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Atakhodzhaeva Gulchekhra Abdunabievna, PhD., assistant of the Chair of Intermediate Level Therapy, military field therapy, work-related occupational diseases, hospital therapy and propaedeutics of internal diseases of the Tashkent Pediatric Medical Institute, Tashkent, Uzbekistan E-mail: atakhodzhaeva@list.ru
АNTI-REMODELING EFFICIENCY OF PREPARATIONS SUCH AS PERINDOPRIL, VEROSHPIRON AND BISOPROLOL APPLIED TO PATIENTS WITH DIASTOLIC CHRONIC HEART FAILURE AND METABOLIC SYNDROME
Abstract: The aim of this work is to study the anti-remodeling efficiency of complex pharmacotherapy of diastolic left ventricular dysfunction of chronic heart failure (CHF) by use of perindopril, veroshpiron and bisoprolol in patients with metabolic syndrome (MS). The study involved 76 male patients with chronic heart failure (CHF) II-III FC, with post infarction cardiosclerosis. Depending on the components of MS the patients were divided into 3 groups: Ist group (n = 27), patients without MS; Group II (n = 24, patients with a combination of dyslipidemia (DLP) with abdominal obesity (AO) and arterial hypertension (AH); Group III (n = 25), patients with a combination of AO, AH and DLP with diabetes 2. A three-month treatment with an implement of the Perindopril, Bisoprolol and Veroshpiron combination in patients suffering from CHF without MS promotes regression of non-adaptive remodeling of myocardial left ventricular and improvement of diastolic function of the heart. The most marked resistance against therapy exists when there is a combination of AO, AH and DLP with diabetes 2 types.
Keyworlds: chronic heart failure, metabolic syndrome, systolic and diastolic left ventricular dysfunction.
The problem of treating the patients with chronic heart failure (CHF) remains to this day one of the unresolved issues of modern cardiology [3]. Traditionally, CHF was associated with a violation of the contractile function of the myocardium. According to modern perceptions about the pathophysiology of CHF syndrome, systolic dysfunction can be considered as one of the variation factors in left ventricular geometry and volumes (LV), myocardial hypertrophy, changes in wall stress and diastolic filling structure, i. e. the concept of LV remodeling [4; 19]. However, in recent years it has been stated widely that an important role in determining both clinical status and prognosis in patients with CHF is also related to diastolic LV myocardial dysfunction [5; 11; 15].
A special significance is acquired by development of diastolic CHF in patients with metabolic syndrome (MS). Structural changes and violations of diastolic function (DF) of the left ventricle are associated with MS components, such as obesity, insulin resistance, hyper-insulinemia and dyslipidemia [10; 13; 14]. Recent studies have demonstrated a relationship between MS and diastolic dysfunction of the myocardium [7; 15]. It has been revealed that MS is associated with an increase of preelection period, namely isovolumic relaxation time of LV, regardless of LV remodeling and afterload intensity. Fuentes L. Et al. (2007) confirmed the diastolic dysfunction in MS patients and demonstrated that diastolic dysfunction is increased with progression of MS regardless
of LV mass [12]. Thus, in pathological myocardial remodeling in case of CHF in patients with MS not only hemodynamic, but also metabolic factor is involved.
The aim of this work is to study the anti-remod-eling effectiveness of complex pharmacotherapy of diastolic LV dysfunction (LV DD) in CHF with application of perindopril, bisoprolol and verospirone in patients with MS.
Methods and materials
The study involved 76 male patients with chronic heart failure (CHF) II-III FC, with postinfarction cardiosclerosis. The recentness of myocardial infarction was from 6 months to 5 years. The diagnosis was verified on the basis of the classification of the New York Heart Association (NYHA), a six-minute walk test (SMWT) and rating scale of clinical state (RSCS). The average indicator for SMWT was 304.7 ± 19.3 m (274-338). 3 groups of patients were differentiated depending on the components of MS: Group I (n = 27), patients without MS; Group II (n = 24) patients with a dyslipidemia combination (DLP) with abdominal obesity (AO) and AH; Group III (n = 25) patients with a combination of AO, AH and DLP with diabetes 2 types.
In MS diagnosis, the diagnostic criteria of the International Diabetes Federation (IDF, 2009) were used. The main components of MS were: abdominal obesity (AO) (> 94 cm for men); level of triglycerides (TG > 1.7 mmol/l); cholesterol level of high-density lipoproteins (CLHDL < 1.03 for men); the level of BP (SBP > 130 mm Hg, DBP > 85 mm Hg), glucose level in the fasting state (> 5.6 mmol/l) or type 2 diabetes mellitus.
The examined patients were on inpatient treatment in Cardiology Department of the City Clinical Hospital No. 7 in Tashkent. The patients were examined on the basis of a contract at the City Medical Consultative and Diagnostic Center in Tashkent. The Echocardiography (Echocardiogram) was fulfilled on the Mindray apparatus (China) using the method of lying and left side in M and B modes in accordance with the requirements of the American Association of Echocardiography (ASE). LV diastolic function was judged by the maximum velocity of the early peak of diastolic filling (VmaxPeak E, 0.62 m/s), the maximum rate of transmittal blood flow during left atrial systole (VmaxPeak A, 0.35 m/s), and the E/A ratio 1,5-1,6), the time of isovolemic relaxation
of the left ventricle (IVRT), the early diastolic filling delay (Dt deceleration time).
All patients were advised to use use perindopril (Prestarium, Servier), bisoprolol (Concor, Nycomed), as well as veroshpirona (Gedeon Richter) 50 mg/day within the three months period. Perindopril titrated at a dose of 4 mg to 8 mg, bisoprolol titrated at a dose of 5 mg to 7.5 mg.
Statistical analysis of the obtained data was carried out on a personal computer of IBM PC/AT type using a package of standard electronic program "biostatic for Windows, version 4.03". The parameters were described in the form of M ± m. In the distribution of values, group comparisons of quantitative variables were carried out using the Student's variation statistical criterion (t).
Research Results
In the third study group, the shortening degree of A-P diameter of the left ventricle in systole decreased by 19.2% (p < 0.01). Patients with MS differ by more pronounced manifestations of diastolic dysfunction, as evidenced by a significant RA increase in patients of the Groups 2 (p < 0.05) and 3 (p < 0.01) groups with a slight decrease in PE, as well as a decrease in E/A ratio by 7.6% (p < 0.05) and 19.5% (p < 0.01), respectively. Violation of the transmittal blood flow is associated with an increase in preejection period, namely iso-volumic relaxation time LV by 8.6% (p < 0.05); 15.9% (p < 0.01), as well as the delay of early diastolic filling by 13.4% (p < 0.05) and 21.7% (p < 0.01) in the 2nd and 3rd groups respectively. Violation of the systolic and diastolic function of the LV causes the intense work of LP. The data obtained indicate that in patients without MS, the changes detected in the left ventricle do not affect the LP condition, while in patients with MS there is an increase in its size. At the same time, if in the second group this indicator is increased by 6.2% (p < 0.05), in the third group the difference reaches 12.1% (p < 0.01) and goes beyond the permissible range.
After 3 months of treatment of patients with CHF by applying perindopril, bisoprolol and veroshpiron, we obtained the data (Table 1), which indicate a significant positive dynamics from Echocardiography and Doppler echocardiography in patients without MS. In patients with MS, especially in Group 3, a weak dynamics of the analyzed indicators was revealed.
Table 1. - The diastolic function of the LV in patients with CHF II-III FC, depending on the M
Indicators Research terms Group I (n = 27) Group II (n = 24) Group III (n = 25)
Dt, mc before treatment 189.67 ± 8.5 215.08 ± 8.91* 230.83 ± 9.52**
after 3 months 166.78 ± 6.88° 189.76 ± 8.68 213.8 ± 10.7**
IVRT, mc before treatment 85.2 ± 2.05 89.28 ± 2.81* 95.29 ± 2.75**
after 3 months 78.15 ± 2.51° 81.82 ± 2.53 88.38 ± 2.51*
%AS,% before treatment 37.16 ± 1.73 35.19 ± 1.34 32.47 ± 1.53*
after 3 months 40.18 ± 1.88 38.49 ± 1.45 35.66 ± 1.42
PE, m/c before treatment 0.59 ± 0.018 0.57 ± 0.019 0.54 ± 0.021
after 3 months 0.65 ± 0.018° 0.61 ± 0.019* 0.57 ± 0.016**
PA, m/c before treatment 0.50 ± 0.016 0.53 ± 0.018* 0.58 ± 0.017**
after 3 months 0.43 ± 0.018° 0.46 ± 0.019° 0.52 ± 0.015°**
E/A before treatment 1.18 ± 0.042 1.08 ± 0.054* 0.93 ± 0.027**
after 3 months 1.51 ± 0.045°° 1.33 ± 0.041°* 1.10 ± 0.039°**
Ps in min before treatment 75.37 ± 1.72 76.92 ± 1.96 77.4 ± 2.36
after 3 months 70.04 ± 1.58° 73.29 ± 1.37 74.72 ± 1.99
Note: * - p<0,05; ** - p < 0,01 the reliability of the difference in indicators in comparison to Group I. Note: ° - p<0,05; °° - p < 0,01 the reliability of the difference in indicators before and after treatment.
The examined patients also differ according to results of influence of treatment on diastolic function of LV. A significant improvement in this function is observed in patients without MS, as evidenced by a statistically significant decrease in preelection period, namely isovolu-mic relaxation time of LV, early diastolic filling delay and maximum atrial systole, as well as an increase in the maximum rate of early diastolic filling of the LV and E/A ratios. However, in patients with MS, especially in the third group, a decrease in Dt and IVRT, the increase in PE was insignificant and the difference in these parameters between the 1st and 3rd group remained high, reaching 28.2% (p < 0.01), 13.2% (p < 0.05) and 12.3 (p < 01), respectively. In addition, despite a decrease in RA (p <0.05), it was 20.9% higher (p < 0.01) and an increase in E/A, this ratio was lower by 27.2% (p < 0, 01) in comparison with the 1st group (Table 1).
It was revealed that there is dependence of the current variations MS type [9], which are not conditioned by hemodynamic factors. However, there are very little data available and they mainly refer to MS in case of AH. According to the results of this study, it was found that in patients with CHF in case of AO, AH and DLP, the structural changes in the myocardium are more pronounced than in patients without MS.
The LVMH is considered as an independent marker of high-risk cardiovascular diseases, including sudden death, and significantly affects the mechanism of diastolic dysfunction (DD) of formation of the left ventricle [19]. In this regard, the important aspect of this problem is the availability of data on the relationship between DD and MS [15]. It can be even regardless of the weight of the LV. The relationship between MS and LV DD was also reflected in the results of this study. Patients with MS (AO+AH+DLP), in contrast to patients without MS, are characterized by more pronounced manifestations of DD, an increase of IVRT, DT and RA, as well as a decrease in E/A. The addition of diabetes 2 types to the above mentioned manifestations of MS significantly worsens DD, which manifests itself in a further increase in IVRT, DT and RA, as well as a decrease in E/A. An important role in this case is given to the time of isovolemic LV relaxation, which increases with MS, regardless of LV remodeling and afterload intensity [14]. Recently, the CHF is more associated with DD in individuals with normal EF (ejection farction) [7; 12]. However, in patients with severe MS symptoms, in Group III, there is a significant decrease in the shortening degree of anteroposterior LV into systole.
ACEI, ^-blockers and spironolactones are considered to be the leading means in the treatment of patients with CHF [6]. Three-month treatment by means ofper-indopril, bisoprolol and veroshpiron in patients without MS is characterized by a positive dynamics of diastolic function (DF) of the LV, which was manifested by a decrease in IVRT, DT, improvement in the transmittal spectrum (decrease in increase in PE and E/A).
After the treatment, against a background of a significant decrease in ^ and an increase in E/, the 2nd group is significantly inferior to patients without MS and in terms of the transmittal spectrum. The results of the comparative analysis showed that the heavier form of MS (AO+AH+DLP+ diabetes 2 types) in patients with CHF reduces the effectiveness of combined use of perindopril, bisoprolol and veroshpiron to a greater extent. Statistically, significant positive dynamics in these patients after treatment is traced only by ^ and
E/A. Despite the positive dynamics of transmittal blood flow, this function in these patients remains significantly low in comparison with patients without MS.
Conclusions
1. The presence of MS in patients with CHF is an important factor in enhancing diastolic LV dysfunction, which is most pronounced in the combination of DLP, AO and AH with diabetes 2 types.
2. A three-month treatment with a combination of perindopril, bisoprolol and veroshpiron in patients with CHF without MS contributes to the improvement of dia-stolic function of the heart.
3. MS in patients with CHF reduces the anti-remod-eling effectiveness of combined drug treatment using perindopril, bisoprolol and veroshpiron, which depends on the representation of its components. The most pronounced resistance to the therapy is available with the combination ofAO, AH and DLP with diabetes 2 types.
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