Chronic Heart Failure in Patients Hospitalized in 2002 and 2021: Comparative Analysis of Prevalence, Clinical Course and Drug Therapy.

AIM: Comparative analysis of the prevalence of chronic heart failure (CHF), clinical and medical history data, and drug therapy of patients admitted to a cardiology hospital in 2002 and 2021. MATERIAL AND METHODS: The study analyzed the medical records of patients with a confirmed diagnosis of CHF who were admitted in 2002 (n=210) and 2021 (n=381) to a specialized cardiology hospital. RESULTS: According to medical records of 2021, the proportion of patients with a confirmed diagnosis of CHF (87.6%) in the cohort of patients admitted to a cardiology hospital was twice as high as in 2002 (46.4%; p<0.001). The majority of patients with CHF in the study sample were patients with preserved left ventricular ejection fraction (HFpEF). The proportion of such patients significantly increased to reach 75.9% in 2021 compared to 58.6% in 2002 (p<0.001). At the same time, the number of severe forms of CHF (NYHA functional class (FC) IV) decreased by 10% and was 13.2% in 2002 and 1.3% in 2021 (p<0.001). In the majority of patients, ischemic heart disease (98.1 and 91.1% in 2002 and 2021, respectively, p<0.001) and hypertension (80.5 and 98.2%, respectively, p<0.001) were diagnosed as the cause for CHF. Furthermore, the incidence of comorbidity increased significantly: atrial fibrillation was detected in 12.3% of patients in 2002 and 26.4% in 2021 (p < 0.001); type 2 diabetes mellitus, in 14.3 and 32% of patients (p <0.001); and obesity, in 33.3 and 43.7% of patients, respectively (p=0.018). The frequency of using the major groups of drugs increased during the analyzed period: renin-angiotensin-aldosterone system blockers were administered to 71.9% of patients in 2002 and to 87.7% in 2021 (p<0.001); beta-blockers were administered to 53.3 and 82.4% of patients (p<0.001); and mineralocorticoid receptor antagonists, to 1.9 and 18.6% of patients, respectively (p=0.004). CONCLUSION: In 2021, the proportion of patients with a confirmed diagnosis of CHF in the patient cohort admitted to a cardiology hospital was twice as high as in 2002; the phenotype with preserved left ventricular ejection fraction predominated in the CHF structure. During the analyzed twenty-year period, the prevalence of comorbidities increased among CHF patients. The prescription frequency of pathogenetic evidence-based therapy has significantly increased by 2021, however, it remains insufficient even in patients with CHF with reduced left ventricular ejection fraction.

[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.

[Cardiovascular effects of omega-3 polyunsaturated fatty acids: position of omega-3 polyunsaturated fatty acids in Russian and international guidelines. Council of Experts].

This Expert Council focuses on the meta-analysis of studies on the risk of atrial fibrillation (AF) in patients taking omega-3 polyunsaturated fatty acids (PUFA) and of data on the omega-3 PUFA treatment in patients with cardiovascular and kidney diseases.The major statements of the Expert Council: the meta-analysis of AF risk in patients taking omega-3 PUFA showed an increased risk of this arrhythmia. However, it should be taken into account that the risk of complications was low, and there was no significant increase in the risk of AF when omega-3 PUFA was used at a dose of ≤1 g and a standard dose of the only omega-3 PUFA drug registered in the Russian Federation, considering all AF episodes in the ASCEND study.At the present time, according to Russian and international clinical guidelines, the use of omega-3 PUFA can be considered in the following cases: • for patients with chronic heart failure (CHF) with reduced left ventricular ejection fraction as a supplement to the basic therapy (2B class of recommendations according to the 2020 Russian Society of Cardiology guidelines (RSC) and the 2022 AHA / ACC / HFSA guidelines); • for patients with hypertriglyceridemia (>1.5 mmol/l) as a part of combination therapy (IIb class of recommendations and B level of evidence according to the 2021 European guidelines on cardiovascular disease prevention, etc.); • for adult patients with stage 3-4 chronic kidney disease (CKD), long-chain omega-3 PUFA 2 g/day is recommended for reducing the level of triglycerides (2C class of recommendations). Data on the use of omega-3 PUFA for other indications are heterogenous, which can be partially explained by using different form and doses of the drugs.

Female and Male Phenotypes of Iron Deficiency in CHF. Additional analysis of the «The Prevalence of Iron Deficiency in Patients With Chronic Heart Failure in the Russian Federation (J-CHF-RF)¼ study.

Aim    To evaluate the incidence of iron deficiency (ID) in men and women with chronic heart failure (CHF) and to compare clinical and functional indexes in patient with and without ID depending on the gender.Material and methods    An additional analysis of the study "Prevalence of Iron Deficiency in Patients With Chronic Heart Failure in the Russian Federation (ID-CHF-RF)" was performed. The study included 498 (198 women, 300 men) patients with CHF, in whom, in addition to iron metabolism, the quality of life and exercise tolerance (ET) were studied. 97 % of patients were enrolled during their stay in a hospital. ID was defined in consistency with the European Society of Cardiology (ESC) Guidelines. Also, and additional analysis was performed according to ID criteria validated by the morphological picture of the bone marrow.Results    ID was detected in 174 (87.9 %) women and 239 (79.8 %) men (p=0.028) according to the ESC criteria, and in 154 (77.8 %) women and 217 (72.3 %) men (p=0.208) according to the criteria validated by the morphological picture of the bone marrow. Men with ID were older and had more severe CHF. They more frequently had HF functional class (FC) III and IV (63.4 % vs. 43.3 % in men without ID); higher concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and lower ET. HF FC III increased the probability of ID presence 3.4 times (p=0.02) and the probability of HF FC IV 13.7 times (p=0.003). This clinical picture was characteristic of men when either method of determining ID was used. In women, ID was not associated with more severe CHF.Conclusion    Based on the presented analysis, it is possible to characterize the male and female ID phenotypes. The male ID phenotype is associated with more severe CHF, low ET, and poor quality of life. In females of the study cohort, ID was not associated with either the severity of CHF or with ET.

[Androgenic status of men with severe COVID-19: the role of testosterone and dihydrotestosterone [within the program FOUNDER (features of a new coronavirus infection course and options therapy depending on the androgenic status)]].

PURPOSE: The aim of this study was to assess the mens androgen status influence on the severity and outcomes (transfer of patients to the ICU or death) of COVID-19 required hospital hospitalization. MATERIALS AND METHODS: The study included 151 hospitalized men with a confirmed diagnosis of COVID-19. To measure the severity of disease have been used Symptomatic Hospital and Outpatient Clinical Scale for COVID-19 (SHOCS-COVID). It includes the severity of the clinical condition (hyperthermia, shortness of breath, oxygen saturation, need for ventilation), the degree of inflammation (CRP), markers of thrombosis (D-dimer), the degree of lung damage according to CT. The patients underwent a study of full blood count, some biochemical parameters, lung CT, and a study of testosterone (T) and dihydrotestosterone (DHT) levels. RESULTS: T deficiency was observed in 46.4% of patients (70/151 men). At the same time, DHT deficiency was observed only in 14.4% of patients (18/125 men). In patients with a T level below the median, there was a significant increase in inflammatory factors (CRP, lymphocytes/CRP index), markers of thrombosis (D-dimer and fibrinogen), extensive lung damage at admission according to CT 25.75% vs. 11.95% (p<0.001), the elevated number of points for SHOCKS-COVID 7 (IQR 5-10) versus 5 (IQR 3-7) (p<0.001) and the longer duration of hospital treatment (3 days difference, p<0.001) in comparison with a group of patients with a T level above the median. At the same time, the T level had no correlation with age. The level of DHT had a weak inverse correlation with the age of patients, but not with the main markers of the severity of COVID-19, including the number of SHOCK-COVID scores. During multivariate regression analysis, it was shown that SHOCKS-COVID is the most significant predictor of admission to the ICU while no association of T and DHT levels with outcomes in COVID-19 was found. However, it was found that the concentration of T, even adjusted for age, has a significant inverse association with the severity of the course of the disease and the number of SHOCK-COVID scores (p=0.041). An analysis of the evaluation of directed acyclic graphs suggests the main role of COVID-19 severity in reducing androgenic function and T concentration, at which its anti-inflammatory effects are lost. There were no correlations between the concentration of DHT and the number of SHOCK-COVID scores and the COVID-19 prognosis. CONCLUSION: SHOCK-COVID is the most sensitive predictor of the COVID-19 outcome in hospitalized men, including adjusting to age. T and DHT do not directly affect the outcomes of the disease. The greater severity of the infection and an increase in SHOCK-COVID scores are associated with a decrease in the concentration of T, and a weakening of its anti-inflammatory and anti-cytokine effects, which indirectly worsens the prognosis of male patients with a new coronavirus infection undergoing hospital treatment. There are no such relationships for DHT.

Role of anticoagulants in therapy and prevention of recurrent venous thromboembolism in patients with cancer: a meta-analysis of randomized trials with apixaban.

Background    Venous thromboembolic complications (VTEC) are a major non-oncological cause of death of patients with malignant neoplasm (MNP). This determines the high significance of antithrombotic therapy for the treatment and secondary prevention of VTEC in this population. During recent years, low-molecular weight heparins (LMWH) have been a "gold standard" for the treatment of cancer-associated venous thrombosis (CAVT). In the recent decade, direct oral anticoagulants (DOACs) have become extensively used for the treatment and prevention of VTEC relapse in non-oncological patients and also for primary prevention of VTEC following orthopedic surgery. Taking into account the oral route of administration, the predictable and convenient pharmacokinetic profile, and the absence of need for coagulation monitoring, it seems possible to use DOACs for the treatment and secondary prevention of VTEС in oncological patients. A meta-analysis of 4 randomized clinical trials (RCTs) showed a higher efficacy of DOACs compared to LMWHs, however, with a greater risk of bleedings in CAVT. In two of four studies using apixaban (more than 40% of weight in meta-analysis), no increase in bleedings was noted.Aim    The aim of this study was to perform a systematic search for comparative clinical studies with apixaban and to perform a meta-analysis to answer the question on clinical efficacy and safety of apixaban in the treatment and secondary prevention of recurrent VTEC in patients with CAVT.Material and methods    The systematic search was performed in three reference databases, Medline (PubMed), Cochrane Library (CENTRAL), and eLibrary. The search was aimed at publications containing results of RCTs using apixaban for the treatment and prevention of VTEC in patients with MNP. A totality of 678 titles was found; 15 articles were selected for detailed studying, and 4 RCTs were included into the final analysis. The meta-analysis was performed according to the criteria of PRISMA guidelines. Relative risk (RR) was used as a measure of the effect. The meta-analysis was performed by the Mantel-Haenszel method using the R software. Statistical heterogeneity was evaluated with the Cochran criterion (I2); heterogeneity was considered significant at I2 ≥50 %, which was a reason for performing a random-effects meta-analysis. For this meta-analysis, the primary outcome measure was new VTECs (symptomatic or detected proximal deep vein thrombosis and/or symptomatic, detected or fatal pulmonary thromboembolism plus symptomatic upper extremity thromboses, celiac veinous thromboses, and cerebral veinous thromboses if they were included into the efficacy endpoint of the primary studies). The primary safety measure was major bleeding according to ISTH criteria. Other variables included major and clinically significant minor bleedings as well as overall death rate.Results    During the systematic search, 4 RCTs were selected. The meta-analysis of the treatment and secondary prevention of VTEC in patients with MNP showed that apixaban was more effective than the active control (88% of LMWHs) in prevention of VTEC relapse. The RR was 0.59; 95 % confidence interval (CI): 0.40-0.86 in the absence of statistically significant differences from the control in the risk of major bleedings (statistically non-significant decrease by 21%), the sum of major and clinically significant minor bleedings, and overall death rate.Conclusion    According to the results of the meta-analysis, the DOAC apixaban may be a drug of choice for the treatment and prevention of VTEC relapse in patients with MNO.

[Coenzyme Q-10 in the treatment of patients with chronic heart failure and reduced left ventricular ejection fraction: systematic review and meta-analysis].

Aim    The aim of the study was evaluation of the effect of the coenzyme Q10 (Q10) treatment on all-cause and cardiovascular mortality of patients with chronic heart failure (CHF). Q-10 increases the electron transfer in the mitochondrial respiratory chain and exerts anti-inflammatory and antioxidant effects. These effects improve the endothelial function and reduce afterload, which facilitates the heart pumping function. Patients with reduced left ventricular (LV) ejection fraction (EF) (CHFrEF) have low Q10.Material and methods    Criteria of inclusion in the meta-analysis: 1) placebo-controlled studies; 2) enrollment of at least 100 patients; 3) publications after 2010, which implies an optimal basic therapy for CHF; 4) duration of at least 6 months; 5) reported cardiovascular and/or all-cause mortality; 6) using sufficient doses of Q10 (>100 mg/day). The search was performed in CENTRAL, MEDLINE, Embase, Web of Science, E-library, and ClinicalTrials.gov databases. All-cause mortality was the primary efficacy endpoint in this systematic review and the meta-analysis. The secondary endpoint was cardiovascular mortality. Meta-analysis was performed according to the Mantel-Haenszel methods. The Cochrane criterion (I2) was used for evaluation of statistical heterogeneity. The random effects model was used at I2≥50 %, whereas the fixed effects model was used at I2<50.Results    Analysis of studies published from 01.01.2011 to 01.12.2021 identified 357 publications, 23 of which corresponded to the study topic, but only 6 (providing results of four randomized clinical trials, RCT) completely met the predefined criteria. The final analysis included results of managing 1139 patients (586 received Q10 and 553 received placebo). Risk of all-cause death was analyzed by data of four RCTs (1139 patients). The decrease in the risk associated with the Q10 treatment was 36 % (OR=0.64, 95 % CI 0.48-0.87, р=0.004). The heterogeneity of studies was low (Chi2=0.84; p=0.84; I2=0 %). Risk of cardiovascular mortality was analyzed by data of two RCTs (863 patients). The decrease in the risk associated with the Q10 treatment was significant, 55% (OR=0.45, 95 % CI: 0.32-0.64, р=0.00001). In this case, the data heterogeneity was also low (Chi2=0.41; p=0.52; I2=0 %).Conclusion    The meta-analysis confirmed the beneficial effect of coenzyme Q10 on the prognosis of patients with CHFrEF receiving the recommended basic therapy.

[Cardiac contractility modulation in heart failure with reduced ejection fraction treatment].

Heart failure with reduced left ventricular ejection fraction (LV EF) (HFrEF) is a significant issue of health care due to increasing indexes of morbidity and mortality. The emergence of a number of drugs and implantable devices for the treatment of HFrEF has allowed improvement of patients' well-being and prognosis. However, high mortality and recurrent decompensated heart failure remain a substantial issue and stimulate the search for new methods of CHF treatment. Cardiac contractility modulation (CCM) is a method of managing patients with HFrEF. Available data from randomized clinical trials (RCT) indicate the efficacy of CCM in improvement of patients' well-being and quality of life. The question remains open: what effect does CCM have on LV reverse remodeling? Experimental data and results of observational studies suggest a possibility of reverse remodeling by CCM; however, this has not been confirmed in RCT. Also, it remains unclear how CCM influences the frequency of hospitalizations for decompensated heart failure and the death rate of patients with HFrEF. Results of both RCTs and observational studies have shown a moderate improvement of quality of life associated with CCM. Furthermore, RCTs have not found any increase in LV EF due to the therapy, nor has a meta-analysis of RCTs revealed any improvement of the prognosis associated with CCM.  Further RCTs are needed to evaluate the effect of CCM on reverse remodeling, survival rate, and to determine the place of CCM in the treatment of patients with CHF.

The Burden of Residual SymptOms That Complicate the Life of Patients Who Have Suffered a new Coronavirus Infection (THROW study).

Aim      To evaluate the prevalence of residual symptoms in patients hospitalized for novel coronavirus infection at 8 months after discharge and the severity of such symptoms depending on demographic characteristics, concurrent diseases, and specific features of the acute period of COVID-19.Material and methods  This study included the patients who were managed for novel coronavirus infection in a COVID-19 hospital and provided their consent to participate in the study (98 patients). At 8 months after discharge from the hospital, a structured telephone interview was performed.Results Only 40 % of patients treated for COVID-19 did not have any complaints at 8 months after discharge from the hospital. The most frequent complaints in the long term were fatigue (30.5 %), weakness (28.4 %), shortness of breath (23.2 %), arthralgia (22.1 %), myalgia (17.9 %), and anosmia (15.8 %). The background of chronic diseases and obesity, percentage of lung damage according to CT data, and the requirement for oxygen support during the acute period in our sample were not related with the presence of symptoms in the long term. The presence and severity of symptoms during the long term were not determined by the clinical condition, volume of lung damage, or requirement for oxygen support but were related with the gender and severity of inflammation upon admission.Conclusion      Independent predictors for persistence of symptoms in the patient sample with severe novel coronavirus infection during the long term included chest and joint pain during the stay in the hospital, female gender, and increased levels of C-reactive protein upon admission.

Epidemiology of atrial fibrillation in a representative sample of the European part of the Russian Federation. Analysis of EPOCH-CHF study.

Aim    To study true prevalence of atrial fibrillation (AF) in a representative sample from the European part of the Russian Federation; to describe characteristics of patients with AF; and to provide the frequency of anticoagulant treatment.Material and methods    Cross-sectional data of the EPOCH epidemiological study (2017) were used. Data were collected in 8 constituent entities of the Russian Federation; the sample size was 11 453 people. The sample included all respondents who had given their consent for participation and were older than 10 years. Statistical tests were performed in the R system for statistical data analysis.Results    The prevalence of AF in the representative sample from the European part of the Russian Federation was 2.04 %. The AF prevalence increased with age and reached a maximum value of 9.6% in the age group of 80 to 89 years. The AF prevalence among females was 1.5 times higher than among men. With age standardization, the AF prevalence was 18.95 and 21.33 per 1,000 people for men and women, respectively. The AF prevalence increased in the presence of concurrent cardiovascular diseases (CVDs) or diabetes mellitus as well as with an increased number of comorbidities in the same person and reached 70.3 and 60.0 % in patients with 4 and 5 comorbidities, respectively. Patients with AF had a greater number of comorbidities and higher CHA2DS2VASc scores (5.0 vs. 2.0, p<0.001) compared to patients with CVDs without AF. Only 22.6 % of patients with CVD and AF took anticoagulants. Only 23.9% of patients with absolute indications for the anticoagulant treatment received anticoagulants.Conclusion    The AF prevalence in the European part of the Russian Federation was 2.04 %; it increased with age and in patients with concurrent CVDs or diabetes mellitus. Most of AF patients (93.2 %) required a mandatory treatment with oral anticoagulants.

Proactive anti-inflammatory therapy in the advanced stages of a new coronavirus infection. Main results of the inpatient phase of the COLORIT study (Colchicin vs. Ruxolitinib and secukinumab in an open, prospective, randomized trial in patients with novel coronavirus infection COVID-19).

Aim      To evaluate clinical efficacy of the proactive anti-inflammatory therapy in patients hospitalized for COVID-19 with pneumonia and a risk of "cytokine storm".Material and methods  The COLORIT study was a comparative study with randomization into 4 groups: colchicine (n=21) 1 mg for the first 3 days followed by 0.5 mg/day through day 12 or discharge from the hospital; secukinumab 300 mg/day, s.c., as a single dose (n=20); ruxolitinib 5 mg, twice a day (n=10); and a control group with no anti-inflammatory therapy (n=22). The effect was evaluated after 12±2 days of inpatient treatment or upon discharge, what comes first. For ethical reasons, completely randomized recruitment to the control group was not possible. Thus, for data analysis, 17 patients who did not receive any anti-inflammatory therapy for various reasons not related with inclusion into the study were added to the control group of 5 randomized patients. Inclusion criteria: presence of coronavirus pneumonia (positive PCR test for SARS-CoV-2 RNA or specific clinical presentation of pneumonia; IDC-10 codes U07.1 and U07.2); C-reactive protein (CRP) concentration >60 mg/l or its threefold increase from baseline; at least 2 of 4 symptoms (fever >37.5 °C, persistent cough, shortness of breath with inspiratory rate >20 per min or blood saturation with oxygen <94 % by the 7th-9th day of disease. The study primary endpoint was changes in COVID Clinical Condition Scale (CCS-COVID) score. The secondary endpoints were the dynamics of CRP and changes in the area of lung lesion according to data of computed tomography (CT) of the lungs from the date of randomization to 12±2 days.Results All three drugs significantly reduced inflammation, improved the clinical course of the disease, and decreased the disease severity as evaluated by the CCS score: in the ruxolitinib group, by 5.5 (p=0.004); in the secukinumab group, by 4 (p=0.096); in the colchicine group, by 4 (p=0.017), and in the control group, by 2 (р=0.329). In all three groups, the CCS-COVID score was 2-3 by the end of observation period, which corresponded to a mild process, while in the control group, the score was 7 (р=0.005). Time-related changes in CRP were significant in all three anti-inflammatory treatment groups with no statistical difference between the groups. By the end of the study, changes in CT of the lungs were nonsignificant.Conclusion      In severe СOVID-19 with a risk of "cytokine storm", the proactive therapy with ruxolitinib, colchicine, and secukinumab significantly reduces the inflammation severity, prevents the disease progression, and results in clinical improvement.

[Iron deficiency in Russia heart failure patients. Observational cross-sectional multicenter study].

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.

The ability of modern therapy to improve the prognosis of patients with HF: role of angiotensin neprilysin inhibitors and sodium-glucose cotransporter inhibitors.

Major principles for treatment of chronic heart failure with reduced left ventricular ejection fraction <40% (HFrEF) include a "triple neurohormonal blockade" as a main approach. However, in recent 6 years, two new classes of drugs for the treatment of HFrEF have appeared, which beneficially influence the prognosis. These drugs are angiotensin receptor neprilysin inhibitors (ARNI) and type 2 sodium-glucose cotransporter 2 (SGLT2) inhibitors.Aim    To compare the net effect of simultaneous treatment with ARNI and SGLT2 inhibitors with the triple neurohormonal blockade in stable or decompensated patients with CHF based on Russian data.Material and methods    We analyzed the risk of death per 100 patient-years in patients with HFrEF. Stable patients were followed up at the A.L. Myasnikov Institute of Cardiology (presently, A.L. Myasnikov Research Institute of Clinical Cardiology of the National Medical Research Center of Cardiology) from 2006 through 2007; data from the EPOCH-Decompensation-CHF study were used for decompensated patients (12.2 % and 36.8 %, respectively).Results    When patients with stable HFrEF were successively switched from renin-angiotensin-aldosterone system (RAAS) inhibitors to ARNI (-16 %) and subsequently supplemented with SGLT2 (-13 %) the risk of death per 100 patient-years decreased from 12.2 % to 8.9 % (total risk decreased by 27 %; to save one patient the ARNI+ SGLT2 combination has to be prescribed to 30 patients). The estimated risk of death upon discharge from the hospital for the patients with decompensated CHF switched from RAAS inhibitors to ARNI (-16 %) and subsequently supplemented with SGLT2 (-13 %) was 26.9 deaths per 100 patient-years, whereas the number of patients to be treated for saving one life was only 10. Based on available data that demonstrate a greater effect of ARNI+ SGLT2 in patients immediately after CHF aggravation, the risk of death was recalculated. According to this analysis, the death rate per 1000 patient-years decreased from 36.8 to 19.9 % (relative risk decrease, 46 %), and to save one life only 6 patients had to be treated after they have achieved compensation of HFrEF.Conclusions    This analysis shows the importance of early initiation of the ARNI+ SGLT2 therapy in patients with both decompensated and with stable HFrEF.

Effect of 24-hour blood pressure and heart rate on the prognosis of patients with reduced and midrange LVEF.

Aim    Optimal combination therapy for chronic heart failure (CHF) currently implies the mandatory use of at least four classes of drugs: renin-angiotensin-aldosterone (RAAS) system inhibitors or angiotensin receptor blocker neprilysin inhibitors (ARNI); beta-adrenoblockers (BAB); mineralocorticoid receptor antagonists; and sodium-glucose cotransporter 2 inhibitors. Furthermore, many of these drugs are able to decrease blood pressure even to hypotension and alleviate tachycardia. This study focused on the relationship of 24-h blood pressure (BP) and heart rate (HR) with the prognosis for CHF patients with sinus rhythm and left ventricular ejection fraction (LV EF) <50 % as well as on suggesting possible variants of safe therapy for CHF depending on the combination of studied factors.Material and methods    Effects of clinical data, echocardiographic parameters, 24-h BP, and heart rhythm (data from 24-h BP and ECG monitors) on the prognosis of 155 patients with clinically pronounced CHF, LV EF <50 %, and sinus rhythm who were followed up for 5 years after discharge from the hospital.Results    The one-factor analysis showed that the prognosis of CHF patients was statistically significantly influenced by the more severe functional class (FC) III CHF compared to FC II, reduced LV EF (<35 %), a lower 24-h systolic BP (SBP) (<103 mm Hg), the absence of hypotensive episodes in daytime, a low variability of nighttime BP (<7.5 mm Hg), a higher 24-h HR (>71 bpm vs. <60 bpm), the absence of therapy with RAAS inhibitors + BAB, and a lower body weight index. The multi-factor analysis showed that more severe CHF FC, lower LV EF, and the absence of RAAS inhibitors + BAB therapy retained the influence on the prognosis. After eliminating the influencing factor of drug therapy, also a low SBP variability significantly influenced the prognosis. An additional analysis determined the following four groups of CHF patients with reduced heart systolic function according to mean 24-h HR and SBP: the largest group (38.1 % of all patients) with controlled HR (≤69 bpm), preserved SBP (>103 mm Hg), and the lowest death rate of 15.3 %; the group with increased HR (>69 bpm) but preserved SBP (30.3 % of all patients) where the death rate was 44.7 %, which was significantly higher than in the first group; the group with normal HR (≤69 bpm) but reduced SBP (≤103 mm Hg) (16.1 % of patients) where the death rate was 40 %, which was comparable with the second group and significantly worse than in the first group; and the group with both increased HR (>69 bpm) and reduced SBP (≤103 mm Hg) (15.5 % of patients), which resulted in the maximal risk of death (70.8 % of patients with CHF and LV EF <50 %), which was significantly higher than in the three other groups.Conclusion    Low SBP (including 24-h SBP with reduced variability in day- and nighttime) in combination with high HR (including by data of Holter monitoring), low LV EF, more severe clinical course of CHF, and the absence of an adequate treatment with neurohormonal modulators (RAAS inhibitors and BAB) significantly increased the risk of death. Isolating four types of FC II-III CHF with sinus rhythm and EF <50% based on the combination of HR and BP identifies patients with an unfavorable prognosis, which will help developing differentiated therapeutic approaches taking into account clinical features.

Hydroxychloroquine in patients with novel coronavirus infection (COVID-19): a case-control study.

Actuality One of the most widely discussed treatments for patients with COVID-19, especially at the beginning of the epidemy, was the use of the antimalarial drug hydroxychloroquine (HCQ). The first small non-randomized trials showed the ability of HCQ and its combination with azithromycin to accelerate the elimination of the virus and ease the acute phase of the disease. Later, large, randomized trials did not confirm it (RECOVERY, SOLIDARITY). This study is a case-control study in which we compared patients who received and did not receive HCQ.Material and Methods 103 patients (25 in the HCQ treatment group and 78 in the control group) with confirmed COVID-19 (SARS-CoV-2 virus RNA was detected in 26 of 73 in the control group (35.6%) and in 10 of 25 (40%) in the HCQ group) and in the rest - a typical picture of viral pneumonia on multislice computed tomography [MSCT]) were included in the analysis. The severity of lung damage was limited to stages I-II, the CRP level should not exceed 60 mg/dL, and oxygen saturation in the air within 92-98%. We planned to analysis the duration of treatment of patients in the hospital, the days until the normalization of body temperature, the number of points according to the original SHOCS-COVID integral scale, and changes in its components (C-reactive protein (CRP), D-dimer, and the percentage of lung damage according to MSCT).Results Analysis for the whole group revealed a statistically significant increase in the time to normalization of body temperature from 4 to 7 days (by 3 days, p<0.001), and the duration of hospitalization from 9.4 to 11.8 days (by 2.4 days, p=0.002) when using HCQ in comparison with control. Given the incomplete balance of the groups, the main analysis included 46 patients who were matched by propensity score matching. The trend towards similar dynamics continued. HCQ treatment slowed down the time to normalization of body temperature by 1.8 days (p=0.074) and lengthened the hospitalization time by 2.1 days (p=0.042). The decrease in scores on the SHOCS -COVID scale was statistically significant in both groups, and there were no differences between them (delta - 3.00 (2.90) in the HCQ group and - 2.69 (1.55) in control, p=0.718). At the same time, in the control group, the CRP level returned to normal (4.06 mg/dl), and with the use of GC, it decreased but remained above the norm (6.21 mg/dl, p=0.05). Side effects requiring discontinuation of treatment were reported in 3 patients in the HCQ group and none in the control group.Conclusion We have not identified any positive properties of HCQ and its ability to influence the severity of COVID-19. This antimalarial agent slows down the normalization of the body's inflammatory response and lengthens the time spent in the hospital. HCQ should not be used in the treatment of COVID-19.

Value of comparative studies of "real clinical practice" in modern cardiology. Position paper based on the expert council discussion dated 12/18/2020.

On December 18, 2020, an expert council was held with the participation of members of the Russian Society of Cardiology, the Eurasian Association of Ther-apists, the National Society for Atherothrombosis, the National Society for Evi-dence-Based Pharmacotherapy, and the Russian Heart Failure Society. The event was devoted to the discussion of the correct use of research data of "real clinical practice" in decision making.

[Expert consensus regarding treatment of iron deficiency in stable and decompensated patients with heart failure].

In recent years there has been significant interest in treating iron deficiency (ID) in patients with heart failure (HF) due to its high prevalence and detrimental effects in this population. As stated in the 2020 Russain HF guidelines, Intravenous ferric carboxymaltose remains the only proven therapy for ID.This document was prompted by the results from the recent AFFIRM-AHF trial which demonstrates that treatment of ID after acute HF decompensation reduces the risk of future decompensations. Experts have concluded that in HF patients with acute decompensation, a left ventricular ejection fraction of < 50% and ID, Intravenous ferric carboxymaltose reduces future HF hospitalisations. Patients with stable HF may also benefit from treatment of ID to improve quality of life and alleviate symptoms.  It is, therefore, reasonable to screen for and treat ID in patients with HF.

[The role of diastolic transthoracic stress echocardiography with incremental workload in the evaluation of heart failure with preserved ejection fraction: indications, methodology, interpretation. Expert consensus developed under the auspices of the National Medical Research Center of Cardiology, Society of Experts in Heart Failure (SEHF), and Russian Association of Experts in Ultrasound Diagnosis in Medicine (REUDM)].

Diagnosis of heart failure with preserved ejection fraction (HFpEF) is associated with certain difficulties since many patients with HFpEF have a slight left ventricular diastolic dysfunction and normal filling pressure at rest. Diagnosis of HFpEF is improved by using diastolic transthoracic stress-echocardiography with dosed exercise (or diastolic stress test), which allows detection of increased filling pressure during the exercise. The present expert consensus explains the requirement for using the diastolic stress test in diagnosing HFpEF from clinical and pathophysiological standpoints; defines indications for the test with a description of its methodological aspects; and addresses issues of using the test in special patient groups.

Proactive anti-inflammatory therapy with colchicine in the treatment of advanced stages of new coronavirus infection. The first results of the COLORIT study.

Actuality The 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.Objective Compare efficacy and safety of colchicine compared to the management of patients with COVID-19 without specific anti-inflammatory therapy.Material and Methods Initially, 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].Results The 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.Conclusions Colchicine 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.