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International Medical Scientific Journal       Issue-2 

10.5281/zenodo.5520856 

116 

    



Art of Medicine           Volume-1 

International Medical Scientific Journal       Issue-2 

10.5281/zenodo.5520856 

117 

 

Art of Medicine International Medical Scientific journal 

 

Founder and Publisher Pascual Izquierdo-Egea 

Published science may 2021 year. Issued Quarterly. 

Internet address: http://artofmedicineimsj.us 
E-mail: info@artofmedicineimsj.us 

11931 Barlow Pl Philadelphia, PA 19116, USA +1 (929) 266-0862 

 

 
 

 

  



Art of Medicine           Volume-1 

International Medical Scientific Journal       Issue-2 

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118 

 

Efficacy of empagliflozin in older patients with chronic heart failure with 

preserved left ventricular ejection fraction 

Tulaboeva G.M., Talipova Yu.Sh., Sagatova X.M., Xusanov A.A., Abdukodirova 

N.M.  

Center for the Development of Qualifications of Medical Workers under the Ministry 

of Health of the Republic of Uzbekistan, Department of Cardiology and Gerontology  

 

Abstract: Chronic heart failure (CHF) is the leading cause of hospitalization in 

Europe, the United States and Asia. Mortality in CHF increases with each 

hospitalization. CHF with preserved ejection fraction (EF) occurs when the heart 

muscle contracts ineffectively and there is reduced blood flow in the body compared 

to a normally functioning heart. Numerous studies have shown that symptoms 

associated with heart failure, such as shortness of breath and fatigue, can negatively 

affect quality of life.  

Keywords: Chronic heart failure,  

Introduction. Despite the availability of a wide choice of medications for the 

treatment of CHF, which can improve the survival rate of patients, the prognosis of 

the disease remains unfavorable [1, 2], therefore, the search for new treatment options 

for this pathology is an urgent task of modern cardiology. There are numerous 

contradictory data regarding the use of empagliflozin in CHF. Empagliflozin, a 

selective inhibitor of the sodium-dependent glucose transporter type 2 (SGLT2), 

became the first antihyperglycemic drug to be superior to placebo in cardiovascular 

safety. 

Empagliflozin, a specific inhibitor of SGLT2, is a representative of a promising 

new class of drugs that lower glucose levels, independent of insulin. In addition to its 

well-proven glycemic effect, ample evidence suggests cardioprotective potential. 

Empagliflozin is able to improve myocardial microvascular perfusion, eNOS activity, 

and endothelium-dependent relaxation. Empagliflozin may have a beneficial effect by 



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inhibiting DM-induced mitochondrial division in a 5'AMP-activated protein kinase 

(AMPK) - dependent manner. On the one hand, the action induced by this drug can 

slow down the aging of endothelial cells by suppressing oxidative stress, which leads 

to an improvement in their viability and barrier function. On the other hand, 

empagliflozin-induced endothelial migration as a result of F-actin homeostasis may 

promote angiogenesis [4]. With the progression of diabetes, endothelial damage is 

detected at an early stage. Thanks to these mechanisms, empagliflozin improves the 

blood supply to the myocardium. Significant data indicate the ability of empagliflozin 

to reduce systolic blood pressure by facilitating osmotic diuresis, influencing the 

microvascular diastolic response by stimulating eNOS phosphorylation, vascular 

remodeling, reducing the level of inflammatory proteins, and decreasing collagen 

synthesis [4]. The principle of action of type 2 sodium glucose cotransporter 

inhibitors is based on a decrease in glucose reabsorption in the proximal renal 

tubules, which leads to an increase in urinary glucose excretion and a subsequent 

decrease in plasma glucose levels. This mechanism of action is insulin-independent 

and, therefore, has a low risk of hypoglycemia [3, 4, 5]. It should be noted that 

earlier, within the framework of the EMPEROR-Reduced study, it was shown that 

the SGLT2 inhibitor empagliflozin reduces the risk of death and hospitalization due 

to CHF decompensation in patients with reduced LVEF by a quarter [8]. It is 

important to note that the EMPEROR-Preserved and EMPEROR-Reduced projects 

are part of a program to study empagliflozin in patients not only with metabolic 

disorders, but also with pathologies of the cardiovascular system and kidneys. Thus, 

the drug is currently being investigated in patients with chronic kidney disease 

(CKD), as well as in patients with acute myocardial infarction and a high risk of CHF 

[8]. 

On the other hand, SGLT-2 inhibitors have also shown a significant reduction 

in the risk of hospitalization not only for CHF, but also for end-stage CKD. As a 

consequence of this growing body of evidence, the focus of T2DM treatment has 

shifted from glucose control to organ preservation. SGLT-2 inhibitors have become a 



Art of Medicine           Volume-1 

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key tool in the treatment of CVD and in reducing the progression of CKD. The 

results of large randomized controlled trials, which included patients with and 

without type 2 diabetes, have shown that glyflozin therapy is associated with a 

decrease in hospital admissions for CHF and the progression of CKD. In T2DM, the 

positive effects of SGLT-2 inhibitors appear early and do not depend on the effect on 

lowering the level of glycemia [6, 7, 8]. The above aspects made it possible to 

determine the purpose of the study. 

 Target. To assess the effect of the inhibitor empagliflozin on exercise 

tolerance, quality of life, on the endpoints of CHF in older persons with preserved left 

ventricular ejection fraction. 

Material and research methods. This study evaluated the efficacy and safety 

of empagliflozin in patients with chronic CHF with preserved LVEF. The present 

study included 115 patients aged from 62 to 78 years (average age 71.2 ± 3.6 years) 

with CHF with verified data of clinical and instrumental analyzes diagnosed with 

CHF functional class (FC) II and III. The New York Heart Association (NYHA) 

Classification by Functional Class was used to enroll patients in the study groups.  

Patients, depending on the therapy performed by the method of "random" 

sampling, were divided into 2 groups: group 1 (n = 75, main group) of patients on the 

background of standard CHF therapy took empagliflozin (Emgalif, Orville services) 

10 mg / day and group 2 (control group, n = 40) who took only standard therapy. The 

observation period was 12 weeks. The study was carried out at the clinical base of the 

Department of Cardiology and Gerontology of the Center for the Development of 

Professional Qualifications of Medical Workers at the Ministry of Health of the 

Republic of Uzbekistan. 

All patients underwent a 6-minute walk test at baseline and at the end of the 

study, and underwent quality of life, blood lipid composition, and resting 

echocardiography. 

The criteria for exclusion from the main study group were: 



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hypertrophic, restrictive, obstructive or dilated cardiomyopathy, constructive 

pericarditis, primary pulmonary hypertension or cor pulmonale, myocarditis; acute 

myocardial infarction (or less than 30 days after its development), coronary artery 

bypass surgery (within 6 months), unstable angina pectoris, valvular heart disease, 

acute cerebrovascular accident (within 6 months), renal or hepatic failure, 

autoimmune or endocrine diseases. 

The data obtained during the study were subjected to statistical processing on a 

Pentium-IV personal computer using the Microsoft Office Excel-2012 software 

package, including the use of built-in statistical processing functions. Methods of 

variational parametric and nonparametric statistics were used with the calculation of 

the arithmetic mean of the studied indicator (M), standard deviation (χ2), standard 

error of the mean (m), relative values (frequency,%), the statistical significance of the 

measurements obtained when comparing the mean values was determined by the 

criterion Student's t (t) with the calculation of the error probability (P) when checking 

the normal distribution (according to the kurtosis criterion) and the equality of 

general variances (F - Fisher's test). 

Research results. The results of the assessment of the severity of the clinical 

condition according to the scale of the assessment of the clinical condition (SACC) 

showed that the patients in the general sample (n = 115) had an average of 4.4 ± 2.0 

points. The average score of the 6-minute walk test (TSW) for the entire group was 

329.8 ± 80 m, while the average survey result on the scale of quality of life 

assessment (MLHFQ) was 42.3 ± 7.8 points. 



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Fig. 1. The results of assessing the main indicators of the severity of CHF 

(score, meter) 

 

Among the patients of the main group, after the therapy (after 12 weeks), 1 

(1.3%) lethal outcomes and 1 (1.3%) cases of FC 2 change to FC 3 were observed. 

Among the untrained, there were 2 (5%) deaths and 2 (5%) cases of changes in FC 

CHF. 

The assessment of the number of visits of patients with CHF according to the 

family polyclinic showed a generally satisfactory level of clinical examination in the 

main group - on average, the indicator of planned visits was 2.3 times (3.1%) in the 

control group. 

The dynamics of the main hemodynamic parameters (the number of heartbeats 

(NHB), systolic blood pressure (SBP) and diastolic blood pressure (DBP) in patients 

in the study groups also had a positive trend. In the main group, the average heart rate 

decreased significantly (p> 0.05) and SBP (p> 0.05) in comparison with the indices at 

the beginning of the study It is noteworthy that in the patients of the control group 

there was an increase in the mean indices of heart rate, SBP and DBP after 12 weeks 

of observation. 

0

50

100

150

200

250

300

350

SACC QoL TSW

4,3 

42,3 

329 



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Table 1. 

Dynamics of hemodynamic parameters in the analyzed groups of patients 

Studied 

indicators 

On the first visit After the therapy 

(after 12 weeks) 

Control group 

(n=40) 

Main group (n=75) 

NHB 75,7±10,3 76,7±10,4 70,1±8,7* 

SBP 142,0±15 141,0±13,9 139,1±15,7* 

DBP 85±11,1 86±11,0 82,2±7,9 

Note: * p> 0.05 - reliability of differences in relation to the initial data. NHB - heart rate, 

SBP - systolic blood pressure, DBP - diastolic blood pressure. 

Indicators of the dynamics of the clinical and functional state of patients in the 

form of SACC and TSW within 12 weeks. from the beginning of observation in the 

compared groups are shown in Figure 2. In the main group, significant differences 

were noted as TSW (p <0.01), SACC (p <0.01) and quality of life (QoL) (p <0.01), 

whereas in the control group, no significant and reliable positive dynamics was 

observed. 

 

Note: * p <0.05: ** p <0.01 - reliability of differences in relation to the initial data 

0

50

100

150

200

250

300

350

400

SACC КЖ TSW

4,3 

42,3 

329 

2,6* 

34* 

367** 

3,2 

37 

342 



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Figure 2. Data of QoL, SACC and TSW in patients of the compared groups 

against the background of the therapy (score, meter). 

Table 3. 

Lipid composition of blood in the analyzed groups  

(М±m) 

Indicators Main Group 

(n=75) 

Control 

Group (n=40) 

Initial Data 

  

(n=115) 

Total CS, mg / dl 196±5,1 202±5,0 219±3,0 

TG, mg / dl 185,0±4,6* 196,0±9.7 208±6,2 

CS LDL, mg / dl 138±2,5* 140± 3,7 148±3,4 

CS HDL, mg / dl 34,2± 1.1 33,2±1,0 33,4± 1.0 

CA, rel. 4.1±0,11 4,3±0,1 4,8±0,3 

Note: * P <0.001-reliability of differences in relation to healthy groups, CS-cholesterol, TG-

triglycerides, LDL-low-density lipoproteins, HDL-high-density lipoproteins, CA-coefficient of 

atherogenicity. 

After 12 weeks. During the course of treatment in patients in the main group, 

there was a significant decrease in triglycerides (p <0.01) and low-density 

lipoproteins (LDL) (p <0.01) in the control group, similar dynamics were not 

revealed. 

Table 4. 

Indicators of LV systolic function in middle-aged patients. 

 Initial data Main group Control group 

EDS, sm 5,0±0,32 4,6±0,3 4,9±0,2 

ESS, sm 4,9±0,2 4,3±0,21 4,7±0,22 

EDV, ml 124,5±52 119,5±42* 121,3±50 

ESV, ml 52±18,0 43±14,0* 49±17,0 

EF, % 56,5±5,0 58,3±4,3 57,2±5,5 

IVS, mm 12,6±1,1 11,0±1,02 12,0±1,1 



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Note: * p <0.05 - reliability of differences in relation to the initial data, EDS-end diastolic size, 

ESS-end systolic size, EDV-end diastolic volume, ESV-end systolic volume, EF-ejection fraction, 

IVS-interventricular septum..  
 

The analysis of echocardiographic parameters in patients in 2 study groups in patients 

with CHF was carried out on the basis of a study of the main indicators of systolic 

and diastolic LV dysfunction. In the main group of patients with CHF, after the 

therapy, a significant decrease in ESV and a relative decrease in EDV in relation to 

the initial values was revealed by 21% (p <0.05). Along with this, IVS in the main 

group also tends to decrease. Whereas in the control group, significant dynamics in 

terms of Echocardiography indicators is not observed. 

Thus, for patients with chronic heart failure with preserved left ventricular 

ejection fraction, the use of the SGLT2 inhibition drug, empagliflozin for 12 weeks 

against the background of the main therapy, demonstrated a positive effect in relation 

to an increase in exercise tolerance according to the data of the 6-minute walk test 

with an improvement in quality parameters. life on the SHOKS scale. 

A positive trend of restoration of the contractility of the left ventricular 

myocardium was shown according to the end-systolic and end-diastolic volumes with 

a positive cardiac effect. 

Therapy with the inclusion of empagliflozin is aimed at preventing 

manifestations such as chronic heart failure, which is aimed at reducing the 

progression of morbidity and mortality in older patients with preserved left 

ventricular ejection fraction. 

 

  



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