CC BY
8L»
BBSM
functions of man // Eurasian Scientific Association. -№ 1 (71). - January 2021. - P. 189 - 193. DOI: 105281/zenodo .4526504. ISSN 2411-1899. [in Russian]
9. Ivliev Y. A. Solution of Beal's Conjecture in the paradigm of quantum mathematics // Asian Journal of Mathematical Sciences. — Jan-Feb 2018 Vol. 2 / Issue 1. — P. 1-5. ISSN 2581-3463.
10. Ivliev Y.A. Alternative proof of Fermat's Last Theorem as introduction to quantum mathematics and
East European Scientific Journal #5(69), 2021 33 quantum psychology // Modern Problems of Science and Education. - 2020. - T.XVIII. - P. 28-30. ISBN 978-5-91327-599-8. [in Russian]
11. Ivliev Y.A. Alternative proof of Fermat's Last Theorem as scientific discovery in mathematical psychology // Scientific Review. Fundamental and Applied Research. - 2020. - №3. DOI: 10.17513/srfar.89.
URL: https://scientificreview.ru/ru/article/view?id=89. [in Russian]
Lysenko V.A.
MD, Postgraduate student of Department of Propaedeutic of Internal Medicine, Radial diagnostic and Radial therapy, Faculty of Medicine, Zaporizhzhia State Medical University, Ukraine.
https://orcid.org/0000-0001-7502-0127 Syvolap V.V.
MD, PhD, DSci, Professor, Head of Department of Propaedeutic of Internal Medicine, radial diagnostic and radial therapy, Faculty of Medicine, Zaporizhzhia State Medical University, Ukraine.
https://orcid.org/0000-0001-9865-4325
INDEPENDENT PREDICTORS OF ADVERSE CARDIOVASCULAR EVENTS IN PATIENTS WITH
CHF OF ISCHEMIC ORIGIN.
DOI: 10.31618/ESSA.2782-1994.2021.1.69.42
Summary. Chronic heart failure (CHF) remains a major burden due to low quality of life, high morbidity, and mortality. An important aspect in the management of heart failure is to provide clinicians necessary knowledge and resources to make better decisions about treatment tactics of such patients. Thus, finding out independent predictors of adverse outcomes of heart failure is still insufficiently studied, and become an important task of internal medicine and cardiology.
The aim: To determine the independent predictors of adverse cardiovascular events in patients with CHF.
Materials and methods: The study enrolled 88 patients (men - 52% (n=46); women - 48% (n=42)) with CHF of ischemic origin, stage II AB, II-IV FC according to NYHA, in which 58 - patients with reduced left ventricle ejection fraction (LV EF <40%,) and 30 - with preserved LV EF (>55%). Patients with different phenotypes of CHF were comparable in age, sex, height, weight, body surface area. Cumulative endpoints considered death, myocardial infarction and progressive angina pectoris, stroke and progressive heart failure.
Results. Analysis of the frequency of endpoints depending on the phenotype of CHF didn't reveal a significant difference between the study groups of 18.97% (11/58) vs. 10% (3/30); log-rank test (p= 0.378). According to univariate models of analysis of proportional hazards of Cox, the relative risk of adverse cardiovascular events in patients with CHF increased in 1.44 times (HR 1.44, 95% CI 1.0142 - 2.0323; p= 0.042) in case of excess of baseline the E/A 0.99 c.u.; in 1.71 (HR 1.71, 95% CI 1.1032 - 2.6642; p= 0.017) times in cases where the peak mitral valve pressure gradient exceeds 1.9 mm Hg; in 1.22 times (HR 1.22, 95% CI 1.0210 -1.4470; p= 0.029) at a plasma sodium concentration <= 142.5 mmol/l; and in 2.16 times (HR 2.16, 95% CI 1.0230 - 4.5799; p= 0.044) in the presence of pulmonary hypertension. At the same time, the presence of inspiratory IVC collapse more than 50% reduced the relative risk of adverse cardiovascular events in patients with CHF by 59% (HR 0.41; 95% CI 0.1796 - 0.9497; p= 0.038). Adverse cardiovascular events were not associated with individual anthropometric parameters of patients; structural and geometric, functional parameters of the heart; parameters of filtration and concentration function of the kidneys, plasma potassium concentration; tubulo- interstitial injury. The multivariate model (p= 0.0014), included factors such as age over 66 years (HR 1.13; 95% CI 1.0230 - 1.2555; p= 0.0172), body weight over 82 kg (HR 1.065; 95% CI 1.0043 - 1.1301; p= 0.036), index TEI LV over 0.52 c.u. (HR 30.69; 95% CI 1.3241 - 711.5572; p= 0,033), peak mitral valve pressure gradient over 1.9 mmHg. (HR 1.22, 95% CI 1.0210 - 1.4470; p= 0.029), the maximum flow velocity in the aorta over 98 cm/sec (HR 1.008; 95% CI 1.0009 - 1.0155; p= 0.0014), was associated with an increase in the relative risk of adverse cardiovascular events in patients with CHF of ischemic origin, regardless of sex, glomerular filtration rate and tubular interstitial injury.
Conclusion: Independent risk factors for adverse cardiovascular events in patients with CHF should be considered: age and body weight, index TEI LV, peak gradient pressure MK and the maximum flow velocity (Vao) in the aorta. Dependent risk factors for adverse cardiovascular events in patients with CHF are baseline sonographic parameters of E/A and mean pressure gradient MK, plasma sodium concentration, the presence of pulmonary hypertension. Inspiratory IVC collapse of more than 50% is associated with a reduction in the relative risk of adverse cardiovascular events in patients with CHF.
Key words: Chronic heart failure, index TEI, adverse cardiovascular events, outcomes.
34 East European Scientific Journal #5(69), 2021
Introduction.
Chronic heart failure (CHF) remains a major burden on the health care system due to low quality of life, high morbidity, and mortality [1].
Every year, nearly 50% of deaths in Europe are caused by cardiovascular diseases, 42% of men and 51% among women [2].
The incidence of heart failure (HF) is gradually increasing due to our aging population. Obesity contributes to a steep rise in the prevalence of HF, which is projected to increase by almost 50% from 2012 to 2030 [3].
An important aspect in the management of heart failure is to provide clinicians and patients with CHF necessary knowledge and resources to make better decisions about their treatment tactics. Prognostic model - is one of these resources, which is the formal combination of several predictors on which we can calculate the risks specific outcome for individual patients [1].
Therefore, finding out independent predictors of adverse course of heart failure is an important task of internal medicine and cardiology.
The aim: To determine the independent predictors of adverse cardiovascular events in patients with CHF.
Materials and methods: The study was performed on the clinical basis of the Department of Propaedeutics of Internal Medicine, Radiation Diagnostics and Radiation Therapy ZSMU in the cardiology department of the City Hospital №6, Zaporizhzhya, in accordance with the standards of good clinical practice and principles of good clinical practice. The study protocol was approved by the Ethics Committee of Zaporizhia State Medical University.
After signing the informed consent, the study enrolled 88 patients (men - 52% (n=46); women - 48% (n=42)) with CHF of ischemic origin, stage II AB, II-IV FC according to NYHA, in which 58 - patients with reduced left ventricle ejection fraction (LV EF <40%,) and 30 - with preserved LV EF (> 55%). Patients with different phenotypes of CHF were comparable in age, sex, height, weight, body surface area. The diagnosis of CHF of ischemic origin was established in accordance with the Recommendations for the diagnosis and treatment of chronic heart failure (2017) of the Association of Cardiologists of Ukraine and the Ukrainian Association of Heart Failure [4]. Cumulative endpoints considered death, myocardial infarction and progressive angina pectoris, stroke and progressive heart failure.
Statistical processing of the material was performed using the software package Statistica 13.0 (StatSoft, USA), license number
JPZ8041382130ARCN10-J and MedCalc 10.2.0.0. The normality of the distribution of quantitative traits was analyzed using the Shapiro - Wilk test. The parameters that had a normal distribution are given as the arithmetic mean and standard deviation (M ± SD). For indicators that had a distribution that differed from normal, descriptive statistics are given as the median and lower and upper quartiles - Me (Q25; Q75).
MB
BtSgSB
Quantitative indicators in the groups were compared using the criteria of Student (for the normal distribution of traits), Mann-Whitney (for the distribution of traits other than normal).
Using regression analysis of proportional hazards of Cox, univariate and multivariate prognostic models were constructed. The ROC analysis was performed to find out the cut-off values of the parameters. The Kaplan - Meier multiple estimation method was used to estimate the survival function. Gehan's Wilcoxon Test, Cox-Mantel Test, Log-rank-test were used to compare cumulative endpoints in groups. The difference at p <0.05 was considered statistically significant. All tests were bilateral.
Results. During the follow-up period (median 396 days [53-1302]), 14 endpoints were registered, which accounted for 15.91% of events: deaths 7 cases (8%), strokes 2 cases (2.3%), myocardial infarction 1 case (1.15%), progressive angina 1 case (1.15%), progressive heart failure 3 cases (3.4%). Analysis of the frequency of endpoints depending on the phenotype of CHF didn't reveal a significant difference between the study groups of 18.97% (11/58) vs. 10% (3/30); logrank test (p= 0.378).
Since, there were no statistically difference in the number of cumulative endpoints between groups of patients with CHF with reduced and preserved LV EF found, in order to determine the predictors of adverse events in this cohort of patients, a single database was created, which combined all patients with CHF regardless of LV EF (n = 88).
According to the results of univariate regression analysis of analysis of proportional hazards of Cox, four covariates (E/A ratio (E/A), peak mitral valve pressure gradient (GE MK), plasma sodium concentration, pulmonary hypertension) were identified, which were associated with an increasing and one (Inspiratory inferior vena cava (IVC) collapse of more than 50%) with a decreasing the relative risk of adverse cardiovascular events in patients with CHF. From these five factors, pulmonary hypertension and inspiratory IVC collapse were categorical and the restquantitative. The following cut-off values were set for quantitative indicators using ROC analysis: E/A > 0.99 c.u. (area under the curve 0.709; 95% CI 0.602-0.801; p= 0.011); GE MK > 1.9 mm Hg (area under the curve 0.676; 95% CI 0.568-0.772; p= 0.0367; plasma sodium concentration <= 142.5 mmol/l (area under the curve 0.461; 95% CI 0.355-0.571; p= 0.6525).
According to univariate models of analysis of proportional hazards of Cox, the relative risk of adverse cardiovascular events in patients with CHF increased in 1.44 times (HR 1.44, 95% CI 1.0142 - 2.0323; p= 0.042) in case of excess of baseline the E/A 0.99 c.u.; in 1.71 (HR 1.71, 95% CI 1.1032 - 2.6642; p= 0.017) times in cases where the GE MK exceeds 1.9 mm Hg; in 1.22 times (HR 1.22, 95% CI 1.0210 - 1.4470; p= 0.029) at a plasma sodium concentration <= 142.5 mmol/l; and in 2.16 times (HR 2.16, 95% CI 1.0230 -4.5799; p= 0.044) in the presence of pulmonary hypertension. At the same time, the presence of inspiratory IVC collapse more than 50% reduced the
UB
ana«
relative risk of adverse cardiovascular events in patients with CHF by 59% (HR 0.41; 95% CI 0.1796 -0.9497; p= 0.038).
Adverse cardiovascular events were not associated with individual anthropometric parameters of patients: age (p= 0.1905), height (p= 0.7635), weight (p= 0.6070), body surface area (p= 0.4657), sex (p= 0.5464). Also, there was no effect on the prognosis of the initial structural and geometric parameters of the heart: left atrium diameter (LAD) (p= 0.4854), LV end-diastolic volume (LV EDV) (p= 0.9683), LVDs (p= 0.9573), PW (p= 0.2307), IVS (p= 0.6972), LV mass index (LVMi) by Penn g/m2 (p= 0.4076), LVMi by ASE g/m2 (p= 0.3676), diameter of right ventricle (RV) (p= 0.7343); functional parameters of the heart: LV EF (p= 0.9691), dp/dt (p= 0.4110), index TEI left ventricle (TEI LV) (p= 0.3757), TEI RV (p= 0.2097), s' medial (p =0.3313), E/e' lateral (p= 0.07936), E/e' medial (p= 0.1073), E/e' mean (p= 0.1223), e' lateral (p = 0.4058), e' medial (p = 0.3901), pulmonary artery systolic pressure (PASP) (p = 0.1029), mean pulmonary artery pressure (p = 0.1371), right atrium pressure (RAP) ( p= 0.8291); parameters of filtration and concentration function of the kidneys, plasma potassium concentration: CKD-EPI (p= 0.6374), MDRD (p= 0.8986), Cockroft-Gold (p= 0.6801), plasma potassium concentration (p= 0.9386), KIM-1, pg/ml (p= 0.3248), NAG, ng/ml (p= 0.2532), NGAL, ng/ml (p= 0.7468).
In the vast majority of cases, there is a simultaneous effect of several factors. Therefore, it is important to build multifactor models to determine the independent factors and relative risks of probable adverse events.
The multivariate model (p= 0.0014) included five parameters: age, body weight, index TEI LV, GE MK, and maximum Vao. In the obtained multivariate model, only the GE MK demonstrated its predictor properties in the univariate model. The remaining indicators showed prognostic ability only in the multifactor model. According to the results of ROC analysis, the TEI LV index => 0.52 (p= 0.935) increased the risk of adverse cardiovascular events in patients with CHF by 30.7 times (HR 30.69; 95% CI 1.3241 - 711.5572; p= 0,033), the age of patients over 66 years increased the risk of adverse cardiovascular events by 13 % (HR 1.13; 95% CI 1.0230 - 1.2555; p= 0.0172), body weight patient at the enrollment in the study of more than 82 kg increased the risk of adverse cardiovascular events by 7% (HR 1.065; 95% CI 1.0043 - 1.1301; p= 0.036), the Vao over 98 cm/sec increased the risk of adverse cardiovascular events in patients with CHF, but only by 0.8% (HR 1.008; 95% CI 1.0009 - 1.0155; p= 0.0014).
The inclusion in the multivariate model parameters of tubulo-interstitial dysfunction (in parentheses indicates the reliability of the models after the inclusion of markers of tubulo-interstitial injury) didn't affect its power (NGAL, p= 0.0160), (NAG, p= 0.0101), (KIM-1, p= 0.0152). The obtained multivariate model also was independent from the glomerular filtration rate (p= 0.0080) and sex (p= 0.0076).
East European Scientific Journal #5(69), 2021 35
Thus, a combination of factors such as age over 66 years, body weight over 82 kg, index TEI LV over 0.52 c.u., peak mitral valve pressure gradient over 1.9 mmHg., the maximum flow velocity in the aorta over 98 cm/sec was associated with an increase in the relative risk of adverse cardiovascular events in patients with CHF of ischemic origin, regardless of sex, glomerular filtration rate and tubular interstitial injury.
Discussion: According to the results of a univariate regression analysis of the analysis of proportional hazards of Cox, out of more than 100 studied parameters, only five factors were identified, which were associated with adverse cardiovascular events in patients with CHF. Among these factors, four covariates (E/A, GE MK, plasma sodium concentration, pulmonary hypertension) increased the relative risk of adverse events. That are dependent risk factors can be considered diastolic LV dysfunction, pulmonary hypertension and hyponatremia.
The results obtained in our research is fully consistent with the results of the study_[5]. According to research Baldasseroni S. et al. (2011) mild to moderate hyponatremia was an independent cause of annual mortality. Although the relationship between sodium concentration and mortality was not linear, a 1 mmol/l decrease in lower than 142.9 mmol/l increased the mortality rate by 10% (HR 1.10; 95% CI 1.07-1.12; p <0.0001) [5].
In our research, hyponatremia < 142.5 mmol/l was associated with an increase in the relative risk of the cumulative end-points by 22% (HR 1.22, p= 0.029).
In the study Su Y. et al. (2020) in a regression analysis of proportional hazards of Cox proved that hyponatremia was an independent predictor of three adverse effects (mortality from all causes: HR 1.54, 95% CI 1.07-2.91, p= 0.034; rehospitalization about HF: HR 1.28, 95% CI 1.16 - 2.47, p= 0.013, stroke: HR 1.78, 95% CI = 1.04-2.89, p= 0.016) . In China, in a cohort of CHF patients with preserved LV EF, hyponatremia on admission to the hospital was significantly associated with all-cause mortality, rehospitalization, and stroke within 24 months. [6]
However, in clinical practice there is no single action of risk factor, but a number of factors, a combination of which determines the prognosis. Many functional scales have been created and are used to unify the prediction of CHF. The choice of (Seattle Heart Failure Model), [1] and MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) [7] is determined by the volume and characteristics of the explorations, the availability of validation, experience.
The most validated scale for outpatients with CHF is SHFM, which was developed on a representative sample of 1125 outpatients with severe HF (III-IV class NYHA, EF <30%) without severe comorbidity. The SHFM scale includes age, sex, ischemic etiology, NYHA class, EF, systolic blood pressure (BP), diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), statins. The scale predicts the survival of patients with HF using available simple clinical features. The scale provides an accurate assessment of 1-, 2- and 3-year
36 East European Scientific Journal #5(69), 2021 survival and allows you to assess the effectiveness of patient therapy. Limitations of the scale include the possibility of its use only in patients with CHF with reduced LV EF, lack of assessment of the frequency of hospitalizations, underestimation or overestimation of risks [1].
The MAGGIC scale was created by an international team of researchers based on an analysis of the database, which includes a large number of registers and studies (39372 patients, 30 studies, 15851 deaths), and allows to estimate annual and three-year mortality of patients with CHF. The scale is the result of analysis of the phenotypes of CHF and LV dysfunction which are predictors of overall mortality in patients with CHF with both reduced and preserved LV EF. The scale includes 13 predictors: age, sex, body mass index, LV EF, NYHA functional class, plasma creatinine levels, diabetes, beta-blockers, ACE inhibitors or ARBs, blood pressure, smoking, chronic obstructive pulmonary disease (COPD). The disadvantages of the MAGGIC scale are the lack of external validation and natriuretic peptide [7].
It should be noted that these scales include such indicators as age, body mass index of the patient, ischemic etiology of CHF, LV systolic function. Similar indicators revealed independent predictor power in our prognostic model. We obtained a multivariate model of Cox's proportional risks (p= 0.0014), which included five indicators: age, weight, index TEI LV, peak mitral valve pressure gradient (GE MK) and maximum flow velocity (Vao) in aorta.
According to our prognosis model, the age of patients with CHF over 66 years increased the risk of adverse cardiovascular events by 13% (p= 0.0172). According to The Swedish Heart Failure Registry (SwedeHF), the median follow-up was 2.2 [0.9-4.1] years, all-cause deaths were reported in 39% (n = 16866) of patients, and rehospitalization for cardiovascular disease in 56% (n= 23960) and rehospitalization due to decompensated CHF in 35% (n= 15111). The frequency of episodes increased with age, regardless of LV EF. The increase in mortality at the age of 65-80 years was associated with coronary heart disease, regardless of the CHF phenotype (p <0.001) [8].
In research [9] demonstrated that according to the results of multivariate regression analysis of proportional hazards of Cox, if the optimal age distribution point is exceeded > 65 years, the risk of cumulative endpoint in patients with CHF of ischemic origin probably increased by 2.75 times (95% CI 1.674.50; p= 0.001).
According to the investigation [7], in follow-up period (mean age 65 ± 13 years) for 3.6 ± 1.8 years, 115 of 407 died (28%), 129 of 407 were hospitalized for HF (32%), 174 of 407 were hospitalized with other cardiovascular causes (43%), 224 out of 406 reached the cumulative endpoint - cardiovascular hospitalization and / or death (55%). The investigators showed that a combination of factors such as age over 65 years, body weight over 82 kg, LV EF < 61%, is associated with an increased relative risk of adverse
UB
BtSSjB
cardiovascular events: rehospitalization for CHF and cardiovascular disease (HR 1.7; 95% CI 1.4 - 2.0; p <0.001), death (HR 2.2; 95% CI 1.8 - 2.7; p <0.001) and cardiovascular events or death (HR 1.8; 95% CI 1.6 - 2.1; p <0.001). The prognosis model obtained by the authors almost coincided with the results obtained by us - age, weight, systolic LV dysfunction.
As for the body weight of the patient with CHF at the time of enrollment over 82 kg, the resulting model shows us the nature of the independent prognostic indicator, which increased the risk of adverse cardiovascular events by 7% (HR 1.065, 95% CI 1.0043 -1.1301; p= 0.036). The association between overweight and CHF has been observed by other authors. Body mass index is a component model SHFM, which significantly increases the risk of cardio-vascular adverse events [1].
Also, in a large study of the Korean population
[10], which involved 11 210 394 participants, found that overweight increases the risk of CHF (HR 2.97, p<0.001), and subsequently the risk of overall death (HR 1.38, CI 1.353-1.423; p<0.001).
Particular attention among the found factors deserve parameter index TEI LV, which reflects not only an impairment of systolic but also diastolic LV function in addition, in the model we built, it demonstrated the greatest predictor power - increased the relative risk of adverse cardiovascular events in patients with CHF more than 30 times (p= 0.033). The TEI index => 0.52 increased the risk of adverse cardiovascular events in patients with CHF by 30.7 times (HR 30.69; p= 0.033).
A number of studies confirmed the viability of our prognostic model for the influence of the TEI index on the risk of adverse cardiovascular events in patients with CHF. In a research by Sasao H. et al. (2004) concluded that a TEI index greater than 0.70 correlated with the development of episodes of heart failure (BP 14,139 95% CI 1,269-157,553). Souza L.P. et al. (2011) found that LV EF <45% was associated with an increased chance of heart failure progression, but only among patients > 60 years of age with a TEI index > 0.57. Biering S0rensen T. et al. (2013) reported that TEI index values greater than (0.59 ± 0.16 vs. 0.52 ± 0.13, P <0.001) was associated with major adverse events, including congestive heart failure, myocardial infarction, and mortality[11].
At the same time, Rahman N. and co-authors (2009) showed that the TEI index value > 0.40 had better sensitivity (86% vs. 65%), specificity (82% vs. 50%) and accuracy (83% vs. 58%) compared with LV EF <40% to predict cardiac complications, including cardiogenic shock, revascularization, rehospitalization, congestive heart failure, and atrioventricular block
[11].
The next parameter that has proven its prognostic properties in our multivariate model is the flow velocity in the aorta over 98 cm/sec. It was associated with a probable increase in the risk of adverse cardiovascular events in patients with CHF, but only by 0.8% (HR 1.008; 95% CI 1.0009 - 1.0155; p= 0.0014). Although the effect is quite small (less than 1%), but a high
L»
BBgM
degree of probability suggests that the deterioration of the damping properties of blood vessels, which cause an increase in blood flow in the aorta, in patients with CHF of ischemic origin has a significant impact on the disease.
Our data were confirmed by a study by Strange G et al. (2019), which proved in the Australian population that with increased flow velocity in the aorta up to 1.5 m/s, the risk of adverse cardiovascular events increases by 2% (HR 1.02; 95% CI 1.01- 1.02; p <0.001). According to the multivariate model of Strange G et al., by supplementing the flow velocity in the aorta with factors such as male sex, age and LV EF, the authors obtained a probable increase in the risk of adverse cardiovascular events [12].
Thus, using a simple reproducible parameter (age, body weight index TEI LV, peak gradient pressure MK and the maximum flow velocity (Vao) in the aorta) can more accurately estimate the annual prognosis in patients with heart failure, regardless of sex, LV EF and renal function.
Conclusion:
1. Independent risk factors for adverse cardiovascular events (death, myocardial infarction and progressive angina, stroke, progressive heart failure) in patients with CHF should be considered: age and body weight, index TEI LV, peak gradient pressure MK and the maximum flow velocity (Vao) in the aorta, which allows to assess the annual prognosis in patients with CHF regardless of sex, LV EF and renal function.
2. Dependent risk factors for adverse cardiovascular events in patients with CHF are baseline sonographic parameters of E/A and mean pressure gradient MK, plasma sodium concentration, the presence of pulmonary hypertension. Inspiratory IVC collapse of more than 50% is associated with a reduction in the relative risk of adverse cardiovascular events in patients with CHF.
Conflicts of interest: authors have no conflict of interest to declare.
References:
1. McGranaghan P., Saxena A., Düngen H.D., et al. Performance of a cardiac lipid panel compared to four prognostic scores in chronic heart failure. Sci Rep. 2021;11(1):8164. Published 2021 Apr 14. doi:10.1038/s41598-021-87776-w
2. Sciomer S., Moscucci F., Salvioni E., et al. Role of gender, age and BMI in prognosis of heart failure. Eur J Prev Cardiol. 2020;27(2_suppl):46-51. doi:10.1177/2047487320961980
3. Carbone S., Lavie C.J., Elagizi A., et al. The Impact of Obesity in Heart Failure. Heart Fail Clin. 2020;16(1):71-80. doi:10.1016/j.hfc.2019.08.008
4. Voronkov, L. H., Amosova, K. M., Bahriy, A. E. et al. Rekomendatsiyi z diahnostyky ta likuvannya
East European Scientific Journal #5(69), 2021 37 khronichnoyi sertsevoyi nedostatnosti
[Recommendations for the diagnosis and treatment of chronic heart failure]. Sertseva nedostatnist'.,2017; dodatok 1:1-66. [in Ukranian].
5. Baldasseroni S., Urso R., Orso F., et al. Relation between serum sodium levels and prognosis in outpatients with chronic heart failure: neutral effect of treatment with beta-blockers and angiotensin-converting enzyme inhibitors: data from the Italian Network on Congestive Heart Failure (IN-CHF database). J Cardiovasc Med (Hagerstown). 2011; 12(10): 723-731. doi:10.2459/JCM.0b013e32834ae87e
6. Su Y., Ma M., Zhang H., et al. Prognostic value of serum hyponatremia for outcomes in patients with heart failure with preserved ejection fraction: An observational cohort study. Exp Ther Med. 2020;20(5):101. doi:10.3892/etm.2020.9231
7. Rich J.D., Burns J., Freed B.H., et al. Meta-Analysis Global Group in Chronic (MAGGIC) Heart Failure Risk Score: Validation of a Simple Tool for the Prediction of Morbidity and Mortality in Heart Failure With Preserved Ejection Fraction. J Am Heart Assoc. 2018;7(20): e009594. doi:10.1161/JAHA.118.009594
8. Chen X., Savarese G., Dahlstrom U., et al. Age-dependent differences in clinical phenotype and prognosis in heart failure with mid-range ejection compared with heart failure with reduced or preserved ejection fraction. Clin Res Cardiol. 2019;108(12):1394-1405. doi:10.1007/s00392-019-01477-z
9. Lashkul, D. A. Predyktory rozvytku nespryiatlyvykh podii u khvorykh na khronichnu sertsevu nedostatnist ishemichnoho henezu zi znyzhenoiu fraktsiieiu vykydu livoho shlunochka ta nyrkovoiu dysfunktsiieiu [Predictors of adverse events in patients with ischemic chronic heart failure with reduced ejection fraction and renal dysfunction]. Zaporozhye medical journal, 2016; 96(3):4-9. https://doi.org/10.14739/2310- 1210.2016.3.76914 [in Ukrainian].
10. Kim Y.H., Han K.D., Jung J.H., et al. Weight change and the incidence of heart failure in the Korean population: data from the National Health Insurance Health checkup 2005-2015 [published online ahead of print, 2020 Nov 5]. Eur J Prev Cardiol. 2020; zwaa049. doi:10.1093/eurjpc/zwaa049
11. Bennett S., Wong C.W., Griffiths T., et al. The prognostic value of Tei index in acute myocardial infarction: a systematic review. Echo Res Pract. 2020;7(4):49-58. doi:10.1530/ERP-20-0017
12. Strange G., Stewart S., Celermajer D., et al. Poor Long-Term Survival in Patients With Moderate Aortic Stenosis. J Am Coll Cardiol. 2019;74(15):1851-1863. doi:10.1016/j.jacc.2019.08.004
