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Mukhamedova Barno Farkhadovna, senior staff scientist, doctoral candidate, chief of emergency cardiology department with emergency therapy № 2, RRCEM (mob.)
E-mail: dofr.med@mail.ru
Alimov Doniyor Anvarovich, M. D., vice-chief doctor on therapy, RRCEM E-mail: donik78@mail.ru
Tursunov Khursand Mukhsunovich, senior staff scientist, doctoral candidate, chief of emergency cardiology department with emergency therapy № 1, RRCEM E-mail: hursand1972@mail.ru
Obeid Moustafa,
cardio-surgeon of Emergency surgery № 4 department, RRCEM (mob.)
E-mail: mous_obeid@hotmail.com
Functional efficiency of myocardial surgical revascularization in patients with unstable angina on the background of diabetes mellitus
Abstract: Aim of investigation is to estimate 6 months effect of myocardium surgical revascularization in patients with unstable angina on the background of diabetes mellitus (DM) on central hemodynamics indexes and exercise performance.
34 patients with acute coronary syndrome (ACS) have been included in investigation who were diagnosed coronary heart disease (CHD): unstable angina on the 3rd day of observation and there were revealed angiographic indications for surgical revascularization which was performed within 1 month. Patients were randomized into 2 groups subject to presence of background II type DM (group DM+ (18) and DM- (16)).
The carried out investigation showed that in patients with unstable angina and with background of DM and angiographic indications for surgical revascularization there was noted more evident LV dilation of left atrium (LA) in compare with patients without DM. In early post-operative period in patients with background DM significant increase of end diastolic volume (EDV) of LV and systolic function decrease of is temporary noted. By the 6th month after surgical revascularization in both groups, in spite of stable keeping of geometrical parameters, significant improvement of LV systolic function and exercise performance is observed. Effect of surgical revascularization on LV systolic function was significantly evident in patients without metabolic abnormalities.
Keywords: unstable angina, diabetes mellitus, myocardium surgical revascularization.
Background
20-25 % of patients with acute coronary syndrome (ACS) have background pathology like diabetes mellitus (DM). In another 40 % disorder of glucose tolerance is noted. "Diabetes and the Heart" investigation in which patients with ACS were observed for glucose tolerance by WHO's standards estimates a share ofpatients with ACS and background DM in 45 % [1; 2]. Disturbance of carbohydrate metabolism is associated with mitochondrial deficit and it increases energy deficiency in cardiac hystiocytes and worsens ACS course.
Aim — to estimate 6months efficiency of myocardium surgical revascularization in patients with unstable angina on the background of diabetes mellitus (DM) on central hemodynamics indexes and exercise performance.
Materials and methods
34 patients (23 men and 11 women) admitted to Intensive Cardiology Department of RRCEM with acute coronary syndrome (ACS) have been included in investigation who were diagnosed coronary heart disease (CHD): unstable angina on the 3rd day of observation and there were revealed angiographic indications for surgical revascularization which was performed within 1 month.
Patients were randomized into 2 groups subject to presence of background II type DM (group DM+ (18) and DM- (16)). The mean age of the patients was in DM+ group 61.80 ± 4.73 years
and in DM- group 58.68 ± 8.33 years (difference between groups — not significant (ns)).
All patients included into the investigation at primary admission, after 1 week and 6 months after surgical revascularization were performed echocardiography by American society of echocardiography standards. The dynamics of left ventricle end diastolic volume (LV EDV, ml.), anteroposterior size of left atrium (LA, mm.) and left ventricle ejection (LV EF, %) as main index of systolic function have been estimated.
For estimation of exercise performance all patients were performed six-minute walking test (6-MWT). Traveled distance (m.) and reason of stopping (angina pectoris, dyspnea, weakness in the legs) have been estimated.
All received data have been written into summary tables of Excel program, mean figures and their standard errors in the groups were counted. Significance of batch-to-batch variation has been estimated with the use of Student's T-criterion. Differences of occurrence frequency have been defined with the use of x2 criterion and estimation of its significance subject to freedom degrees by standard nomograms.
Results and discussion
Groups were comparable by CHD duration (4.96 ± 1.89 and 5.35 ± 1.4, years correspondingly), presence of arterial hypertension
Functional efficiency of myocardial surgical revascularization in patients with unstable angina on the background.
(16 and 13 patients correspondingly) and myocardial infarction in anamnesis (in 11 and 10 patients; at average 2.1 ± 0.89 and
I.24 ± 0.60, correspondingly). Duration from pain starting to admission to hospital in DM+ group was 9.27 ± 1.75 hours DM- group — 8.42 ± 2.01 hours (ns). ST-segment's rise at ECG to admission time has not been noted in any cases. Express-test on T troponin was negative in 100 % cases.
All patients within first 24 hours have been performed examination including echocardiography and coronarography and indications for surgical revascularization were revealed. It has been detected that in patients of DM+ group it has been noted more evident ischemic structural-functional re-modeling of heart left chambers (table 1): so, anteroposterior size of LA significantly exceeded the index typical for DM- group (p < 0.05), also EDV of LV was higher and LV EF was lower than in patients without metabolic disorders, though significance level of differences by those indexes was not reached. During angiography there were detected 111 he-modynamicaly significant stenosis: 58 in patients of DM+ group (at average 3.22 stenosis/patient) and 53 in DM- group (at average 3.31 stenosis/patient). Lesion the left coronary artery trunk was noted in 7 patients in DM+ group (38.89 %) and in 4 patients in DM-group (25.00 %, x2 = 0.75, ns). All patients were underwent standard treatment for ACS including double antiaggregant, anticoagulative therapy, beta blockers, angiotensin-converting enzyme inhibitors, angiotensin receptors blockers, statins and nitrates, anti-arrhythmics by indications. Patients condition in hospital was stabilized: transformation into IV functional class of angina pectoris has been noted in 4 patients of DM+ group and in 3 ones of DM- group, into III functional class — in 10 and 9 patients and into II — in 4 and 4 patients correspondingly (x2 = 0.08, ns). 6-MWT performed after stabilizing of condition detected the tendency to reduction of test's distance in patients of DM+ group in compare with patients without metabolic disorders, though differences between groups were not significant. Worse structural-functional condition of cardio-vascular system in patients of DM+ group can be explained by concomitant dysmetabolic cardiopathy followed by mitochondrial energy deficit due to diversion of energy metabolism to sorbitol way [3]. As the result, the function ofATP-depending calcic pump is reduced, calcic re-setting occurs and myocardium ventricles' rigidity is increased and it leads to disorder of active diastolic relaxation and overload of LA myocardium.
After discharging all patients were recommended to continue standard basic therapy of CHD.
All patients included into investigation, within 1 month after coronary angiography were performed surgical revascularization (3 patients in DM+ group and 2 ones in DM- group in the conditions of cardiopulmonary bypass, x 2 = 0.11, ns). Mammary-coronary bypass grafting have been performed in 2 patients of DM+ group
II.11 %) and in 2 cases — in DM- group (12.5 %, x2 = 0.02, ns). Mean duration of surgery was 316.82 ± 34.92 minutes in DM+ group and 273.26 ± 10.17 minutes in DM- group (ns), mean quantity of bypass grafts for one patient — 3.55 ± 0.22 in DM+ group and 2.97 ± 0.10 in DM- group (p < 0.05).
1 week after surgical revascularization all patients were performed control examination including echocardiography and 6-MWT. It has been detected that direct effect of surgical revascu-larization on functional condition of cardio-vascular system was unfavorable: as in patients without metabolic disorders EDV of LV after surgery was increased to 11.90 %, LA size — to 10.72 %, and LV EF was reduced to 3.31 %. But the distance walked in 6-MWT has been increased to 26.52 %, in spite of unfavorable changes of
geometry and LV functions. All indicated changes did not reach confidence level. In patients with background DM post-operative dynamics was more evident: increase of EDV was 22.50 % (differences with presurgical data — p < 0.05, differences of relative dynamics of LV EDV between groups DM+ and DM--ns), as the
result, by the 1st week after surgical revascularization EDV of LV in patients of DM+ group became significantly higher (p < 0.05) than in patients of DM- group. LV EF reduced to 5.00 % (significance with presurgical data — p < 0.05, differences of relative dynamics and absolute value of LV EF by the end of the 1st post-operative week between groups — ns). LA diameter increased to 11.46 % (differences of absolute values with initial data — ns, with data on the 1st post-operative week in DM- group — ns differences of relative dynamics between groups DM+ and DM--ns). More evident negative dynamics of echocardiography indexes in patients of DM+, is probably connected with dismetabolic cardiomyopathy and more evident post-operative inflammation on the background of mitochondrial deficit [4; 5]. Stated changes has led to negative changes of 6-MWT — reduction of traveled distance to 3.29 % has been observed (ns with initial data and with dynamics in DM- group). As the result, by the 1st post-operative week, distance of 6-MWT in DM+ group was significantly less (p < 0.001) than in the group without metabolic disorders. Standard therapy of CHD has been continued after discharge. The second control examination has been performed at the end of the 6th month after surgery. It is revealed that by the 6th month after surgical revascularization the sizes of heart left chambers in both clinical groups returned to initial ones (relative dynamics of EDV of LV in patients of DM+ group made up 2.64 % with initial data — ns and -14.19 % with post-operative values, p < 0.001, in DM- group -2.52 % — ns and -13.65 %, p < 0.05, correspondingly; LA diameter -5.68 % — ns, and -12.93 %, p < 0.01 and -4.78 % — ns and -12.17 % — p < 0.01, correspondingly). At the same time neither absolute values by the 6th month of observation nor relative dynamics during the whole time of observation did not differ. But the changes of functional indications — LV EF and 6-MWT were significant: so, LV EF for the whole period of investigation increased in DM+ group to 9.44 % and in DM- one — to 11.90 % and for the post-operative period — to 15.40 % and 19.02 % correspondingly (differences of relative dynamics between groups in both periods — ns). Consequently, by the 6th month of LV EF observation in both groups significantly exceeded not only post-operative values (p < 0.001 for both groups), but also initial ones (p < 0.01 for both groups). End value of LV EF reached by the end of the 6th month of observation in DM- group was significantly (p < 0.05) higher than in DM+ group. Also 6-MWT: relative dynamics in DM+ group made up 93.24 % with initial data and 112.76 % with post-operative ones (p < 0.001 significance of absolute values differences in both groups), in DM- group — 67.99 % and 47.39 % correspondingly (p < 0.001 for both comparisons, differences of relative dynamics both periods are not significant).
Conclusion
So, investigation showed that in patients with unstable angina on the background of diabetes mellitus and angiographic indications for surgical revascularization more evident dilatation ofLA in compare with patients without DM has been pointed. In early postoperative period in patients with background DM evident increase of LV EDV and reduce of systolic function has been noted. By the 6th moth after surgical revascularization in both groups, in spite of stable keeping geometric parameters we have observed significant improvement of LV systolic function and exercise performance. Efficiency of surgical revascularization on LV systolic function was significantly evident in patients without metabolic disorders.
Table 1. - Dynamics of echocardiography and 6-MWT indexes in patients with unstable angina after surgical revascularization subject to background DM (DM+ group is in numerator n = 18; DM- group is in denominator; n = 16)
LV EDV, ml LV EF, % LA, mm 6-MWT, m
initialy 144.78 ± 7.89 53.33 ± 1.56 39.06 ± 1.37 259.00 ± 25.66
131.50 ± 8.39 56.13 ± 1.74 34.75 ± 1.61* 308.63 ± 21.35
After CABG 169.89 ± 9.25A 50.33 ± 1.11A 42.28 ± 1.43 223.33 ± 13.34
143.00 ± 5.68* 53.25 ± 2.10 37.88 ± 1.70* 357.50 ± 24.76***
6 months 140.06 ± 8.78### 57.94 ± 1.39AA### 36.28 ± 1.04## 433.33 ± 32.69AAA###
119.88 ± 5.77# 62.19 ± 1.32*AA### 32.56 ± 1.15*## 491.25 ± 16.89AAA###
Relative dynamics of indexes
% after CABG 22.50 -5.00 11.46 -3.29
11.90 -3.31 10.72 26.52
% 6 months -2.636 9.448 -5.684 93.240
with initial -2.521 11.899 -4.778 67.988
% 6 moths with -14.19 15.40 -12.93 112.76
CABG -13.65 19.02 -12.17 47.39
Note: * — significance of difference between groups DM+ and DM-; A — significance of difference with initial data; # — significance of difference with post-operative data (1 week after surgical revascularization); one sign — p < 0.05, two signs — p < 0.01, three signs — p < 0.001
References:
1. Maier B., Thimme W., Kallischnigg G., Graf-Bothe C., Rohnisch J. U., Hegenbarth C., Theres H. Berlin Myocardial Infarction Registry. Does Diabetes Mellitus Explain the Higher Hospital Mortality of Women with Acute Myocardial Infarction? Results from the Berlin Myocardial Infarction Registry//J Investig Med. - 2006 Apr. - 54(3): 143-151.
2. Kakorin S. V., Shashkova L. S., Mkrtumyan A. M. Acute coronary syndrome in patients with carbohydrate metabolism disorders// Heart. - 2012. - 11(1): 8-12.
3. Task Force Members, Lars Ryden et al. Guidelines on diabetes, pre-diabetes, and cardiovawscular diseases: executive summary//Eur Heart J. - 2007. - 28: 88-136.
4. DeFronzo R. A. International Textbook of Diabetes Mellitus. 3 ed. - Chichester, West Sussex; Hoboken, NJ; John Wiley. - 2004.
5. American Diabetes Association. Standards of medical care in diabetes//Diabetes Care. - 2005. - 28 (Supp. 1): S. 4-36.
Nabieva Umida Pulatdjanovna, Immunology Institute of Science Academy of the Republic of Uzbekistan, Scientific Secretary, Laboratory of Immunopathology and immunopharmacology
E-mail: Inf-ledi@mail.ru
Ismailova Adolat Abdurahimovna,
Adilov Djamshid Gayratovich
Prognosing significance of molecular-biologic methods in antiviral therapy of chronic viral hepatitis C
Abstract: Complete the pathological infectious process in chronic viral hepatitis C, leading to cirrhosis and HCC is possible using antiviral therapy. The effectiveness of an antiviral therapy is influenced by various factors and the virus and the body. In this study, we obtained evidence that the genotype of hepatitis C virus genotype and IL-28B gene are independent and reliable factors predictive of SVR.
Keywords: Chronic hepatitis C, antiviral therapy for hepatitis C, virus genotype, interleukin-28, genetic predictors.
Introduction
The actuality of the problem of chronic virus Hepatitis C (HCV) is explained by the high prevalence, the defeat of the most socially active groups in population, high costs and limited effectiveness of treatment, as well as projected in the nearest 20 years with significant increase of patients with cirrhosis and liver cancer [1, 27-36].
To prevent the development of liver cirrhosis and hepatocellular carcinoma also to suspend the progression of the disease allows the eradication of the infectious agent with using antiviral therapy (AVT). It is well known that the low effectiveness of an antiviral
therapy is primarily associated with virus factors as genotype 1, high viral load, the absence ofviremia reduction after 4 weeks after the AVT and liver fibrosis [3, 237-244; 5, 1219-1225].
The polymorphism of interferon-^ (IFN-X.3) is the most significant genetic factors that influence the effectiveness of the therapy at the patients. In 2009, three independent groups of researchers conducting genome-wide comparison on numerous groups of patients who achieved and not achieved a sustained virologic response (SVR) during AVT have shown that a single nucleotide polymorphism with the IL-28B gene is associated with a high probability of
