Aim     To determine the array of metabolomic profiles and structural and functional parameters of the vascular wall associated with the risk of cardiovascular toxicity of antitumor therapy (ATT) in oncohematological patients.

Material and methods            This study included 59 patients, among them 34 patients with lymphomas (non-Hodgkin and Hodgkin lymphoma) and 25 with multiple myeloma. Before and after 3 courses of ATT (anthracyclines, proteasome inhibitors), finger photoplethysmography and transthoracic echocardiography were performed as well as metabolomic profiling (98 metabolites) by high-performance liquid chromatography in combination with tandem mass spectrometry. Statistical analysis of the results included parametric and nonparametric tests, logistic regression, and cross-validation.

Results            The study showed that even before the initiation of ATT, cancer patients had signs of endothelial dysfunction and increased vascular wall stiffness (increased aSI, RI, and IO indices), which significantly worsened after the specific treatment. Metabolomic profiling identified a set of metabolites associated with the risk of cardiovascular toxicity, including increased concentrations of amino acids (asparagine, serine, glutamate, glutamine, taurine, citrulline), short-chain acylcarnitines (C18:1 OH-carnitine, C16:1 OH-carnitine, C14OH-carnitine, C2 carnitine), choline metabolism intermediates (TMAO, dimethylglycine, choline), tryptophan metabolites (hydroxyindoleacetic acid, kynurenic acid). Additionally, a logistic regression model was developed based on the analysis of the metabolomic profile, which showed a high prognostic power (AUC = 0.84) for predicting cardiovascular toxicity of ATT.

Conclusion      The study identified key metabolites and structural and functional parameters of blood vessels that allow detection of an increased risk of cardiovascular complications of ATT in patients with lymphomas and multiple myeloma before the initiation of a specific treatment. Increased concentrations of amino acids, acylcarnitines, and choline metabolites may serve as an additional risk factor for the onset/progression of cardiovascular complications. The proposed integrative approach, including both metabolomic profiling and non-invasive assessment of the vascular wall condition, opens broad prospects for personalized cardioprotection of cancer patients and more accurate monitoring of the cardiovascular status during ATT.

Aim     In a prospective observational study of risk stratification in patients with ischemic heart disease (IHD) using stress echocardiography (Stress ECHO), to evaluate the significance of left ventricular (LV) global longitudinal strain (GLS) as an independent prognostic marker or as an adjunct to the existing markers.

Material and methods            This study included 273 patients (60.4% men, mean age 60.9±9.5 years) with known (n=109; 39.9%) or suspected (n=164; 60.1%; IHD pretest probability (PT): 17 [11-26]% (interquartile ranges: Me [Q1; Q3])) IHD. All patients underwent Stress ECHO with physical exercise (PE) on a recumbent bicycle ergometer (n=165; 60.4%), vasodilator (adenosine triphosphate (ATP), n=74; 27.1%), and other stress tests (n=34; 12.5%). The Stress ECHO protocol included assessment of local contractile disorders (LCD), B-lines, LV contractile reserve (CR), and heart rate reserve. Additionally, LV GLS was assessed at rest and at the test peak, and GLS reserve and GLS change (ΔGLS) were calculated. The prospective follow-up period was 20 [13-25] months. The composite cardiovascular end point (CVE) included death from cardiovascular causes, acute coronary syndrome, revascularization, and stroke/transient ischemic attack, and was calculated until the first event.

Results            Prognostic values were obtained for 272 (99.6%) patients. During the follow-up period, 114 cardiovascular complications (CVC) occurred in 87 (31.9%) patients (1 to 3 in each patient). According to the multivariate regression analysis of the Stress ECHO results, the independent predictors for the CVE were the emergence of new LCDs at the peak of stress testing (odds ratio (OR) 2.95; 95% confidence interval (CI): 1.51-5.76; p=0.02) and ΔGLS (OR 0.90; 95% CI: 0.81-0.99; p=0.039). With the use of ATP, the risk of developing CVC was described by a similar model, that had an even higher level of significance (OR for LCD 36.21; 95% CI: 3.09-424.09; p=0.004; OR for ΔGLS 0.48; 95% CI: 0.25-0.94; p=0.032). In PE Stress ECHO, the GLS index added to the LCD did not demonstrate an independent prognostic value. The ROC analysis identified a threshold value for ΔGLS as a predictor of unfavorable prognosis. The threshold absolute value was 1.2 in the entire group and 0.2 in the ATP Stress ECHO subgroup. In case of difficulties in assessing the LCD at the testing peak, an alternative model was used with evaluation of the IHD PT (OR 1.09; 95% CI: 1.04-1.14; p<0.001), emergence of angina at the testing peak (OR 5.07; 95% CI: 1.81-14.26; p=0.002), reduced LV CR (OR 2.18; 95% CI 0.73-6.53; p=0.162), and ΔGLS (OR 0.83; 95% CI 0.72-0.95; p=0.008).

Conclusion      In Stress ECHO performed for risk stratification in IHD, the ΔGLS value, regardless of and in addition to LCDs, is a predictor of CVC. The absolute value of ΔGLS <1.2 in the entire group and ΔGLS <0.2 in the ATP subgroup indicates an unfavorable prognosis for the next 1.5 years.

Aim     Clinical and economic analysis of the feasibility of using new-generation drugs of the PCSK-9 inhibitor class (alirocumab and evolocumab) and the drugs that utilize in their action the effect of ribonucleic acid interference (inclisiran) in the treatment of patients with a high risk of cardiovascular events in medical organizations of the Moscow Region (MR).

Material and methods            Based on statistical and literature data on morbidity, as well as data from real-life practice about using alirocumab, evolocumab, and inclisiran in medical organizations of the MR, populations of patients with hypercholesterolemia and cardiovascular pathology were identified in that region. Two analytical models were developed that include the structure and number of patients receiving a combination therapy (high-dose statins + ezetimibe + alirocumab/evolocumab/inclisiran). To estimate the economic feasibility of the treatment with innovative drugs, direct medical costs were calculated for various therapeutic regimens. The cost of pharmacotherapy was calculated per patient per one-year course. A budget impact analysis (BIA) and a sensitivity analysis of the results were performed. The modeling period of the study was 3 years.

Results            The number of patients in different populations receiving the combination therapy will be 12,228 and 895 people in the first year, and 12,973 and 950 people in the third year, taking into account the determined increase in the patient number. The total costs of treating one patient with hypercholesterolemia and cardiovascular diseases during the first year of therapy with inclisiran are 23.31 and 27.66% lower than with evolocumab and alirocumab, respectively. The BIA revealed a slight increase in the total cost of treating patients in each population (by 1.39 and 1.69% compared to 2024). The increase in the regional budget will be related only with the annual increase in the number of patients with hypercholesterolemia. The sensitivity analysis showed the robustness of the results to changes in the initial parameter values.

Conclusion      The treatment of patients with dyslipidemia and high risk of cardiovascular events with alirocumab/evolocumab/inclisiran as part of the combination therapy is an economically justified strategy in the settings of the regional healthcare system.

Aim     To monitor the dynamics of biomarkers during chemotherapy, targeted chemotherapy and targeted monotherapy in patients with HER2-positive breast cancer (BC); to analyze the emergence timing of these changes; to compare early biochemical and echocardiographic criteria; and to determine the best time for assessing latent subclinical cardiac dysfunction.

Material and methods            Patients with BC (229 women aged 57±11 years) treated sequentially with anthracyclines, a combination of docetaxel and trastuzumab, and trastuzumab monotherapy were examined during three blocks of BC therapy until the development of clinical cardiotoxicity. Time-related changes in high-sensitivity cardiac troponin I, N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular (LV) global longitudinal strain (GLS) and LV ejection fraction (EF) (up to 12 speckle-tracking echocardiograms/up to 12 laboratory tests) were analyzed. Clinical cardiotoxicity was defined as a symptomatic decrease in LV EF ≥10% from the baseline value of 54% or more.

Results            Clinically significant cardiotoxicity developed in 6.3-10.9% of cases depending on the treatment option for BC. Early manifestations of cardiotoxicity were detected already at 3 weeks after the start of the first course of chemotherapy. For the BC treatment with anthracyclines and targeted chemotherapy with docetaxel and trastuzumab, the markers of clinical cardiotoxicity were high-sensitivity cardiac troponin I, NT-proBNP and GLS LV. For the trastuzumab monotherapy, only GLS LV had a prognostic value. No statistically significant changes in the concentrations of high-sensitivity troponin I and NT-proBNP were found.

Conclusion      For timely detection of clinical cardiotoxicity, laboratory tests (high-sensitivity troponin I, NT-proBNP) and echocardiography (GLS LV) are recommended to be performed every 3 weeks before the next course of BC therapy. While doing so, their sensitivity will depend on the treatment option for BC.

Aim    Development and implementation of the M-Cardio mobile application for remote monitoring of patients with chronic heart failure (CHF) at the outpatient stage with an assessment of clinical effectiveness.
Material and methods        This study included 244 patients with NYHA functional class (FC) II-III CHF of ischemic etiology. During the inpatient phase, the patients were taught the basics of self-monitoring and self-care in CHF. In addition, patients of the main group were trained in using the M-Cardio mobile application. Patients were randomized into 2 groups: Group 1 was the main group, with further remote monitoring using the mobile application (n = 127), Group 2 was a control group, with standard outpatient monitoring at the patient’s residence (n = 117). The original version of the mobile application was downloaded to the smartphones of the participants in the main group. The app contained a developed algorithm of clinical indicators, which allows real-time assessment of the patient’s condition based on the quantitative deviations above or below threshold values. This algorithm includes 7 items, shortness of breath, position in bed, palpitation, edema, body weight, blood pressure (BP), and heart rate (HR), which the patient fills in twice a week or every day if necessary. A possibility is also included for automated information of the doctor and the patient to specify recommendations and timely adjust the treatment. The follow-up period was 12 months. 
Results        244 patients with NYHA FC II-III CHF of ischemic etiology were selected and enrolled in the study, including 155 (63.5%) men and 89 (36.5%) women (mean age, 61±7.4 years). NYHA FC II CHF was detected in 50 (20.4%) patients and NYHA FC III CHF in 194 (75.5%) patients. The mean left ventricular ejection fraction was 41.6±10.7%.
Conclusion    Preliminary results of the study indicated that the use of remote monitoring of CHF patients was significantly associated with an improvement in their quality of life, ability for self-care, and the functional status. The effectiveness of the M-Cardio mobile application in the remote monitoring of outpatients is based on a decreased frequency of rehospitalizations and an increased survival.

Experts of the working groups of the Russian Society of Cardiology and the Russian Society of Psychiatrists, the Baikal and Siberian Psychosomatic Associations have developed guidelines on the diagnosis and treatment of common mental disorders in patients with cardiovascular diseases. The provisions of the document are based on the results of the most reliable scientific research and recommendations of authoritative medical societies, and are intended to inform physicians about good clinical practice. This document reflects the position of professional organizations on a relevant interdisciplinary problem.
The agreed document is intended for cardiologists, general practitioners, psychiatrists, and other medical specialists who provide care to patients with cardiovascular diseases and comorbid mental disorders.

It is of interest to study a possibility of switching a patient from one class of lipid-lowering drugs, inhibitors of proprotein convertase subtilisin/kexin type 9 (iPCSK9), to another (inclisiran), when the patient has already reached the target level of low-density lipoprotein cholesterol (LDL-C). From a pharmacological point of view, iPCSK9 and small interfering RNA (siRNA) drugs are completely different classes of drugs, although they affect the same target reducing the degradation of low-density lipoprotein (LDL) receptors. Alirocumab and evolocumab directly block circulating PCSK9 in the blood, which leads to an immediate decrease in the blood concentration of LDL-C clinically manifested already on the 1st day after injection. However, inclisiran has a different mechanism of action; it binds to PCSK9 matrix RNA, and shows a clinical effect of reduced the blood level of LDL-C later. In this article, we described several clinical cases of such switches and analyzed the risks for the patient associated with these situations. When changing an iPCSK9 targeted drug in clinical practice, we observed a change in the blood lipid composition, which affected the achievement of the LDL-C goal by the patient. Alirocumab demonstrated the greatest reduction in LDL-C (-56.5% compared to baseline in the first clinical case and -53% in the second), while the inclisiran treatment resulted in 31.4% and 36.2% decreases in LDL-C from baseline, respectively. These cases support a practical approach to changes in therapy; there is no need to change the PCSK9-targeted drug if the patient has achieved the LDL-C goal. However, if a change in therapy is necessary for a number of independent reasons, it is important to monitor blood levels of LDL-C on a regular basis due to the different lipid-lowering efficacy of the drugs. These cases illustrate the importance of a balanced approach to changes in the therapy for dyslipidemia when the patient has achieved the goal and is tolerating the treatment well.