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Kardiologiia

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Vol 58, No 7 (2018)

ISCHEMIC HEART DISEASE

5-13 1120
Abstract
Objective: to analyze long-term outcomes and to develop a model for determining the risk of long-term adverse сardiovascular events after elective percutaneous coronary interventions (PCI). Materials and Methods. We included in this study 148 patients, sent from 2009 to 2011 for routine endovascular intervention for chronic ischemic heart disease on the background of stenotic coronary artery atherosclerosis. Outcomes of interventions were assessed over 6 years after the index PCI by analyzing medical records and telephone interviews. The primary composite endpoint of the study was major adverse cardiovascular event (MACE), including cardiovascular death, acute coronary syndrome (ACS), acute cerebrovascular accident (CVA). Results. Cardiovascular death was registered in 10.6%, acute coronary syndrome occurred in 34.4%, stroke - in 6.6% of patients. Overall МАСЕ occurred in 40.4% of patients. Patients with MACE were initially significantly more likely to have chronic obstructive pulmonary disease (16.4 vs. 4.4%, p=0.02), multifocal atherosclerosis (32.8 vs. 17.8%, p=0.034). They were initially more often diagnosed with atrial fibrillation (AF) (23 vs. 7.8%, p=0.016) and were more likely to have family history of cardiovascular disease (50.8 vs. 24.4%, p=0.0009). They had significantly higher levels of CRP before PCI (6 (5-11.5) vs. 5 (4.7) mg/L, p=0.034) and restenosis of previously installed stent (8.2 vs. 1.1%, p=0.04). Most significant predictors of MACE identified using stepwise logistic regression and included in the developed model were: family history of cardiovascular disease, treatment with statins at time of PCI, initial level of postprandial blood glucose, high risk of contrast induced nephropathy (CIN) (11-15 points on Mehran CIN risk score). AUC values for the found model was 0.852 [95% CI 0.749-0.956]. Conclusion. The use of our model in patients with the upcoming PCI with the aim of stratifying the risk of long-term adverse cardiovascular events allows to identify groups of patients, who require the timely administration of more active follow-up strategies, through the use of simple clinical characteristics.
14-22 951
Abstract
Purpose: to analyze possible associations of clinical and genetic factors with development of ischemic stroke after exacerbation of ischemic heart disease (IHD). Materials and methods: RAe Russian multicenter study aimed at assessment of risk of unfavorable outcomes after exacerbation of IHD "Exacerbation of IHD: logical probabilistic ways to course prognostication for optimization of treatment” (meaning of Cyrillic acronym - oracle) was conducted in 16 centers of 7 cities in Russia. We included into the study 1 208 patients with unstable angina and ST-elevation or non-ST-elevation myocardial infarction (MI). Data on outcomes were known for 1 193 patients, 15 patients were lost for follow-up. Results. Mean duration offollow-up was 644±14.45 (4-1 995) days. Shortest, longest, and mean time before development of stroke was 22, 1433 and 389±56.6 days after inclusion. Patients with strokes were older, more often had history of IHD prior to index hospitalization, arterial blood pressure level compatible with stage 3 arterial hypertension, less often were smokers, and more often had MI recurrences or repetitive episodes of severe ischemia during the index hospitalization. Patients also more often had documented atrial fibrillation during hospitalization, and lower level of glomerular filtration rate. Of studied genetic markers carriage of A allele of polymorphic marker G (-1082) A of interleukin-10 gene was significantly associated with risk of stroke development. Using linear regression analysis, we constructed a model of estimation of the stroke development risk. Comparison of diagnostic value of different scales for stroke risk assessment showed that area under the curve was 0.656, 0.686, and 0.756 for the GRACE, CHA2DS2-VASc, and ORACLE scores, respectively.

ACUTE CORONARY SYNDROME

23-31 858
Abstract
Purpose: to assess changes in the management of patient with ST-Elevation (STE) Acute Coronary Syndrome (ACS) which occurred during recent several years by means of comparing data from the series of Russian ACS registries RECORD - “old” (RECORD and RECORD-2, 2007-2011) and “new” (RECORD-3, 2015). Results. Numbers of included patients were 967 and 868, proportion of invasive centers - 56 and 55% in “old” and “new” registries, respectively. Most anamnestic characteristics of both populations (of old registries group and the new registry) were similar. In RECORD-3 compared with old registers level of troponins was significantly more often determined, median time from symptoms onset until seeking medical help and until hospitalization was higher, and significantly more patients were transferred directly to catheterization laboratory. TTere were no significant differences in rates of primary percutaneous interventions (PCI) and use of thrombolytic therapy (TLT) between “old” registries and RECORD-3: 36.3 vs. 39.0% (р=0.24), 32.2 vs. 32.1% (p=0.98), respectively. However, compared with RECORD (2007-2008) rates of primary PCI, prehospital TTL, use of pharmacoinvasive approach, and any PCI during hospitalization in RECORD-3 were significantly higher: 20 vs. 39% (р<0.0001), 24 vs. 51% (p<0.0001), 25 vs. 52% (р<0.0001), 47 vs. 55% (p=0.0009), respectively. Patients in RECORD-3 during hospitalization significantly more often received dual antiplatelet therapy, enoxaparin, fondaparinux, statin, but significantly less often they were given aspirin, intravenous unfractionated heparin, IIb/IIIa receptor blockers, nitrates, and loop diuretics. Rates of mortality as well as sums of the following events: “death + myocardial infarction [MI]”, “death + MI + stroke” in RECORD-3 and “old” registries did not differ significantly: 9.8 vs. 11.4% (р=0.27), 12.4 vs. 14.6% (р=0.18), 13.0 vs. 15.2% (р=0.18), respectively. But rate of new MIs during hospitalization in RECORD-3 was significantly lower: 3.5 vs. 5.8% (p=0.019). Conclusion. Russian ACS registry RECORD-3 revealed some improvement of treatment of patients with NSTEACS compared with older registries RECORD and RECORD-2. However, there were no significant changes of primary PCI, TLT rates, and of hospital mortality, while rate of inhospital MIs significantly decreased.
32-40 719
Abstract
Purpose: to study the role of clinical factors and treatment tactics in the development of adverse outcomes in patients with non-ST-elevation acute coronary syndrome (NSTEACS) for five years follow up. Materials and Methods. The study included 415 patients with NSTEACS observed for 60±4 months from the date of discharge. Adverse events (AE) were unstable angina (UA), myocardial infarction (MI), ischemic stroke or patient’s death. The favorable 5-year outcome was identified in 200, adverse outcome - in 178 patients. Statistical processing was performed using STATISTICA 8.0 software package and MedCalc 11.0. Results. Total mortality for 60 months was 16.1% (n=61). Highest mortality, maximal number of hospitalizations due to MI (41.1%) and UA (49.6%) were observed during first 12 months. Greatest impact on the development of AE produced: history of MI, higher GRACE score, age >54 years (p=0.0021), stenosis in brachiocephalic arteries, ischemic changes on admission ECG and reduced left ventricular ejection fraction (LVEF) < 52% (p=0.0001). Five-year survival rate was influenced by coronary angiography (p=0.0001) and percutaneous coronary intervention (PCI) during index hospitalization (p=0.0039). Discussion. Mortality and frequency of AE in this register were close to generally reported. The observed adverse impact on the long-term outcome of such risk factors such as age over 60 years, history of MI, ischemic ECG changes at admission, decreased LVEF corresponded to literature data. Our study proved the need for coronary imaging in patients with NSTEACS to determine treatment strategy in in hospital period as these factors affected the 5-year survival. Conclusion. During five-year follow-up AE occurred in 47.1% of patients with NSTEACS. Maximal number of patients with AE was registered during the first (24.7%) and fifth (13.8%) year of observation. The development of AE was associated with older age, history of MI and coronary artery bypass grafting, ischemic ECG changes, decreased LVEF, higher GRACE score, and brachiocephalic artery stenosis. Carrying out diagnostic coronary angiography and PCI with stenting during hospitalization in patients with NSTEACS was associated with favorable 5-year outcome.
41-52 1070
Abstract
Purpose: to study elucidate association of active cytomegalovirus (CMV) infection with endothelial dysfunction in patients with acute myocardial infarction (AMI). Materials and Methods. The study included 42 volunteers without ischemic heart disease (IHD) and 63 patients with AMI. Blood samples for analysis of the deoxyribonucleic acid (DNA) of CMV in plasma by real-time polymerase chain reaction were taken in patients - before coronary angiography, in volunteers - at admission. In addition, in patients with AMI and volunteers without IHD, endothelial function was analyzed using endothelium-dependent vasodilatation (EDVD) test of the brachial artery. Results. We showed that in patients with AMI, the concentration of CMV DNA in plasma was statistically significantly increased when compared with that in volunteers without IHD, which reflects active CMV infection - 1185.7 (0; 3003.0) vs. 0 (0; 910.8) copies of DNA/ml plasma (p=0.011). In comparison with volunteers without IHD, patients with AMI also more often had endothelial dysfunction - 11.5 (7.5, 15.2) % vs. 4.4 (0; 9.6) % of cases (p<0.0001), what significantly correlated with activity of CMV production (R= -0.35, p=0.002). Discussion. In patients with AMI, in addition to disturbance of endothelial function in the acute phase of the disease, increased production of cytomegalovirus DNA was also detected. In this study, for the first time found a negative correlation between the activity of cytomegalovirus infection and endothelium-dependent vasodilation, not only in healthy volunteers, but also in patients with AMI. The relationship between CMV activation and endothelial dysfunction can explain the role of cytomegalovirus in the development of complications of atherosclerosis due to the activation and damage of endothelial cells infected by it. Conclusions. In this study, we confirmed the presence of endothelial dysfunction and active CMV infection in patients with AMI. We found a negative correlation between the activity of CMV infection and EDVD in volunteers without IHD and patients with AMI.

PULMONARY HYPERTENSION

53-58 1090
Abstract
Aim: to study lung diffusion capacity and efficiency of pulmonary ventilation in patients with chronic thromboembolic pulmonary hypertension (CTEPH) depending on the severity of pulmonary hypertension. Materials and Methods. The study included 139 patients with CTEPH. The parameters of body plethysmography, lung diffusion capacity, efficiency of pulmonary ventilation and their interrelation with results of angiopulmonography were assessed. Results. Patients were divided according to systolic pulmonary artery pressure (SPAP): group 1 - < 50, group 2 - 50-80, group 3 - > 80 mm Hg. The lung diffusion capacity and the efficiency of pulmonary ventilation in patients with CTEPH were reduced against the background of normal spirometric parameters, most pronouncedly in group 3. Regression analysis revealed an inverse relationship between severity of pulmonary hypertension and lung diffusion capacity (regression coefficient -13.7 [-19.1; -8.3], p<0.001), pulmonary ventilation efficiency (regression coefficient -1.4 [-3.5; -0.1], p=0.046), and arterial oxygenation (regression coefficient -1.3 [-2.0; -0.7], p=0.001). Conclusion. In patients with CTEPH against a background of normal basic spirometric parameters, the lung diffusion capacity and efficiency of pulmonary ventilation were significantly decreased, most pronouncedly at SPAP > 80 mm Hg. The results of the study demonstrate the close relationship between pulmonary hypertension and respiratory ventilation-diffusion disorders in patients with CTEPH.

CARDIAC ARRHYTHMIAS

59-65 1031
Abstract
Background. Epicardial adipose tissue (EAT) has certain paracrine functions, which could be associated with proinflammatory and fibrotic changes in myocardium even in patients without structural heart disease but with atrial fibrillation (AF). Purpose: to evaluate interrelationship between clinical data, parameters of tissue Doppler imaging (TDI), EAT thickness estimated by magnetic resonance imaging (MRI), and biochemical markers of fibrosis and inflammation in patients with nonvalvular AF without concomitant ischemic heart disease (IHD). Materials and Methods. We included in this study 39 AF patients without valvular pathology or IHD with normal or moderately increased left atrial (LA) dimension (mean age 50.8±13.9 years, 49% men). The following groups were distinguished for analysis: with idiopathic AF (iAFgroup, n=21); with AF and arterial hypertension (AF+AH group, n=18); with normal (<4.5cm) (n=29), and with slightly enlarged (>4.5cm) LA dimensions (n=10). Besides standard ECG and echocardiography (ECHO), all patients underwent TDI and cardiac MRI with late gadolinium enhancement (LGE). Periventricular EAT thickness and LA fibrosis were calculated by MRI. Examination also included measurement of levels of matrix metalloproteinases (MMP-2, MMP-9), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), transforming growth factor β1 (TGF-β1), and soluble intercellular adhesion molecule (sICAM). Results. Most close correlations were found between EAT thickness and levels of the following biomarkers were found to closest: MMP-9 (τ=0.65; Tcr=0,16), TIMP-1 (τ=0,71; Tcr=0,18) in iAF group; and TGF-β1 (τ=0.22; Tcr=0.19) in the whole group. The LA fibrosis (%) was associated with TIMP-1 with strongest correlation in iAF group (τ=0.72; Tcr 0.21). Myocardial mass was significantly associated with TGF-β1 in the group with LA<4.5cm (τ=0.92, Tcr 0.14), and with LA>4.5cm (τ=0.81, Tcr 0.24). E/e’ by TDI correlated with levels of MMP-9 and TIMP-1 (τ=0.65, Tcr=0.16, and τ=0.56, Tcr=0.21, respectively), and with TGF-β1 being closest in the group with LA <4.5 cm (τ=0,57; Tcr 0,14). Among clinical factors body mass was slightly associated with EAT (τ=0.33, Tcr=0.26). Conclusion. The EAT and LA fibrosis by LGE MRI is significantly associated with markers of fibrosis (MMP-9, TIMP-1, TGF-β1 in patients with AF without structural heart disease. Elevation of MMP-9 and TIMP-1 levels are associated with LV diastolic dysfunction in these patients, what can reflect initial signs of atrial cardiomyopathy even in patients with nonvalvular “nonischemic” AF with normal or slightly enlarged LA.

EXPERIMENTAL CARDIOLOGY

66-76 1425
Abstract
Aim. To study effects of intravenous infusion of a cardioprotective drug metilin, developed at the “National Medical Research Center of Cardiology” on indices of cardiac function in rabbits in vivo after prolonged administration of doxorubicin. Materials and Methods. Animals of the experimental group were intravenously injected with doxorubicin (2 mg/kg once a week) for 8 weeks, animals of the control group received the same volume of saline. Myocardial damage was characterized by an increase in concentration of malondialdehyde (MDA), troponin (TnI) and MB-fraction of creatine kinase (CK-MB) in venous blood and by disturbances in the left ventricle (LV) structure at morphological examination. Metilin effects on cardiac function were assessed by echocardiography and LV catheterization by the Millar catheter tip pressure transducer. Results. Doxorubicin administration led to a decrease of the body mass of animals, an increase of the plasma concentration of cardiac markers CK-MB and TnI, lipid peroxidation (LPO) product MDA in venous blood, and pronounced disturbances in the structure of LV fibers and microvessels. At the same time, a significant decrease of myocardial contractility indices was observed. Manifestations of this decrease were increase of the end-diastolic and end-systolic dimensions (EDD and ESD, respectively), and decreases in the shortening fraction and ejection fraction (SF and EF, respectively) com pared to baseline values. These changes indicated development of chronic heart failure (CHF) in animals of the experimental group. Against this background, intravenous infusion of metilin significantly increased SF and EF, but did not affect the heart rate. Beneficial effects of metilin on the indices of cardiac contractility and relaxation were maintained after the infusion was stopped. Noteworthy, metilin exerted greater influence on cardiac function of rabbits with CHF compared to control animals that did not receive doxorubicin. Conclusion. The obtained results indicate the potential of metilin to reduce LV dysfunction during chemotherapy with doxorubicin.

MISCELLANEOUS

77-84 841
Abstract
Purpose: to investigate associations of single nucleotide polymorphisms (SNPs) rs2046934, rs1126643, rs5918, rs6065, rs4244285; rs4986893 with cardiovascular complications (CVC) in patients after CABG. Materials and Methods. We enrolled in this study 130 patients with stable functional class II-IV angina. After CABG 69 patients received ASA (100 mg of enteric form), 61 patients received dual antiplatelet therapy (ASA 100 mg + clopidogrel 75 mg). Mean follow up period was 10.9±5.2 months. The primary composite endpoint included all-cause mortality, myocardial infarction (MI), and ischemic stroke. The control group comprised 185 healthy volunteers. Platelet function was assessed using light transmission aggregometry with ADP (5^M) and arachidonic acid (1 mM). The following single nucleotide polymorphisms (SNPs) were identified by real-time PCR: rs2046934 (H1/H2) on P2RY12 [encoding platelet ADP receptor] (n=100); rs1126643 (C807T, Phe224Phe) on ITGA2 [encoding collagen receptor] (n=87); rs5918 (176 T-kC, Leu33Pro) on ITGB3 [encoding fibrinogen receptor) (n=91); rs6065 (Thr145Met) on GP1BA [encoding platelet receptor for Von Willebrand factor] (n=114); rs4244285 (*2) (n=84), and rs4986893 (*3) (n=83) on CYP2C19 [encoding cytochrome P450 activity]. Results. The prevalence of rs5918, rs6065, rs4244285, rs4986893, rs2046934 did not differ significantly between patients and healthy volunteers. The mutant allele (T ) of ITGA2 was detected more often in healthy volunteers: 67.2% vs 51.7% (р=0.021). Before and after CABG there was no significant difference in platelet aggregation between carries and non-carries of the mutant ITGA2 allele. Number of CVCs registered during follow-up was 12: 3 strokes, 6 MIs, 3 deaths. Patients with composite mutant alleles of ITGB3+СYP2C19*2 or СYP2C19*2+ITGA2, and with the mutant allele (*2) of CYP2C19 met end points more often than patients with other gene combinations (wild type homozygotes, presence of one mutant allele of ITGB3 or ITGA2, the composite of mutant alleles of ITGB3+ITGA2 or ITGB3+ITGA2+ СYP2C19*2) (hazard ratio 4.0, 95% confidence interval 2,19-7.29, р=0.008). Carriers of ITGB3 mutant allele showed higher AA-induced platelet reactivity on the 1st-3rd day after CABG. Amplitude of platelet aggregation in carriers of mutant allele was 27.5% vs 12.7% in wild type (p=0.016). No differences in platelet reactivity among carriers of other mentioned mutant alleles and wild types were observed. Conclusion. Carriage of the combination of mutant alleles ITGB3+СYP2C19*2 or СYP2C19*2+ITGA2 or СYP2C19*2 is possible predictor of CVC in patients after CABG.

PRACTICAL CARDIOLOGY SUPPLEMENT FOR PRACTISING PHYSICIANS. CLINICAL SEMINARS

85-94 3097
Abstract
In this article we present data of scientific studies of prevalence of diabetes mellitus (DM) among patients with chronic heart failure (CHF), pathogenetic and risk factors of CHF development patients with DM (hyperglycemia, elevated body mass index, age, ischemic heart disease, nephropathy, proteinuria, DM duration, etc.). The article also contains results of analysis of mortality of patients with and without DM in dependence of ejection fraction value. After characterization of drugs for treatment of CHF in general and specifically in patients with DM we make focus on perspective directions in treatment of this group of patients. Sodium-glucose co-transporter 2 (SGLT2) inhibitors can be effective in patients with DM and CHF, in the first place empagliflozin with proven positive cardiac effects. In obese patients with and without DM efficacy of treatment at the background of lifestyle modification with the help of weight reduction, physical exercise, diet etc has been shown to be effective. In addition, there are data on positive effects of metformin which in patients with CHF and DM lowers availability of energy substrate at the account of reduction of volume of endogenous glucose.
95-100 1084
Abstract
Ee article contains the review of current understanding of the etiology and pathogenesis of degenerative aortic stenosis, approaches to surgical treatment depending on various factors, e. g. severity of defect and comorbidity, description of endovascular techniques (balloon valvuloplasty and transcatheter aortic valve implantation), and features of the selection of patients for these procedures. Ee authors also present assessment of results of operations performed from 2011 to 2016 in the city hospital № 2 in Saint-Petersburg. ^ey analyze data from 72 high-risk aortic stenosis patients aged 81±6 years treated with transcatheter aortic valve implantation. In 68 out of 72 patients (94.4%) clinical improvement was achieved with reduction of dilation of left ventricular cavity, decrease of functional class of heart failure, and decrease of mean pressure gradient across the aortic valve. A conclusion is made that these results confirm advantages and perspectives of the use of endovascular methods of treatment in this complicated group of patients.


ISSN 0022-9040 (Print)
ISSN 2412-5660 (Online)