16 IN T E R N A L m E d Ic IN E ISSN 2413-6077. IJmmR 2017 Vol. 3 Issue 2 dOI 10.11603/IJMMR.2413-6077.2017.2.8242 LEfT VENTRIcULAR dIAsTOLIc dYsfUNcTION ANd OXYgEN sUPPLY Of LOWER EXTREmITIEs IN PATIENTs WITh sTAbLE IschEmIc hEART dIsEAsE ANd cONcOmITANT TYPE 2 dIAbETEs mELLITUs N. I. Yarema, N. V. Pasechko, A. I. Khomitska, I. P. Savchenko, I. V. Smachylo, L. V. Naumova, L. V. Radetska, A. O. Bob, M. E. Havrylyuk, O. О. Bob, N. M. Havrylyuk, O. I. Kotsyuba I. HORBACHEVSKY TERNOPIL STATE MEDICAL UNIVERSITY, TERNOPIL, UKRAINE Background. The peculiarities of diastolic heart failure and indices of arterial and venous blood oxygenation in patients with stable ischemic heart disease and concomitant type 2 diabetes mellitus are presented in the article. Obvious left ventricular diastolic dysfunction with the increased levels of natriuretic peptide, uric acid and decreased indices of arterial and venous blood oxygenation in the presence of comorbid type 2 diabetes mellitus have been revealed. Objective. The research was aimed to study the peculiarities of left ventricular diastolic function disorders, levels of NT-proBNP, uric acid and indices of arterial and venous blood oxygenation in patients suffering from stable exertional angina with underlying comorbid type 2 diabetes mellitus. Methods. 70 patients with IHD: stable exertional angina of the ІІІ functional class, were examined. The first group comprised 39 patients with stable exertional angina of the ІІІ functional class with left ventricular diastolic dysfunction; the second group – 31 patients with stable exertional angina of the ІІІ functional class with left ventricular diastolic dysfunction and concomitant type 2 diabetes mellitus. All the examined patients underwent BD- echocardioscopy, with the detailed evaluation of left ventricular diastolic function, NT-proBNP and uric acid levels in venous blood were determined by immunoenzyme method, indices of arterial and venous blood oxygenation were evaluated too. Results. The correlation between left ventricle diastolic function and oxygen volume consumed by the tissues of lower extremities in patients with stable ischemic heart disease and concomitant type 2 diabetes mellitus was determined. Conclusions. In patients with stable IHD, left ventricular diastolic dysfunction and concomitant type 2 diabetes mellitus the levels of NT-proBNP, uric acid and oxygen supply of lower extremities are significantly higher as compared to patients with IHD without type 2 diabetes mellitus. KEY WORDS: stable ischemic heart disease; left ventricular diastolic dysfunction; diabetes mellitus; natriuretic peptide; blood oxygenation. Corresponding author: Alla Khomitska, Department of Internal Medicine №1, I. Horbachevsky Ternopil State Medical Univer- sity, 1 Clinichna Street, Ternopil, Ukraine, 282004 Phone number: +0976860500 E-mail: balabanai@tdmu.edu.ua Introduction Stable ischemic heart disease (IHD) in pa- tients with type 2 diabetes mellitus is diagnosed in 2–4 times more often than in people of the same age without diabetes [1]. According to some authors, diabetes mellitus negatively influences on left ventricular diastolic function, and the increase of diabetes mellitus duration is accompanied by chronic heart failure devel- opment [4]. There are some findings that left ventricular diastolic dysfunction may be caused by diabetes mellitus development regardless of the presence of IHD or arterial hypertension [2]. The results of some researches show that the prevalence of asymptomatic left ventricular diastolic dysfunction in patients with type 2 diabetes mellitus is 63.2 % and increases with age [4]. One of the main markers of chronic heart failure is N-terminal brain natriuretic propeptide (NT-proBNP), its levels increase as chronic heart failure develops [3]. An asymp- tomatic hyperuricemia is also an important risk factor in the development of cardiovascular complications. Therefore early diagnostic of this pathology is important for proper drug-induced correction in patients with IHD, left ventricular diastolic dysfunction and concomitant type 2 diabetes mellitus [5]. International Journal of Medicine and Medical Research 2017, Volume 3, Issue 2, p. 15–19 copyright © 2017, TSMU, All Rights Reserved N. I. yarema et al. 17 IN T E R N A L m E d Ic IN E ISSN 2413-6077. IJmmR 2017 Vol. 3 Issue 2 N. I. yarema et al. The research was aimed to study the pecu- liarities of left ventricular diastolic dysfunction, the levels of NT-proBNP, uric acid and indices of arterial and venous blood oxygenation in patients with stable exertional angina with comorbid type 2 diabetes mellitus. Methods 70 patients with IHD: stable exertional an- gina of the ІІІ functional class, were examined. The average age of the examined patients was (58.38±0.64) years old. The first group com- prised 39 patients suffering from stable exer- tional angina of the ІІІ functional class with left ventricular diastolic dysfunction; the second group counted in 31 patients with stable exer- tional angina of the ІІІ functional class with left ventricular diastolic dysfunction and concomi- tant type 2 diabetes mellitus. All patients were diagnosed with relaxation type of left ventricu- lar diastolic dysfunction, and left ventricular ejection fraction in all examined patients was higher than 45%, which means that systolic function of the left ventricle was preserved. The control group comprised 20 healthy individuals of the same age and sex. All the examined pa- tients underwent BD-echocardioscopy with the detailed evaluation of left ventricular diastolic function, NT-proBNP and uric acid levels in venous blood were determined by immunoen- zyme method, indices of arterial and venous blood oxygenation were evaluated too (satura- tion of arterial (Sa.O2) and venous (Sv.O2)) blood – with pulse oximeter; arterial (Ca.O2) and venous (Cv.O2) blood oxygenation in vitro including the assessment of oxygen volume consumed by the tissues of lower extremities Da.O2-Dv.O2) – with Oximeter Unistat apparatus (USA). All statistical analyses were performed with Statistica 6.0 and Microsoft Excel. Data are ex- pressed as means±standard deviation or as number (%). Continuous variables were analy- zed by the Student’s t­test and the Mann–Whit- ney test. P<0.05 was considered statistically significant. The authors had full access to infor- mation and take full responsibility for the in- tegrity of the data. All authors have read and agreed to the manuscript as written. Institu- tional review committee approval and informed consents were obtained. Results In patients with IHD and concomitant type 2 diabetes mellitus correlation of Е/А was by 34.8% (p<0.01) lower than in the control group and by 15.1% (p<0.05) higher than in patients with IHD without concomitant type 2 diabetes mellitus (Table 1). IVRT and DT values also dif- fered considerably in patients with IHD, left ventricular diastolic dysfunction and concomi- tant type 2 diabetes mellitus, specifically: DT value was by 30.5% (p˂0.01) higher than in the control group and by 24.1% (p<0.05) higher than in patients with IHD without type 2 diabe- tes mellitus. Е' value was by 50.5% (p<0.01) lower in the 2nd group of patients as compared to the control group, and by 26.8% (p<0.05) lower than in patients with IHD without type 2 diabetes mellitus. In patients with stable IHD correlation of Е/E' was increasing to (9.83±0.14) because of significant decrease in Е' and was in 1.8 times higher than in the control group and by 25.9% (p<0.01) higher as compared to the patients with IHD without type 2 diabetes mellitus that proves an increased inflexibility of myocardium in patients with comorbidity of IHD and type 2 diabetes mellitus. NT-proBNP value in patients with stable IHD and concomitant type 2 diabetes mellitus was (566.07±22.01) pg/ml and was by 35.6% (р˂0.01) higher as compared to the first group of the examined patients and by 78.7% (р˂0.01) higher as compared to the control group that evidences more significant chronic heart failure development in patients with stable IHD and concomitant type 2 diabetes mellitus (Fig. 1). In patients with IHD, left ventricular dia- stolic dysfunction and concomitant type 2 dia- betes mellitus the level of uric acid was by 53.3% (р˂0.01) higher as compared to the control group and by 21.3% (р˂0.05) higher as com- pared to the examined patients without con- Fig. 1. Level of NT-proBNP in the examined patients 18 IN T E R N A L m E d Ic IN E ISSN 2413-6077. IJmmR 2017 Vol. 3 Issue 2N. I. yarema et al. comitant type 2 diabetes mellitus. The data obtained in our research confirm the results of some authors that hyperuricemia is an inde- pendent risk factor in the development of cardiovascular complications in patients with IHD and has negative effect on the clinical course of chronic heart failure. In patients with stable exertional angina and concomitant type 2 diabetes mellitus the decrease in arterial and venous blood oxygena- tion indices as compared to the patients with stable IHD without type 2 diabetes mellitus was determined (Table 2). Sa.O2 was slightly lower in the 2nd group than in the 1st group. Sv.O2 value in the 2 group of patients with comorbid type 2 diabetes mellitus was by 21.8% (p<0.05) lower as compared to the patients of the 1st group. Са.О2 and Cv.O2 values were consider- ably lower in patients with left ventricular dia- stolic dysfunction and type 2 diabetes mellitus as compared to the patients without diabetes mellitus, respectively by 21.2% (p<0.01) and 18.5% (p<0.01), which indicates the deficiency of oxygen saturation of lower extremities tis- sues as the result of transvenous and transcap- illary blood flow difficulties. The volume of oxygen consumed by tissues of lower extremities Da.O2–Dv.O2 in patients with stable IHD and type 2 diabetes mellitus was (44.85±0.94) ml·l-¹ and was by 9.6% (р<0.05) lower as compared to the patients without type 2 diabetes mellitus. So, in patients with stable IHD and concomitant type 2 diabetes mellitus the decrease in oxygen volume, which is trans- ported to the tissues of lower extremities, was accompanied by the decrease in oxygen volume consumed by the tissues of lower extremities. The direct correlation between the decrease in value of E' decline and decrease oxygen vo- lume consumed by the tissues of lower extre- mities in patients with stable ischemic heart disease and concomitant type 2 diabetes mel- litus was revealed. Discussion According to the recent literature [6,8], vio- lation of oxygen transporting processes of in the organism is predefined by insufficiency of pumping function of myocardium, by decelera- tion of blood stream in the vessels of greater circulation, by uneven distribution of blood in the system of microcirculation [7]. Таble 1. Rates of left ventricular diastolic function in patients with IHD and concomitant type 2 diabetes mellitus Index Control group,n=20 Group 1, n=39 Group 2, n=31 р1-2 Е, sm/sec 0.72±0.01 0.62±0.02* 0.56±0.02* р1-2<0.05 А, sm/sec 0.54±0.03 0.65±0.04* 0.70±0.03* р1-2˃0.05 Е/А 1.21±0.04 0.93±0.05* 0.79±0.04* р1-2<0.05 Е', sm/sec 0.121±0.010 0.082±0.007* 0.060±0.006* р1-2<0.05 Е/Е' 5.34±0.18 7.81±0.12* 9.83±0.14* р1-2<0.01 DT, msec 172.12±3.02 181.26±5.23* 224.76±13.62* р1-2<0.05 IVRT, msec 80.14±1.32 98,04±4,25* 112.61±3.62* р1-2<0.05 Notes: 1. * – significant differences of indices in comparison with the control; 2. р1–2 – significant differences of indices between two groups of patients. Таble 2. Rates of arterial and venous blood oxygenation in patients with stable IHD, left ventricular diastolic dysfunction and type 2 diabetes mellitus Index Control group,n=20 1 group, n=39 2 group, n=31 р1-2 Sa.O2, % 99.10±0.41 96.12±0.74* 91.53±0.51* р1-2<0.05 Sv.О2, % 70.31±0.33 67.26±0.41* 52.64±0.58* р1-2<0.01 Са.О2, ml·l -¹ 149.20±0.62 142.10±1.53* 112.57±2.65* р1-2<0.01 Сv.O2, ml·l -¹ 98.33±0.62 94.14±1.41* 76.75±2.57* р1-2<0.01 Da.О2-Dv.O2, ml·l -¹ 50.96±0.66 47.91±0.62* 43.85±0.94* р1-2<0.05 Notes: 1. * – significant differences of indices in comparison with the control, 2. р1-2 – significant differences of indices between two groups of patients. 19 IN T E R N A L m E d Ic IN E ISSN 2413-6077. IJmmR 2017 Vol. 3 Issue 2 For patients with stable ІHD the circulatory hypoxia is of systemic nature, develops in the presence of chronic heart failure and develops in comorbid states [4, 7], type 2 diabetes mel- litus in particular. It was established that in efficiency of oxygen transporting to the tissues of the organism, a functional ability of cardio- vascular system is crucial [8], and that is why a search for effective methods of comorbid states treatment is a topical issue. Conclusions In the examined patients with stable IHD and concomitant type 2 diabetes mellitus more severe impairment of left ventricular diastolic function and the increase of its rigidity, caused by type 2 diabetes mellitus, were revealed. In patients with stable IHD, left ventricular diastolic dysfunction and concomitant type 2 diabetes mellitus the levels of NT-proBNP and uric acid were significantly higher as compared to the patients with IHD without type 2 diabetes mellitus, which means that comorbidity with diabetes mellitus was the reason for more severe diastolic heart failure. In patients with stable exertional angina and concomitant type 2 diabetes mellitus there was obvious oxygen deficiency in peripheral tissues with the decrease in oxygen volume consumed by the tissues of lower extremities, which worsens the course of chronic heart failure. References 1. Arques S. Current clinical applications of spec- tral Tissue Doppler echocardiography as a noninva- sive surrogate for left ventricular diastolic pressures is the diagnosis of heart failure with preserved left ventricular systolic function. Cardiovascular Ultra- sound. 2007;5:28–16. 2. Danzmann LC. Left atrioventricular remodel- ing in the assessment of the left ventricle diastolic function in patients with heart failure: a review of the currently studied echocardiographic variables. Cardiovascular Ultrasound. 2008;6:69–56. 3. Exiara T. Left ventricular diastolic dysfunction in diabetes mellitus type 2. Hypertension. 2010;28: 294–289. 4. Galderisi M. Diastolic dysfunction and dia- betic cardiomyopathy: evaluation by Doppler echo- cardiography. Journal American College Cardiology. 2006;48:1551–1548. 5. Koh M. Management of stable coronary ar- tery disease. European Heart Journal. 2013;38:2949– 2300. 6. Kovakenko VM. Stable ischemic heart disease. Reccomendations of Association of Cardiologists of Ukraine. 2016;1:176–1. 7. Roe MT. Patterns and prognostic implications of blood oxigention in patients with ischemic heart disease. European Heart Journal. 2014;29:2488– 2480. 8. Owan TE. Trends in prevalence and outcome of heart failure with preserved ejection fraction. National England Journal of Medicine. 2012;355: 254–251. Received: 2017-09-08 N. I. yarema et al.