Assessment of platelet functional activity in healthy individuals and patients receiving antiplatelet therapy. Possible inconsistencies between aggregation and flow cytometry tests.

Platelet functional activity was assessed in healthy volunteers (HV, n=92), patients with stable angina pectoris (SA, n=42) and acute coronary syndrome (ACS, n=73), treated with acetylsalicylic acid (ASA) + clopidogrel and ASA + ticagrelor, respectively. In all HV and patients we have compared parameters of platelet aggregation (maximum light transmission and velocity, Tmax and Vmax) and parameters, characterizing exposure of platelet activation markers, evaluated by flow cytometry. HV platelets were activated by 10 µM, 1 µM TRAP, and 20 µM, 5 µM, 2.5 µM ADP; patient platelets were activated by 10 µM TRAP and by 20 µM and 5 µM ADP. Strong and significant correlations between the aggregation and flow cytometry parameters (the r correlation coefficient from 0.4 up to >0.6) most frequently were registered in HV platelet during activation by 1 µM TRAP and in SA patients during platelet activation by 20 µM and 5 µM ADP. However, in many other cases these correlations were rather weak (r < 0.3) and sometimes statistically insignificant. In HV the differences in PAC-1 binding parameters between platelets activated by 10 µM TRAP (the strongest agonist) and all ADP concentrations were negligible (≤ 10%), while CD62P binding (at all ADP concentrations) and LTA parameters for (5 µM and 2.5 µM ADP) were significantly lower (by 40-60%). Antiplatelet therapy in patients decreased all parameters as compared to HV, but to varying extents. For 10 µM TRAP the MFI index for PAC-1 binding (40-50% decrease) and for both ADP concentrations the Tmax values (60-85% decrease) appeared to be the most sensitive in comparison with the other parameters that decreased to a lesser extent. The data obtained indicate a possibility of inconsistency between different LTA and flow cytometry parameters in assessing platelet activity and efficacy of antiplatelet drugs.

[Right ventricle free wall rupture during transcatheter occluder implantation in a patient with postinfarction rupture of the interventricular septum and COVID-19-associated myocarditis. Case report].

Intraventricular septum rupture is a rare mechanic complication of myocardial infarction associated with high mortality. This case describes STEMI in recovered patient after COVID 19 associated pneumonia, which was complicated by ventricular septum rupture followed by cardiogenic shock. It was managed by percutaneous occluder implantation. The procedure was complicated by right ventricular wall rupture. Postmortem examination of myocardium showed the signs of inflammation infiltrate and myocyte necrosis, according to histopathological Dallas criteria diagnosis of COVID-19 associated myocarditis was established. The COVID-19 pandemic has contributed to increasing cardiovascular mortality. This is typically attributed to diminishing resources for timely and appropriate medical care, and patients' late presentations for fear of contracting the infection. Cardiovascular complication of COVID-19 may be another contributing factor. Further research is needed to improve our understanding of the mechanisms and long-term sequelae of myocardium damage in COVID-19, to optimize treatment strategy and subsequent follow-up in such patients.

The role of platelet glycoprotein IIb / IIIa inhibitors in current treatment of acute coronary syndrome.

Current management of patients with acute coronary syndrome (ACS) includes a dual antiplatelet therapy with acetylsalicylic acid and a platelet P2Y12 receptor inhibitor. For patients without a high risk of bleeding, prasugrel and ticagrelor are preferred, since their effect is more pronounced, less dependent on metabolism of a specific patient, and occurs faster that the effect of clopidogrel. The prescription rate of platelet glycoprotein IIb/IIIa (GP IIb / IIIa) receptor inhibitors has considerably decreased. However, these drugs remain relevant in percutaneous coronary interventions in patients with a high risk of coronary thrombosis or a massive coronary thrombus, in thrombotic complications of the procedure, and in the "no-reflow" phenomenon. The intravenous route of GP IIb / IIIa inhibitor administration provides their effectiveness in patients with difficulties of drug intake or with impaired absorption of oral medications. This review presents clinical and pharmacological characteristics of various GP IIb / IIIa inhibitors and data of randomized clinical studies and registries of recent years that evaluated results of their use in patients with ACS.

Computed Tomography Myocardial Perfusion Imaging With Transesophageal Atrial Pacing Stress Test in Patients With Borderline Stenoses in the Coronary Arteries: a Comparison With Fractional Flow Reserve.

Aim      To evaluate the diagnostic accuracy of cardiac perfusion computed tomography (PCT) with transesophageal electrocardiostimulation (TE ECS) for detection of ischemia in patients with borderline coronary stenosis (50-75 %) compared to measurements of fractional flow reserve (FFR).Material and methods  The study included 25 patients with borderline (50-75 %) coronary stenosis as per data of computed tomography angiography (CTA) or coronary angiography (CAG). Later the patients underwent invasive measurement of FFR and cardiac PCT on a 320-row detector tomograph in combination with the TE ECS stress test.  FFR values <0.8 indicated the hemodynamic significance of stenosis. Myocardial perfusion was evaluated visually based on consensus of two experts.Results All patients completed the study protocol. Cardiac pacing duration was 6 min for all patients. Four patients required intravenous administration of atropine sulphate. PCT with TE ECS detected significant for FFR stenoses with sensitivity, specificity, and predictive value of a positive result and predictive value for a negative result of 47, 90, 87, and 53 %, respectively.Conclusion      PCT with TE ECS in combination with CTA can be considered as an informative method for simultaneous evaluation of the condition of coronary arteries and detection of myocardial ischemia. This method is particularly relevant for assessing the hemodynamic significance of borderline coronary stenoses.

Correlations between clinical and laboratory findings and prognostically unfavorable CMR-based characteristics of acute ST-elevation myocardial infarction.

Aim To evaluate factors associated with unfavorable predictive characteristics of ST-segment elevation acute myocardial infarction (STEMI) as per data of magnetic resonance imaging (MRI).Material and methods The study included 52 patients with STEMI who underwent a primary percutaneous coronary intervention (pPCI). Contrast-enhanced cardiac MRI was performed for all patients on days 3-7. Delayed contrast-enhancement images were used for assessing infarct size, presence of microvascular obstruction (MVO) areas, and heterogeneity zones.Results Multifactorial analysis showed that independent predictors of MVO were type 2 diabetes mellitus (DM) (relative risk (RR) 1.9, confidence interval (CI): 1.1-3.26, р=0.012), increased levels of brain natriuretic peptide (BNP) (RR 2.04, CI: 1.39-2.99, р=0.004) and creatine kinase (CK) (RR 2.06, CI: 0.52-0.80, р=0.02), and infarct size (IS) (RR 2.81; CI: 1.38-5.72, р=0.0004). Construction of ROC curves provided the quantitative values of study indexes, at which the risk of MVO increased. For BNP, this value was ≥276 pg/ml (sensitivity, 95.7 %; specificity, 37.9 %); for CK ≥160 U/l (sensitivity, 74.1 %; specificity, 61.9 %); and for IS ≥18.8 % (sensitivity, 79.3 %; specificity, 69.6 %). Correlation analysis of risk factors for increased size of the heterogeneity zone showed significant correlations of the heterogeneity zone size with older age of patients (r=0.544, р<0.0001), higher concentrations of BNP (r=0.612, р<0.0001), CK (r=0.3, 95 % CI: 0.02-0.5, р=0.03), and C-reactive protein (CRP) (r=0.59, CI: 0.3-0.7, р=0.0001). Increased levels of CK (r=0.53, 95 % CI: 0.29-0.70, р=0.0001) and BNP (r=0.55, 95 % CI: 0.28-0.70, p=0.0003) significantly correlated with increased IS.Conclusion Risk of MVO formation as per MRI data increased in the presence of type 2 DM and IS ≥18.8 % (р<0.05). Formation of MVO in patients with STEMI was associated with increased levels of BNP ≥276 pg/ml and CK ≥160 U/l (р<0.05). Increased levels of BNP, CK, and CRP were associated with a larger size of heterogeneity zone according to data of the correlation analysis. A larger heterogeneity zone was more typical for older patients. Increased levels of CK and BNP were also associated with larger IS. The correlation analysis did not show any significant interactions between the size of heterogeneity zone, IS, and MVO size (р>0.05).

[The clinical case of successful combined treatment of refractory arterial hypertension. Case report].

In recent years, there has been an increase of patients with arterial hypertension, one of the variants of which is refractory arterial hypertension. This unfavorable clinical variant of the course of hypertension worries clinicians, due to the higher risk of developing cardiovascular complications, realizing the need for a better control of blood pressure. The presented clinical case demonstrates the successful combined treatment of refractory hypertension using antihypertensive therapy and renal denervation.

[Possibilities of Stress Computed Tomography Myocardial Perfusion Imaging in the Diagnosis of Ischemic Heart Disease].

Computed tomography angiography (CT-angiography, CTA) allows noninvasive visualization of coronary arteries (CA). This method is highly sensitive in detecting coronary atherosclerosis. However, standard CTA does not allow evaluation of the hemodynamic significance of found CA stenoses, which requires additional functional tests for detection of myocardial ischemia. This review focuses on possibilities of clinical use, limitations, technical aspects, and prospects of a combination of CT-angiography and CT myocardial perfusion imaging in diagnostics of ischemic heart disease.

[Spontaneous Coronary Artery Dissection].

During several recent decades spontaneous coronary artery dissection (SCAD) has been known as one of causes of development of acute coronary syndrome (ACS). It has been assumed that this condition is extremely rarely met and is associated with pregnancy and postpartum period. The use in clinical practice of high sensitivity troponin, coronary angiography (CAG) in early period of ACS, in conjunction with the growing awareness of doctors about this pathology led to a revision of the viewse on prevalence of the disease. At present SCAD is considered as one of the causes of ACS in young and middle-aged women. In this review we present results of studies of pathogenesis, diagnostics, and treatment of SCAD, describe various angiographic types of this disease, and discuss problems of choice of optimal strategy of management of patients with SCAD.

[Complications of the Catheter Treatment of Atrial Fibrillation: Stenosis of All Pulmonary Veins after Radiofrequency Ablation].

Radiofrequency ablation is the "gold standard" in atrial fibrillation treatment. The frequency of complications is about 3.5-3.9 %. The symptomatic pulmonary vein stenosis is one of the most severe complications. In this report we present a clinical case of stenosis of all four pulmonary veins after redo catheter ablation of atrial fibrillation in 61year-old patient, and discussion of possible causes, specific features of diagnosis, and possible approaches to treatment of this complication.

[Endovascular closure of a ventricular septal defect from Takotsubo Syndrome].

Takotsubo Syndrome is a transient condition characterized by left ventricular systolic dysfunction. Although the prognosis is excellent in most cases, rare cases of serious complications can occur. We present a case of a 81-year - old woman with Takotsubo Syndrome complicated by ventricular septal rupture that was successfully closed with an occluder Occlutech with good immediate and long - term outcomes.

[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.

[The first experience with X-ray endovascular closure of the left atrial auricle using an Amplatzer Cardiac Plug in patients with atrial fibrillation].

Atrial fibrillation is the most common cardiac arrhythmia in clinical practice. Long-term anticoagulant therapy is used to prevent thrombosis in the left atrial (LA) auricle and, as a consequence, thrombolisms. However, some patients have contraindications to its use. The paper considers different alternative methods for preventing thromboembolic events and particularly one of the most common presently encountered ones - percutaneous transcatheter LA auricle excision, by applying the Amplatzer Cardiac Plug. There are also data on the authors' experience in using this device.

[One-stage PCI of left main stenosis and infarct-related left main major branches in STEMI patients].

AIMS: to determine immediate and long-term results, safety and efficacy of one-stage PCI of LMCA and infarct-related LAD or CxA in STEMI. METHODS: 81 patients with STEMI treated with one-stage PCI of LMCA and infarct-related LAD or CxA were included into the study. LAD was infarct-related in 53 (65.4%) patients, circumflex (CxA) involved in 28 (34.6%) cases. Distal LMCA lesion was in 45 patients (55.6%). RESULTS: All patients were treated with drug-eluting stents. Radial access was used in 66 (81.4%) cases, in 38 (46.9%) patients intra-aortic balloon contrapulsation supported the procedure. IVUS was performed in 19 (23.4%) patients. Mortality during the procedure was 2.5% (2 patients with cardiogenic shock owing to infarct-related LAD). All other cases were technically successful. Two more patients died during the hospitalization, so short-term mortality was 4.9%. Angina symptoms persisted in 27 patients (33.3%) and were due to lesions in other coronary arteries. In these cases, the second PCI was performed. The mean follow-up period was 32-39 months. During follow-up 7 patients (8.6%) died due to various reasons. Target lesion revascularization was performed in 10 (12.3%) patients, including 3 repeated PCI of LMCA. Repeated revascularization due to atherosclerosis progression in other segments was done in 11 (13.5%) patients. MACCE-free survival was 60.7%. CONCLUSIONS: one-stage PCI of LMCA and infarct-related LAD or CxA seems to be effective and safe treatment in patients with STEMI but larger studies with prolonged follow-up are needed.

[Broken heart syndrome or Takotsubo cardiomyopathy. (Literature review and clinical observations)].

Takotsubo cardiomyopathy is an acute cardiac syndrome that mimics ST segment elevation myocardial infarction. It is characterized by transient local contractility disturbances as akinesis of the apical and middle segments of the left ventricle concurrent with hyperkinesis of its basal portions in the absence of significant coronary artery changes. A description of 2 clinical cases and a review of literature on this rare myocardial disease are given.

[Glycoprotein IIb-IIIa antagonist Monafram in primary angioplasty of patients with acute coronary syndrome without st segment elevation].

Glycoprotein (GP) llb-llla anagonist monafram is the F(ab)2 fragments of anti GP llb llla monoclonal antibody FraMon (CRC64). Efficacy and safety of monafram in primary coronary angioplasty of patients with acute coronary syndrome without ST segment elevation (non ST ACS) was evaluated in this study. Monafram was introduced intravenously to 284 patients just before angioplasty at standard dosage - 0.25 mg/kg as single i.v. bolus. Control group included 203 patients. All patients received aspirin (loading dose 300 mg and then 75 mg daily) and more than 90% - clopidogrel (loading dose 300-600 mg and then 75 mg daily). Within 30 days of follow up period monafram decreased by more than 2.5 fold the total amount of unfavorable outcomes (cardiovascular death, myocardial infarction and indications for repeat revascularization due to angina recurrence) - from 19.2% to 7.4% (p<0.001). The rate of indications for revascularization was most strongly decreased - by more than 7 times - from 7.9% to 1.1% (p<0.001). The number of myocardial infarctions was reduced by more than 2 times - from 8.4% to 3.9% (p=0.057). The amount of lethal outcomes did not differ between two groups (2.9% and 2.4% in the control and monafram groups, respectively). In the control group 8.9% patients received monafram during primary angioplasty due to urgent indications. Monafram did not cause any allergic reaction in all tested patients. Major bleeding was registered in one (less than 0.5%) and deep thrombocytopenia (<20000 platelets per 1 ul) - in 3 (1.1%) out of 284 patients. The data obtained indicated that monafram decreased the number of thrombotic complications in non ST ACS patients undergoing angioplasty upon the dual antiplatelet therapy (aspirin+clopidogrel) and without significant increase of dangerous side effects.

[Results of clinical trials of a novel glycoprotein IIb-IIIa antagonist framon in high-risk coronary angioplasty].

New glycoprotein (GP) IIb-IIIa antagonist preparation framon (Monafram), is the F(ab')(2) fragment of a monoclonal antibody FRaMon directed against GP IIb-IIIa. This preparation blocks GP IIb-IIIa binding with fibrinogen and inhibits platelet aggregation both in vitro and upon intravenous administration. Safety and ability of framon to prevent thrombotic complications in high risk coronary angioplasty (CA) was evaluated in the present study. FRAMON was injected intravenously into 153 patients just before the start of procedure as a single bolus at the dose of 0.25 mg/kg. Control group was formed of 126 patients who underwent angioplasty without GP IIb-IIIa blockers. After framon administration there were no allergic reactions or major bleedings, deep thrombocytopenia (< 50000/microl) developed in 1 patient (< 1%), and antibodies against framon were detected in less than 5% of patients. Number of unfavorable outcomes (cardiovascular death, myocardial infarction, angina recurrence) within 1 month after CA was 3 times higher in control group than in the group of patients treated with framon (11.4% and 3.3%, respectively, p = 0.018). The effect of framon was most strongly pronounced within the first day after procedure -- administration of the drug reduced number of acute thromboses from 6.5% to 0.7% (p = 0.013). Significant differences between numbers of end points was still preserved at 6 months after procedure (25.7 and 14.2% in control and framon groups, respectively, p = 0.023). The data obtained proved safety and clinical efficacy of framon administration in coronary angioplasty with high risk of thrombotic complications.

[Antiplatelet effects of glycoproteins IIb-IIIa antagonist monafram]. / Antitrombotsitarnye éffekty antagonista glikoproteinov IIb-IIIa monaframa.

First Russian glycoprotein (GP) IIb-IIIa antagonist, preparation Monafram, is the F(ab')2 fragment of anti-GP IIb-IIIa monoclonal antibody FRaMon. In in vitro experiments it was shown that Monafram blocked platelet aggregation induced by ADP and thrombin; reduced secretion from platelet granules; and due to simultaneous interaction with two GP IIb-IIIa molecules almost irreversibly bound to platelet surface. Monafram clinical trials were performed in healthy volunteers (n = 10) and in patients with ischemic heart disease undergoing high risk coronary angioplasty (n = 153). Monafram intravenous bolus administration at 0.25 mg/kg decreased ADP-induced platelet aggregation by more than 90, 80, 60 and 30% at 1, 12, 24 and 72 h after injection, respectively. No significant differences were detected between antiaggregatory effects of Monafram and ReoPro introduced at 0.25 mg/kg bolus + 12 h infusion at 0.125 microg/kg per min. Durable inhibition of aggregation after Monafram administration was mediated by platelet-bound preparation--free Monafram was cleared from plasma within 12 h, while platelet-bound preparation occupied more than 90, 70-80 and 40-50% of GP IIb-IIIa at 1, 12-24 and 72 h after injection, respectively. Major bleedings and allergic reactions were detected in none of patients, deep thrombocytopenia--in one patient and antibodies against Monafram--in 5% of patients. Within one month after coronary angioplasty Monafram decreased the number of end points (fatal and nonfatal myocardial infarction and angina recurrence) from 11.4 to 3.3%.