Tolerability of an Individualized Physical Rehabilitation Program in Patients Dependent on Inotropic Support With End-Stage Chronic Heart Failure.

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 (SpO2) <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.

[Prospects for use of Vericiguat in HFrEF: Implications of VICTORIA Trial Results. Advisory Board Summary].

In September 2021, an online meeting of the Council of Experts was held. The proposed focus of discussion was publishing the results of an international prospective, randomized, double-blind, placebo-controlled study VICTORIA. The objective of the VICTORIA study was evaluation of the efficacy and safety of supplementing a standard therapy with vericiguat at a target dose of 10 mg twice a day as compared to placebo for prevention of cardiovascular death and hospitalization for heart failure (HF) in patients with clinical manifestations of chronic HF and left ventricular ejection fraction <45% who have recently had an episode of decompensated HF. The aim of the meeting was interpretation of the VICTORIA study results on efficacy and safety of vericiguat for a potential use in a Russian population of patients after a recent episode of decompensated chronic HF with reduced ejection fraction.

COVID-19 management in heart transplanted recipients: registry of Almazov National Medical Research Centre.

Aim      This study presents the experience of managing patients with COVID-19 after cardiac transplantation (CT).Material and methods  Infectious complications (IC) following CT are a leading cause for morbidity and mortality. A prolonged incubation period, atypical IC symptoms, and originally altered results of laboratory and instrumental diagnosis are characteristic of recipients due to immunosuppression. In 2020, the coronavirus infection (COVID-19) rapidly spread worldwide, and timely diagnosis and searching for effective treatments for this disease became a major challenge. From January 2010 through July 2020, 148 patients received orthotopic heart transplants at the V.A. Almazov National Medical Research Center; 34 of these patients died by the present time and were excluded from this analysis. 114 patients were included into the retrospective evaluation of results. These patients had been a part of the group followed up at the Center for more than a month.Results From March through July 2020, 12 (10.5 %) of 114 CT recipients were infected with the virus SARS-CoV-2. In 75 % (n=9) of the sick patients, the COVID-19 infection developed after more than one year after CT. From the first day of clinical symptoms, mycophenolic acid/everolimus were temporarily suspended. The outpatient treatment was started on the first day and included an antiviral therapy (oseltamivir), mucolytics (bromhexine), vitamin C, and anticoagulants. If the disease onset was associated with pyretic fever the empiric antibacterial levofloxacin treatment was administered due to a high risk of mixed infection. Hospitalized patients with moderately severe COVID-19 (n=3) were treated with oxygen inhalation through nasal cannula and prone position with a positive effect.Conclusion      Remote counseling of patients after CT and consistency of the outpatient treatment with recommendations of managing transplant physicians provided timely diagnosis of IC, early administration of treatment, and the absence of COVID-19 complications. Reducing the regimen of immunosuppressive therapy (antiproliferative agents) for up to 14 days facilitated infection control and was not associated with acute rejection crisis and/or impairment of the transplant function.

[The use of diuretics in chronic heart failure. Position paper of the Russian Heart Failure Society].

The document focuses on key issues of diuretic therapy in CHF from the standpoint of current views on the pathogenesis of edema syndrome, its diagnosis, and characteristics of using diuretics in various clinical situations.

[Arterial hypertension after heart transplantation].

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.

[Heart reHeart remodeling in patients with severe systolic dysfunction due tocancer chemotherapymodeling in patients with severe systolic dysfunction due tocancer chemotherapy.]

Objective Comparative analysis of structural and functional specific features of the heart in patients with toxic cardiomyopathy (TCMP) with a low left ventricular ejection fraction (LVEF) and severe, chronic heart failure (CHF) and in patients with idiopathic dilated cardiomyopathy (DCMP) and similar LVEF and CHF severity.Materials and Methods This observational, single-site study included 15 patients with TCMP (12 of them received treatment including anthracycline antibiotics and 3 patients received targeted therapies) and 26 patients with idiopathic DCMP. Data of echocardiography were compared for patients with TCMP and DCMP with comparably low LVEF of <40 %.Results In patients with severe heart damage associated with antitumor therapy with low LVEF, volumetric and linear indexes of left and right ventricles and the left atrium (left atrial volume index (LAVI), 33.7 (21.5-36.9) ml / m2; right ventricular end-diastolic dimension (RVDd), 2.49 (1.77-3.53) cm; and end-diastolic volume index (EDVI), 78.0 (58.7-90.0) ml / m2) were considerably less than in the DCMP group (LAVI, 67.1 (51.1-85.0) ml / m2; RVDd, 4.05 (3.6-4.4) cm; and EDVI, 117.85 (100.6-138.5) ml / m2, p<0.0001). Furthermore, LV wall thickness and pulmonary artery systolic pressure did not differ in these groups. Both in men and women with TCMP, LAVI and EDVI were significantly less than in men and women with DCMP.Conclusion The study showed significant differences in parameters of cardiac remodeling. In TCMP patients as distinct from DCMP patients, despite a pronounced decrease in LVEF, LV dilatation was absent or LV volumetric parameters were moderately increased with a more severe somatic status.

[Characteristic of infectious status in patients with acutely decompencated chronic heart failure and its impact on annual prognosis].

AIM: The assessment of infectious status in patients with acutely decompensated chronic heart faiure (ADCHF) without evident signs of acute inflammatory stress and its impact on the 1 year prognosis. MATERIAL AND METHODS: Totally, 65 patients with ADCHF of ischemic origin investigated, age 67,3±2,3 y.o. All patients were taken markers of phagocytosis and inflammatory stress as well as antibodies to Streptococcus, Cytomegalovirus (CMV), Epstein-Barr virus (VEB), Candida albicans, Toxoplasma gondii, Aspergillus, Mycoplasma hominis and pneumonia and also level of lipopolysaccharids (LPS) of gram-negative bacteriae. RESULTS: More often LPS of gram-negative bacteriae were revealed in patients with ADCHF and further in decreasing order - antibodies to CMV, VEB, Streptococcus, Candida, Aspergillus and LPS. All patients have been infected by at least 2 pathogens, more than 90 % of them had 3 ones or more. Mortality in first 12 months observation correlated with quantity of patient`s pathogenic patterns (r=0,52, p=0,004). Dependency of one-year mortality from degree of viral-bacterial mixt contamination was almost linear. CMV was a monopathogen with strongest correlation with mortality (r=0,39, p=0,001). In patients with more significant infection bigger rate of re-hospitalizations about new ADCHF correlated with number of pathogens was observed (r=0,61, p=0,001). CONCLUSION: Chronic latent infection with a significant number of pathogens is characteristic of patients with low-ejection ADCHF of ischemic genesis with a significant number of pathogens: more than 90 % of patients had three or more. The most common exogenous pathogens in the study sample of patients with chronic obstructive heart failure were CMV, EBV, and hemolytic streptococcus, of the potentially endogenous ones, gram-negative intestinal bacteria. The number of infectious agents in patients with chronic obstructive heart failure has a direct correlation with deaths and re-admission to hospital with total heart failure within 1 year after discharge from the hospital.

Skeletal Muscle Resident Progenitor Cells Coexpress Mesenchymal and Myogenic Markers and Are Not Affected by Chronic Heart Failure-Induced Dysregulations.

BACKGROUND AND PURPOSE: In heart failure (HF), metabolic alterations induce skeletal muscle wasting and decrease of exercise capacity and quality of life. The activation of skeletal muscle regeneration potential is a prospective strategy to reduce muscle wasting; therefore, the aim of this project was to determine if functional properties of skeletal muscle mesenchymal progenitor cells (SM-MPC) were affected by HF-induced functional and metabolic dysregulations. METHODS: Gastrocnemius muscle biopsy samples were obtained from 3 healthy donors (HD) and 12 HF patients to purify mRNA for further analysis and to isolate SM-MPC. Cells were expanded in vitro and characterized by immunocytochemistry and flow cytometry for expression of mesenchymal (CD105/CD73/CD166/CD146/CD140b/CD140a/VIM) and myogenic (Myf5/CD56/MyoG) markers. Cells were induced to differentiate and were then analyzed by immunostaining and Q-PCR to verify the efficiency of differentiation. The expression of genes that control muscle metabolism and development was compared for HD/HF patients in both muscle biopsy and in vitro-differentiated myotubes. RESULTS: The upregulation of MYH3/MYH8/Myf6 detected in HF skeletal muscle along with metabolic alterations indicates chronic pathological activation of the muscle developmental program. SM-MPC isolated from HD and HF patients represented a mixed population that coexpresses both mesenchymal and myogenic markers and differs from AD-MMSC, BM-MMSC, and IMF-MSC. The functional properties of SM-MPC did not differ between HD and HF patients. CONCLUSION: In the present work, we demonstrate that the metabolic and functional alterations we detected in skeletal muscle from HF patients do not dramatically affect the functional properties of purified and expanded in vitro SM-MPC. We speculate that skeletal muscle progenitor cells are protected by their niche and under beneficial circumstances could contribute to muscle restoration and prevention and treatment of muscle wasting. The potential new therapeutic strategies of HF-induced skeletal muscle wasting should be targeted on both activation of SM-MPC regeneration potential and improvement of skeletal muscle metabolic status to provide a favorable environment for SM-MPC-driven muscle restoration.

[Experience of general surgical procedures in patients after heart transplantation].

PURPOSE: To study the frequency of general surgical diseases development snd their features in patients after heart transplantation (HTx). METHODS: From January 2010 to December 2018 it was performed 112 HTx (mean age - 46.7±14.0 years old; 82 - male, 30 - female). During 30 days after HTx 9 patients died. After discharge all recipients (n=98) were included in dispensary observation list. We retrospectively analyzed patients (n=35) who underwent general surgery manipulations in more than 30 days after HTx. All surgical interventions have been done under the reduction of immunosuppression therapy. RESULTS: During 9 years of post-heart transplant follow-up 45 surgical interventions were performed, 7% (n=3) of them due to infectious complications, 31% (n=14) - oncology and others (62%, n=28). Most of manipulations were planned (39 from 45, 87%), the following general surgery interven- tions prevailed: laparoscopic cholecystectomy (n=13) and those to remove inguinal and umbilical hernia (n=12). During the 1st year the frequency of diseases required surgical treatment was 26% (n=11), infectious causes took place in 5 patients, non-infectious - in 6. Subsequently the incidence of infectious complications decreased that could be associated with the minimization of immunosuppressive therapy. Oncology was more frequent long-term after HTx - more than 3 years: among them the development of colon polyps prevailed and all recipients underwent polypectomy. There was no impact of age, gender, causes of chronic heart failure, obesity, immunosuppressive regimen (including the induction) on the frequency of general surgery diseases development (p>0.05). CONCLUSION: Based on our experience, we proposed an algorithm of examination, the features of surgical tactics and preparation for it in heart transplanted recipients are described. The important role of post-heart transplant follow-up in the timely detection of diseases requiring general surgical care is given.

[Results of Russian Hospital Chronic Heart Failure Registry in Three Subjects of Russian Federation].

Aim of the RUssian hoSpital Heart Failure Registry (RUS-HFR) was to analyze clinical and epidemiological characteristics, application of modern drug and non-drug therapy among hospitalized patients with systolic chronic heart failure (CHF) in 3 subjects of Russian Federation. MATERIAL AND METHODS: We conducted a prospective multicenter observational study in 3 cardiological centers (Petersburg, Orenburg, Samara) in which we recruited patients aged 18-75 years with left ventricular ejection fraction less or equal 40% without ongoing myocardial infarction or pulmonary thromboembolism. RESULTS: Between October 2012 and June 2014 we included 524 patients (mean age 60 years, >79% men) mostly with NYHA class III CHF. Main etiological factors were ischemic heart disease and arterial hypertension, which was not corrected by the time of admission in 20-40.7% of patients. Portions of patients who had undergo the myocardial revascularization, surgery because of valvular heart defects, and implantation of permanent pacemaker including device for cardiac resynchronizing therapy were 11-41, 0-4, and 0-19.5%, respectively. In up to 25% of patients therapy with one of main medications or diuretic was initiated after hospitalization. At discharge 82.3-8.3, 76.3-95.8, 65.9-81.1, 80.7-94.6% of patients received ACEI/ARB, -adrenoblockers, MRA, diuretic therapy, respectively. Implantation of cardioverter ICD/CRT, ICD and heart transplantation were considered indicated in 0-21.2 and 0-6.6% of patients, respectively. Duration of hospitalization was 26+/-14, 15+/-10, and 13+/-5 bed-days in Petersburg, Orenburg, and Samara, respectively. CONCLUSIONS: Compared with data obtained 10 years earlier portrait of a patient with in general remained unchanged. However portion of patients who had undergone cardio-surgical and electrophysiological interventions became tangible, and numbers of patients receiving therapy with ACEI/ARB, -adrenoblockers, and MRA became comparable with those in European registries. Significant deviations from guidelines on drug therapy were revealed at prehospital stage; and high-technology methods of therapy were insufficiently often recommended in participating hospitals. Portion of hospitalizations not related to acute decompensation was 5-37%, while duration of such hospitalizations as well as hospitalizations because of acute decompensation of CHF significantly exceeded this parameter in EU and USA. Absence of obligatory drug therapy prior to admission in a part of patients in RUS-HF raises questions on correction of patients compliance and on creation of a system of specialized ambulatory surveillance of CHF patients after discharge from hospital.