Молодежный инновационный вестникМолодежный инновационный вестник2415-7805Федеральное государственное бюджетное образовательное учреждение высшего образования "Воронежский государственный медицинский университет имени Н.Н. Бурденко" Министерства здравоохранения Российской Федерации7402Conference ProceedingsEVALUATION OF THE EFFECTIVENESS OF PHYSICAL ACTIVITY IN PATIENTS WITH COMORBID CURRENT OF THE CHRONIC HEART FAILURE AND CHRONIC OBSTRUCTIVE PULMONARY DISEASEGlavatskikhYuliya О.Yuliyag36@gmail.comhttps://orcid.org/0000-0002-2398-5987DrobyshevaValeria R.drobyshevavr@gmail.comhttps://orcid.org/0000-0001-6636-6644TokmachevRoman E.r-tokmachev@mail.ruhttps://orcid.org/0000-0001-6379-4635BudnevskayaSofia A.Yuliyag36@gmail.comhttps://orcid.org/0000-0003-3649-5642VSMU named after N.N. Burdenko30062022116126151003202202042022Copyright © 2022, Glavatskikh Y.О., Drobysheva V.R., Tokmachev R.E., Budnevskaya S.A.2022<p>One of the most frequent combinations of pathologies is chronic obstructive pulmonary disease (COPD) associated with chronic heart failure (CHF).The comorbidity of these diseases often results in a pronounced deterioration in the well-being of such patients as well as a deterioration in the long-term prognosis, which requires further study of the progression mechanisms of CHF, Improving the diagnosis and treatment of this category of patients.</p>
<p>Evaluate the influence of physical training on clinical flow, laboratory and instrumental indicators in patients with comorbid current of CHF and COPD with different LV EF.Study the clinical pathogenic relationship between comorbid diseases COPD and CHF.</p>
<p>The study included a group of patients (n=80) with comorbid currents CHF and COPD,with an average age of 67.55.9 years. By LV EF, patients were divided into two groups.Two subgroups were formed in each group, depending on whether physical training was included in the treatment programme.At the time of inclusion and 12 months later, they conducted a definition of tolerance to physical load, laboratory and instrumental examination.The statistical analysis was carried out with the help of the Statistica10 software package.</p>
<p>A follow-up survey 12 months later in subgroups undergoing physical rehabilitation revealed a statistically significant (p0.05) decrease in the pro-inflammatory cytokines.There has been an increase in the tolerance of physical exertion,which is assessed with the help of 6MWT.</p>
<p>The combination of COPD and CHF amplifies systemic inflammation and myocardial remodeling processes determined by the level of the pro-inflammatory cytokines and NT-proBNP.The negative influence of the COPD on the functional status of CHF patients with different EF has been established, which is manifested by the lower values of 6MWT and the ratio of 6MWD/6MWD(i).Physical rehabilitation of patients with comorbid COPD and CHF is accompanied by significant improvement of hemodynamic performance during load tests (6MWT), decrease of pro-inflammatory cytokines, hs-CRP, NT-proBNP.</p>CHFCOPDCytokine profileFunctional statusХСНХОБЛЦитокиновый профильФункциональное состояние<p><strong> Relevance</strong></p>
<p>Chronic obstructive pulmonary disease (COPD), associated with chronic heart failure (CHF), is a frequent combination of pathologies in patients with CHF. The comorbidity of these diseases often results in a pronounced deterioration in the well-being of such patients as well as a deterioration in the long-term prognosis, which requires further study of the progression mechanisms of CHF, Improving the diagnosis and treatment of this category of patients [1.2]. It is estimated that 25% to 42% of people with CHF suffer from COPD. Numerous advantages of exercise exercises are described, but they are not widely used due to various factors, despite significant improvements in physical fitness, quality of life, and risk of hospitalization [3].</p>
<p><strong></strong></p>
<p><strong>The research objective</strong></p>
<p>Evaluate the influence of physical training on clinical flow, laboratory and instrumental indicators in patients with comorbid current of chronic heart failure and chronic obstructive pulmonary disease with different emission fraction.Study the clinical pathogenic relationship between comorbid diseases COPD and CHF.</p>
<p><strong></strong></p>
<p><strong>Methods</strong></p>
<p>In accordance with the presence of comorbid COPD, the study included a cohort of patients (n = 80) with comorbid course of CHF and COPD (of which 48 men (60.0%) and 32 women (40.0%), whose average age was 67.55.9 years.) All patients included in the study with COPD (GOLD 2, group D) corresponded to the "phenotype with frequent exacerbations" (2 or more per year) and needed to be prescribed glucocorticosteroids and / or antibiotic therapy. According to the value of LV IF, the selected patients were divided into two groups. Patients with chronic heart failure with an intermediate ejection fraction (EF 40-50%) and a reduced ejection fraction (FV40%) were combined into a group of patients with CHF with reduced EF (EF50%). Accordingly, in the first group, COPD and CHFpEF (EF50%) were noted in 36 patients (group 1), COPD and CHFrEF (EF50%) - in 44 patients (group 2). After the initial examination, each of the 2 groups was divided 2 subgroups: 1 subgroups included patients receiving standard drug therapy and undergoing additional physical rehabilitation; The 2nd subgroups included patients receiving exclusively standard drug therapy.</p>
<p>After a year of observation of the selected cohort, the patients underwent a second examination, which included laboratory, clinical and instrumental research methods. Exercise tolerance (6MWT) was re-determined using a cardiorespiratory analysis complex and a monitoring system for patients with chronic heart failure, and a 6-minute walking test (6MWT). The distance covered within 6 minutes (6MWD) was measured in meters and compared with the proper 6MWD (i) value. The value of 6MWD (i) was calculated using the following formulas that take into account age, body mass index (BMI). The formula for calculating 6MWD (i) for men: 6MWD (i) = 1140 5.61 x BMI-6.94 x age. The value of 6MWD (i) for women was defined as: 6MWD (i) = (1017 6.24 x BMI 5.83 x age. Laboratory methods were also repeated: general clinical and enzyme immunoassays of blood with the determination of the levels of NT-proBNP, Hs-CRP, IL-1, IL-6, TNF-. According to echo-KG, the mass, size and volume of the myocardium (by departments), FVLJ were evaluated. In addition, the ratio of peak velocities of early transmittal blood flow and early diastolic movement of the mitral ring (E / e'), the left atrium volume index (IOLP), systolic excursion of the ring were evaluated.tricuspid valve (TAPSE) as an indicator of the function of the right ventricle.</p>
<p>All patients received treatment according to clinical guidelines for the diagnosis and treatment of chronic heart failure (2020) and GOLD (revision 2020). Consent to voluntary participation in the study was signed by all patients.</p>
<p>Statistical analysis was carried out using the Statistica 10 software package. The normality of the data distribution was assessed using a test (Shapira-Wheelka). The initial continuous variables were presented as a meanstandard deviation and compared using the Student's t-criterion, in the form of a median and interquartile range, and compared using the Mann-Whitney and Kruskal-Wallis test. Categorical ones were compared using an exact the Fisher method. The differences between the subgroups were considered statistically significant at a significance level of p 0.05.</p>
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<p><strong> The results and discussion</strong></p>
<p>When the subgroups were repeatedly compared by biomarker levels, the following results were obtained. The mean serum NT-proBNP level in subgroup 2.1 (patients with COPD and CHFrEF undergoing additional physical rehabilitation) was 1401211 ng/L, which was significantly higher than its value in patients in subgroup 1.1 with COPD and CHFpEF 981156 ng/L (p0.001). NT-proBNP level serum in subgroup 2.2 (patients with COPD and CHFrEF receiving exclusive drug therapy) was 1835241 ng / l, which also exceeded the value of this biomarker in patients of subgroup 1.2 with COPD and CHFpEF 1209203 ng / l (p0.001).</p>
<p>Patients with COPD, CHF are in a state of prolonged hypoxia: permanent (chronic respiratory failure) or intermittent. Hypoxia is involved in the pathogenesis of atherosclerosis and cardiosclerosis: systemic and vascular inflammation, increased levels of C-reactive protein, oxidative stress.</p>
<p>The study studied the dynamics of the level of the biomarker of endogenous inflammatory processes hs-CRP (highly sensitive C-reactive protein) in all 4 subgroups of patients with COPD and CHF. A follow-up examination of patients revealed that the level of hs-CRP in subgroup 2.1 (patients with COPD and CHFrEF undergoing additional physical rehabilitation) was 3.10.6 mg / l, which also reflected a statistically significant decrease in this biomarker of endogenous inflammation (p0.05 compared with subgroup 4 in 2020). In subgroup 2.2 in patients with COPD and CHFrEF receiving exclusive drug therapy, statically significant changes could not be detected (the level of the level of 2.2) in patients with COPD and CHFrEF receiving exclusive drug therapy, statically significant changes could not be detected (the level of the level of hs-CRP=3,90,73 mg/l, p0.05). In turn, in the subgroups of patients with COPD and CHFpEF, the level of highly sensitive C-reactive protein was higher than in patients of the fourth subgroup with COPD and CHFrEF. So, in subgroup 1.1 - 4.40.78 mg / l (p 0.03; p 0.001 compared with subgroup 3 in 2020), in subgroup 1.2 - 4.60.8 mg / l (p 0.05; p 0.02 compared to subgroup 3 in 2020).</p>
<p>Similar and statistically significant differences (p 0.05) were obtained for the level of IL6 markers, and TNF-. Thus, IL6 in patients with COPD and CHFPEF who underwent additional physical rehabilitation (Subg.1.1) was 376.7 55.7 pg / ml, against 290.1 37.6 pg / ml COPD and CHFrEF (subg.2.1). In the subgroups that did not undergo physical rehabilitation, the level of this marker was also higher in the COPD and CHFpEF subgroup 399.8 60.5 pg/ ml and 182.1 28.8 pg / ml, respectively, in the COPD and CHFrEF group.</p>
<p>TNF- in subgroup 1.1 (COPD, CHFpEF) was 235.9 31.6 pg/mL, versus 177.226.5 pg/ml COPD, CHFrEF (Subg.2.1). In the subgroups that did not undergo physical rehabilitation, the level of this marker was also higher in the COPD, CHFpEF subgroup, 256.8 33.7 pg / ml and 198.4 28.1 pg / ml, respectively, in the COPD, CHFrEF group.</p>
<p>The distance covered within 6 minutes, the ratio of 6MWD / 6MWD (i) in patients who underwent additional physical rehabilitation, regardless of FV, statistically significantly improved, both in comparison with the control subgroups (1.2, 2.2) (p1 = 0.004; p2 = 0.01 / p1 = 0.01; p2 = 0.001), and in comparison with the initial indicators in the initial examination of patients (p 0.001).</p>
<p>The functional status of the patients included in the study was assessed using a cardiorespiratory analysis complex and a monitoring system for patients with chronic heart failure. Thus, the distance covered in 6 minutes in patients with comorbid course of COPD and CHFrEF was less than in patients with COPD and CHFpEF (p1 = 0.04; p2 = 0.03). A similar trend was observed in the assessment of the ratio 6MWD/6MWD(i).</p>
<p>A decrease in NT-proBNP obtained during a study in groups of patients undergoing physical rehabilitation may indicate a positive effect during the CHF of correctly selected physical activity.</p>
<p>The main systemic effect and characteristic of COPD is systemic inflammation.A re-examination of the cytokine status indicators showed that the elevated level of pro-inflammatory cytokines in all subgroups studied remained.In the groups of patients who were additionally subjected to physical rehabilitation, the content of IL-1, IL-6, TNF- has definitely decreased in comparison with the group receiving exclusively medicinal therapy.</p>
<p>The higher levels of IL-1, IL-6, FN-, hs-CRP in the CHF with preserved EF and CHF subgroups (subg. 1.1 and 1.2) compared to the subgroups with CHF with reduced EF (subg. 2.1 and 2.2) may reflect the significance of the contribution of systemic inflammation to the development and progression of HF. At the same time, the high level of pro-inflammatory cytokines observed in patients with comorbid COPD and CHF shows an amplification of systemic inflammation (Hs-CRP, pro-inflammatory cytokines) and therefore a close pathogenetic relationship between the two pathologies.</p>
<p>The follow-up survey shows a reliable statistically significant improvement in the functional status of patients who have undergone additional physical rehabilitation, as assessed in the 6MWT.</p>
<p><strong></strong></p>
<p><strong> Conclusion</strong></p>
<p>Patients with chronic heart failure with a preserved ejection fraction have higher levels of Hs-CRP, pro-inflammatory cytokines compared to patients with CHF with reduced ejection fraction, reflecting the importance of the contribution of the immuno-inflammatory component in the development of CHF with preserved EF.</p>
<p>The combination of COPD and CHF amplifies systemic inflammation and myocardial remodeling processes determined by the level of the high-sensitive C-reactive protein, pro-inflammatory cytokines and NT-proBNP.Thus, in patients with COPD and CHF, hypoxia, systemic subclinical inflammation causes damage and apoptosis of cardiomyocytes resulting in structural-functional (hypertrophy, diastolic and systolic dysfunction, fibrosis) and electrical (atrial fibrillation, ventricular extrasystolic) ventricular remodeling with the formation of heart failure.</p>
<p>The negative influence of the COPD on the functional status of CHF patients with different ejection fraction has been established, which is manifested by the lower values of 6MWT and the ratio of 6MWD/6MWD(i).</p>
<p>Physical rehabilitation of patients with comorbid COPD and CHF is accompanied by significant improvement of hemodynamic performance during load tests (6MWT), decrease of pro-inflammatory cytokines, high-sensitive C-reactive protein, NT-proBNP.</p>[Tokmachev R.E., Kravchenko A.Ya., Budnevsky A.V., et al. Features of the functional status and cytokine profile of patients with chronic heart failure in combination with chronic obstructive pulmonary disease. International Journal of Biomedicine. 2021; 11(1): 9-13.][Drobysheva E.S., Tokmachev R.E., Budnevsky A.V., Kravchenko A.Ya. // Prognostic value of cardiac cachexia biomarkers in chronic heart failure. Cardiovascular therapy and prophylaxis. 2016; 15(4): 80-83. (In Russ.)][Drapkina O.M., Koncevaya A.V., Kravchenko A.YA., et al.// Biomarkers st2 and interleukin 33 in assessing cardiac inflammation, fibrosis and prognosis in patients with heart failure Rossijskij kardiologicheskij zhurnal. 2021; 26.(S3): 79-85. (In Russ.)]