[The impact of carbohydrate metabolism disorders on the early and long-term clinical outcomes of patients with COVID-19 according to the AKTIV and AKTIV 2 registries].

BACKGROUND: Numerous studies indicate a high incidence of various disorders of carbohydrate metabolism against the new coronavirus infection. These disorders aggravate the course of infection and increase mortality. Thereby, analysis of risk factors for unfavorable outcomes and assessment of the long-term consequences of COVID-19 in patients with impaired carbohydrate metabolism is of great importance. AIM: To investigate the association between carbohydrate metabolism disorders in COVID-19 patients and mortality, course of infection, long-term consequences, as well as to identify risk factors for an unfavorable disease course. MATERIALS AND METHODS: A retrospective analysis of data from the combined multicenter non-interventional real-world AKTIV and AKTIV 2 registries was performed. The sample included 9290 patients who had COVID-19 with varying severity from June 29, 2020, to November 29, 2020 (AKTIV) and from October 01, 2020, to March 30, 2021 (AKTIV 2). The patients were divided into 3 groups: Group 1 - patients with intact carbohydrate metabolism, n=6606; Group 2 - patients with newly diagnosed hyperglycemia (NDH), n=1073; Group 3 - patients with a history of type 2 diabetes mellitus (DM2), n=1611. The groups were assessed for clinical and laboratory parameters, comorbidities, mortality, carbohydrate metabolic status, and well-being during the infection and at 12 months. RESULTS: The prevalence of carbohydrate metabolism disorders (CMD) was 28,9%, with DM2 patients accounting for 17,3% and patients with newly diagnosed hyperglycemia (NDH) for 11,6%. The mortality rate of patients with hyperglycemia of any origin was 10.6%, which was significantly higher compared to patients without hyperglycemia (3,9%). The probability of lethal outcome increased 2,48-fold in the group of patients with DM2 and 2,04-fold in the group of patients with NDH. At the same time, the probability of a lethal outcome decreased 2,94-fold in patients without CMD. At 12 months, patients with CMD showed a significantly higher frequency and longer persistence of complaints. This trend was more pronounced in patients with DM2 than in those with NDH. Only 1,7% of patients from the NDH group had type 2 diabetes and were receiving oral hypoglycemic medications one year after the infection. A prognostic model was developed to determine the risk of lethal outcome. The model included such known predictors as concomitant ischemic heart disease, history of myocardial infarction or stroke, blood glucose level, and age. CONCLUSION: Carbohydrate metabolism disorders aggravate the course of COVID-19 and increase mortality. One year after infection, patients with DM2 and NDH were more likely to have symptoms typical for post-COVID syndrome, and NDH resolved in most cases after the infection.

[The impact of BMI on the course of the acute SARS-COV-2 infection and the risks that emerge during the first year after the hospital discharge. Subanalysis evidence of the AKTIV and AKTIV 2 registries].

BACKGROUND: There is enough evidence of the negative impact of excess weight on the formation and progression of res piratory pathology. Given the continuing SARS-CoV-2 pandemic, it is relevant to determine the relationship between body mass index (BMI) and the clinical features of the novel coronavirus infection (NCI). AIM: To study the effect of BMI on the course of the acute SARS-COV-2 infection and the post-covid period. MATERIALS AND METHODS: AKTIV and AKTIV 2 are multicenter non-interventional real-world registers. The АКТИВ registry (n=6396) includes non-overlapping outpatient and inpatient arms with 6 visits in each. The АКТИВ 2 registry (n=2968) collected  the  data  of  hospitalized  patients  and  included  3  visits.  All  subjects  were  divided  into  3  groups:  not  overweight  (n=2139), overweight (n=2931) and obese (n=2666). RESULTS: A higher BMI was significantly associated with a more severe course of the infection in the form of acute kidney injury (p=0.018), cytokine storm (p<0.001), serum C-reactive protein over 100 mg/l (p<0.001), and the need for targeted therapy (p<0.001) in the hospitalized patients. Obesity increased the odds of myocarditis by 1,84 times (95% confidence interval [CI]: 1,13-3,00) and the need for anticytokine therapy by 1,7 times (95% CI: 1,30-2,30).The  patients  with  the  1st  and  2nd  degree  obesity,  undergoing  the  inpatient  treatment,  tended  to  have  a  higher  probability  of  a  mortality  rate.  While  in  case  of  morbid  obesity  patients  this  tendency  is  the  most  significant  (odds  ratio  -  1,78; 95% CI: 1,13-2,70). At the same time, the patients whose chronical diseases first appeared after the convalescence period, and those who had certain complaints missing before SARS-CoV-2 infection, more often had BMI of more than 30 kg/m2 (p<0,001).Additionally, the odds of death increased by 2,23 times (95% CI: 1,05-4,72) within 3 months after recovery in obese people over the age of 60 yearsCONCLUSION.  Overweight  and/or  obesity  is  a  significant  risk  factor  for severe  course  of  the  new  coronavirus  infection  and  the associated cardiovascular and kidney damage Overweight people and patients with the 1st and 2nd degree obesity tend to have a high risk of death of SARS-CoV-2 infection in both acute and post-covid periods. On top of that, in case of morbid obesity patients this tendency is statistically significant. Normalization of body weight is a strategic objective of modern medicine and can contribute to prevention of respiratory conditions, severe course and complications of the new coronavirus infection.

[ACTIV SARS-CoV-2 registry (Analysis of Chronic Non-infectious Diseases Dynamics After COVID-19 Infection in Adult Patients). Assessment of impact of combined original comorbid diseases in patients with COVID-19 on the prognosis].

AIM: Study the impact of various combinations of comorbid original diseases in patients infected with COVID-19 later on the disease progression and outcomes of the new coronavirus infection. MATERIALS AND METHODS: The ACTIV registry was created on the Eurasian Association of Therapists initiative. 5,808 patients have been included in the registry: men and women with COVID-19 treated at hospital or at home. CLINICALTRIALS: gov ID NCT04492384. RESULTS: Most patients with COVID-19 have original comorbid diseases (oCDs). Polymorbidity assessed by way of simple counting of oCDs is an independent factor in negative outcomes of COVID-19. Search for most frequent combinations of 2, 3 and 4 oCDs has revealed absolute domination of cardiovascular diseases (all possible variants). The most unfavorable combination of 2 oCDs includes atrial hypertension (AH) and chronic heart failure (CHF). The most unfavorable combination of 3 oCDs includes AH, coronary heart disease (CHD) and CHF; the worst combination of 4 oCDs includes AH, CHD, CHF and diabetes mellitus. Such combinations increased the risk of lethal outcomes 3.963, 4.082 and 4.215 times respectively. CONCLUSION: Polymorbidity determined by way of simple counting of diseases may be estimated as a factor in the lethal outcome risk in the acute phase of COVID-19 in real practice. Most frequent combinations of 2, 3 and 4 diseases in patients with COVID-19 primarily include cardiovascular diseases (AH, CHD and CHF), diabetes mellitus and obesity. Combinations of such diseases increase the COVID-19 lethal outcome risk.

Analysis of influence of background therapy for comorbidities in the period before infection on the risk of the lethal COVID outcome. Data from the international ACTIV SARS-CoV-2 registry («Analysis of chronic non-infectious diseases dynamics after COVID-19 infection in adult patients SARS-CoV-2¼).

Aim      To study the effect of regular drug therapy for cardiovascular and other diseases preceding the COVID-19 infection on severity and outcome of COVID-19 based on data of the ACTIVE (Analysis of dynamics of Comorbidities in paTIents who surVived SARS-CoV-2 infEction) registry.Material and methods  The ACTIVE registry was created at the initiative of the Eurasian Association of Therapists. The registry includes 5 808 male and female patients diagnosed with COVID-19 treated in a hospital or at home with a due protection of patients' privacy (data of nasal and throat smears; antibody titer; typical CT imaging features). The register territory included 7 countries: the Russian Federation, the Republic of Armenia, the Republic of Belarus, the Republic of Kazakhstan, the Kyrgyz Republic, the Republic of Moldova, and the Republic of Uzbekistan. The registry design: a closed, multicenter registry with two nonoverlapping arms (outpatient arm and in-patient arm). The registry scheduled 6 visits, 3 in-person visits during the acute period and 3 virtual visits (telephone calls) at 3, 6, and 12 mos. Patient enrollment started on June 29, 2020 and was completed on October 29, 2020. The registry completion is scheduled for October 29, 2022. The registry ID: ClinicalTrials.gov: NCT04492384. In this fragment of the study of registry data, the work group analyzed the effect of therapy for comorbidities at baseline on severity and outcomes of the novel coronavirus infection. The study population included only the patients who took their medicines on a regular basis while the comparison population consisted of noncompliant patients (irregular drug intake or not taking drugs at all despite indications for the treatment).Results The analysis of the ACTIVE registry database included 5808 patients. The vast majority of patients with COVID-19 had comorbidities with prevalence of cardiovascular diseases. Medicines used for the treatment of COVID-19 comorbidities influenced the course of the infectious disease in different ways. A lower risk of fatal outcome was associated with the statin treatment in patients with ischemic heart disease (IHD); with angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor antagonists and with beta-blockers in patients with IHD, arterial hypertension, chronic heart failure (CHF), and atrial fibrillation; with oral anticoagulants (OAC), primarily direct OAC, clopidogrel/prasugrel/ticagrelor in patients with IHD; with oral antihyperglycemic therapy in patients with type 2 diabetes mellitus (DM); and with long-acting insulins in patients with type 1 DM. A higher risk of fatal outcome was associated with the spironolactone treatment in patients with CHF and with inhaled corticosteroids (iCS) in patients with chronic obstructive pulmonary disease (COPD).Conclusion      In the epoch of COVID-19 pandemic, a lower risk of severe course of the coronavirus infection was observed for patients with chronic noninfectious comorbidities highly compliant with the base treatment of the comorbidity.

Selection of the optimal respiratory muscle training mode in patients with class II-III chronic heart failure.

Aim To study the effect of various types of respiratory muscle training (RMT) in patients with functional class (FC) II-III chronic heart failure (CHF) and more than 70% preserved diaphragm muscle mass.Material and methods 53 patients (28 men and 25 women) aged 50-75 years with NYHA FC II-III ischemic heart disease (IHD) and arterial hypertension with more than 70% preserved diaphragm muscle mass of >70% were randomized to one of four RMT types: static loads, dynamic loads, their combination, and breathing without applied resistance as a control. Peak oxygen consumption (VO2 peak) and maximum inspiratory pressure (MIP) were evaluated at baseline and in 6 months.Results All study groups showed significant improvement of physical endurance indexes compared to baseline values (р<0.05). In pairwise comparison, the groups significantly differed (р<0.01). The greatest improvement was observed for patients of dynamic and combined training groups. Furthermore, in the combined training group, results were significantly higher than in the group of isolated dynamic loads. The most significant (р <0.01), positive changes in the force of inspiratory muscles were observed in groups of dynamic and combined trainings with the best results displayed by patients of the combined training group.Conclusion With preserving more than 70 % of diaphragm muscle tissue (as determined by MIP >60 cm H2O), a combination of static and dynamic RMT is most effective for patients with FC II-III CHF.

[International register "Analysis of Chronic Non-infectious Diseases Dynamics After COVID-19 Infection in Adult Patients (ACTIV SARS-CoV-2)"].

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[Use of Statins, Anticoagulants, Antiaggregants and Antiarrhythmic Drugs in Patients With COVID-19. The Agreed Experts' Position of Russian Society of Cardiology, Eurasian Association of Therapists, National Society on Atherothrombosis, Societies of Experts in Urgent Cardiology, Eurasian Arrhythmology Association].

This article discusses relevant aspects in the treatment of patients with COVID-19. Up-to-date information about principles for administration of statins, antithrombotics, and antiarrhythmics is presented. The authors addressed in detail specific features of reversing heart rhythm disorders in patients with coronavirus infection and the interaction of antiarrhythmic and antiviral drugs. Recommendations are provided for outpatient and inpatient antithrombotic therapy for patients with COVID-19. Issues of antithrombotic and antiviral drug interaction are discussed.

[The Agreed Experts' Position of the Eurasian Association of Therapists on Some new Mechanisms of COVID-19 Pathways: Focus on Hemostasis, Hemotransfusion Issues and Blood gas Exchange].

The article discusses pathogenesis and treatment of COVID-19. The authors presented state-of-the-art insight into hemostatic disorders in patients with COVID-19 and clinical recommendations on prevention of thrombosis and thromboembolism in patients infected with SARS-CoV-2. The article discussed in detail a new hypothesis proposed by Chinese physicians about a new component in the pathogenesis of COVID-19, namely, about the effect of SARS-CoV-2 virus on the hemoglobin beta-chain and the formation of a complex with porphyrin, which results in displacement of the iron ion. Thus, hemoglobin loses the capability for transporting oxygen, which aggravates hypoxia and worsens the prognosis. The article stated rules of hemotransfusion safety in the conditions of COVID-19 pandemic.

Morphofunctional Features of The Diaphragm in Patients With Chronic Heart Failure.

AIM: to study changes in the volumes of muscle, fat, and connective tissue in postmortem issue samples (autoptates) from diaphragm, right ventricle, lower limb (gastrocnemius muscle), as well as morphological changes of the diaphragm muscular structure in patients with different functional classes of heart failure (HF), and to compare them with some intravital parameters of external respiration (with maximal inspiratory pressure and its amplitude simultaneously measured by ultrasound method in particular). MATERIALS AND METHODS: Autoptates of the diaphragm muscle, right ventricle, lower limb (n=39) from 20 men and 19 women (with in vivo diagnosis CHF NYHA functional class (FC) I-IV, hypertension, ischemic heart disease) were examined within 24 hours after the fatal outcome. Light optical microscopy was used to assess the percentages of muscle, connective, adipose tissue, numbers of fibroblasts, and collagen fibers. Spirometric measurements, measurement of respiratory muscles strength, and examination of the diaphragm contractile function were performed by echolocation 56.7±11.9 days before death. RESULTS: In patients of all NYHA FCs most pronounced changes of volume of muscle tissue were observed in the right ventricle and diaphragm, while less pronounced - in the gastrocnemius muscle. The increase in the volume of adipose tissue in patients with I-III FC CHF was most pronounced in the right ventricle and diaphragm, and less pronounced - in the gastrocnemius muscle. The greatest increase in the adipose tissue volume was recorded in the diaphragm of patients with IV FC. Changes of connective tissue volume did not follow linear dependence. The largest "leap-like" increase in the volume of connective tissue occurred in the diaphragm of patients with III FC, what significantly outstripped this process in peripheral muscles and right ventricular myocardium. There was stable relationship between structure of tissue of the diaphragm, maximal inspiratory thickness of diaphragmatic muscle, and maximal inspiratory pressure. This relation (correlation) was positive for pairs muscle tissue volume - muscle thickness and muscle tissue volume - inspiratory pressure, and negative for pairs connective tissue volume - muscle thickness, connective tissue volume - inspiratory pressure, adipose tissue volume - inspiratory pressure (r>0.85, p<0.01 for all these correlations). CONCLUSION: Morphofunctional changes in the diaphragm are caused by progressive decrease in the content of muscle tissue, increases of volumes of adipose and connective tissues. These changes correlate with the CHF FC, maximal inspiratory thickness of diaphragmatic muscle, and maximal inspiratory pressure. Severity of these morphological changes is maximal in patients with FC III CHF.

[Significance of adipose tissue mass for the clinical course of pneumonia associated with decompensated CHF].

BACKGROUND: Pneumonia is one of most important causes of in-hospital mortality in patients with decompensated chronic heart failure (CHF). AIM: To evaluate the effect of adipose tissue mass and body weight index (BWI) on prognosis for patients with communityacquired pneumonia and decompensated CHF. MATERIALS AND METHODS: The study included 286 patients aged 53-90 with BWI 18.5-24.9 kg/m2 who were hospitalized in cardiology and therapy departments of an emergency care hospital for decompensated CHF and pneumonia, which was verified within the first day of admission. Body composition was analyzed using a bioimpedance analyzer of body water sectors (ABC-01, Medass); BWI was calculated for all patients. Sputum samples collected with proper observation of sterility rules were analyzed in a specialized microbiological laboratory. Statistical analysis was performed with methods of binary logistic regression, Kaplan-Meier, Cox regression, and two-step cluster analysis using the IBM SPSS Statistics 20 software. RESULTS: Assessing the body composition showed that groups with sputum Str. Pneumonia and mixed infection differed in indexes of lean body mass and adipose tissue mass but not in BWI. In-the mixed group, the in-hospital mortality was 38.71% and the one-year mortality - 95.16%. In the group with Str. Pneumonia in the sputum culture, the in-hospital mortality was 18.52% and the one-year mortality - 42.59%. The two-step cluster analysis allowed to isolate two clusters in the structure of the studied totality. All patients of the first cluster died during the first 9 months of the year following hospitalization. They were distinguished by lower values of lean body mass and BWI, older age, and the presence of mixed infection in the sputum culture in 39.1% of cases. CONCLUSION: In the structure of the studied totality, the most important risk factor for in-hospital mortality and one-year death was the value of adipose tissue mass.

Differences between passport and biological (actual) age in the population of Russian patients suffering from arterial hypertension (analysis of the «Hyperion¼ register).

AIM: The aim of the study was to analyze the severity of the difference in these values in real clinical practice in patients suffering from arterial hypertension (AH) on the basis of an open multicenter register to monitor the effectiveness of therapy in patients with hypertension "HYPERION", conducted by the Eurasian Association of Therapists with the support of the company "Gedeon Richter" (Hungary). MATERIALS AND METHODS: The study was carried out within the open multi-center register "HYPERION". The final analysis of the register included 1441 patients, including 638 men (44%), 803 women (56%) aged 24 to 90 years. All patients were observed in primary health care (55 centers in 47 cities of Russia) for hypertension, received at least two hypotensive drugs. According to the data on 1424 patients using the qrisk-2 scale of 2017 modification, the biological age was calculated. RESULTS: The absolute majority of patients (83,7%) had biological age >70 years, while the passport age of the absolute majority (65,3%) is in the range ≥50, but ≤69 years. Median difference between biological and passport age was 15 years. On average, in men suffering from hypertension, the biological age exceeded the passport age by 17.6 years, and in women - by 13.4 years. The difference between the value of biological and passport age and the level of systolic pressure in all age groups had a direct correlation. At systolic blood pressure >181 mm Hg. the difference between biological and passport age was the maximum, reaching the highest values in the youngest age group (30-39 years). CONCLUSION: Analysis of the actual (biological) age should be a mandatory procedure that allows a more complete assessment of the initial therapeutic status of the patient, which is especially important in patients aged 30-50 years. This is necessary not only from the standpoint of changing the current procedure, but also to understand the patient's prognosis.

[Prognostic role of body composition in patients with pneumonia associated with decompensated CHF].

AIM: To evaluate the effect of body composition on prediction of community-acquired pneumonia caused by Str. pneumoniae in patients with decompensated CHF. MATERIALS AND METHODS: The study included 216 patients. The pneumonia agent was identified by sputum culture. Body composition with determining lean body mass and fat mass was evaluated using a bio-impedance analysis; body mass index (BMI) was calculated. Patients with BMI 18.5-24.9 kg/m2 were included into the study. Statistical analysis of obtained data was performed using the IBM SPSS Statistics 20 software. RESULTS: The in-hospital mortality was 13.4 %; the one-year mortality was 29.6 %. Fat mass strongly, negatively correlated with a fatal outcome within a year, and the degree of lean body mass shortage moderately, positively correlated with the life span of patients. CONCLUSION: Body composition is significantly predictive for patients with decompensated CHF and community-acquired pneumonia caused by Str. pneumoniae.

[Impact of the dosing of basic drugs on the risk of rehospitalization in patients with chronic heart failure].

AIM: To investigate the impact of doses of the drugs, which have been achieved during adjustment and account for less or more than 50% of the maximal therapeutic ones on the risk of rehospitalization. SUBJECTS AND METHODS: The data of the Pavlov Register were used to assess the treatment of patients with chronic heart failure. To assess the risk of rehospitalization in relation of the dose of a drug, all the doses were represented in percentage terms depending on the maximum therapeutic one. RESULTS: The risk of hospitalization during 6 months in the patients receiving angiotensin-converting enzyme inhibitors at a dose of 25% or less of the therapeutic one was 21.18% (odds ratio (OR), 1.41; 95% confidence interval (CI), 1.13-1.76), that at doses of 50 and 100% of the therapeutic one was 16% (OR, 0.71; 95% CI, 0.56-0.88) and 34% (OR, 0.51; 95% CI, 0.43-0.60), respectively. The risk of rehospitalization in the patients taking ß-blockers at doses of 25, 50, and 100% of the therapeutic one was 26% (OR, 1.05; 95% CI, 0.94-1.17), 23% (OR, 0.902; 95% CI, 0.75-1.07), and 6.25% (OR, 0.19; 95% CI, 0.07-0.56), respectively. The combined analysis of the dose and use frequency of diuretics showed that the highest risk of rehospitalization turned was noted in the patients using a single dose of 100 mg of furosemide (4.2% of cases) once weekly and was as high as 39% (OR, 0.45; 95% CI, 1.04-1.98). CONCLUSION: The risk of rehospitalization is largely determined by the dosing factor in outpatient settings. Increasing the doses during adjustment reduces the risk of rehospitalization.

[First Open Study of Syndrome of Acute Decompensation of Heart Failure and Concomitant diseases in Russian Federation: Independent Registry ORAKUL].

Aim of the study was to assess mortality and rate of repetitive hospital admissions on days 30, 90, 180, 360, of observation as well as prevalence of concomitant diseases in patients with congestive heart failure (CHF). The register was formed in 41 centers of 20 cities of Russian Federation. Number of included patients with signs of chronic heart failure (CHF) was 2498. Data on 2404 was available for final analysis. Rehospitalization rate was 31, 11, 11, and 9.5% during 30 days, and during periods 31-90, 91-180, 181-360 days after discharge from hospital, respectively. Hospital mortality was 9%, 30 days and 1 year total mortality was 13 and 43%, respectively. Risk of death was most strongly affected by pneumonia, liver cirrhosis, and chronic kidney disease (mortality 49.5, 45.7, and 47.2%, respectively). Prognostic value of factors was ranked in the following order (descending): age, body mass index < 19 kg/m2, systolic blood pressure < 100 mm Hg, heart rate (HR) > 70 bpm, body temperature < 36.5 C. Each predictor was assigned weight of 1 point. Score 5 meant that risk of death with a high degree of probability approached 100%. Patients included into ORAKUL compared with those included in Euro HF register were more severely ill: in ORAKUL ejection fraction < 40% was observed 1.89 times more often, and more patients had "wet-cold" profile. Patients in ORAKUL had greater HR, smaller ejection fraction, lower glomerular filtration rate, and worse compliance to scientifically based treatment.

[First Open Study of Syndrome of Acute Decompensation of Heart Failure and Concomitant Diseases in Russian Federation: Independent Registry ORAKUL].

Aim of the study was to assess mortality and rate of repetitive hospital admissions on days 30, 90, 180, 360 of observation as well as prevalence of concomitant diseases in patients with congestive heart failure (CHF). The register was formed in 41 centers of 20 cities.

N-terminal and C-terminal fragments of IGFBP-4 as novel biomarkers for short-term risk assessment of major adverse cardiac events in patients presenting with ischemia.

OBJECTIVES: Pregnancy Associated Plasma Protein A (PAPP-A)-derived N- and C-terminal fragments of IGF-binding protein-4 (NT- and CT-IGFBP-4) released from vulnerable atherosclerotic plaques are proposed to be used for cardiovascular risk assessment. DESIGN AND METHODS: NT- and CT-IGFBP-4 were measured by novel immunoassays in EDTA-plasma of 180 patients admitted to the emergency department with symptoms of myocardial ischemia but without ST-segment elevation. Six-month incidence of major adverse cardiac events (MACE), including myocardial infarction, cardiac death, percutaneous coronary interventions, and coronary artery bypass grafting was recorded. RESULTS: Sixteen patients met the endpoint. NT- and CT-IGFBP-4 were strong predictors of MACE: area under ROC curve (AUC) 0.856 and 0.809, respectively. NT-IGFBP-4 concentrations≥214µg/L and CT-IGFBP-4 concentrations≥124µg/L were associated with increased risk of future MACE: adjusted hazard ratio 13.79 and 7.93, respectively. CONCLUSIONS: IGFBP-4 fragments can be utilized as biomarkers for MACE prediction in patients with suspected myocardial ischemia.