AIM:Comparative analysis of clinical, anamnestic, and laboratory and instrumental data of patients with chronic heart failure (CHF) and iron deficiency (ID) diagnosed according to the AHA/ESC/RSC criteria, and CHF patients diagnosed with ID based on decreased transferrin saturation (TSAT) ≤19.8% or serum iron (Fe) ≤13 μmol/l. MATERIAL AND METHODS:An additional analysis of the ID-CHF-RF study was performed. The analyzed population included 498 patients (198 women) with CHF. In addition to the ID criteria provided by the protocol (AHA/ESC/RSC criteria: ferritin <100 μg/l or ferritin from 100 to 299 μg/l and TSAT<20%), concentrations of ID biomarkers were assessed, which showed high sensitivity and specificity for the diagnosis of ID compared to the morphological picture of the bone marrow (TSAT<19.8% or Fe ≤13 μmol/l). Subgroups of patients with ID determined only by the AHA/ESC/RSC criteria, only by the TSAT≤19.8% and Fe ≤13 μmol/l criteria, and by both were analyzed. RESULTS:ID diagnosed by the AHA/ESC/RSC criteria was found in 83.1% of patients. The TSAT ≤19.8% and Fe ≤13 μmol/l criteria revealed ID in 74.5% of patients. In 341 patients (76.8%), ID was diagnosed using both criteria. Patients with ID diagnosed by the TSAT≤19.8% and Fe≤13 μmol/l criteria, compared with patients with ID diagnosed by the AHA/ESC/RKO criteria, had a 50% lower Fe (9.8 μmol/l vs. 19.4 μmol/l) and a higher incidence of anemia (43.3% vs. 23.3%) and diabetes mellitus (DM) (36.7% and 24.7%). Also, these patients had higher values of body mass index (BMI) and NT-proBNP concentration (2317 [1305;9092] vs. 1691 [709;3856] pg/ml), and lower LV EF values (41.5 [29.0;54.5]% vs. 45.0 [34.0;54.0]%), respectively. The most severe course of CHF and the greatest changes in laboratory tests associated with ID and anemia were observed in patients with ID determined by two criteria. Patients in this group were older, with a higher BMI, more frequent presence of atrial fibrillation, and higher NT-proBNP (4182 [1854;9341] pg/ml). CONCLUSION:Patients with isolated low ferritin are characterized by less severe clinical and functional impairment compared to patients with low TSAT or Fe. At the same time, patients with ferritin higher than 300 μg/l and low TSAT and/or Fe were characterized by very severe CHF and a low functional status, although this may not be related with ID. Thus, the use of the ferritin-based criteria of ID may lead to overdiagnosis of ID in some patients and, at the same time, miss some of the most "severe" patients who likely require the ID correction. Patients with ID who show a decrease in all three parameters are likely to benefit most from Fe supplementation. It is advisable to perform additional studies on the effect of Fe supplements on the course and prognosis of the disease in this cohort of patients.

The review is devoted to the influence of central sleep apnea and Cheyne-Stokes breathing on the prognosis of patients with chronic heart failure. The connection between sleep breathing disorders and an increased risk of ventricular arrhythmias and the mechanisms of these interactions are discussed, and options for approaches to therapy are considered.

Aim      To evaluate the role of iron deficiency (ID) identified by various criteria, anemia, and the combination of ID and anemia in determining the severity of the clinical course of chronic heart failure (CHF) in a retrospective analysis of data from 498 patients who participated in the ID-CHF-RF Russian multicenter program.Material and methods  ID was diagnosed by the following three criteria established by the European Society of Cardiology (ESC) and the Russian Society of Cardiology (RSC): 1) ferritin concentration <100 μg/l or ferritin concentration 100-299 μg/l in combination with a decreased transferrin saturation (TS) <20%; 2) ID criteria that showed a high sensitivity and specificity when compared with bone marrow morphology (BMM): TS ≤19.8% or serum iron (SI) ≤13 μmol/l; and 3) a composite index including a ferritin concentration <100 μg/l in combination with TS <20% and SI ≤13 μmol/l. The presence of anemia was defined as a hemoglobin concentration of less than 12.0 g/dl in women and less than 13.0 g/dl in men according to the criteria of the World Health Organization.Results Concomitant anemia was detected in 40.3% of patients with CHF; in 85.1% of cases, anemia was combined with the SI concentration below normal. CHF patients with concomitant anemia were significantly older and had low levels of not only red blood cells and hemoglobin but also all parameters of iron metabolism, i.e., SI, ferritin concentration, and TS. The mean deviation of the red blood cell size, that characterizes the degree of anisocytosis, was significantly increased in patients with anemia, especially with a low SI. These patients had a higher CHF functional class, elevated levels of N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) and walked a shorter distance in the 6-minute walk test, which reflects significantly more severe manifestations of CHF with concomitant anemia, particularly in combination with a low SI. The incidence of ID was 83.1% (including 23.3% in combination with anemia) according to the ESC/RSC criteria; 74.5% (including 43.3% with anemia) according to the BMM criteria; and 51.6% (including 51.7% with anemia) according to the composite index, which seems to be stricter compared to the first two criteria. Regardless of the assessment method (by total weighted average data), in ID combined with anemia, not only the hemoglobin concentration was significantly reduced but all three analyzed parameters of iron metabolism were also significantly reduced (SI 9.0 μmol/l vs. 10.4 μmol/l; ferritin 41 μg/l vs. 59 μg/l; TS 8.5% vs. 12.9%) compared to ID without anemia, respectively. The CHF severity and the NT-proBNP concentration were also maximum for the combination of ID and anemia, in contrast to ID without anemia, regardless of the ID criterion used. A more accurate comparison of the methods for determining ID in CHF in the context of their prognostic value will be obtained by analyzing the data of a two-year follow-up of patients in this study, which will be the subject of the next article.Conclusion      This analysis suggests that the presence of concomitant ID without anemia or anemia without ID moderately affects the severity of clinical manifestations of CHF and may be rather markers than factors determining the course of the disease, and in this case, does not require special correction with iron medications. And only ID anemia (a combination of ID with anemia) in patients with CHF can be considered a condition requiring special correction (for example, with intravenous medication) in addition to optimal therapy for CHF. This conclusion does not change depending on the used criteria for ID and requires verification in new RCTs.

Издание представляет собой учебно-методическое пособие, необходимое при освоении дисциплины «Поликлиническая терапия». Пособие разработано в соответствии с самостоятельно установленным МГУ образовательным стандартом для реализуемых основных профессиональных образовательных программ высшего образования по специальности 31.05.01 «Лечебное дело» (уровень образования – специалитет). Пособие призвано подытожить приобретенные студентами умения и навыки, интегрировать их в общую систему медицинских знаний, полученных в результате изучения патологии, фармакологии и др. теоретических и клинических дисциплин. Пособие предназначено для студентов 5-6 курсов медицинских вузов.

Aim    To evaluate the prevalence of iron deficiency (ID) in Russian patients with heart failure (HF).Material and methods    Iron metabolism variables were studied in 498 (198 women, 300 men) patients with HF. Data were evaluated at admission for HF (97 %) or during an outpatient visit (3 %). ID was determined according to the European Society of Cardiology Guidelines.Results    83.1 % of patients had ID; only 43.5 % of patients with ID had anemia. Patients with ID were older: 70.0 [63.0;79.0] vs. 66.0 years [57.0;75.2] (p=0.009). The number of patients with ID increased in parallel with the increase in HF functional class (FC). Among patients with ID, fewer people were past or current alcohol users (p=0.002), and a greater number of patients had atrial fibrillation (60.1 vs. 45.2 %, p=0.016). A multiple logistic regression showed that more severe HF (HF FC) was associated with a higher incidence of ID detection, whereas past alcohol use was associated with less pronounced ID. An increase in N-terminal pro-brain natriuretic peptide (NT-proBNP) by 100 pg/ml was associated with an increased likelihood of ID (odds ratio, 1.006, 95 % confidence interval: 1.002-1.011, p=0.0152).Conclusion    The incidence rate of HF patients is high in the Russian Federation (83.1 %). Only 43.5 % of these patients had anemia. The prevalence of ID in the study population increased with increases in HF FC and NT-proBNP.

ActualityThe course of the novel coronavirus disease (COVID-19) is unpredictable. It manifests in some cases as increasing inflammation to even the onset of a cytokine storm and irreversible progression of acute respiratory syndrome, which is associated with the risk of death in patients. Thus, proactive anti-inflammatory therapy remains an open serious question in patients with COVID-19 and pneumonia, who still have signs of inflammation on days 7–9 of the disease: elevated C-reactive protein (CRP)>60 mg/dL and at least two of the four clinical signs: fever >37.5°C; persistent cough; dyspnea (RR >20 brpm) and/or reduced oxygen blood saturation <94% when breathing atmospheric air. We designed the randomized trial: COLchicine versus Ruxolitinib and Secukinumab in Open-label Prospective Randomized Trial in Patients with COVID-19 (COLORIT). We present here data comparing patients who received colchicine with those who did not receive specific anti-inflammatory therapy. Results of the comparison of colchicine, ruxolitinib, and secukinumab will be presented later.ObjectiveCompare efficacy and safety of colchicine compared to the management of patients with COVID-19 without specific anti-inflammatory therapy.Material and MethodsInitially, 20 people were expected to be randomized in the control group. However, enrollment to the control group was discontinued subsequently after the inclusion of 5 patients due to the risk of severe deterioration in the absence of anti-inflammatory treatment. Therefore, 17 patients, who had not received anti-inflammatory therapy when treated in the MSU Medical Research and Educational Center before the study, were also included in the control group. The effects were assessed on day 12 after the inclusion or at discharge if it occurred earlier than on day 12. The primary endpoint was the changes in the SHOCS-COVID score, which includes the assessment of the patient’s clinical condition, CT score of the lung tissue damage, the severity of systemic inflammation (CRP changes), and the risk of thrombotic complications (D-dimer) [1].ResultsThe median SHOCS score decreased from 8 to 2 (p = 0.017), i.e., from moderate to mild degree, in the colchicine group. The change in the SHOCS-COVID score was minimal and statistically insignificant in the control group. In patients with COVID-19 treated with colchicine, the CRP levels decreased rapidly and normalized (from 99.4 to 4.2 mg/dL, p<0.001). In the control group, the CRP levels decreased moderately and statistically insignificantly and achieved 22.8 mg/dL by the end of the follow-up period, which was still more than four times higher than normal. The most informative criterion for inflammation lymphocyte-to-C-reactive protein ratio (LCR) increased in the colchicine group by 393 versus 54 in the control group (p = 0.003). After treatment, it was 60.8 in the control group, which was less than 100 considered safe in terms of systemic inflammation progression. The difference from 427 in the colchicine group was highly significant (p = 0.003).The marked and rapid decrease in the inflammation factors was accompanied in the colchicine group by the reduced need for oxygen support from 14 (66.7%) to 2 (9.5%). In the control group, the number of patients without anti-inflammatory therapy requiring oxygen support remained unchanged at 50%. There was a trend to shorter hospital stays in the group of specific anti-inflammatory therapy up to 13 days compared to 17.5 days in the control group (p = 0.079). Moreover, two patients died in the control group, and there were no fatal cases in the colchicine group. In the colchicine group, one patient had deep vein thrombosis with D-dimer elevated to 5.99 µg/mL, which resolved before discharge.ConclusionsColchicine 1 mg for 1-3 days followed by 0.5 mg/day for 14 days is effective as a proactive anti-inflammatory therapy in hospitalized patients with COVID-19 and viral pneumonia. The management of such patients without proactive anti-inflammatory therapy is likely to be unreasonable and may worsen the course of COVID-19. However, the findings should be treated with caution, given the small size of the trial.

The risk factors, clinical manifestations, pathophysiology, diagnosis and treatment options for central sleep apnea and Cheyne-Stokes respiration in patients with heart failure are highlighted in this review. The effectiveness and prospects of therapeutic approaches are discussed: CPAP therapy, adaptive servo ventilation, transvenous stimulation of the phrenic nerve.

Introduction The aim of this study was to assess the efficacy and safety of a combination of bromhexine at a dose of 8 mg 4 times a day and spironolactone 50 mg per day in patients with mild and moderate COVID 19.Material and methods It was an open, prospective comparative non-randomized study. 103 patients were included (33 in the bromhexine and spironolactone group and 70 in the control group). All patients had a confirmed 2019 novel coronavirus infection (COVID 19) based on a positive polymerase chain reaction (PCR) for SARS-CoV-2 virus RNA and/or a typical pattern of viral pneumonia on multispiral computed tomography. The severity of lung damage was limited to stage I-II, the level of CRP should not exceed 60 mg / dL and SO2 in the air within 92-98%. The duration of treatment is 10 days.Results The decrease in scores on the SHOKS-COVID scale, which, in addition to assessing the clinical status, the dynamics of CRP (a marker of inflammation), D-dimer (a marker of thrombus formation), and the degree of lung damage on CT (primary endpoint) was statistically significant in both groups and differences between them was not identified. Analysis for the group as a whole revealed a statistically significant reduction in hospitalization time from 10.4 to 9.0 days (by 1.5 days, p=0.033) and fever time from 6.5 to 3.9 days (by 2.5 days, p<0.001). Given the incomplete balance of the groups, the main analysis included 66 patients who were match with using propensity score matching. In matched patients, temperature normalization in the bromhexine/spironolactone group occurred 2 days faster than in the control group (p=0.008). Virus elimination by the 10th day was recorded in all patients in the bromhexine/spironolactone group; the control group viremia continued in 23.3% (p=0.077). The number of patients who had a positive PCR to the SARS-CoV-2 virus on the 10th day of hospitalization or longer (≥10 days) hospitalization in the control group was 20/21 (95.2%), and in the group with bromhexine /spironolactone -14/24 (58.3%), p=0.012. The odds ratio of having a positive PCR or more than ten days of hospitalization was 0.07 (95% CI: 0.008 - 0.61, p=0.0161) with bromhexine and spironolactone versus controls. No side effects were reported in the study group.Conclusion The combination of bromhexine with spironolactone appeared effective in treating a new coronavirus infection by achieving a faster normalization of the clinical condition, lowering the temperature one and a half times faster, and reducing explanatory combine endpoint the viral load or long duration of hospitalization (≥ 10 days).

The article is devoted to the treatment of the new coronavirus infection (COVID-19) in the advanced stages of the disease. The types of response of the immune system to the viral load of SARS-CoV-2 with the start of the inflammation process are considered. The situation is analyzed in detail in which the growing autoimmune inflammation (up to the development of a "cytokine storm") affects not only the pulmonary parenchyma, but also the endothelium of the small vessels of the lungs. Simultaneous damage to the alveoli and microthrombosis of the pulmonary vessels are accompanied by a progressive impairment of gas exchange, the development of acute respiratory distress syndrome, the treatment of which, even with the use of invasive ventilation, is ineffective and does not really change the prognosis of patients with COVID-19. In order to interrupt the pathological process at the earliest stages of the disease, the necessity of proactive anti-inflammatory therapy in combination with active anticoagulation treatment is substantiated. The results of the first randomized studies on the use of inhibitors of pro-inflammatory cytokines and chemokines (interleukin-6 (tocilizumab), interleukin-17 (secukinumab), Janus kinase blockers, through which the signal is transmitted to cells (ruxolitinib)), which have potential in the early treatment of COVID- 19. The use of a well-known anti-inflammatory drug colchicine (which is used for gout treatment) in patients with COVID-19 is considered. The design of the original COLORIT comparative study on the use of colchicine, ruxolitinib and secukinumab in the treatment of COVID-19 is presented. Clinical series presented, illustrated early anti-inflammatory therapy together with anticoagulants in patients with COVID-19 and the dangers associated with refusing to initiate such therapy on time.

The review presents results of clinical studies of efficacy and safety of thiazide and thiazide-like diuretics in the treatment of patients with arterial hypertension. In this work we have compared the role of diuretics in modern clinical recommendation on control of arterial pressure, and assessed in comparative aspect metabolic effects of thiazide-like diuretics.

Loop diuretics take the lead in the treatment of patients with symptomatic heart failure. Torasemide is the most effective and safe loop diuretic with the optimal pharmacokinetic profile, the additional properties associated with simultaneous blockade of the renin-angiotensin-aldosterone system and with the antiadrenergic effects of the drug, its positive impact on myocardial fibrosis and minimal severe potential negative effects. Sustained-release torasemide provides a more comfortable removal of excess liquid and does not deteriorate quality of life.

Аннотация Петлевые диуретики занимают ведущее место в лечении больных с симптоматической сердечной недостаточностью (СН). Торасемид — наиболее эффективный и безопасный петлевой диуретик с оптимальным фармакокинетическим профилем, дополнительными свойствами, связанными с одновременной блокадой ренин-ангиотензин-альдостероновой системы и антиадренергическими эффектами препарата, положительным влиянием на миокардиальный фиброз и минимально выраженными потенциально негативными эффектами. Форма торасемида с замедленным высвобождением обеспечивает более комфортное выведение излишков жидкости и не ухудшает качество жизни пациентов.

OBJECTIVE:to evaluate the relationship between arterial stiffness and bone metabolism in women with mild to moderate risk of cardiovascular disease (CVD). METHODS:In 103 postmenopausal women (mean age 57.0 years, 95% CI 50.0-64.0) with mild to moderate risk of CVD (SCORE<5), no more than mild hypertension, normal function of thyroid gland, without coronary artery disease, diabetes mellitus and secondary causes of osteoporosis pulse wave velocity between carotid and femoral sites (cfPWV, by applanation tonometry) and ankle and brachial sites (baPWV, by volume sphygmography) as well as bone mineral density at lumbar spine and femoral neck (by dual-energy X-ray absorptiometry) and blood serum levels of markers of bone turnover (total procollagen type I amino-terminal propeptide (PINP), osteocalcin, collagen type 1 cross-linked C-telopeptide (-CTX) by electrochemilumininescence immunoassay) were assessed. RESULTS:Compared with patients with normal mineral bone density (BMD) (n=27), patients with osteoporosis (n=31) had higher cfPWV and baPWV values (p<0.05). Patients with osteopenia did not differ from other groups (p>0.05). In osteoporosis group there were greater years since menopause, less body mass index than in normal BMD (in all cases p<0.05; ns between osteoporosis and osteopenia groups). Between all three groups there were no significant differences in age, smoking status, visit blood pressure, lipid levels and medication. CfPWV and baPWV values significantly positively correlated with age, systolic arterial pressure, years since menopause, procollagen type I N propeptide (all p<0.05), and significantly negatively correlated with BMD at hip neck (all p<0.05). Relationship between cfPWV and BMD at lumbar spine did not reach significant value (r=-0.18, p=0.068). No relationship was found between parameters of arterial stiffness and CTX and osteocalcin (all p>0.05). In the multivariate analysis cfPWV was significantly and independently associated with systolic blood pressure (=1.03, 95% CI 1.00-1.06, p=0.03) and BMD at hip neck (=0.01, 95% CI 0.001-0.07, p=0.003). CONCLUSION:Revealed association between arterial stiffness and bone metabolism may probably explain general mechanisms of arterial and bone damage in postmenopausal women with mild to moderate risk of cardiovascular disease.