP2], insulin-like growth factor-binding protein 7 [IGFBP7], liver-type fatty acid-binding protein [L-FABP], receptor-interacting protein kinase 3 [RIPK3], and N-acetyl-β-D-glucosaminidase [NAG]). Receiver operating characteristic (ROC) curves were used to assess the predictive value of biomarkers. Multivariate logistic regression analysis was performed to identify independent predictors of AKI.
Results AKI occurred in 52 (16 %) patients. Traditional markers showed no difference between groups within 12 h post-PCI, with differences emerging only at 24 h (p<0.001). Novel biomarkers demonstrated inter-group differences at 24 h (p<0.001), with TIMP2, IGFBP7, L-FABP, RIPK3, and NAG showing elevated concentrations in the AKI group as early as 2 h post-PCI (all p<0.001). The novel biomarker combination demonstrated superior predictive performance (AUC 0.89, 95 % CI 0.84–0.94) compared to traditional markers (AUC 0.71, 95 % CI 0.65–0.77, p<0.001), with NGAL showing the highest individual predictive value (AUC 0.85, 95 % CI 0.79–0.91). Multivariate analysis revealed that elevated NGAL >150 ng / ml at 2 h post-PCI was the strongest independent predictor of AKI (OR 3.8, 95 % CI 2.1–6.9, p<0.001). The AKI group had longer hospital stays (8.5±3.2 days vs 5.2±2.1 days), higher rates of major adverse cardiac events (18.5 % vs 7.3 %), and increased 30 day mortality (5.8 % vs 1.5 %) compared to the non-AKI group (all p<0.01).
Conclusion Novel renal injury biomarkers, particularly NGAL, KIM-1, IL-18, along with TIMP2, IGFBP7, L-FABP, RIPK3, and NAG, provide superior early detection of post-PCI AKI compared to traditional markers, with abnormal elevation detectable as early as 2 h post-procedure. Elevated NGAL at 2 h post-PCI emerged as the strongest independent predictor of AKI occurrence. Integration of novel biomarker monitoring into routine post-PCI care would facilitate early identification of high-risk patients and timely implementation of renoprotective strategies.
REVIEWS
Inflammation is an integral part of the pathophysiological processes leading to damage or regeneration of the heart and blood vessels. Interest to the "inflammatory theory" of cardiovascular disease is once again at the peak of scientific research, driven by the discovery of new laboratory and instrumental methods, as well as the emergence of new cardiotropic viruses, including SARS-CoV-2. Colchicine, the most effective and safe drug used to modulate excessive inflammation in heart disease, is included in guidelines for the treatment of perimyocarditis and ischemic heart disease with a high class of evidence. Furthermore, it has been shown that colchicine can reduce the innate and, to some extent, the acquired immune response. Thereby, colchicine can affect the arrhythmia substrate and trigger, the inflammatory component of chronic myocardial degeneration during the development of heart failure. Also, colchicine can exert specific and nonspecific positive effects on the cardiac complications of COVID-19. The use of this medication in cardiology practice is limited by insufficient awareness of its indications and side effects, while in rheumatology practice, it is limited by a lack of knowledge about colchicine's additional properties in cardiac conditions. This review summarizes medical studies available online that assess the clinical efficacy of colchicine medicines in the conditions not yet included in official guidelines for its use, such as atrial fibrillation, autoinflammatory diseases, heart failure, and cardiac complications of COVID-19. For each of these conditions, colchicine can be used with the consideration of specific indications. This article includes published in the internet medical studies, abstracts, and meta-analyses with no publication date restrictions up to July 2025. The PubMed, ScienceDirect, Google Scholar, and CENTRAL databases were used to review 520 literature sources that described the clinical efficacy of colchicine medicines and the heterogeneity of its effects across different regimens for various cardiovascular diseases.
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