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Myocardial fibrosis plays a key role in the pathogenesis of heart failure. A family of small non-coding signaling molecules, microRNAs (miRNAs), has been identified as promising profibrogenic biomarkers capable of signaling a possible risk of adverse events after heart transplantation.Objective: to identify and evaluate the diagnostic significance of miRNAs, as well as comprehensive miRNA-based tests in heart recipients with graft myocardial fibrosis.Materials and Methods. The study included 83 heart recipients aged 16 to 64 (48.4 ± 13.1) years. The expression levels of five microRNAs (miR-27, -101, -142, -339, -424) in venous blood plasma were measured by quantitative real-time polymerase chain reaction; galectin-3 serum levels were determined by enzyme immunoassay.Results. Morphological signs of graft myocardial fibrosis were verified in 48 recipients. The miR-27 and miR-339 expression levels were significantly higher in heart recipients with myocardial fibrosis than in those without myocardial fibrosis (p = 0.018 and p = 0.043, respectively). Diagnostically significant threshold levels of miR-27 and miR-339 for detection of myocardial fibrosis in heart transplant recipients were determined (–4.33 and –5.24 units, respectively). The relative risk of detecting graft myocardial fibrosis in recipients with miR-27 expression value above the threshold level was RR = 1.5 ± 0.157 [95% CI 1.104-2.039], p = 0.009; for miR-339, RR = 1.31 ± 0.130 [95% CI 1.018-1.692], p = 0.036. When miR-27 expression levels and galectin-3 serum levels simultaneously exceeded their estimated thresholds, the risk of transplanted heart myocardial fibrosis increased to RR = 2.7 ± 0.456 [95% CI 1.090-6.524], p = 0.032; when miR-339 and galectin-3 simultaneously exceeded threshold values, the risk was RR = 2.0 ± 0.316 [95% CI 1.076-3.717], p = 0.028).Conclusion. The miR-27 and miR-339 expression levels are associated with the presence of fibrotic changes in the graft myocardium. The combination of molecular-genetic and proteomic biomarkers in one test improves the diagnostic characteristics of these expressions with respect to post-transplant complications in heart recipients.

As the survival rate of cardiac recipients improves, higher incidence of malignancy in the late postoperative period becomes essential for their prognosis. Immunosuppressive therapy is one of the key prerequisites for successful transplantation. However, long-term use of immunosuppressive agents increases the incidence of malignant tumors compared to the general population. The risk of their development after organ transplantation increases by 2–4 times compared to the general population. For patients who have undergone transplantation since 2000, the risk of developing malignant neoplasms 1–5 years after surgery is estimated at 10–12%. Timely comprehensive examination of patients, development of new immunosuppression schemes, treatment of those predisposing to the development of malignant neoplasms and giving up harmful habits will reduce the risk of malignant tumors and help diagnose these serious complications at an early stage, which, in turn, will increase the life expectancy of solid organ (particularly the heart) recipients.

Objective: to analyze the correlation between the expression levels of microRNA-101, microRNA-142, microRNA-27, microRNA-339, and microRNA-424 and the plasma concentrations of biomarkers that are potentially significant for the diagnosis of post-transplant complications in heart recipients. Materials and methods. The study enrolled 72 heart recipients, among whom were 56 men (77.8%). The average age of recipients was 48.6 ± 10.9 (16 to 70) years. There were 38 patients with severe chronic heart failure, among whom were 29 men (76.3%). Patients’ mean age was 48.8 ± 9.9 (26 to 70) years. The control group consisted of 12 healthy individuals who did not differ significantly by sex and age. microRNA expression levels in blood plasma were measured via quantitative polymerase chain reaction. Plasma concentrations of VEGF-A, PLGF, MCP-1, and sCD40L were determined using a multiplex method. ST2 and Galectin-3 concentrations were measured via enzyme-linked immunosorbent assay. Results. Patients with end-stage chronic heart failure were found to have significantly higher expression levels of microRNA-27, microRNA-339 and microRNA-424 in blood plasma compared with the healthy individuals. In potential heart recipients, the expression le vels of microRNA-339 and microRNA-424 correlated with serum galectin-3 concentrations, microRNA-101 expression levels correlated with PLGF-1 concentrations, while microRNA-27 expression levels correlated with plasma MCP-1 concentrations. In the early post-transplant period, the expression levels of microRNA-101, microRNA-339, and microRNA-424 in heart recipients were significantly lower than in patients with severe chronic heart failure. In the early post-transplant period (one year or more after transplantation), microRNA-101 and microRNA-27 expression levels were significantly higher than in heart recipients. A year or more after transplantation, the following correlations were found in heart recipients: microRNA-142 expression level correlated with serum levels of galectin-3 (p = 0.05), microRNA-27 and microRNA-424 expression levels correlated with ST2 concentrations (p = 0.02), microRNA-27 expression level correlated with PLGF-1 concentrations (p = 0.02), while microRNA-101 expression level correlated with serum levels of PAPP-A (p = 0.05). Conclusion. In heart recipients, the expression levels of microRNA-142, microRNA-27, microRNA-424, and microRNA-101 correlate with the concentration levels of biomarkers of fibrosis (Galectin-3), rejection (ST2), neoangiogenesis (PLGF), and tissue destruction (PAPP-A). A comprehensive analysis of pre- and post-translational markers may open up new perspectives in diagnosis, assessment of the risks of post-transplant complications, and in understanding the processes leading to their development.

Aim: to study plasma galectin-3 levels in heart recipients and to determine the potential significance of galectin-3 level in acute transplant rejection and fibrosis.Methods. The study included 107 heart transplant recipients, aged 16 to 70 (48 ± 13) years, of which 90 (84%) were men. Dilated cardiomyopathy was diagnosed in 57 patients prior to heart transplantation, end-stage ischemic heart disease in 50. Galectin-3 concentrations and placental growth factor (PlGF) were measured using enzyme-linked immunosorbent assay (ELISA); vascular endothelial growth factors (VEGF-D and VEGF-A), monocyte chemoattractant protein-1 (MCP-1), platelet-derived growth factors (PDGF-BB), and soluble CD40 ligand (sCD40L) were measured using multiplex technology xMAP. Acute graft rejection and myocardial fibrosis were verified through morphological examination of endomyocardial biopsy specimens.Results. Galectin-3 concentrations in patients with congestive heart failure (15.92 [11.80; 23.65] ng/ ml) were significantly higher than in healthy individuals (11.08 [7.71; 14.47] ng/ml), p = 0.00. No correlation was found between galectin-3 levels and sex, age and pre-transplant diagnosis. A month after transplantation, plasma galectin-3 level was significantly higher than before transplantation; a year later, the levels decreased to pre-transplant levels (18.71 [13.14; 25.41] ng/ml). By the end of the first year after transplantation, the levels were significantly higher both in patients with 1-2 episodes and in the patients after 3 or more episodes of acute rejection, in contrast to recipients who were not diagnosed with rejection. By the end of the first year after heart transplantation in patients with fibrosis, plasma galectin-3 levels were significantly higher than in patients without fibrosis. By the end of the first year after heart transplantation, galectin-3 levels in the recipients were associated with the nature of myocardial fibrosis: in patients with diffuse focal fibrosis (22.52 [20.98; 26.08] ng/ml), plasma concentrations of galectin-3 were significantly higher than in patients without fibrosis (15.36 [11.95; 22.42] ng/ ml, p = 0.01).Conclusion. Plasma levels of galectin-3 in heart recipients by the end of the first year after transplantation is associated with previous crises of acute graft rejection, irrespective of the number of rejection episodes. Elevated plasma levels of galectin-3 in heart recipients in the long term after transplantation is associated with myocardial fibrosis; galectin-3 levels are associated with the morphological characteristic of fibrosis in the transplanted heart (diffuse focal fibrosis).

Despite improvements in immunosuppressive therapy, antibody-mediated rejection (AMR) remains one of the most important risk factors for poor prognosis for survival of recipients, cardiac graft dysfunction, and cardiac allograft vasculopathy (CAV) after heart transplantation.Aim: to assess the incidence of case of antibodymediated rejection and cardiac allograft vasculopathy depending on the gender of the patients who underwent heart transplantation in our Center from January 2010 to December 2017.Methods. The median observation was 42 months. The study comprised 606 patients (84 [14%] women) who underwent heart transplantation in 2010 to 2017. We analyzed all the episodes of antibody-mediated rejection, which were diagnosed by the results of endomyocardial biopsies.Results. We comparing the total incidence of antibody-mediated rejection and we are found significant differences among men and women who underwent heart transplantation (p < 0.05), the survival rate during the first year after heart transplantation was 95 and 92%, respectively. The incidence of antibody-consistent rejection was significantly higher among women who had a history of pregnancy and/or use of mechanical circulatory support systems (UNOS status 1A) in the pre-transplantation history (p < 0.05), and we also found significant differences in the incidence of cardiac allograft vasculopathy in women diagnosed with AMR (p < 0.05). The survival rate among women within a year after the diagnosis of AMR is 83% compared to 96% of the recipients free from AMR.Conclusions. Women are at higher risk for AMR after heart transplantation and it increases their risk for cardiac allograft vasculopathy. Females recipients may more frequent myocardial control biopsies and a personalized approach in prescribing immunosuppressive therapy. Women-recipients of transplanted heart should undergo These measures will help to identify in time the development of antibodymediated rejection and reduce the incidence of cardiac allograft vasculopathy after heart transplant.

Tricuspid valve insuffi ciency is one of the most common variants of valve pathology of transplanted heart. The review is sanctifi ed to the analysis of modern looks to on causes, potentially infl uencing on development of tricuspid valve insuffi ciency of transplanted heart, and also methods sent to declines risk his development.

Aim. The study was aimed to assess the prevalence and risk factors of hypertension in cardiac recipients.Materials and methods. End-stage heart failure patients who received cardiac transplant between 01.01.2013 and 31.12.2016 in V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs (Moscow) and survived 3 months after surgery were included and followed up for 999.4 ± 774.3 (108–1587) days. Young patients (Results.353 cardiac recipients aged 45.6 ± 1.6 years (18.1% females and 81.9% males) were enrolled into the study. Hypertension was prevalent in 17.6, 42.8, 62.3 and 71.4%, respectively, before, in 3 months, in 1 year, and 3+ years after the transplantation. The study revealed significant relationship between post-transplant hypertension incidence and pre-op body mass index (р = 0.026), serum creatinine (р < 0.001), preexisting hypertension (RR = 1.36, р = 0.022) and renal failure, as well as donor heart posterior wall thickness (р = 0.034), post-transplant dialysis (RR = 1.85, р < 0.001), and antibody mediated rejection episodes (RR = 1.7, р = 0.001). Uncontrolled hypertension in cardiac recipients was related to poor compliance and new-onset post-transplant renal failure.Conclusion. Hypertension is highly prevalent among our population of cardiac recipients. The combination of various etiologic mechanisms, multiplex therapy and subjective factors calls for the careful individual patient management.

Hypertension is a common syndrome in adult and pediatric cardiac transplant recipients affecting the great majority of patients. Elevated blood pressure is a major potentially modifiable risk factor associated with cardiac graft failure, vasculopathy, arrhythmias, stroke, renal failure and premature death. This review discusses the magnitude of the problem, its distinct mechanisms, and certain issues of prevention and treatment of post-transplant hypertension.

Aim. To examine the assumption that significant concentrations of cystatin C in urine are the manifestation of the tubular necrosis and, respectively, the severity of kidney damage after heart transplantation (HTx).Materials and methods. In this study we evaluated 33 heart recipients (6 women and 27 men, aged from 24 to 68 years old) who had risk factors of acute kidney injury: serum creatinine level >113 μmol/l and/or mechanical circulatory support requirement (20 patients, in 14 cases before HTx). Cystatin C concentration in serum and in urine was measured by DyaSis particle-enhanced immunoturbidimetric assay test «Cystatin C FS».Results. Recipients were divided into two groups according to the levels of cystatinuria. In the group with the significant (more than 0.18 mg/l) urinary cystatin C concentrations the requirement of renal replacement therapy (RRT) was 2.5-fold higher, and the mean duration of RRT was more than 10-fold longer. In 2 patients with the significant cystatinuria acute kidney injury (AKI) has transformed into end-stage renal disease (ESRD).Conclusion. Due to data obtained we may suppose that significant concentrations of cystatin C in urine are the marker of the tubular necrosis with the prolonged RRT requirement. Further studies are needed to justify this relationship.

Aim: to determine the association between plasma concentrations of biomarkers (sCD40L, PDGF-BB, PlGF-1, ST2) with histochemical and immunohistochemical signs of heart rejection.Materials and methods.The study included 98 heart recipients aged from 12 to 69 (mean age 43 ± 14) years, of which 78 men. In 68 patients dilated cardiomyopathy was diagnosed, 30 recipients were diagnosed with coronary heart disease. The concentrations of placental growth factor (PlGF-1), platelet-derived growth factor (PDGF-BB), soluble CD40 ligand (sCD40L) were measured using xMAP technology. The concentrations of ST2 cardiac biomarker were measured by ELISA.Results.No correlation was found between the levels of biomarkers (sCD40L, PDGF-BB, PlGF-1, ST2) and gender, age and diagnosis. The rejection was diagnosed via biopsy in 49 biopsies taken from 37 recipients. 1A rejection was found in 25 patients (34 biopsies), 1B rejection was identifi ed in 2 patients (3 biopsies), 3A rejection was diagnosed in 4 patients. Immunohistochemical signs of humoral rejection were identifi ed in 3 patients. The combination of acute cellular and humoral rejection was found in 4 patients (5 biopsies). The PDGFBB level was measured at the same day as the biopsy was taken, and it was shown to be signifi cantly higher in patients with rejection (p = 0.02). Rejection frequency was signifi cantly higher in patients with high PDGF-BB level (≥2473.7 pg/ml, RR = 1.64 ± 0.23; 95% CI [1.03–2.61]). Rejection frequency increased to 2.11 ± 0.34 [95% CI [1.08–4.11]] in recipients with ST2 and PDGF-BB concentration higher than the median value. The highest predictive value for heart rejection can be reached by a panel of three biomarkers: sCD40L, PlGF-1 and ST2 (RR = 2.51 ± 0.38; 95% CI [1.18–5.3]).Conclusion. PDGF-BB has moderate predictive value for heart rejection. The highest predictive value for heart rejection was reached by a panel of three biomarkers: sCD40L, PlGF-1 and ST2.

Introduction. Increase in the number of older patients with terminal CHF results in increase in their proportion among potential recipients requiring mechanical circulatory support and/or heart transplantation (HT) [Abecassis M., Bridges N.D. et al., 2012].Aim.To analyze our own experience of HT in recipients of older 60 years.Materials and methods. The study included 63 patients (56 men (93.3% ) and 4 (6.7%) women) aged 60–74 years (63.0 ± 0.8) with body weight of 76.6 ± 1.4 kg, body surface area of 1.7 ± 0.02 m2, and body mass index of 23.4 ± 0.6. Indications for heart transplantation: dilated cardiomyopathy – 24 (38.1%), coronary heart disease – 34 (54.0%), hypertrophic cardiomyopathy – 2 (3.2%), irreversible cardiac graft dysfunction – 3 (4.7%). 46 (73.0%) patients had NYHA functional Class III and 17 (23.0%) patients – Class IV. Transpulmonary pressure gradient was 11.2 ± 2.7 mmHg, pulmonary vascular resistance – 3.5 ± 1.3 Wood units. According to UNOS algorithm 10 (15.9%) patients were listed as Status 1A of urgency of orthotopic cardiac transplantation (VA ECMO, n = 8, and implantable left ventricular assist device, n = 2), 21 (33.3%) patients as Status 1B, and 32 (50.8%) patients as Status 2. Recipients had the following comorbidities: arterial hypertension (n = 51; 81.0%), diabetes mellitus (n = 6; 9.5%), cerebrovascular disease (n = 13; 20.6%), history of stroke (n = 9; 14.3%), dialysisindependent renal dysfunction (n = 21; 33.3%). Before cardiac transplantation 9 (14.2%) recipients underwent various thoracic surgeries, 2 (3.2%) recipients – brain surgery. Heart donors (49 (77.8%) men and 14 (22.2%) women) were aged 18–59 (34.3 ± 10.4) years.Results. ICU hospitalization lasted for 4–15 (8.2 ± 0.5) days. In 61.9% of cases (n = 39) early postoperative and hospital periods were uncomplicated. Early on-table postoperative activation («early» tracheal extubation) was performed in 32 (50.8%) patients in 48 ± 6 minutes after surgery completion. 2 (3.2%) recipients demonstrated early graft dysfunction and required VA ECMO. Complications other than graft dysfunction were in 24 (38.1%) recipients: renal dysfunction (n = 8; 12.7%), renal and hepatic dysfunction (n = 4; 6.3%), infections (bacterial pneumonia, n = 3, [4.8%]), dyscirculatory encephalopathy (n = 9; 14.3%). 12 (19.0%) patients required continuous renal replacement therapy, 10 of them (15.9%) demonstrated renal function recovery. In 2 (3.2%) cases long-term hemodialysis was used. Hospital lethality (n = 6; 9.5%) was due to multiple organ failure syndrome and sepsis.Conclusion.Our own experience demonstrates satisfactory short-term and long-term survival after heart transplantation in recipients of 60 years and older.

In this article, the review of the literature on various aspects of the noncompaction cardiomyopathy is presented. Non-compaction cardiomyopathy is a relatively rare congenital heart disease characterized by an excessive prominence of trabecular meshwork, and deep recesses of the ventricular myocardium. The most frequent is left ventricular noncompaction (LVNC). LVNC can occur in isolation or coexist with other cardiac and systemic anomalies. Noncompaction can be detected with an echocardiography or cardiac magnetic resonance imaging. The clinical presentation varies ranging from asymptomatic patients to patients who develop ventricular arrhythmias, heart failure, thromboembolism.

Introduction.Venoarterial extracorporeal membrane oxygenation (VA ECMO) is one of the most widely used methods of temporary mechanical circulatory support (MCS) during the preparation and performance of heart transplant surgery (HT) [Barth E. et al., 2012; Kittleson M.M. et al., 2011].Aimof this study was to assess the effectiveness of using peripheral VA ECMO as a method of mechanical circulatory support in potential heart transplant recipients that urgently required transplantation.Materials and methods. The study included 125 potential heart transplant recipients (107 (86%) men and 18 (14%) women) aged from 12 to 72 (43 ± 1.2) years with a peripheral VA ECMO system installed within the period from April 01, 2011 till August 12, 2016. The indication for the start of its use was rapidly progressing congestive heart failure (CHF) of level 1 or 2 by the INTERMACS scale. Femoral blood vessel cannulation was performed using both open (surgical) and closed (puncture) methods. 23 and 25 F venous cannulae were utilized for femoral vein cannulation, and 15 and 17 F arterial cannulae were utilized for femoral artery cannulation. In all cases superfi cial femoral artery catheterization (14 F single-lumen catheter) or cannulation (8 or 10 F arterial cannula) was performed in the descending (anterograde) direction for the prevention of lower limb ischemia on the side of the femoral artery cannulation.Results.The peripheral cannulation method was used to perform VA ECMO in 100% (n = 125) observations. In 69 (55.2%) patients the severity of progressive CHF corresponded to INTERMACS level 1; in 51 (40.8%) cases it corresponded to INTERMACS level 2. During VA ECMO the average volumetric extracorporeal circulation fl ow rate ranged from 2.2 to 4.5 (3.2 ± 0.4 l/min) or 1.6 ± 0.2 l/min/m2 with the average rotation speed of the centrifugal pump of 3.216 ± 105 rpm. 113 (90.4%) of 125 potential recipients underwent HT. The duration of VA ECMO prior to HT (n = 113) was from 8 hours to 40 (7.1 ± 2.7) days: in 37 (32.7%) of 113 patients – up to 3 days, in 43 (38.1%) cases – from 4 to 7 days, in 21 (18.6%) cases – from 8 to 14 days, in 8 (7.1%) cases from 15 to 21 days, in 4 (3.5%) cases – more than 3 weeks. In the course of VA ECMO, 12 (9.6%) of 125 potential recipients (11 men and 1 women aged from 21 to 63 (40 ± 4) died before they could receive HT. In 2 (16.7%) of 12 cases the cause of death was brain death associated with a thromboembolic cerebrovascular event. The majority of patients (n = 10; 83.3%) died of progressive multiple organ failure and sepsis. 6 of 12 patients showed clinical and instrumental signs of acute unilateral (n = 2) or bilateral (n = 4) polysegmental pneumonia.Conclusion. Peripheral VA ECMO provides a successful bridge to heart transplant procedure in 90% of potential recipients who need pre-transplant MCS. The timely initiation of VA ECMO before the development of pronounced hemodynamic, organ, electrolyte and metabolic disorders creates the conditions for a successful use of MCS in potential heart transplant recipients.

In the review a comparative analysis of the treatment of end-stage chronic heart failure using heart transplantation and durable mechanical circulatory is conducted. It shows the main advantages and limitations of heart transplantation and the prospects of application of durable mechanical circulatory support technology. The main directions of this technology, including two-stage heart transplant (bridge to transplant – BTT), assisted circulation for myocardial recovery (bridge to recovery – BTR) and implantation of an auxiliary pump on a regular basis (destination therapy, DT).

Introduction. The Quilty Effect (lymphoid-cellular infiltration of the endocardium) is a frequent finding in biopsies of the transplanted heart. The role of this phenomenon in the rejection of the transplanted heart remains unclear. Aim. Retrospective analysis of endomyocardial biopsies of the transplanted heart and assessment of the relationship between acute cellular rejection and Quilty Effect. Methods and results. 112 endomyocardial biopsies with Quilty Effect were identified out of 883 studied biopsies during the period from January 2010 to June 2014. The frequency of Quilty damage occurrence in acute cellular rejection is significantly higher than in its absence (17.7% and 5.6%; р < 0.001). The combination of acute cellular rejection with acute antibodymediated rejection significantly increases the frequency of Quilty damage (р = 0.039). Isolated acute antibodymediated rejection of the transplanted heart does not affect the frequency of Quilty Effect occurrence and is not a direct etiologic and pathogenetic factor of this phenomenon. In the absence of acute cellular rejection, Quilty Effect is a predictor of its later development. Mild acute cellular rejection in conjunction with the Quilty Effect causes the risk of more severe degree of rejection. Quilty Effect type B occurs much less frequently than type A (1.9% and 10.8%; р = 0.001) and is observed primarily in acute cellular rejection of grade G2R (р = 0.001); the frequency of these morphological types at various periods after heart transplant was not significantly different (р > 0.05). Conclusion. The Quilty Effect is a kind of manifestation of acute cellular rejection of the transplanted heart when immunosuppressive therapy with calcineurin inhibitors is used.

Aim:to determine the clinical significance of vascular endothelial growth factors VEGF-A, VEGF-D, PlGF-1 to assess the risk of cardiovascular complications in heart recipients.Materials and methods.103 patients, aged 16 to 73 years, 85 males and 18 females. 65 recipients (47 men and 18 women) had dilated cardiomyopathy, 38 – coronary heart disease (CHD). The concentration of VEGF-A, VEGF-D, PlGF-1 was measured using xMAP technology with sets of reagents Simplex ProcartaPlex™.Results.After HTx the level of VEGF-A significantly decreased, p = 0.001. There were no correlations between the levels of VEGF-A, VEGF-D and PlGF-1 with age, gender and diagnosis. After HTx VEGF-A level was higher in recipients with ACR than in those without it (p = 0.001). ACR frequency was significantly higher in patients with high VEGF-A level (≥316.5 pg/ml, RR = 5.8 ± 0.5, AUC = 0.779). After HTx PlGF-1 level was higher in recipients with ACR too (p = 0.039). ACR frequency was significantly higher in patients with high PlGF-1 level (≥5.33 pg/ml, RR = 1.8 ± 0.5, AUC = 0.65). There were no correlations between VEGF-D level with ACR and all three biomarkers with AMR. ACR frequency was significantly higher with both high VEGF-A and PlGF-1 levels (RR = 6.4).Conclusion.Serum levels of VEGF-A and PlGF-1 after HTx may be regarded as indicators of increased risk of ACR.

Aim of study: multiplex analysis of the levels of biomarkers of neoangiogenesis and inflammation in cardiac transplant recipients. Materials and methods. 59 pts. with heart failure III–IV according to NYHA FC, waiting for a heart transplant, aged 22 to 73 years, 48 males and 11 females. 41 recipient (30 men and 11 women) had dilated cardiomyopathy, 18 – coronary heart disease (CHD). The concentration of VEGF-A, VEGF-D, PlGF, PDGF-BB, FGF, sCD40L, MCP-1 was measured using xMAP technology, the sets of reagents Simplex ProcartaPlexTM (Affymetrix, USA). Results. There are four levels of seven biomarkers of neoangiogenesis and inflammation method for multiplex analysis in patients with heart failure. A year after transplantation, the mean levels of biomarkers VEGF-A (p = 0.001), PDGF-BB (p = 0.018), MCP-1 (p = 0.003) was significantly decreased, and the others had a tendency to decrease relative to the level before transplantation. It was shown individual differences of levels of VEGF-A, VEGF-D and PlGF before and after transplantation. There were found different dynamics of the concentrations of biomarkers and growth factors before and after heart transplantation in patients with cardiovascular complications and without them. Conclusion. Multiplex analysis allows to measure the concentration range of analyte biomarkers of neoangiogenesis, inflammation in one sample of blood serum of patients with severe heart failure and after transplantation. There are marked individual differences in the concentration of biomarkers in different clinical situations that may have clinical significance in the conduct and supervision of recipients after transplantation.

Allograft rejection would entail an increase in certain blood biomarkers and active substances derived from activated inflammatory cells which could influence entire vascular endothelial function and deteriorate arterial wall stiffness. We propose that carotid wall functional indices measured with non-invasive ultrasound could we valuable markers of the subclinical cardiac allograft rejection. Aim. Our goal was to analyze the clinical utility of functional common carotid wall (CCW) variables measured with high-resolution Doppler ultrasound as a non-invasive screening tool for allograft rejection in cardiac transplant patients (pts). Methods. One hundred and seventy one pts included 93 cardiac recipients, 30 dilated cardiomyopathy waiting list pts, and 48 stable coronary artery disease (SCAD) pts without decompensated heart failure were included. Along with resistive index (Ri), pulsative index (Pi), and CCW intima-media thickness (IMT), CCW rigidity index (iRIG) was estimated using empirical equation. Non-invasive evaluation was performed in cardiac transplant recipients prior the endomyo- cardial biopsy. Results. Neither of Ri, Pi, or CCW IMT were different in studied subgroups. iRIG was signifi- cantly lower in SCAD pts when compared to the dilated cardiomyopathy subgroup. The later had similar values with cardiac transplant recipients without rejection. Antibody-mediated and cellular rejection were found in 22 (23.7%) and 17 (18.3%) cardiac recipients, respectively. Mean iRIG in pts without rejection was significantly lower in comparison to antibody-mediated rejection and cell-mediated (5514.7 ± 2404.0 vs 11856.1 ± 6643.5 and 16071.9 ± 10029.1 cm/sec 2 , respectively, p = 0.001). Area under ROC for iRIG was 0.90 ± 0.03 units 2 . Analysis showed that iRIG values above estimated treshold 7172 cm/sec 2 suggested relative risk of any type of rejection 17.7 (95%CI = 6.3–49.9) sensitivity 80.5%, specificity – 81.1%, negative predictive value – 84.3%. Conclusions. Increased carotid wall stiffness is found in patients with both antibody-mediated and cellular car- diac allograft rejection. Non-invasive measurement of carotid artery wall rigidity index with triplex ultrasound is a simple screening tool for risk stratification. Having a functional marker would enable preventive measures to be taken at the early stages.

The analysis of clinical outcomes of cardiac transplantation is presented. The main directions of research on the development and implementation of methods for early diagnosis of adverse events and treatment of patients with heart transplant in V.I. Shumakov Federal Research Center of Transplantology and Artifi cial Organs of the Ministry of Healthcare of the Russian Federation are given. Among the non-invasive methods of forecasting, assessment of the risk of cardiovascular complications in heart recipients being developed are: analysis of laboratory biomarkers involved in the formation of relationship of the graft and the recipient; ultrasound diagnosis of functional and structural remodeling of peripheral arteries. The issues of improving drug therapy are discussed. The importance of multidisciplinary approach, continuity in management of the patients with heart transplant is emphasized.