Author Archives: Vitali Nesukaj

L.K. Sokolova, V.M. Pushkarev, O.I. Kovzun, V.V. Pushkarev, M.D. Tronko Diabetes and atherosclerosis: epigenetic mechanisms of pathogenesis. A review

The review summarizes and analyzes epigenetic changes accompanying cardiovascular complications in diabetes. Data on the participation of epigenetic modifications in pathological changes of endothelial cells, smooth muscle cells and macrophages leading to atherosclerosis are presented. The role of various miRNAs in the differentiation, activation, inflammation, proliferation and migration of vascular cells is described. It has been shown that histone modifications, DNA methylation and miRNA spectrum change participate in the initiation and development of cardiovascular diseases in diabetes, and their study and application of the acquired data has great diagnostic, prognostic, and therapeutic potential.

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M.V. Hrebenyk, S.М. Masliy Clinical experience of pharmacotherapy of arrhythmias: focus on ethacizine – effectiveness and safety profile

The aim – to evaluate the place of ethacysin in the contemporary treatment of arrhythmias by means of retrospective analysis of 30 years experience in the treatment of heart rhythm disorders in a cohort of cardiorheumatology patients, including comorbidity with diabetes mellitus and chronic obstructive pulmonary disease; to investigate catamnesis and survival of these patients for 15 years.

Material and methods. A 30 years’ experience of treatment of extrasystoles and paroxysmal / persistent atrial fibrillation (AF) with ethacizine in 74 patients without significant structural heart disease has been analyzed retrospectively. Maximal duration of continuous therapy was 12 years, maximal duration of intermittent therapy was 20 years. In different periods, ECG, Holter ECG monitoring, echocardiography, heart rate variability analysis, dispersion of repolarization, late ventricular potentials, exercise stress testing, pharmacological tests were used along taking into account underlying condition and monitoring of treatment effectiveness.

Results. The use of ethacizine was effective in 71.3 % of patients, including AF interruption – in 61.7 %, ventricular ectopy control – in 78.9 %, maintenance of sinus rhythm in patients with paroxysmal AF – in 58.4 % cases. Therapy was more effective in vagus-mediated AF in which the use of antiarrhythmic agents is limited. No serious adverse events were registered throughout the whole period of observation, indicating at acceptable ethacizine safety profile. Most of adverse reactions were predictable (22.7 %) and described in the medication insert. These were related to the antiarrhythmic effect and might be classified into 3 categories: 1) general, extracardiac (4.5–9.1 %); 2) associated with electrophysiological effect upon myocardium (18.1 %), considered to be within the normal limits; 3) occasional cases (right bundle branch block, Brugada type 1 ECG pattern, asymptomatic episode of ventricular tachycardia), leading to the discontinuation of the drug.

Conclusions. Overall, ethacizine was effective and safe even for the long-term use provided the patients are selected properly (those without significant structural heart disease) and the recommended algorithm of use and control is followed.

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E.G. Nesukay, I.I. Giresh Dynamics of left heart deformation parameters in patients with essential hypertension under long-term treatment

The aim – to investigate remodeling of left heart chambers in patients with essential hypertension and left ventricular hypertrophy (LVH) under one-year treatment with renin-angiotensin system blockers by means of longitudinal, circular deformation of left ventricle (LV) myocardium and contractile, reservoir and conductive functions of left atrium (LA).

Material and methods. The study involved 64 patients (women – 56 %) with arterial hypertension. Patients were divided into groups. 22 patients receiving angiotensin II receptor blockers (ARB), mean age 57.5±1.6 years, constituted group 1. The 2nd group included 26 patients on angiotensin-converting enzyme inhibitors (ACEI), mean age 59.4±1.4 years. Besides, patients were divided depending on LVH severity: group A was presented by 35 patients with mild and moderate LVH; group B – 13 patients with severe LVH. In all patients we performed echocardiography and speckle tracking echocardiography with analysis of longitudinal global systolic strain (LGSS), circumferential global systolic strain (CGSS) and their rates, early (EDSR) and late LV diastolic strain, LA early and late diastolic SR, LA systolic deformation (LASD).

Results and discussion. Longitudinal contractile LV function improved under treatment. This was supported by LGSS increase by 6 and 5 % in groups 1 and 2, respectively. When diastolic function was analyzed, EDSR was found to be higher by 6 and 4 % in groups 1 and 2, respectively at the end of observation period. Also, LASD was revealed to be higher in groups 1 and 2 by 9 and 8 %, respectively, compared to that before treatment. Thus, treatment with ARBs and ACEIs resulted in improvement of both systolic and diastolic functions of LV and reservoir LA function.

Conclusion. In groups A and B myocardial mass index decreased by 5 and 10 %, respectively. In the group with severe LVH along with longitudinal improvement CGSS reliably increased by 10 % compared to that before treatment.

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N.V. Ponych Regression of left ventricle hypertrophy in patients with critical aortic stenosis after aortic valve replacement

The aim – to determine the predictors of regression of left ventricular hypertrophy (LVH) in patients with critical aortic stenosis (AS) after aortic valve replacement (AVR).

Material and methods. In one-center study, the results of a prospective observation in 119 patients with AS sequentially examined before and 6–12 months after the AVR surgery were analyzed. Among them were 74 (62.2 %) men and 45 (37.8 %) women, median age 63 years (quartiles 56.5–72.0 years). All patients underwent clinical, laboratory and instrumental studies before the operation, including transthoracic echocardiography (TTE) and coronary angiography. Depending on the changes of the left ventricular myocardial mass index (IMM LV) 6–12 months after AVR, all patients were retrospectively divided into two groups: in 52 (43.7 %) patients, the relative decrease in the IMM LV was from 0 to 30 %, and in 67 (56.3 %) – more than 30 % (maximum – 63 %).

Results. Median relative decrease of IMM LV after AVR after 6–12 months was 32.31 % (quartiles 23–40 %). Patients with less dynamics of IMM LV were characterized by a greater frequency of concomitant hypertension, angina pectoris and a large number of hemodynamically significant stenoses of the coronary arteries. The group of patients with large LVH regression was characterized by larger volume of the left atrium, larger IMM LV, lower initial left ventricular ejection fraction (LVEF), higher Tei index, lower MAPSE and systolic wave s, longer corrected QT interval. According to the multivariate analysis, the predictors of more severe LVH regression were the initial IMM LV, LVEF, mitral regurgitation, the duration of the corrected QT interval, and the absence of concomitant multivessel lesions of the coronary arteries. The accuracy of the prediction of the group with weaker dynamics of the IMM LV was 73.3 %, with a pronounced LVH regression – 79.7 %, the overall accuracy of the model was 76.9 %.

Conclusions. The severity of the IMM LV decrease is one of the most important indicators of the long-term effect of AVR in patients with critical AS. Output LVM, LVEF, mitral regurgitation, the duration of the corrected QT interval, and the absence of concomitant multivessel coronary artery lesions are independent predictors of a more favorable dynamics of IMM LV 6–12 months after AVR.

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Yu.I. Zalizna, K.O. Mikhaliev, O.J. Zharinov Predictors of arrhythmia recurrence after the first episode of atrial fibrillation during 6-months follow-up

The aim – to determine the clinical, anamnestic characteristics and indicators of the structural and functional state of the myocardium, which may predict arrhythmia recurrence in patients with reverse episode of the first-diagnosed atrial fibrillation (AF) during 6-months follow-up.

Material and methods. Among 124 patients with first diagnosed AF in 88 patients AF episode terminated with sinus rhythm restoration. In order to compare the baseline clinical, anamnestic and instrumental characteristics, groups of patients with (n=44) and without (n=44) documented recurrence of AF were formed retrospectively. In these groups, the frequency of detection of risk factors, concomitant diseases, laboratory parameters, the course of the first episode of AF, data on echocardiography, and daily ECG monitoring after recovery of sinus rhythm were compared. Multifactor analysis was performed to determine the independent predictors of AF relapse.

Results.The relapsing course of AF is associated with older age, higher incidence of certain concomitant diseases, in particular, heart failure, hypertension and diabetes, and more severe left ventricular hypertrophy. The most significant predictors of the occurrence of arrhythmia recurrence after the first episode of AF after the restoration of sinus rhythm were CHA2DS2-VASc score (≥ 2 versus 0: odds ratio (OR) 3.135 (95 % confidence intervals (CI) 1.341–7.333); Р=0.008) and C-reactive protein level (≥ 6 mg/L versus < 6 mg/L: OR 3.041 (95 % CI 1.656–5.584) P<0.001). Conclusions. During 6-months follow-up arrhythmia recurrence was registered in 50 % patients with first episode of AF. Independent predictors of the AF recurrence were CHA2DS2-VASc score two or more, as well as the CRP ≥ 6 mg/L. These aspects should be taken into account at individualized assessment of the need for antiarrhythmic and antithrombotic therapy in patients with first detected AF after restoration of sinus rhythm.

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T.V. Mikhalieva, O.S. Sychov, T.V. Getman, V.G. Gurianov, K.O. Mikhaliev Predictors of arrhythmia recurrence in patients with non-valvular atrial fibrillation after sinus rhytmh restoring: the role of the rs10465885 polymrphism in connexin-40 gene

The aim – to determine the predictors of arrhythmia recurrence in patients with non-valvular atrial fibrillation (AF) after the sinus rhythm (SR) restoring, and to establish the role of the rs10465885 polymorphism in connexin-40 (Cx40) gene.

Material and methods. We enrolled 104 patients (pts) with non-sustained non-valvular AF (average age (53±10) years, 80 (76.9 %) men). The distribution of rs10465885 polymorphic variants in Cx40 gene (n=73) was as follows: TT – 17 (23.3 %) pts, CT – 33 (45.2 %), СС – 23 (31.5 %). We analyzed 122 cases of SR restoring: 32 (26.2 %) – pharmacological cardioversion (29 pts); 63 (51.6 %) – electrical cardioversion (ECV) (53 pts); 27 (22.2 %) – radiofrequency catheter ablation (RFA) (22 pts). The follow-up median was 23 months. According to the phenotypic parameters, associated with rs10465885, the sample of 104 pts (122 SR restoring cases) was stratified into 4 phenotypic clusters (PC): PC1 – 43 pts (57 SR restoring cases), PC2 – 24 (26); PC3 – 18 (20); and PC4 – 19 (19). According to PC and rs10465885 status (carriage or relatively high probability of non-CC or CC variant), the sample of 104 pts (122 SR restoring cases) was stratified into 4 integral clusters (IC): IC1 (PC1 + non-СС) – 26 pts (32 SR restoring cases); IC2 (PC1 + СС) – 17 (25); IC3 (combined group [РC234] + non-СС) – 49 (50); IC4 (РC234 + СС) – 12 (15).

Results. The risk of AF recurrence after ECV was 1,429 times higher than that of RFA. In addition, the risk of AF recurrence after restoration of SR in patients with the CHA2DS2-VASc scale score 1 was 1,550 times lower than in patients with 0 and ≥ 2 score. PC1, in comparison with PC234, was associated with a higher frequency of rs10465885 СС variant (taking into account the pts with a relatively high probability of СС carriage). PC1 was presented mainly by men under 40 years of age, with no pronounced structural and functional changes of the left ventricle. Additionally, PC1 was characterized by an earlier AF onset, the higher prevalence of subclinical AF, and a lower risk of stroke by the CHA2DS2-VASc scale. IC2 (vs IC4) was most significantly associated factor with the AF recurrence at 90 and 180 days after SR restoring.

Conclusions. The variant of SR restoring and the CHA2DS2-VASc score were the predictors of AF-free survival. The carriage (or relatively high probability of carriage) of the polymorphic variant rs10465885 СС in Cx40 gene additionally increases the risk of arrhythmia recurrence at the 3- and 6-month follow-up after SR restoration in patients with non-valvular AF and the PC1 features (as compared to PC234).

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L.G. Voronkov, O.L. Filatova, A.V. Lyashenko, N.A. Tkach, N.G. Lipkan Predictors of 24-month survival in patients with chronic heart failure and reduced left ventricular ejection fraction depending on gender

The aim – to compare survival rates and predictors of the onset of lethal outcome in men and women with chronic heart failure (CHF) with reduced left ventricular ejection fraction (LVEF) during 24-months follow-up.

Material and methods. 356 patients with ischemic CHF (NYHA II–ІV) and LVEF < 40 % were examined. Cumulative survival was calculated by Kaplan – Meier method. Comparison of survival in groups was performed by Mantel – Cox test. Predictors of survival were determined by multiple logistic regression. Cut-off values of clinical variables associated with non – survival during 24 months of follow-up were determined. Results. Analysis of survival in patients with CHF and reduced LVEF showed that cumulative survival at the end of 24 manth of follow-up was not significantly different (P=0.092), 68 % in men and 72 % in women. Factors associated with poor prognosis varied significantly depending on gender. We determined indicators associated with poor survival by cluster analysis. In men these were: left ventricle free wall thickness < 0,75 сm, ureic acid > 627 mkmol/L, LVESV index > 110 cm/m2, LVEF < 25 %, LVEDV > 340 mL (ОR 6.8–5.7). In women, these were glucose level > 11,4 l/L, LVESV > 287 mL, LVEDV > 302 mL, LVESD > 6,5 cm, IVS thickness less than 0,7 cm, LVEDV index > 176 cm/m2 (ОR 16.2–11.2).

Conclusion. Survival of men and women with CHF and reduced LVEF during 24-month of follow-up not significantly different, while predictors of lethal outcome are different.

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N.D. Oryshchyn, Yu.A. Ivaniv Predictors of ischemic mitral insufficiency in patients with systolic left ventricular dysfunction after myocardial infarction of different localization

The aim – to estimate the role of geometric parameters of mitral valve deformation and remodeling of the left ventricle (LV) in the formation of mitral insufficiency in patients with systolic dysfunction after myocardial infarction (MI) of different localization.

Material and methods. We assessed 99 patients with left ventricular (LV) systolic dysfiunction after MI with mild to severe mitral insufficiency. We evaluated mitral insufficiency by means of echocardiography through determining EROA (effective regurgitant orifice area), assessed indexes of LV global and local remodeling. mitral insufficiency was moderate and severe in 36 patients with anterior MI (group 1) and in 43 patients with inferior/posterior MI (group 2), the control group consisted of 21 healthy individuals.

Results. In both groups of patients rates of global and local LV remodeling were significantly higher than in the control group (P<0.0001). Sphericity index was significantly higher in group 1, compared to group 2 (P=0.003). The indexes of local remodeling were significantly higher in group 1, especially anterior papillary muscle (PM) tethering distance (Р=0.03), posterior displacement of the anterior PM (Р=0.03), PM height (Р=0.01), interpapillary distance (Р=0.02). Correlation between EROA and sphericity index in group 1 was revealed (Kendall τ 0.46, P<0.0001), in group 2 this correlation was weak (Kendall τ 0.23, Р=0.016). In group 1 correlation of EROA with anterior and posterior PM tethering distance was revealed (Kendall τ 0.41 and 0.52, P<0.0001). In group 2 EROA correlation with posterior PM tethering distance and anteroposterior mitral valve diameter was revealed (Kendall τ 0.36 and 0.48, P<0,0001). Correlation between EROA and inferior apical segment akinesia and WMSI of posterior PM was revealed in group 1 (Kendall τ 0.71 and 0.51, P<0.0001), and relation between mitral insufficiency and obstructive lesion in circumflexus (Cx) and right coronary artery (RCA) (Р=0.0008 та Р=0.002) in this group. Conclusions. LV spherisation and PM dislocation are more pronounced in ischemic CMP after anterior MI, compared to inferoposterior MI. Apical and posterior PM displacement, akinesia of inferior apical segment, Cx and RCA obstruction are major determinants of ischemic mitral insufficiency after anterior MI, while posterior PM tethering and anteroposterior mitral annular dilatation are determinants of mitral insufficiency after inferoposterior MI. The obtained data might determine surgical approaches in ischemic mitral insufficiency of different mechanisms.

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V.Y. Tseluyko, O.D. Yarova Results of Holter ECG monitoring in patients with atherosclerosis of the arteries of lower extremities and factors associated with the revealed disorders

The aim – to evaluate the results of ECG daily monitoring in patients with peripheral arterial disease (PAD) of the lower extremities and to investigate association with clinical and genetic (T(–786)C polymorphism of the eNOs gene promoter parameters.

Material and methods. The study involved 100 men with lower extremities PAD, average age 60.7±0.9 years. We performed Holter monitoring, echocardiography, Doppler ultrasound of the lower extremities and carotid arteries, selective coronary angiography. The study of allelic polymorphism of eNOs gene promoter was performed by polymerase chain reaction.

Results and discussion. The patients were divided into 2 groups: I – 63 (63 %) without ischemic heart disease (IHD), ІІ – 37 (37 %) patients with IHD. Decreased glomerular filtration rate (GFR), which was more often recorded in group II, was related to the ventricular arrhythmias (Р=0.03) and atrial fibrillation (Р=0.02). Supraventricular arrhythmias were found in 42 patients. Patients of the II group, in which supraventricular arrhythmias were registered, more often were carriers of C allele (Р=0.008). Ventricular arrhythmias were detected in 27 patients. Among them, patients with concomitant coronary artery disease were more likely to be carriers of C allele (Р=0.002). There was a relationship between atrial fibrillation and angina (Р=0.045), past myocardial infarction (MI) (Р=0.02, including repeated one, Р=0.0001), decrease in GFR (Р=0.02). Conduction defects were more often recorded in group II (Р=0.01).

Conclusions. Ischemic ECG changes are significantly associated with the younger age (Р=0.045), the earlier onset of PAD (Р=0.02), the presence of the C allele the polymorphism eNOs promoter gene (Р=0.002), symptoms of carotids damage (p=0.004) and suffered acute cerebrovascular disorders (Р=0.007). According to Holter ECG monitoring, arrhythmias and blockades were detected in both clinical groups.

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