[Long-term Outcomes of Elective Percutaneous Coronary Interventions].

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 MAСE 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.

[Prevention of periprocedural kidney ingury by loading doses of statins in elective percutaneous сoronary interventions].

PURPOSE OF THE STUDY: To compare the effect of loading doses of atorvastatin and rosuvastatin on the value of the acute kidney injury and acute inflammatory response to elective percutaneous coronary interventions. MATERIALS AND METHODS: An open prospective comparative study included 68 patients referred for elective percutaneous coronary intervention (PCI). At baseline, all patients had been taking statins for a long time as a standard lipid-lowering therapy. The first group included 33 patients who received a loading dose of 80 mg of atorvastatin (As) 12 hours before the intervention with saving this dose for 2-6 days. The second group included 35 patients treated with rosuvastatin (Rs) 40 mg / day in the same manner. The levels of creatinine and cystatin C in the blood were determined at baseline and 12, 24, 48 and 72 hours after the intervention. HsCRP level was determined at baseline and 72 hours after PCI. RESULTS: AKI was diagnosed in 5 patients (7.94 %): 4 patients (12.1 %) in group As and 1 patient (3.3 %) in group Rs (p = 0.36). The increase of serum creatinine level in the group As patients was 43.4 % higher than one in the Rs group patients (p = 0.024). The decrease of glomerular filtration rate (GFR) in group As was 15.5 % higher than one in group Rs (p = 0.09). Initially, the level of cystatin C in the groups did not differ (698.9 (560.2-869.6) ng / ml in group As vs 759.5 (673.8-899.9) ng/ml in group Rs, p = 0.75). Significant intergroup differences were found in the level of serum cystatin C 12 hours after PCI (718.3 (555.6-839.6) ng/ml in group As vs 470.6 (378.2-689.4) ng/ml in the Rs group, p = 0.007) that persisted 24 hours after the intervention (732.1 (632.3-887) ng/ml vs 526.4 (357.4-802.7) ng/ml, respectively, p = 0.02). From the second day after PCI, intergroup differences in serum cystatin C disappeared. The level of hsCRP significantly increased 72 hours after the intervention in group As (1.65 (0.9-4) mg/l at baseline vs 4.55 (1.6-8.7) mg/l 72 hours after PCI, p = 0.01). The level of hsCRP did not change significantly at the same time in the Rs group (2.8 (0.8-6.8) mg/l at baseline vs 2.75 (1.5-6.5) mg/l 72 hours after PCI, p = 0.16). CONCLUSION: The loading dose of rosuvastatin better prevents periprocedural kidney injury in PCI and more significantly reduces the overall inflammatory response to intervention compared to the loading dose of atorvastatin.

[Evaluation of long-term adverse cardiovascular events risk after elective percutaneous coronary intervention].

OBJECTIVE: The aim of our study was to analyze long-term outcomes, to identify their predictors and to develop a model for determining the risk of long-term adverse сardiovascular events after elective percutaneous coronary interventions (PCI). MATERIALS AND METHODS: A retrospective study included 151 patients 6 years after the elective PCI. Outcomes were assessed by analyzing medical records and telephone interviews. The primary composite end point of the study was a major adverse cardiovascular event (MACCE), including death from cardiovascular causes, acute coronary syndrome, acute cerebrovascular accident. RESULTS: Death from cardiovascular events was reported in 10.6 % of patients, acute coronary syndrome occurred in 34.4 %, stroke - in 6.6 %. Thus MAСCE occurred in 40.4 % of patients. MACCE predictors in the long-term period were chronic kidney disease, contrast-induced acute kidney injury, baseline C-reactive protein more than 5.5 mg/l. Restenosis of previously installed stents increases the risk of MACCE at 8.09 times, chronic obstructive pulmonary disease - 3.4 times PT - 2.84 times, family history for cardiovascular disease (CVD) - in 2.94 times, a very high risk of contrast-induced nephropathy (CIN) (≥11 points on the R. Mehran scale) - 2.15 times. The most significant MACCE's predictors identified using stepwise logistic regression and included in the developed model are: family history for СVD, statins reception during the procedure of PCI, the initial level of postprandial blood glucose, high risk of CIN (11-15 points on a scale of R. Mehran). AUC values for the found model was 0.852 [95 % CI 0.749-0.956]. CONCLUSION: The use of our model of risk stratification in patients after elective PCI allows, on the basis of simple clinical characteristics, to distinguish groups of patients with a high residual risk of adverse cardiovascular events that require the timely application of more active follow-up strategies.

[Association of ITGB3, P2RY12, and CYP2C19 gene polymorphisms with platelet functional activity in patients with coronary heart disease during dual antiplatelet therapy]. / Assotsiatsiia polimorfizmov genov ITGB3, P2RY12, CYP2C19 s funktsional'noi aktivnost'iu trombotsitov u patsientov s ishemicheskoi bolezn'iu serdtsa na fone dvukhkomponentnoi antiagregantnoi terapii.

AIM: To assess the association of CYP2C19 G681A, P2RY12 H1/H2, and ITGB3 T1565C polymorphisms with the extent of platelet aggregation in patients with coronary heart disease (CHD) during antiplatelet therapy. SUBJECTS AND METHODS: 166 male patients with CHD, living in the Western Siberian Region, were examined. All the patients underwent a test for platelet aggregation induced by ADP (2.5 and 5.0 µm) and epinephrine (0.2 µm). Genotyping was performed using an allele-specific polymerase chain reaction technique. RESULTS: The polymorphic variants of the P2RY12 and ITGB3 genes were ascertained to have no impact on the extent of platelet aggregation in patients receiving clopidogrel and acetylsalicylic acid. An association was found between CYP2C19 681A allele carriage and the increased extent of platelet aggregation induced by ADP. CONCLUSION: The carriage of the cytochrome P450 CYP2C19 681A allele rather than platelet receptor gene polymorphisms determines a risk for clopidogrel resistance in patients with CHD.

[Association of I/D and -786 Polymorphisms of ACE and NOS3 Genes With Features of the Course of Ischemic Heart Disease and Diabetes Mellitus Type 2].

AIM: to study relationship of ACE insertion-deletion (I/D) polymorphism and NOS3 T-786C polymorphism with characteristics of the course of ischemic heart disease (IHD) at the background of diabetes mellitus. MATERIALS AND METHODS: Were examined 114 patients with IHD, 29.8% of patients had type 2 diabetes mellitus. ACE and NOS3 polymorphisms were determined by allele-specific polymerase chain reaction with primers by "Lytech". RESULTS: Patients with combined pathology belonged to older age group, had increased frequency of obesity and predominance of functional class II chronic heart failure. In this group we detected association of D allele of the ACE gene with higher frequency of dyslipidemia and obesity. Among patients with IHD without diabetes we observed associations of ACE I/D and NOS3 T-786C polymorphisms (close and moderate, respectively) with severity of effort angina. We also found that frequency of dyslipidemia among carriers of II and TT genotypes was lower than among carriers of other genotypes. CONCLUSION: Presence of type 2 diabetes as background pathology leads to a change of character of association of ACE I/D and NOS3 T-786C polymorphisms with clinical characteristics of patients with IHD.

[CARDIAC AMYLOIDOSIS. DIAGNOSTICS AND TREATMENT OF AMYLOID CARDIOMYOPATHY. CASE REPORT].

Cardiac amyloidosis (amyloid cardiomyopathy) is a systemic disorder of protein metabolism with the predominant deposition of amyloid (fibrillar beta-protein) in myocardium and coronary artery walls. Early diagnostics of this condition remains a challenge because it has a poor prognosis and leads to rapid progress of the disease. Difficultis of its diagnostics are discussed with reference to an original observation.

[Pharmaco-invasive Approach Aimed at Preserved Left Ventricular Function in Patients With Stable Coronary Heart Disease Background Carbohydrate Metabolism Disorders].

Performed an open, prospective, randomized, controlled clinical trial, including 63 patients stable coronary artery disease on the background of carbohydrate metabolism disorders. All patients underwent elective coronary stenting. Patients of the main group (n=32) within 2 weeks before the intervention received trimetazidine 35 mg x 2 times a day in addition to standard therapy. Patients in the control group (n=31) PCI and follow-up was performed with standard therapy and without the use of metabolic drugs. Revealed that long reception of myocardial cytoprotector trimetazidine leads to a significant improvement of the contractile function of the left ventricular myocardium at a distant period according to echocardiography (reducing end diastolic index by 5.5%, decrease in end-systolic index by 4.4%, increase in LVEF of 2.5% in 12 months after endovascular revascularization compared with baseline).

[Microviscosity of erythrocyte membranes in chronic coronary insufficiency in patients of middle and older age groups].

We examined the ratios microviscosity in the area of integral and annularly lipid membranes of erythrocytes of peripheral blood in patients of 35-50 and 60-75 years with chronic ischemic heart disease, as well as age-matched healthy controls. In healthy donors coefficients microviscosity in the area of integral and annularly lipids proved to be significantly higher in the older age group (60-75 years). In CHD, regardless of the age of the patients, erythrocyte membranes can be characterized as raising and lowering the parameters microviscosity of lipid-lipid interactions. In the protein-lipid contacts for patients aged 35-50 years an increase is typical, while for patients of 60-75 years, on the contrary, a decrease of the coefficient of microviscosity. It is concluded that the values of the microviscosity of erythrocyte membranes in patients of different age groups in the development of chronic ischemic heart disease, reflect both the implementation of the general mechanisms of adaptive changes of cell membranes, and the specifics of an individual, determined by their lipid and protein composition.

[Influence of the long-term administration of torasemide on morphometric characteristics of cardiac muscle under conditions of developed experimental postinfarction cardiosclerosis].

The possible antifibrotic effect of torasemide used for the treatment of model chronic heart failure (CHF) has been studied in rats aged 12 months with developed postinfarction cardiosclerosis (PICS). The antifibrotic effect was evaluated of the course of torasemide administration in a daily dose of 0.13 mg/kg. A comparative analysis showed that torasemide did not affect the state of connective tissues in cardiac muscles of both intact rats and those with PICS. It was concluded that manifestations of the antifibrotic effect of torasemide can be related to the nosological form of CHF.

[Resistance to clopidogrel and polymorphism of P2RY12 and GPIIIA genes in patients with chronic coronary heart disease].

We studied the association between clopidogrel resistance, H1/NH2 polymorphism of the P2RY12 gene and T156C polymorphism of the GpIIIa gene in residents of Western Siberia suffering chronic CHD. It was shown that the occurrence of H1 and H2 haplotypes of the P2RY12 gene and 1565T and 1565C alleles of the GpIIIa gene was similar to that reported for European populations. Patients showing variable platelet response to the inhibitory action of clopidogrel were not significantly different in terms of P2RY12 and GpIIIa genotype distribution. To conclude, the study revealed no association between the risk of clopidogrel resistance and the presence of polymorphic variants of platelet receptor genes P2RY12 and GpIIIa.

[D allele of the angiotensin converting enzyme gene is a putative risk factor of restenosis after coronary stenting in patients with coronary heart disease].

We undertook a comparative analysis of allele frequency distribution and I/D polymorphism of the angiotensin converting enzyme (ACE) gene in patients with coronary heart disease (CHD) undergoing coronary stenting with and without signs of restenosis. There were no significant difference between the groups in the genotype frequency distribution of I/D polymorphism of the CAE gene (p = 0.061). The occurrence of D allele in the patients with restenosis was higher than that of I allele (chi-square test 4.117, p = 0.042). Relative risk for the carriers of D and I alleles was 0.35 and 2.83 respectively. It is concluded that the presence of D allele of I/D polymorphism of the CAE gene in patients with chronic CHD may be a risk factor of restenosis of stented coronary arteries.

[Age-related features of intracellular calcium homeostasis in rat cardiomyocites in postinfarction heart remodeling].

Research results of features of an intracellular calcium homeostasis in 4 and 12-month's rat cardiomyocites at postinfarction cardiosclerosis are presented. It is shown that the myocardium of animals in the old rats group is more susceptible to extrasystolic impacts. In the pathology conditions additional extrasystolic influences also had the expressed age specificity of inotropic response. The data testifying to almost identical dynamics of postextrasystolic cycles of intact myocardium in animals of investigated age groups has been obtained. The different postextrasystolic potentiation in the remodeled myocardium in old and young rats testified to different of sarcoplasmic reticulum ability to accumulate additional calcium ions. The conclusion was made that the myocardium of animals in the old rats group has more chance for development of hemodynamic significant disturbance of cardiac rhythm as a consequence of age-related changes processes of the electromechanical coupling in cardiomyocites.

[Effect of nonselective beta-adrenoblocker carvedilol on extrasystolic and postextrasystolic contractility in the rat myocardium after experimental infarction].

Features of the extrasystolic and postextrasystolic contractility of myocardium isolated from rats aged 4 months (group I, n = 30) and 12 months (group II, n = 30) after postinfarction remodeling of the heart (PIRH) and long-term treatment with carvedilol have been studied. Each age group included in 10 intact control animals, 10 animals with postinfarction cardiosclerosis (PICS), and 10 rats with PICS treated with carvedilol (2.1 mg/kg) during 28 days, beginning with the 45th day after coronary occlusion. The isometric contractility of myocardium was monitored at an electric stimulation frequency of 0.5 Hz. The extrasystolic effect was produced by an electric pulse applied within 0.2 - 5 s interval after the basic stimulation. It is established that the inotropic response of myocardium to the extrasystolic impulse exhibits age-dependent features both the intact rats and in the rats with PICS. The differences can be related to the age-dependent involvement of the ion-transport systems of sarcolemma and sarcoplasmic reticulum into the modulation of excitation--contractility coupling during PIRH. The long-term treatment with carvedilol led to restoration of the Ca(2+)-accumulation reserve of sarcoplasmic reticulum to the age-normal level in young animalsand decreased the risk of development of hemodynamically significant heart rate disturbances in old rats.

[System thrombolytic therapy in acute myocardial infarction in the elderly].

The paper presents a retrospective cohort study of the records of 430 patients with myocardial infarction aged 60 to 91. Group I (main group) consisted of 234 patients who received system thrombolytic therapy (TLT); group II (controls) consisted of 196 patients who received conventional therapy. Hospital and long-term lethality, the course of the disease, and the complications of thrombolysis were evaluated. The study found no effect of TLT itself on the end points; there were differences between subgroups with effective and non-effective thrombolysis. Thus, comparison of these variables in patients aged 60 to 74 showed a decrease in the hospital lethality in the main group: 6.6% vs. 20.6% in the control group (p = 0.00072), and an increase in five-year survival (p = 0.0057). Cardiac arrhythmias (CA) and chronic heart failure were much less frequent in group I. Transient hypotension occurred in 36% of patients on thrombolytic therapy; reperfusion-related CA were noted in 25% of patients receiving thrombolysis. There were no cases of serious hemorrhage or cerebral strokes. None of the complications resulted in a lethal outcome. The study demonstrates that TLT is not contra-indicated in the elderly with myocardial infarction; complications are, as a rule, insignificant and easily reversible. When reperfusion is successful, thrombolysis lowers early and long-term lethality and improves the course of the disease in this very complex category of patients.

[Changes in the binding properties of albumin in patients with myocardial infarction].

The purpose of the study was to measure the levels of albumin and to evaluate its binding properties in patients with acute large-focal myocardial infarction (AMI) hospitalized within the first 24 hours of AMI onset. Two groups were formed: group one--41AMI patients without cardiogenic shock (CS) and group two--15 patients with AMI complicated by true CS. Blood samples were taken from an ulnar vein on the first, second, third, fifth, seventh, and fourteenth day after AMI onset. The properties of binding albumin centers were determined using fluorescent method (K-35 probe). Total albumin concentration (TAC), effective albumin concentration (EAC), and albumin binding reserve (ABR) were determined. The results were presented as M +/- m. A significant increase in TAC on the fifth day (from 43 +/- 1 to 40 +/- 1 g/l) and EAC on the second, third, fifth, and seventh days (from 36 +/- 1 to 32 +/- 1 g/l with the minimal level on the fifth day), and in ABR on the second day (from 83.3 +/- 1.3 to 78.8 +/- 8%) were registered in group one. TAC returned to the normal level on the seventh day, EAC did not become normal until the fourteenth day, while ABR did not normalize within the period of two weeks. Eleven patients in group two died (hospital CS-associated mortality was 73.3%). TAC and EAC in discharged patients were 43.4 +/- 0.9 g/l and 35.8 +/- 0.8 g/l, respectively, while these parameters in the deceased were 35.5 +/- 1.7 g/l (p < 0.0001) and 27.3 +/- 1.7 g/l (p < 0.0001), respectively. CS developed in 70% of cases (seven out of ten patients) in whom TAC was less than 36 g/l vs. 17.4% of cases (eight out of 46) with a TAC of 36 g/l or more (p = 0.0013). When EAC was less than 30 g/l CS developed in 72.7% of cases (eight out eleven patients) vs. 15.6% of cases (seven out of 45) with an EAC of 30 g/l or more (p = 0.0003). Six out of ten patients (60%) with a TAC of less than 36 g/l died. Lethal outcome also occurred in five cases out of 46 or 10.9% with a TAL of 36 g/l or more (p = 0.0008). Seven out of eleven or 63.6% patients with an EAC of less than 30 g/l died. Four out of 45 patients (8.9%) with an EAC of 30 g/l or more died (p = 0.0001). Thus, the study found that a low (less than 36 g/l) TAC and EAC (less than 30 g/l) during the first 24 hours of AMI was associated with a significantly higher frequency of true CS and with a significantly higher hospital lethality. Determining albumin parameters during the first 24 hours of AMI will be useful in distinguishing a group of patients with a high risk of lethal outcome, which will make it possible to begin early aggressive therapy directed towards limiting myocardial necrosis.

[Effectiveness of external mechanical recanalization in the treatment of cardiogenic shock in patients with myocardial infarction].

Attempts of mechanical coronary artery recanalization (angioplasty) were undertaken in 52 patients with acute myocardial infarction and cardiogenic shock. In 28 patients (53.9%) recanalization was successful while in 24 it was not (in-hospital mortality 39.3 and 87.5%, respectively, p<0.001). Overall 11 and 21 patients died among those with (n=28) and without (n=24) successful recanalization, respectively. Among patients with successful recanalization survivors compared with nonsurvivors had shorter time from onset of myocardial infarction to recanalization (11.44+/-2.86 vs 16.8+/-3.4 hours, respectively). No serious complications occurred during invasive interventions.

[Study of stability of lactate dehydrogenase isoenzymes in leucocytes of elderly people]. / Izuchenie stabil'nosti izofermentov laktatdegidrogenazy leikotsitov liudei starcheskogo vozrasta.

In this paper was investigated stability of isoenzymes of lactatdehydrogenase (LDH) of leukocytes of peripheral blood of persons at the age of 20 years (n=10) and more than 65 years (n=8). Extraction of the leukocytes was conducted by centrifugation of human blood on a double gradient of density. Leukocytes were destroyed by hypotonic shock in combination with vibration. Separation of LDH isoenzymes from destroyed leukocytes was conducted by the method of native electrophores. The revealing of activity of LDH isoenzymes was conducted by the method of restoration of nitroblue tetrasolium. Isoenzymes stability was evaluated according to alteration of activity after the incubation of destroyed leukocytes with urea in various concentrations (1M, 2M and 3M). Was shown the presence of three isoenzymes of LDG (LDH-1, LDH-2, LDH-3) in human leukocytes. As the age-dependent alteration of activity of isoenzymes of lactatdehydrogenase in human leukocytes was shown. It can be caused by age-related changes of physico-chemical properties of leukocytes' membranes and/or isoenzymes stability. Stability of LDH-3 was decreased with the age. Observed decrease of LDH-3 stability can be caused by age-related modification of M-subunits of the studied isoenzymes.

[Effect of the bioantioxidant histochrome on myocardial injury in reperfusion therapy on patients with myocardial infarction]. / Vliianie bioantioksidanta gistrokhroma na povrezhdenie miokarda pri reperfuzionnoi terapii u bol'nykh infarktom miokardom

AIM: To evaluate effects of histochrome on severity of reperfusion damage in opening of the coronary artery in patients with acute myocardial infarction (MI). MATERIAL AND METHODS: 86 acute MI patients were randomized into three groups. 26 patients of group 1 A received 100 mg histochrome 10 min before and 1 hour after intravenous bolus administration of thrombolytic streptokinase; 20 patients of group 1 B received histochrome by the same scheme on the disease day 1 followed by 100 mg/day for 10 days; 40 control patients have undergone thrombolysis without prophylactic histochrome. RESULTS: In the control group ventricular extrasystoles (VES) arose in 100% patients, in groups 1A and 1B--in 27%. The same picture was observed in relation to episodes of accelerated idioventricular rhythm. Coronary reperfusion was accompanied by fast dynamics of ST segment and ORS complex in the control group. MI focus measured by the Selvester ECG method was less in histochrome groups. After myocardial reperfusion malonic dialdehyde in the serum rose 6 times in the control groups and was slightly elevated in groups 1A and 1B. CONCLUSION: Preventive administration of histochrome before thrombolytic therapy to reperfuse myocardium diminishes reperfusion damage: inhibits activity of lipid peroxidation and development of necrosis focus in acute period of MI.