[The evolution of myocardial infarction treatment over the past decades. The significance of E.I. Chazov works].

The review is a brief historical insight into the study of myocardial infarction, in which the main discoveries are analyzed that have played an important role in improving the diagnosis and treatment of the disease. A special place in the review is occupied by the work of the outstanding cardiologist and health care organizer E.I. Chazov. More than the half - age, E.I. Chazov investigated various aspects of myocardial infarction, organized a system of medical care for heart attack at all stages. Many studies E.I. Chazov are recognized worldwide.

[Carotid Plaque Instability in Patients With Acute Coronary Syndrome as Assessed by Ultrasound Duplex Scanning].

AIM: to study carotid plaques structure in patients with acute coronary syndrome by ultrasound duplex scanning. MATERIALS AND METHODS: We included in this study143 patients with acute coronary syndrome (ACS) aged 32-83 years and 28 patients with documented coronary heart disease (CHD) aged 46-83 years. Duplex scanning of carotid arteries was carried out with Philips iU22 ultrasound system and L9-3 linear array transducer. Atherosclerotic plaques in CCA, CCA bifurcation, and ICA from right and left side were investigated. Off-line analysis of B-mode images and plaque gray scale median (GSM) was performed with computer semiautomated workstation MultiVox. RESULTS: 378 plaques of ACS and 59 plaques of CHD patients were studied. We assessed traditional (heterogenous structure, hypoechogenic component, irregular plaque surface) as well as additional (positive remodeling, "layered" structure of plaque, local calcification) criteria of plaque instability. In ACS compared with CHD group there were more plaques with hypoechogenic component (43.4 and 28.8%, p=0.0459), heterogenous structure (77.8 and 64.4%, p=0.0327), irregular surface including irregularities more than 2.0 mm (22.5 and 6.8%, p=0.0048, respectively). There was significant difference in "layered" structure (55.7 and 35.8%, p=0.0011) and insignificant difference in positive remodeling (16.3 and 7.5%, p=0.06, respectively). There were no differences of GSM value (53.1 and 57.2, p=0.24) and local calcification (23.2 and 24.5%, p=0.23, respectively). CONCLUSION: In our study ultrasound duplex scanning revealed that signs of plaque instability in carotid arteries in patients with ACS were more frequent than in patients with stable CHD. The newly introduced parameter "layered" structure of atherosclerotic plaque was found to be most significant.

[Myocardial Hypoenhancement on Multidetector Computed Tomography in Patients With Non-ST Elevation Acute Coronary Syndrome].

The purpose of our study was analysis of myocardial hypoenhancement areas (MHAs) found by multidetector computed tomography (MDCT) in patients with non-ST elevation acute coronary syndrome (NSTEACS) and comparison of these findings with results of standard methods of diagnostics of myocardial infarction and ischemia [electrocardiography (ECG) and echocardiography (ECHO)]. METHODS: MHAs were found in 18 of 21 patients with non-ST segment elevation myocardial infarction (NSTEMI) (85.7%) and only in 3 of 22 patients with unstable angina (UA) (13.6%, p.

Platelet subpopulation bearing leukocyte specific antigen and tissue factor.

Platelets bearing leukocyte antigen CD45 were identified in the blood of patients with myocardial infarction (MI) and healthy donors by flow cytofluorimetry. Part of these platelets contained tissue factor (TF)-primary initiator of blood clotting. The number of CD45+ and CD45+/TF+ platelets in MI patients at the first day was comparable with their level in healthy donors, but was increased at 8-12 days after MI onset. At that time in some patients the amount of CD45+ and CD45+/TF+ platelets reached 5-6 and 2-3% of their total number. It is assumed that CD45+/TF+ platelets could be formed as a result of platelet interaction with leukocytes or leukocyte produced membrane microparticles.

[Combined Effect of Genetic Factors, Age, and Smoking on the Risk of Developing Myocardial Infarction].

OBJECTIVE: to elaborate a complex model for myocardial infarction (MI) risk assessment considering the combined effect of genetic predisposition, age and smoking. MATERIALS AND METHODS: The study included two independent samples of ethnic Russians: 325 patients with MI and 185 individuals without history of cardiovascular diseases (controls) from the Moscow region, and 220 patients and 197 controls from the Republic of Bashkortostan. Genotyping of polymorphic loci of genes CRP (rs1130864), IFNG (rs2430561), TGFB1 (rs1982073), FGB (rs1800788) and PTGS1 (rs3842787) was performed. To construct the predictive models, we used logistic regression with stepwise inclusion of variables. The predictive value was evaluated by the area under the curve (AUC) in a ROC-analysis. The factor was considered as a marker at pAUC <0.05 calculated by the method of DeLong. The marker was considered effective at AUC >0.60. RESULTS: Three separate genetic variants FGB rs1800788*T, TGFB1 rs1982073*TT, CRP rs1130864*TT, and biallelic combination IFNG rs2430561*A + PTGS1 rs3842787*T whose association with MI we described earlier, were used to construct the composite genetic marker (AUC=0.66 in the training and test samples) by the logistic regression method. Adding to the obtained composite genetic marker such parameters as age and smoking allowed to create a complex MI risk marker, which was characterized by the predictive value stability (AUC=0.77 in the training sample and 0.82 in the test sample). CONCLUSION: The obtained complex model for MI risk assessment was reproduced in two independent samples of Russian ethnicity individuals from different regions of Russia with different gender identities, and allowed to have a reasonable chance (about 80%) of distinguishing patients and healthy individuals.

[Comparison of Atherosclerotic Lesions in Patients With Acute Myocardial Infarction and Stable Angina Pectoris Using Intravascular Ultrasound].

AIM: to compare noninfarct-related lesions in patients with acute myocardial infarction (MI) with culprit and non-culprit lesions in patients with stable angina pectoris (SAP) using intravascular ultrasound virtual histology (VH-IVUS). MATERIAL AND METHODS: Overall 70 patients were enrolled: 38 with ST elevation (STE) MI and 32 with stable angina pectoris (SAP). All patients underwent three-vessel coronary angiography and gray-scale and VH-IVUS after percutaneous coronary intervention (PCI) of infarct-related lesion in STEMI or culprit lesion in SAP. RESULTS: A total of 130 plaques were examined: 70 in patients with STEMI and 60 in patients with SAP. Noninfarct-related lesions in acute MI compared with non-culprit lesions in SAP had significantly larger plaque burden and plaque volume, smaller minimum lumen area, and more positive remodeling. STEMI, hyperlipidemia, plaque burden, and hypertension were independent predictors of unstable plaques.

[Comparison of Atherosclerotic Lesions in Patients With Acute Myocardial Infarction and Stable Angina Pectoris Using Intravascular Ultrasound].

AIM: to compare noninfarct-related lesions in patients with acute myocardial infarction (MI) with culprit and non-culprit lesions in patients with stable angina pectoris (SAP) using intravascular ultrasound virtual histology (VH-IVUS). MATERIAL AND METHODS: Overall 70 patients were enrolled: 38 with ST elevation (STE) MI and 32 with stable angina pectoris (SAP). All patients underwent three-vessel coronary angiography and gray-scale and VH-IVUS after percutaneous coronary intervention (PCI) of infarct-related lesion in STEMI or culprit lesion in SAP.

[Cardiovascular diseases and mannose-binding lectin].

The role of innate immunity factors in the pathogens of ACS is not well studied, although there is evidence in the literature about their impact on the course of cardiovascular diseases. Mannose-binding lectin (MBL)--one of the key factors of the humoral innate immune system that activates one of complement activation pathways. The literature suggests an ambiguous, complex role of MBL, which can in different clinical situations either improve the prognosis of patients, or be a risk factor for complications. MBL could potentially be relevant to all main links in the pathogenesis of coronary artery disease and myocardial infarction: inflammation, thrombosis, apoptosis, and so on. At different stages of atherogenesis, including the formation and destabilization of the atherosclerotic plaque, thrombosis, MBL may have a significant impact. The review analyzes currently available literature on the impact of MBL on atherosclerosis, ischemic heart disease and acute coronary syndrome. Moreover, in the review there is data on the role of MBL in physiological reactions in innate immunity, gene structure of MBL2 and possible mutations leading to deficiency of MBL in blood, and the role of MBL in the pathogenesis of various diseases.

[Level of mannose-binding lectin and phagocytic activity of leukocytes in patients with acute coronary syndrome].

UNLABELLED: Mannose-binding lectin (MBL) is a key component of innate immunity that starts one of the ways of complement activation. Factors of neutrophil activation are cell factors of innate and acquired immunity. AIM: to study MBL levels and factors of neutrophil activation in patients with acute coronary syndrome (ACS). METHODS: A total of 45 patients with ST elevation (STE) ACS and non ST-elevation (NSTE) ACS were enrolled in the study, 15 persons were age-matched controls. RESULTS. Compared with control group MBL level was higher in patients with ACS (52.7 vs 127.2 hg/ml, respectively, p = 0.07), and significantly higher in patients with NSTE ACS (52.7 vs. 164.7 hg/ml, p = 0.03). There was no difference between MBL levels in STE ACS and NSTE ACS patients. Patients with inferior myocardial infarction (MI) had significantly higher MBL level than those with anterior MI (182.8 -92.7 hg/ml, p = 0.02). Patients with concomitant diabetes had statistically higher MBL level than patients without diabetes (225 vs 100 hg/ml, OR 2.25, p = 0.03). MBL level was lower in patients with low (<40%) ejection fraction - 92.7 vs 148.9 hg/ml in patients with EF > or = 40% (p = 0.19). No difference of neutrophil activation factors between ACS patients and controls was found (phagocytic activity of neutrophils 74.5 vs 74.3%, phagocytic number 3.34 vs 4.36, phagocytic reserve 88 vs 85.5 in ACS and control group, respectively). CONCLUSION: Elevated innate immunity factor (MBL) level was associated with ACS, especially in patients with diabetes mellitus. No association between cell immunity factors with ACS was found.

[Invasive methods of detection of unstable atherosclerotic plaques in coronary arteries].

In most cases direct cause of acute coronary syndrome and sudden death is an intracoronary thrombus formed on a surface of unstable atherosclerotic plaque (UAP). The following are main characteristics of UAP: active inflammation; large lipid rich nucleus occupying a 40% of plaque volume; thin (< 65 mm) fibrous cap; erosions of intima over plaque; tear of plaque cap; superficially located calcium nodules; intraplaque hemorrhage. Visualization of UAP in coronary arteries is a very important direction in diagnostics. During recent years both invasive and noninvasive methods of detection of UAP have been actively developed. In this review we present main invasive techniques used for detection of UAP: intravascular ultrasound study with virtual histology; optical coherent tomography; near-infrared spectroscopy; thermography; intravascular magnetic resonance imaging; direct visualization by angioscopy. In the review we have covered main advantages and limitations of each invasive method of UAP detection and delineated perspectives of development of this direction.

[Factors influencing platelet aggregation in patients with acute coronary syndrome].

AIM: To study factors influencing platelet aggregation in patients with acute coronary syndrome (ACS). SUBJECTS AND METHODS: The investigation enrolled 147 patients with ACS. Their blood was sampled on days 1, 3-5, and 8-12 days after the onset of ACS. All the patients received acetylsalicylic acid (ASA) 300 mg on day 1, then 100 mg/day and clopidogrel 300-600 mg on day 1, then 75-150 mg/day. Platelet aggregation was analyzed in 65 patients on day 1 after ASA intake, but prior to clopidogrel therapy. The aggregation was induced by 5 and 20 pmol of ADP. RESULTS: With the use of clopidogrel 75 mg/day on day 3-5, platelet aggregation was reduced by 2.1 and 1.7 times for 5 and 20 µmol of ADP, respectively, as compared to day 1 (ASA without clopidogrel) and remained unchanged on days 8-12. Increasing the dose of clopidogrel up to 150 mg/day potentiated its antiaggregatory effect. On day 1 (ASA without clopidogrel), there was a direct correlation between platelet aggregation levels and mean platelet volume (MPV) (correlation coefficients (r), 0.526 (p < 0.001) and 0.368 (p = 0.015) for 5 and 20 µmol of ADP, and between platelet aggregation levels and glycoprotein (GP) IIb-IIIa (r = 0.387; p = 0.002 and r = 0.411 (p < 0.001) for 5 and 20 µmol of ADP. No similar correlations were found on days 3-5 and 8-12 of administration of ASA and clopidogrel. The genetic polymorphism of GP lIb-Illa (GP Ila Leu33Pro) was not noted to affect platelet aggregation. Examining the effects of genetic variations in cytochrome P450 isoform CYP2C19 (a clopidogrel metabolizer) revealed the enhanced aggregation stimulated with 20 µmol of ADP in the carriers of slowly clopidogrel-metabolizing haplotype of CYP2C19 (differences were found on days 3-5 as compared to rapidly and routinely metabolizing haplotypes). CONCLUSION: In the patients with ACS, platelet aggregation is influenced by MPV, GP IIb-IIIa levels, and CYP2C19 polymorphism and is not by GP IIb-IIIa polymorphism.

Spontaneous platelet aggregation in patients with acute coronary syndrome.

Spontaneous platelet aggregation was evaluated in patients with acute coronary syndrome on days 1, 3-5, and 8-12 of the disease. On day 1, aggregation was analyzed after aspirin, but before clopidogrel administration; during other periods after both antiaggregants. The mean levels of spontaneous aggregation after antithrombotic therapy did not change during different periods after the onset of acute coronary syndrome, in contrast to ADP-induced aggregation that decreased after the development of clopidogrel effects (days 3-5 and 8-12). Spontaneous aggregation during different periods directly correlated (r>0.4, p<0.01) with spontaneous and ADP-induced aggregation during different periods (r=0.372, r=0.447, and r=0.543 on days 1, 3-5, and 8-12, respectively; p<0.01). No relationship between spontaneous aggregation and plasma concentration of von Willebrand's factor was detected. Spontaneous aggregation was completely suppressed after in vitro addition of prostaglandin E1 (platelet activation inhibitor), slightly (by ≈20%) decreased in the presence of antibodies to glycoprotein Ib, blocking its reactions with von Willebrand's factor, and did not change in the presence of aptamer inhibiting thrombin activity.

[The role of multispiral computed tomography in assessment of viability of the myocardium and prognostication of left ventricular remodeling in patients with ST-elevation myocardial infarction].

Aim of the study was to assess perfusion defect and viability of the myocardium by the method of multispiral computed tomography (MSCT) in patients with ST-elevation acute myocardial infarction (AMI) and to assess their prognostic role in development of remodeling of the left ventricle (LV). We included into the study 117 patients with AMI. MSCT with intravenous contrast enhancement was carried out on days 3-4 and at 12 months after AMI. In the arterial phase we estimated volume of myocardial perfusion defect, LV end diastolic and end systolic volumes (LVEDV and LVESV), and LV ejection fraction (EF). Three types of myocardial opacification were distinguished on tomograms in delayed phase of MSCT: type I - subendocardial residual defect (RD), type II - transmural RD, type III - transmural delayed hyper enhancement (DE). Patients were divided in 3 groups: (1) with subendocardial RD (n=63), (2) with transmural RD (n=28), (3) with transmural DE (n=26). Development of LV remodeling was registered if at repeat MSCT LVEDV increased more or equal 20% from baseline. In patients with signs of viable myocardium (group 1) volume of perfusion defect was substantially smaller than in patients with nonviable myocardium (groups 2 and 3): 1cm3 (0.4-2.4) vs. 7.3 cm3 (5.3-10.0) and 6.3 cm3 (5.0-15.0), respectively, p<0.001. Compared with groups 2 and 3 patients of group 1 more often were female (p=0.04), had inferior MI (p<0.001), and spontaneous reperfusion (p<0.001). After 12 months LV remodeling was registered in 19.3% of patients, all had signs of nonviable myocardium in more or equal 3 LV segments. In patients with perfusion defect more or equal 10 cm3 probability of development of LV remodeling exceeded 50%. Disturbances of perfusion abnormalities and number of nonviable LV segments were main predictors of LV remodeling.

[Endovascular closure of the left atrial appendage in patients with atrial fibrillation: review of modern data and own experience of application].

Atrial fibrillation (AF) is the most often disturbance of cardiac rhythm met in clinical practice. Long term therapy with anticoagulants is used for prevention of thrombi formation in left atrial appendage and consequent thromboembolism. However some patients have contraindications to this therapy. This article contains consideration of various alternative methods of prevention of thromboembolic complications in particular those 2 which are most widely used at present - percutaneous transcatheter isolation of left atrial appendage with Amplatzer Cardiac Plug () or Watchman Device. We present also data on own experience of the use of the ACP device.

[Comparison of characteristics of atherosclerotic plaques in patients with acute coronary syndrome and stable ischemic heart disease: data of multispiral computed tomography].

AIM: To elucidate possibilities of multispiral computed tomography (MSCT) for assessment of morphology of atherosclerotic plaques in coronary arteries of patients with acute coronary syndrome (ACS) or stable ischemic heart disease (SIHD). MATERIAL AND METHODS: Assessment of internal relief of coronary arteries and composition of atherosclerotic plaques was carried out in 85 patients with ACS and 41 patients with SIHD. MSCT was performed with the use of computed tomograph. Visual assessment included determination of plaque type (calcified, soft, and heterogeneous) and contour (regular, irregular). Quantitative assessment included determination of plaque density and index of remodeling. RESULTS: Among patients with ACS we found 194 plaques (60--soft, 72--heterogeneous, and 62--calcified). Plaques in symptom related compared with non-symptom related arteries had higher index of remodeling (1.4 +/- 0.3 and 1.2 +/- 0.2, respectively, p < 0.0001), and more frequently had irregular contour (60.0 and 12.8%, respectively, p < 0.0005). Soft plaques and plaques with irregular contour prevailed in ACS group (68.0%) while calcified plaques were more frequent in SIHD group (66.4%). Plaques with irregular contour were more frequent and index of remodeling was higher in ACS compared with SIHD group (33.5 vs 7.2%, p < 0.0005, and 1.3 +/- 0.2 vs 1.0 +/- 0.2, p < 0.001, respectively). CONCLUSION: According to MSCT data main characteristics of atherosclerotic plaques in patients with ACS were low density and inclusions of microcalcinates. Specific features of plaques in symptom related arteries were irregular contour and positive remodeling index.

[Value of allele gene polymorphism of the inflammation system for prognosis of patients with myocardial infarction].

In recent years levels of a number of inflammatory markers namely C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor (TNF) etc. are measured for the purpose of postinfarction risk evaluation. Dynamics of inflammatory markers concentrations can reflect processes occurring in atherosclerotic plaque and coronary arteries. Concentrations of inflammatory markers depend particularly on genetic factors affecting transcription levels of individual genes. This data suggest that genotypes which determine increased inflammatory markers levels in blood can increase risk of unfavorable events after myocardial infarction. STUDY PURPOSES: Analysis of influence of allelic polymorphisms C1444T of CRP gene (rs1130864), G(-174)A of IL6 gene (rs1800795), A(-308)G of TNF gene (rs1800629), G252A of LTA gene (rs909253), (-509) of TGFB1 gene (rsl800469) and delta32 (w/d) of CCR5 gene (rs333) on development of cardiac unfavorable events in Russian patients with MI during two years follow-up. 211 Russian patients were included (52.3+/-10.3 years), 160 men (50.1+/-10.6 years) and 51 women (55.2+/-10.1 years). After two years of follow-up patients were examined in hospital, or telephon call occurred for determination of patient's condition or end point assessment. The end points were cardiac death, recurrent MI, recurrent hospitalization with unstable angina or stroke, CABG or PTCA performing. The genotyping was performed by methods based on polymerase chain reaction (PCR): PCR-SSP and PCR-RFLP. Analysis revealed association of allele T (p=0.036, OR=1.6, 95%CI: 1.052.6) and of allele T carriage (genotypes CT+TT) (p=0.046, OR=1.9, 95%CI: 1.053.6) of polymorphism C1444T of CRP gene with unfavorable events development. Analysis of survival rate by Kaplan-Meier estimation showed that cumulative part of patients without unfavorable events was significantly lower among allele T carriers than among carriers of genotype C/C of polymorphism C1444T CRP. Allele A of polymorphism A252G of LTA gene was also associated with unfavorable events risk (p=0.034, OR=1.96, 95%CI: 1.073.06). There was no association of polymorphisms delta 32 (w/d) of CCR5 gene, A(-308)G of TNF gene, G(-174)C of IL-6 gene, C(-509)T of TGFB1 gene with unfavorable events development.

Glycoprotein IIb-IIIa content and platelet aggregation in healthy volunteers and patients with acute coronary syndrome.

Glycoprotein (GP) IIb-IIIa (αIIbß3-integrin) is the central receptor of platelet aggregation. Activated GP IIb-IIIa binds fibrinogen or von Willebrand factor, which forms molecular bridges between aggregating platelets. This review summarizes data on the relationship between GP IIb-IIIa expression on the platelet surface and platelet aggregating activity. GP IIb-IIIa number, measured as maximal binding of complex-specific monoclonal antibody, varied by approximately two fold in both healthy volunteers (n = 35) and patients with acute coronary syndrome (ACS) (n = 65). In healthy volunteers positive associations were observed between GP IIb-IIIa number and the level of ADP-induced aggregation when this relationship was analysed in untreated platelet-rich plasma (PRP) as well as upon in vitro addition of aspirin or non-saturating concentrations of GP IIb-IIIa blockers. In the same group of volunteers almost no differences in aggregating activity were detected between donors carrying the GP IIIa Pro33 allele (n = 15) and those with the GP IIIa Leu33Leu33 genotype (n = 20). No significant relationships were revealed between platelet aggregability and variations of plasma fibrinogen concentration. Positive correlation of the level of ADP-induced aggregation and GP IIb-IIIa content was detected in patients with ACS within the first hour upon admission to the hospital when they had already received aspirin, but not clopidogrel. However, there were no correlations between these parameters at days 3-5 and days 8-12 (before discharge). At these time points patients were treated not only with aspirin but were saturated with clopidogrel as well. In ACS patients we also evaluated the expression of another platelet adhesive receptor, GP Ib, and found a significant positive correlation between GP IIb-IIIa and GP Ib content. A strong association was also revealed between the number of both receptors and mean platelet volume. The latter observation indicated that individual variations of the number of glycoprotein molecules are mainly affected by platelet size but not the density of their expression on the platelet membrane. Possible usefulness of measuring GP IIb-IIIa content as a marker of increased platelet reactivity is discussed.