Introduction. Hypertrophic cardiomyopathy (HCM) with midventricular obstruction (MVO) represents a subgroup of increased risk of adverse outcomes. It contributes to development of apical aneurysm, which is an anatomical substrate for the development of malignant arrhythmias, thromboembolism, as well as progression to end stage systolic heart failure. Genetic causes of HCM with MVO are poorly described in Russian and foreign literature.Brief description. We present a case of a 54-year-old female patient with a familial HCM with isolated MVO and rare missense variants in the MYH7, FHOD3 and BAG3 genes. The clinical performance was represented by a paroxysmal atrial fibrillation, as well as episodes of nonsustained ventricular tachycardia.Discussion. According to the European HCM Risk-sudden cardiac death (SCD) calculator, the patient was stratified into an intermediate risk group. However, we also took into account gadolinium-enhanced myocardial areas according to magnetic resonance imaging, as well as no conditions for MVO surgery. This was key in determining the indications for a cardioverter-defibrillator implantation within primary SCD prevention.

Aim. To determine the correlation between the results of the 6-minute walk test (6MWT) and peak oxygen consumption (VO2peak) for populations of patients with chronic heart failure with pronounced clinical and demographic differences; to study a possibility of indirect measurement of VO2peak based on the results of 6MWT using the formulas available from the literature.Material and methods. Two databases were analyzed: 50 patients included in the AEROFIT study (group A), and 31 patients from the Almazov National Medical Research Center (group B). The inclusion criteria were the availability of data from the cardiopulmonary stress test and the 6MWT. The possibility of predicting VO2peak was calculated based on the results of 6MWT using the formulas reported in the literature (L. P. Cahalin et al., 1996; R. M. Ross et al., 2010; R. A. Adedoyin et al., 2010). The predictive accuracy of the models was assessed using the coefficient of determination (R2). The relationship between functional and clinical-demographic indicators was assessed using the Pearson or Spearman correlation analysis.Results. The study groups differed significantly in all parameters, except for the proportion of men and the mean VO2peak. Group B patients were 20 years younger than group A patients, had a lower left ventricular ejection fraction (24.06±7.75 and 41.52±10.48 %, respectively; p<0.001), and covered a 130 m shorter distance in the 6MWT. Despite the absence of a significant difference in VO2peak between groups A and B (13.6 and 13.1 ml / kg / min, respectively; p=0.6581), 61 % of group B patients and 20% of group A belonged to Weber functional class IV. In group A, the 6MWT distance correlated closely with VO2peak (R=0.78; p<0.01) and weakly with age (R=0.4) and body mass index (R=0.3). In group B, the 6MWT distance correlated only with VO2peak (R=0.77; p<0.01). For group A, the R.M. Ross et al. model demonstrated high accuracy in determining the mean VO2peak value with a 0.06% prediction error normalized to measured VO2peak. For group B, none of the models showed satisfactory predictive accuracy. The Ross and Cahalin models showed the best coefficients of determination for groups A and B: Group A, Ross et al. (R2=0.58) and Cahalin et al. (R2=0.59); Group B, Ross et al. (R2=0.59) and Cahalin et al. (R2=0.6).Conclusion. In two groups of patients with a statistically insignificant difference in the mean values of VO2peak, the mean values of 6MWT distance were significantly different, although these indicators correlated closely. The VO2peak prediction models showed satisfactory accuracy for estimation of mean VO2, but poor accuracy for estimation of individual values. A better predictive accuracy is determined by similar clinical and demographic characteristics between the training and testing populations, and likely also by models based on larger, more diversified populations.

Alterations in the proteostasis network and accumulation of misfolded protein aggregates — is one of the new pathogenesis concepts of chronic heart failure. We hypothesis in addition to well-known transthyretin (ATTR) and AL-amyloidosis some patients may represent amyloid lesion in myocardium came from undescribed amyloidogenic precursors due to misfolding of myocardial structural proteins. Here, we report on the case of patient with hypertrophic and restrictive phenotype of cardiomyopathy, biventricular heart failure, considered for heart transplant, and excluded known types of amyloidosis. Genetic testing revealed extended deletion in the gene of giant protein titin ( TTN ). We present with the use of bioinformatic analysis and molecular modeling how this mutation could lead to unfolding of corresponding protein and open its amyloidogenic motifs for intermolecular interactions, therefore, provide amyloidogenic ability. This data enables in more detail to decipher the pathogenesis of chronic heart failure on the background of cardiomyopathy, planning further studies for development of personalized risk profiling in different types of amyloidosis and elaborate more personalized treatment approach for such patients in the future.

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.

Aim. To assess the change in ergoreflex activity in heart failure patients with reduced left ventricular systolic function in the study of the effectiveness of physical training (PT) with original regimen, compared with PT with conventionally estimated regimen.Material and methods. Single-center open-label study of 297 patients with class III HF. The patients were divided into two groups: main group (MG) — patients, in whom the PT intensity was estimated based on lactate threshold (LT); comparison group (CG), in whom the PT intensity was estimated based on 60% VO2peak. We analyzed ergoreflex activity, the relationship of ergoreflex with exercise tolerance (ET), routine systemic inflammation markers, clinical manifestations of HF, and ET based on VO2peak.Results. An increase in gait velocity at the LT level after 3 months of PT was registered in 94% (n=210) of the MG patients. After 3 months, the PT regimen was recalculated according to 60% VO2реак; an increase in gait velocity at this level after 3 months of PT was registered in 70% of CG patients (n=35). The severity of HF decreased in both groups, but the dynamics was more pronounced in the MG, where class II was achieved by 75% of patients (in CG — 44%, p=0,003). In the MG, to a greater extent than in the CG, the ET increased. Ergoreflex activity (according to ΔVE) decreased by ≥15% in 230 (97%) MG patients and in 31 (63%) patients with CG. After the completion of the PT period, when in some patients the HF severity decreased to class II, we revealed a direct association of the ergoreflex value (according to ΔVE) with a greater severity of HF (r=-0,57, p=0,01) and the relationship between the decrease in ergoreflex activity (according to ΔVE), an increase in VO2LT (r=-0,55, p=0,001), VO2peak (r=0,49, p=0,001), a decrease in monocyte count (r=0,63, p=0,01).Conclusion. In stable patients with class III HF receiving the proper disease-modifying therapy, ergoreflex activity is increased and is associated with functional class, ET, and systemic inflammation activity. In the course of physical rehabilitation, a decrease in ergoreflex activity is accompanied by a decrease in functional class, an increase in EF, which is more pronounced with personalized aerobic exercise using LT regimen assessment.

Objective : to assess the incidence, determine the peculiarities of the course of invasive pulmonary aspergillosis (IPA) and identify risk factors for IPA in heart transplant recipients. Materials and methods . From January 2010 to December 2019, 137 heart transplantations (HT) were performed: mean age 46 ± 14 years; male 102 (74%) and female 35 (26%). All patients received a three-component immunosuppressive therapy: calcineurin inhibitors, mycophenolate mofetil (MMF) and Glucocorticoid (GCs). Induction therapy consisted of Basiliximab (81%, n = 111) and antithymocyte immunoglobulin (15%, n = 20). A retrospective analysis of patients with identified post-HT invasive IPA was performed; risk factors for IPA were assessed. In patients with early IPA, the length of stay in the intensive care unit (ICU), the duration of mechanical ventilation, and the initial severity of the condition were studied. All patients with suspected pneumonia underwent bronchoscopy with examination of bronchoalveolar lavage (BAL) and chest computed tomography (chest CT scan). Results . During the follow-up, there were 58 episodes of pneumonia, of which 16 (28%) were IPA (age 33 to 64 years). All patients had a target level of immunosuppressive drugs concentration in blood; basiliximab was used as induction therapy in 15 of 16 patients. Half of the recipients developed IPA in the early post-HT period (less than 3 months after HT), in the rest (n = 8) – at a later date (3 months to 1 year after HT). The diagnosis was verified: 14 out of 16 patients showed an increase in the Aspergillus antigen positivity in the BAL to 7.2 (2.8 ± 1.6); chest CT scan revealed specific changes. In two patients, there were no diagnostic criteria for IPA, but the diagnosis was made based on the results of histological examination after resection of the left lower lobe of the lung. All patients received voriconazole therapy for 2 to 6 months, their immunosuppressive therapy was adjusted (tacrolimus and MMF dose adjustment) and their white blood cell count was monitored. Complete cure of the disease was achieved in 13 (81%) patients. Two patients died within 30 days after HT in the intensive care unit, one died from urogenital diseases caused by bacterial flora and leading to urosepsis, 4 months after IPA treatment was initiated. All patients had risk factors for IPA: taking immunosuppression, including GCs (n = 16), prolonged ICU stay (n = 14), inotropic support exceeding 2 days in the early post-transplant period (n = 10), cachexia during HT (n = 6), leukopenia (n = 9) and neutropenia (n = 14). Conclusion . In heart transplantat recipients, the incidence of IPA among respiratory tract infections is 28%. The risk of developing IPA was highest during the first year following HT. In the majority of recipients, the disease was detected at the early stages; diagnosis required surgical intervention in 12% of cases. A decrease in the risk of developing IPA was associated with correction of the following risk factors for this disease in all patients: volume of immunosuppressive therapy during the first year after transplantation and prevention of the development of neutropenia as a marker of infectious complications or immunosuppression overdose. Early diagnosis of IPA allowed for initiation of timely specific therapy in most recipients and achievement of a positive effect in 80% of them.

Aim. To compare the effectiveness of standard heart failure therapy with and without combined immunosuppressive therapy in patients with documented lymphocytic myocarditis (LM) based on data from actual clinical practice.Material and methods. This observational study included 70 patients with documented LM, 40% (n=28) of whom received immunosuppressive therapy. All patients underwent standard echocardiographic and laboratory investigations, endomyocardial biopsy with histological, immunohistochemical and molecular genetic analysis. Contrast-enhanced cardiac magnetic resonance imaging was performed in 74% of patients. All patients received standard therapy for heart failure at baseline.Results. The groups did not differ in demographic and echocardiographic characteristics. The appointment of immunosuppressive therapy was accompanied by an increase in ejection fraction by 12,2% compared to 6,4% (p=0,02). There were no significant differences in combined endpoints (survival and the need for heart transplantation) depending on therapy regimen (log-rank p=0,97).Conclusion. The prognosis of patients with chronic LM depends on the process activity, the severity of impaired hemodynamics and ventricular arrhythmias, as well as on the presence of persistent viral infection. Compliance with patient selection algorithm before prescribing immunosuppressive therapy is associated with the improvement in myocardial global contractility.

Aim. To assess the effect of physical rehabilitation on dynamics of oxygen and lactate status indicators in inotrope-dependent patients with stable chronic heart failure (CHF) of IIIIV functional class (FC). Material and methods. A randomized prospective study included 120 men, aged 1865, hospitalized at Almazov National Medical Research Centre due to CHF IIIIV FC, left ventricular ejection fraction (LVEF) 30%; with blood pressure (BP)90/60 mm Hg. Patients who received dobutamine or dopamine for 2 weeks were randomized into 3 groups: 1st participating in the program of physical training (PPT), 2nd not participating; 3rd group patients without inotropic support participating in PPT. Results. Oxygen extraction ratio (O2ER) at rest was increased, while central venous oxygen saturation (ScvO2) was decreased in all groups at baseline, after 3 and 6 months. Initially, at rest, central venous blood lactate (lactate) was normal in all groups. By the 6th month, lactate in group 2 became higher than in group 1 (p=0.005) and group 3 (p=0.008). Initially, after 3 and 6 months, at peak of exercise in groups 1 and 3, lactate and O2ER increased, and ScvO2 decreased without development of life-threatening adverse events. By the 6th month, in groups 1 and 3, the distance of 6-minute walk test increased: p=0.004 and p0.00001 and the strength of hand muscles increased: p=0.01 and p=0.005. Conclusion. In patients with CHF IIIIV FC at rest, regardless of participation in PPT and inotropic therapy, there were comparable disturbances of oxygen status, characterized by decreased level of ScvO2 and increased level of O2ER, in the absence of decrease in arterial blood saturation. At peak of aerobic exercise of mild and moderate intensity in patients with advanced CHF, regardless of inotropic support, there was a comparable increase in the level of lactate and O2ER, as well as a decrease in ScvO2, which was not accompanied by life-threatening adverse events. The participation of inotrope-dependent patients in PPT is associated with decrease in blood lactate at rest, which, along with increase in hand muscle strength and exercise tolerance, may indicate an improvement in condition of muscle tissue.

Abstract Purpose To evaluate changes of functional state and metabolism of skeletal muscle fiber (MF) after aerobic physical rehabilitation (PR), based on original method; to study relationship between clinical data dynamics and indicators of skeletal muscle metabolism after PR. Methods 100 patients; heart failure (HF) with reduced ejection fraction (HFrEF), NYHA III, mean age 52±5,2 years, ejection fraction (EF) 27,3±4,2%, BMI 23,5±2,8 kg/m2. Before inclusion in PR program cardiopulmonary exercising test (CPET), echocardiography (EchoCG), quality of life (QOL), exercise tolerance (ET) were estimated. Physical training intensity was based on lactate threshold achievement during CPET. PR efficiency was estimated on the basis of peak oxygen uptake (VO2peak), EF, QOL and ET dynamics after 6 months PR. Shin muscle biopsy was performed at baseline and after 3–6 months PR. In muscle samples activity of alkaline phosphatase (AP), lactate dehydrogenase (LDH) and succinate dehydrogenase (SDG) was evaluated with plag-method. Data were statistically processed using software package “Statistika, 9.0”. Results After 6 months of training EF increased by 10,5±2,3%, ET increased by 9,7±0,5 points (p1,2 <0,05), QOL changed by 24,8±3,5 points (significant regression of symptoms), VO2peak increased by 5,2±0,5 ml/min/kg (p3,4 <0,05). MF diameter (dMF) after PR slightly decreased in 6 patients, in 2 patients it did not change. After 3–6 months of training AP activity increased by 24,2% (p<0,05); LDH activity in glycolytic MF decreased by 24,4%, in oxidative MF it decreased by 6,0% only (p1 <0,05, p2>0,05). SDG activity in glycolytic MF increased by 20%, in oxidative MF it increased by 30% (p1 <0,05, p2<0,05). There was a positive relationship between heart failure functional class dynamics and dMF (r=0,4, p=0,05), increase in CPET parameters was associated with AP activity (r=0,5, p=0,05). Conclusion Aerobic physical rehabilitation in stable HF pts, selected on the basis of LT achievement, was effective in improving values of EF, QOL, VO2peak and ET. After 3–6 months PR dMF slightly decreased; Participating in the PR program decreased LDH activity in both oxidative and glycolytic muscle fibers; it also increased AP and SDG activity significantly. This may indicate an increase in oxidative metabolism activity and decrease in MF edema, improvement in skeletal muscles microcirculation. Funding Acknowledgement Type of funding sources: None.

Aim. To determine the clinical features of arrhythmogenic right ventricular dysplasia (ARVD) in recipients on heart transplant waiting list (WL) and after a heart transplantation (HTx).Material and methods. From January 2010 to December 2018, we included 192 recipients in heart transplant waiting list (HTx WL) on behalf of Almazov National Medical Research Center. ARVD was diagnosed in 4 subjects (F Marcus et al. criteria, 2010). All 4 patients (female, mean age 46,5 years-old (16-54-year-old)) underwent HTx. Prior to HTx, arrhythmias (atrial fibrillation, atrial flutter) were diagnosed in 3 recipients. In patient №2, pacemaker in VVI mode was implanted due to sick sinus syndrome (SSS) and tachycardia-bradycardia syndrome and others underwent ICD implantation.Results. Survival after HTx was 30,9 (3,9-46,2) months. All recipients were treated with triple-drug immunosuppressive therapy (calcineurin inhibitors, mycophenolic acid, steroids) and induction with Basiliximab. All patients experienced high sensitivity to immunosuppressive therapy (agranulocytosis), and therefore a colony-stimulating factor was administered to all of them. After immunosuppression reduction (Tacrolimus plus Methylprednisolone) agranulocytosis did not recur.Conclusion. ARVD is a rare disease in the structure of end-stage heart failure in recipients in HTx WL. An examination of this pathology is necessary to manage patients on-time with surgical treatment (ICD, HTx). According to our results, causal variants in desmosome genes were determined in 1 from 4 patients and simultaneous presence of two unique genetic variants in the RKR2 gene were found in one. A special feature of post-HTx management was the development of agranulocytosis, which once again underlines the need for a personalized approach to the selection of the immunosuppressive therapy.

Little is known about the electrophysiological characteristics of telocytes found in the working myocardium and sinoatrial node (SAN). Telocyte expres -sion of HCN4 suggests the ability to generate pacemaker potentials. To prove the impulse conduction, the presence of voltage-gated sodium channels is required. It is assumed that telocytes are also located in the atrioventricular node (AVN).Aim. Morphological and electrophysiological study of AVN and SAN telocytes.Material and methods. Fragments of the right atrium, AVN of 7 hearts of recipients and 3 hearts of pigs were taken, respectively, during heart transplantation and after the experiment. Isolation of telocyte cultures, histological, immunohis tochemical tests with anti-CD117, anti-NaV1.5 (SCN5A), anti-CD34 antibodies, intravital confocal laser microscopy were carried out. The patch-clamp technique was used.Results. In AVN cultures, CD117+ cells with long processes were found. There was a potassium current with a density of 700 pA/pF during membrane depolarization up to +90 mW in humans and pigs using the patch-clamp technique. Calcium oscillations with a period of about 200 seconds in a pig with an increase in calcium concentration. In elongated cells located between cardiomyocytes and among the fibrous tissue of SAN perifocal zone, the co-expression of anti-NaV1.5 and anti-CD34 antibodies was revealed.Conclusion. In AVN, telocytes were found, in whose cultures potassium current and calcium oscillations were determined. SCN5A sodium channels were found in telocytes of the perifocal area of human SAN. This fact indicates the ability of cells to conduct an electrical impulse.

Aim. Heart failure (HF) is accompanied by skeletal muscle atrophy and exercise intolerance. The aim was to study the molecular mechanisms underlying the therapeutic effect of personalized exercise in patients with HF.Material and methods. RNA sequencing obtained from skeletal muscle biopsies before and after a 12-week exercise course was used to identify changes in gene expression and signaling pathways induced by the physical rehabilitation program for patients with HF.Results. We have shown that personalized exercise program in patients with HF stimulates the activation of molecular pathways regulating the differentiation and functioning of skeletal muscles: commitment of muscle progenitor cells; mechanisms regulating the calcium release and sensitivity of myofibrillar contraction, electrical excitability of the muscle membrane, synaptic vesicle proton gradient creation, maintenance of electrochemical gradients of Na+ /K+ . Also, the analysis of differentially expressed genes revealed an increase in the expression of transcription factors MyoD and MEF2, which are responsible for the differentiation of muscle stem cells, and sarcomeric genes MYOM1, MYOM2, MYH7. Along with this, we observed activation of the CYR61 expression — a potential prognostic biomarker for HF patients.Conclusion. Our data show that the beneficial effect of personalized aerobic exercise in patients with HF depends, at least in part, on an improvement in the physiological and biochemical parameters of skeletal muscle.

Aim. To assess the response of skeletal muscle and myocardium to original aerobic exercise (AE) program in patients with heart failure (HF) with reduced ejection fraction (HFrEF); to assess morphometric changes in skeletal muscle fiber after AE.Material and methods. The study included 100 patients with class III HFrEF (age — 52±5,2 years; body mass index (BMI) — 23,5±2,8 kg/m2). At baseline and after 6 months of AE, an echocardiogram, peak oxygen uptake (VO2peak), exercise tolerance and quality of life (QOL) were evaluated. Lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) activity were evaluated in biopsy material of lower leg muscles.Results. After 6 months of AE, the left ventricular ejection fraction (LVEF) increased by 10,5±2,3%, QOL — by 24,8±3,5 points, exercise tolerance — by 9,7±0,5 points, VO2peak — by 5,2±0,5 ml/min/kg (p1,2,3,4< 0,05). In 6 patients, the diameter of muscle fiber decreased slightly. The activity of ALP (initially — 0,33±0,09 D) increased by 24,2% (p< 0,05); LDH in glycolytic fibers was initially 0,213±0,08 D, in oxidative fibers — 0,083±0,04, and after 6 months of AE, decreased by 24,4% and 6,0%, respectively (p1 <0,05, p2 >0,05). A positive relationship was found between the dynamics of HF class and fiber diameter (r=0,4, p=0,05); an increase in сardiopulmonary exercise test was associated with ALP activity (r=0,5, p=0,05).Conclusion. 1. Dosed aerobic exercise in patients with stable class III HFrEF, normal BMI, based on reaching the lactate threshold, had a positive effect on LVEF, QOL, exercise tolerance and VO2peak. 2. With exercise training, a decrease in fiber diameter and LDH activity in both oxidative and glycolytic fibers, an increase in ALP activity were revealed. 3. The functional relationship between the increase in exercise tolerance and ALP content in muscle tissue was revealed.

Objective: to assess the impact of baseline pulmonary hypertension (PH) on early and long-term outcomes following heart transplantation (HT). Materials and methods. From January 2010 to December 2018, 112 HTs were carried out. Based on right heart catheterization results, all recipients were divided into 2 groups: Group 1 with PH (n = 76; mean pulmonary arterial pressure (mPAP) ≥25 mm Hg), Group 2 – without PH (n = 36; MPAP <25 mm Hg). The average age of Group 1 patients was 46.4 ± 14.9 years, baseline pulmonary vascular resistance (PVR) was 3.5 ± 1.5 Wood units, PVR after reversion test (nitric oxide – 80 ppm, iloprost 20 μg) – 2.8 ± 1.0 Wood units, systolic PAP (sPAP) – 50.1 ± 13.4 mm Hg. The average age in Group 2 was 47.3 ± 12.2 years, baseline PVR – 2.1 ± 0.8 Wood units, sPAP – 27.4 ± 5.3 mm Hg. The dynamics in indicators of early postoperative period (duration of mechanical ventilatory support, use of vasodilators and inotropic support and the length of stay in intensive care unit (ICU), 30-day mortality) and long-term post-HT echocardiography results were assessed. Results. Due to acute right-ventricular failure (RVF) developing after heart transplantation, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was done in 8 patients (11%) from Group 1 and one patient (3%) from Group 2. Presence of PH did not affect duration of mechanical ventilatory support, inotropic support, and length of stay in ICU. Levosimendan therapy in the early postoperative period was more often performed in Group 1 (n = 29) than in Group 2 (n = 6) (p = 0.048). Nitric oxide inhalation was also more often administered in Group 1 (n = 54); Group 2 (n = 7), (p = 0.003). Sildenafil therapy after HT was comparable in both groups Group 1 (n = 25); Group 2 (n = 6), (p = 0.048). In early post-HT stages, 14 patients died, 30-day mortality was comparable in both groups (p = 0.12). Six months after HT, no differences were found in the sPAP (p = 0.21) and PVR (p = 0.07) levels. Conclusion. Patients with baseline PH after HT have a more severe early postoperative period, including a higher RVF incidence, with the need for ECMO implantation. A PVR level >3.5 Wood units is not a threshold for HT. Patients with baseline PVR >3.5 Wood units following HT show comparable results with patients without baseline PH. This allows such patients (baseline PVR >3.5 Wood units) to be considered for inclusion in the heart transplant waiting list. In addition, 30-day mortality and duration of mechanical ventilatory support after HT in patients with and without baseline PH did not differ. Regardless of the baseline level of sPAP and PVR, all patients showed improvement in these parameters after HT. Six months after HT, no differences were found in sPAP and PVR levels in the patients, regardless of whether there was baseline PH or not.

Abstract Purpose To evaluate the efficiency of aerobic physical rehabilitation (PR), selected on the basis of lactate threshold achievement during cardiopulmonary exercising test (CPET), in heart failure patients with normal body mass index (BMI); to study metabolism changes in skeletal muscle fibers (MF) after PR. Methods 100 patients; heart failure with reduced ejection fraction (HFrEF), NYHA III, mean age 52±5.2 years, ejection fraction (EF) 27.3±4.2%, BMI 23.5±2.8 kg/m2. The original estimated CPET, exercise tolerance (ET), quality of life (QOL) and echocardiography (EchoCG). Effects of physical rehabilitation were estimated on the basis of peak oxygen uptake (VO2peak), EF, QOL and ET dynamics after 6 months of training. Shin muscle biopsy was performed at baseline and after 3–6 months of training programm. In muscle samples activity of lactate dehydrogenase (LDH), succinate dehydrogenase (SDG) and alkaline phosphatase (AP) was evaluated with plag-method. Data were statistically processed using software package Statistika, 9.0. Results After 6 months of physical training ET increased by 9.7±0.5 points and QOL improved by 24.8±3.5 points (p1,2 <0.05), EF increased by 10.5±2.3% and VO2 peak increased by 5.2±0.5 ml/min/kg (p3,4 <0.05). After 3–6 months of training AP activity increased by 24.2% (p<0.05). LDH activity in glycolytic MF decreased by 24.4%, in oxidative MF it decreased by only 6.0% (p1 <0.05, p2>0.05). SDG activity in glycolytic MF increased by 30% and in oxidative – by 20% (p1,2 <0.05). There was a positive relation between SDG activity and VO2 peak dynamics (r=0.6, p=0.04), increase in CPET parameters was associated with AP activity (r=0.5, p=0.05). Conclusion Aerobic physical training in stable HFrEF patients with normal BMI was effective in improving values of EF, VO2 peak, QOL and ET; Participating in the rehabilitation program decreased LDH activity in both oxidative and glycolytic muscle fibers; it also significantly increased AP activity and SDG activity in both oxidative and glycolytic MF. This may indicate a decrease in glycolytic metabolism activity and aerobic metabolism activation; The relation between the increase in exercise tolerance and endothelium condition marker (AP activity in muscle tissue), SDG activity and VO2 peak dynamics has been revealed. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): Project was partially funded by the Russian Science Foundation grant 16-15-1017

Aim To evaluate incidence of arterial hypertension (AH) in the posttransplantation period and to identify risk factors for this complication.Materials and methods From January, 2010 through December, 2017, 96 heart transplantations (HT) (70 men and 26 women aged 46.5±13.9 years) were performed. During the first month following HT, 8 recipients died and were excluded from the analysis. The retrospective evaluation of results included 88 patients followed up for more than one year.Results For the entire post-HT period (maximum 92 months), AH was observed in 75 of 88 (85%) recipients. Post-HT AH was correlated with male gender (r=0.24; p=0.031), history of smoking before HT (r=0.45; p<0.001), history of ischemic heart disease (IHD) (r=0.28; p=0.01), older age (r=0.35; p=0.001), higher body weight index (r=0.37; p=0.0005), creatinine level (r=0.37; p=0.001), and low-density lipoprotein cholesterol level (r=0.27; p=0.04). Interrelations with other AH risk factors were not found. Most patients developed AH within the first two years after HT. During the first year, AH was diagnosed in 60% (53 of 88) of patients (relapse, 85% (n=29); newly diagnosed, 45% (n=24), p=0.0003). At two years, AH was detected in 79% (46 of 58) of patients (relapse, 53% (n=18); newly diagnosed, 53% (n=28), p=0.9). All recipients received an adequate antihypertensive therapy. 40-63% of patients required a single-drug therapy at different points of follow-up; from 29 to 45% of patients required a two-drug therapy, and 5-15% of patients required three or more drugs. During all 5 years of treatment, most patients used angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) (70-87%) and slow calcium channel blockers (SCCB) (48-53%). The presence of AH following HT was associated with development of all cardiovascular events (CVE; r=0.31; p=0.012) whereas persistent AH, which required a combination antihypertensive treatment, was associated with a high mortality (r=0.61; p=0.015).Conclusion AH is a frequent complication of HT (85%), which is newly diagnosed in most patients during the first two years. AH incidence was higher for male recipients with a history of IHD, hypertension, and smoking. Approximately half of patients required only a single-drug antihypertensive therapy. After HT, the most frequently prescribed drugs included ACE inhibitors or ARBs and SCCBs (70-87% and 48-53%, respectively, depending on the time elapsed after HT). Persistent AH requiring a treatment with two or more antihypertensive drugs was associated with development of all CVEs and a higher long-term mortality.

Objective . To assess and compare the impact of physical training (PT) on functional and hemodynamic characteristics in patients with chronic heart failure (CHF) depending on continuous inotropic support. Design and methods . Prospective randomized study included 120 men aged 18–65, admitted to the Almazov National Medical Research Center (St Petersburg, Russia) from 2014 to 2019 due to decompensated CHF of III–IV functional class (FC), with left ventricular ejection fraction (LVEF) ≤ 30 %; blood pressure (BP) ≥ 90/60 mmHg (with or without inotropic therapy). Patients receiving dopamine or dobutamine for ≥ 2 weeks were randomized into two groups: group 1 participated in program of physical training (PPT), and group 2 did not participate in PPT. Patients of group 3 had CHF of III–IV class without inotropic therapy and participated in PPT. Initially, all groups were comparable by clinical, functional and hemodynamic parameters. The follow-up lasted 6 months. During months 3 and 6, hemodynamic parameters — BP and heart rate (HR), respiration rate (RR) at rest and peak of exercise, echocardiographic and central hemodynamics at rest, parameters at rest, number of arrhythmias were evaluated. Results . Patients of group 1, after 3 and 6 months, showed no increase in systolic (BPs) and mean BP (BPm) at peak of exercise, in contrast to patients of group 3 who demonstrated a significant increase in BPs (p ≤ 0,002) and BPm (p ≤ 0,005) after 3 months, and BPs (p ≤ 0,001) and BPm (p ≤ 0,002) after 6 months. By 6-month follow-up, intergroup analysis did not show significant changes in HR, LVEF, end-diastolic volume, stroke volume and pulmonary pressure. Initially, ECG monitoring showed a higher number of unstable ventricular tachycardia (VT) in group 1 compared with group 3 (p = 0,01), after 3 and 6 months in all groups the number of VT was comparable. During 6 months, implantable cardioverter defibrillator (ICD) shocks were compared in all groups: 2 per group (5 %). Conclusions . “Inotrope-dependent” survivors with CHF at peak of exercise did not significantly increase BPs and BPm in contrast to “inotrope-independent” patients. Individually developed aerobic PPT of low and intermediate intensity in “inotrope-dependent” survivors did not influence negatively on echocardiographic parameters, parameters of hemodynamics at rest and during the peak of exercise, did not increase mortality and number of life-threatening cardiac arrhythmias and ICD shocks.

Objective: to assess the personal psychological profile of heart transplant recipients as the first stage in the development of post-transplant personalized rehabilitation programs. Materials and methods. From January 2010 to July 2019, 129 HTs were performed (mean age 46.6 ± 14.1 years; 74% (n = 95) were men, 26% (n = 34) were women). All patients in the heart transplant waiting list were examined by a clinical psychologist and a psychotherapist to exclude contraindications to transplant surgery. To assess personal traits, we used the standard multifactorial questionnaire by Cattell R., 16 PF (version A), which included 187 questions. Heart transplantation and absence of post-transplant severe cognitive impairments were the selection criteria for this study. Patients were surveyed before they were discharged from the hospital – 30–60 days following HT: during the period of complete recovery after surgery. In the present study, a retrospective assessment of the results was performed in 107 patients (n = 76 – men; n = 31 – women). Results. Analysis of the personality portrait revealed that over half of recipients were reserved, distant (factor A – schizothymia) and restrained (factor F – restraint; F2 – introvert; F4 – conforming) with lower mental capacity (factor B), and were shy, timid (factor H), with low super ego (factor G: irresponsible, tolerates disorder, flexible, open to change). Our results showed that 47% of patients (n = 18 out of 38 patients, n = 22 are pensioners) with a weak degree of factor C (reactive, affected by feelings) are workers to 42% (n = 29 out of 69, n = 28 – retirees) with a strong degree of the same factor. One year after HT, the number of physically active patients was higher among those with low anxiety compared with high anxiety (41% (18 of 44) and 32% (20 of 63), respectively, p = 0.41). Conclusion. Personality factors are non-modifiable characteristics of patients. They affect human behavior, return to work and to social life, as well as physical and psychological recovery from HT. Knowing the personal traits of recipients would allow to develop a personalized approach to their rehabilitation and a technique for timely examination after HT.

Aim. To determine whether the skeletal muscle of patients with chronic heart failure (CHF) retains the ability to regenerate and grow; to compare the effectiveness of long aerobic trainings, calculated by an individualized method, and conventionally calculated trainings (VO2peak values), in relation to the severity of heart failure, exercise tolerance (ET), and ergoreflex activity (ERGO).Material and methods. The study included 297 patients with stable III functional class (FC) CHF, receiving optimal therapy. The presence of heart failure was found in all patients at least 6 months before the start of the study (age — 18-65 years, body mass index (BMI) — 19-28 kg/height, m2. Initially, the study performed a cardiorespiratory test (CRT) with an assessment of gas composition, acid-base balance of the blood and ERGO activity. Patients were randomized into 2 groups: experimental (EG) and control (CG). For EG, based on the determination of the lactate threshold (LT), after 1 and 3 months the CRT was repeated and the training walking mode was dynamically recounted according to the new LT level. For CG, the training walking mode was calculated based on the VO2peak values. All patients trained for 6 months. At the end of the training, diagnostic CRT was performed, and the activity of EGO was evaluated. Eleven patients with CHF and 3 healthy donors before the start of the training underwent a biopsy of the gastrocnemius muscle.Results. It was shown that the potential for muscle differentiation of satellite skeletal muscle precursor cells obtained from patients with CHF with a reduced ejection fraction (HFrEF) does not differ in vitro from the potential of satellite cells of healthy donors. After 6 months of training, the severity of CHF decreased to FC II in 75% of EG patients, and among CG patients — in 44%; the main indicators of the stages of compensatory mechanisms activation during physical exertion (VO2LT and VO2peak) in EG increased more than in the CG (10,8±0,4, 18,7±0,7 ml/min/kg and 9,5±0,8, 15,3±0,9 ml/min/kg, with p1<0,01, p2<0,05, p3<0,01, respectively). Conclusion. In vitro, the potential for muscle differentiation, regeneration and growth of satellite skeletal muscle precursor cells obtained from patients with HFrEF does not differ from the potential of satellite cells of healthy donors. Aerobic training in patients with III FC chronic heart failure calculated by definition of LT, relating to safety is not worse than the results calculated by the level of VO2peak. Aerobic training in patients with III FC chronic heart failure calculated by definition of LT, compared with the usual mode of training walking, significantly reduce the activity of ergoreflex, increase ET, reduce the severity of CHF. In patients with III FC CHF, training walking for more than 1,5 hours/day determined by the level of LT, contributes to the development of physiological reverse myocardial remodeling to a greater extent than aerobic training calculated by the conventional method.