Влияние физических тренировок на функциональные и гемодинамические показатели пациентов с хронической сердечной недостаточностью III–IV функционального класса в зависимости от потребности в инотропной поддержке

One of the urgent tasks is the search for early and specific markers of cardio­vascular diseases (CVD) in order to stratify the cardiovascular risk, develop methods for their prevention, early diagnosis and treatment. In recent decades, considerable attention has been paid to plasma cell-free nucleic acids free: circulating cell-free DNA (сfDNA) and circulating non-coding RNA, in particular microRNA, which are considered as promising prognostic and diagnostic bio­markers of many pathological conditions, since they play a key role in the regu­lation of physiological and pathophysiological processes. This review covers current understanding of the potential of plasma cfDNA and microRNA assessment in cardiovascular patients as specific biomarkers for diagnosis, risk stratification, severity assessment and monitoring of CVD, with a focus on coronary artery dise­ase, heart failure and cardiac allograft rejection, where this area of research is promising.

Background/Clinical Significance: Development of acute antibody-mediated rejection (AMR) of allograft is one of the leading causes of mortality in heart-transplant recipients; however, the standard therapy does not always resolve severe forms of rejection. Extracorporeal photopheresis (ECP) is a method of immunomodulatory therapy that involves separating a patient’s white blood cells and treating them with a photosensitizer and ultraviolet A irradiation. Case Presentation: An 18-year-old female patient was urgently hospitalized with complaints of shortness of breath. She had undergone heart-transplant surgery 9 months before due to congenital heart disease restrictive cardiomyopathy, complicated with end-stage chronic heart failure. During the admission she admitted that for 3 weeks she discontinued tacrolimus and mycophenolate mofetil. AMR3 and CAV were verified. Conclusions: The use of standard approaches in the treatment of acute AMR is not always able to suppress an expressed immune reaction against the cardiac allograft, which leads to disruption of its function and rejection in the early or long-term follow-up. The inclusion of ECP in the treatment regimen allowed us to stabilize the patient’s condition and achieve regression in the severity of the AMR. It is believed that an important role in this was played by the activity of the immune system, which we assessed by changing the profile of cytokines, chemokines, and other growth factors. Thus, ECP demonstrated its effectiveness in the treatment of AMR of the cardiac allograft, with a change in the severity of the cytokine storm, as well as with an increase in the contribution of cytokines associated with the Th17 response.

Aim To assess the tolerability of an individualized physical rehabilitation program (PRP) in inotrope-dependent patients with end-stage chronic heart failure (CHF). Material and methods This prospective randomized study included 120 men aged 18-65 years with left ventricular ejection fraction ≤30 % and blood pressure ≥90 / 60 mm Hg. Patients who have received dobutamine or dopamine for ≥2 weeks were randomized into two groups: group 1, 40 patients who participated in the PRP and group 2, 40 patients who did not participate in the PRP. Group 3 included 40 patients without inotropic support who participated in the PRP. Results Patients of groups 1 and 3 attended >80 % of the scheduled classes without developing life-threatening adverse events (AEs) associated with exercise (E). After 6 months of the study, the exercising patients achieved a comparable (average) E intensity: 44 [35; 50]% and 45 [40;52]% of heart rate reserve and Borg scale scores 14 [12; 14] and 13 [11; 14] in groups 1 and 3, respectively (p>0.05). Initially, after 3 and 6 months at the peak of physical activity in groups 1 and 3, there was no decrease in arterial blood oxygen saturation according to pulse oximetry (SpO ₂ ) <93 %. At baseline, lactate levels in central venous blood at rest were normal in all groups. After 6 months, the lactate concentration was 1.1 mmol / l in group 1, 2.3 mmol / l in group 2, and 1.4 mmol / l in group 3 (р1-2=0.005; p2-3=0.008, respectively). At the E peak at baseline, after 3 and 6 months, comparable increases in lactate not exceeding 3 mmol / l were detected in groups 1 and 3. Conclusion The study allowed assessment of the tolerability of individualized PRP performed at the aerobic level of energy supply, in inotropic-dependent patients with CHF. Individualized 6-month PRP in inotropic-dependent patients with end-stage CHF, provided safety criteria are met, is well tolerated and does not increase the number of AEs associated with CHF and physical rehabilitation (PR). Continued inotropic support with dopamine or dobutamine should not be considered as a contraindication to PR in patients with CHF in the absence of E intolerance or life-threatening AEs.

Background: Heart transplantation (HT) remains the primary treatment for end-stage heart failure, but graft rejection—including acute cellular rejection (ACR), antibody-mediated rejection (AMR), and chronic rejection such as cardiac allograft vasculopathy (CAV)—significantly impacts long-term patient outcomes. This study investigates the role of circulating plasma extracellular vesicle profiles as potential biomarkers for distinguishing between different rejection types following HT. Methods: We enrolled 85 HT patients with post-transplant follow-up ranging from 2 to 140 months. The cohort included patients diagnosed with AMR (n = 23), ACR (n = 11), CAV (n = 20), and those without rejection (R0, n = 31). Extracellular vesicle profiles were analyzed using the MACSPlex Exosome Kit, and associated cytokine profiles were assessed using the MILLIPLEX Human Cytokine Panel A. Statistical analysis involved the Kruskal Wallis test followed by Dunn’s post-hoc test for multiple comparisons and discriminant analysis. Results: Circulating plasma extracellular vesicle profiles demonstrated significant differences across post-transplantation time strata and varied according to the type of transplant rejection. During the first year post-HT, the main discriminant factors were extracellular vesicles (EVs) characterized by tetraspanins (CD9+, CD63+) and platelet markers (CD62P+, CD42a+). Five years post-transplantation, significant differences emerged in patients with AMR and ACR (both compared to each other and to the CAV/R0 groups). This difference corresponded with an increase in EV markers associated with immune cell activity (CD3+, CD4+, CD49e+, CD86+, CD20+, CD14+, CD209+, CD1c+, CD29+). Levels of prominent EV subpopulations correlated with IL‑22 in CAV patients, whereas in AMR patients, they correlated with IL‑17 and IL‑25. Conclusions: These findings support the hypothesis that extracellular vesicles may participate in both direct and indirect antigen presentation and in the regulation of immune responses leading to allograft rejection after HT. Plasma extracellular vesicle profiles hold promise as non-invasive biomarkers for monitoring and differentiating rejection types in heart transplant recipients.

The aim of the study was to assess the likelihood of infectious complications (IC) in heart transplant (HTx) recipients receiving grafts from donors with a positive blood culture, as well as to evaluate the microbiological status of donors and the levels of inflammatory biomarkers and immunoglobulins. The study is relevant due to the need to improve heart transplantation safety and minimize the risk of IC, which remain one of the leading causes of postoperative complications and mortality in the early postoperative period. A single-center retrospective study was conducted on 43 HTx procedures performed in 2024 at the Republican Scientific and Practical Center “Cardiology.” Donors and recipients were divided into two groups according to the results of donor blood bacteriological testing. The analysis included blood cultures for sterility, cultures from central venous catheter (CVC) samples, and left atrial tissue of donor hearts, as well as the determination of C-reactive protein, procalcitonin, and immunoglobu- lin levels. According to the obtained data, a positive donor blood culture was not associated with an increased risk of IC in recipients during the early postoperative period. No significant association was found between positive CVC cultures and donor bacteremia, nor between positive donor blood cultures and the detection of microorganisms in donor heart tissue. The most frequently identified microorganisms were S. epidermidis and A. baumannii. Donors with positive blood cultures exhibited significantly higher IgA levels compared to those with negative blood cultures, while other inflammatory markers and immuno- globulins showed no statistically significant differences. The findings justify the need to expand the sample size and further investigate the role of microbiological and immunological factors in the development of IC in heart transplant recipients.