Participation of transcriptional factor ZBTB16 in the processes of physiological bone tissue formation and in pathological calcification of the aortic valve

Degenerative calcific aortic valve stenosis is the most common type of heart valve disease in the Western world. Patients with severe stenosis are associated with 50 percent chance of mortality within two years in the absence of intervention. Surgical interventions are the only treatment method for severe calcific aortic valve stenosis to date. Pharmacological approaches have so far failed to affect the course of the disease. Thus, there is an urgent need to develop novel treatment strategies that could slow down the progression of the stenosis. ZBTB16 is a zinc finger protein with N-term BTB/POZ domain (protein-protein interaction motif) and 9 zinc finger domains (DNA binding motif) in C-term. There is growing evidence proving the participation of ZBTB16 in skeletal development. ZBTB16 has been shown to play a role in the specification of limb and axial skeleton patterning. Moreover, the expression of ZBTB16 is increased in patients with ectopic bone formation. Nowadays, the evidence supports that the mechanisms that play key roles in the formation of bone tissue are similar to the processes occurring during the development of ectopic ossification of the aortic valve. Thus, it can be assumed that ZBTB16 is heavily involved in osteogenic transformation in the aortic valve. Understanding similarities and differences in the mechanisms that mediate osteogenic differentiation of stem cells during bone formation and pathological ossification of tissues can help to find the ways to control the osteogenic differentiation in the human body. The aim of this review is to summarize data on the role of ZBTB16 and its products in the regulation of differentiation and proliferation of cells involved in osteogenesis and in the development of ectopic calcification of the aortic valve. The study of the dynamic changes of ZBTB16 expression in aortic valve calcification is a new and relevant study field.

Immediate clinical results of the new biological support ring for correction of mitral insufficiency

Aim. To make the first clinical experience evaluation of the new biological closed support ring for mitral valve.Methods. 26 patients (16 men, 10 women, mean age 55 [49; 62] years) with dysplastic mitral insufficiency were implanted “NEORING” biological ring for the first time from March 2020 to June 2021. The etiological factor of the defect formation in all cases was the connective tissue dysplasia. The mean functional class of heart failure before surgery was 2 [2; 3] according to NYHA, the effective regurgitant orifice (ERO) was 0.4 [0.3; 0.5], vena contracta was 0.7 [0.6; 0.8]. Ten patients received rings of 28 mm diameter, ten patients – 30 mm, six patients – 32 mm.Results. No significant adverse events such as death from any causes, strokes, myocardial infarction, cardiac complications, bleeding, and return of regurgitation or failure of plastic surgery requiring reoperation, infective endocarditis after the intervention were observed. In two cases a permanent pacemaker was implanted due to sinus node dysfunction. At discharge all patients had no regurgitation (ERO 0), medium transvalvular gradient was 4.0 [3.0; 5.3] mm Hg. All the patients were assigned to NYHA functional class I heart failure after the surgery.Conclusion. New biological support ring “NEORING” (“NeoKor”, Kemerovo) use in the middle age group of patients showed high hemodynamic efficiency, the absence of specific complications in the early stages after the surgery. It is planned to expand the clinical material on the use of the biological ring, as well as to evaluate the long-term results in the format of a prospective, randomized trial and compare the new device with the existing ones.

Experience in treatment of patients with arterial and venous thrombosis with proven COVID-19

Background. COVID-19 is represented by a large number of different phenotypes, ranging from asymptomatic progress to the development of severe multiple organ dysfunction syndrome. The mechanisms of development of multiple organ dysfunction syndrome are multifactorial, including hypercoagulation with the formation of blood clots. They are often diagnosed as thrombotic complications with detection of blood clots not only in the veins and pulmonary arteries, but also in the heart and main arteries. An observational study shows that the incidence of venous and arterial thrombosis is as high as 31% in patients with COVID-19 pneumonia. However, large studies have not yet been conducted.Aim. To generalize and analyze our own observations of the clinical course of patients with thrombosis and COVID-19.Methods. The study included 5 male patients who had arterial and venous thrombosis and COVID-19 positive test. Results The experience of treatment of 5 patients with COVID-19 with arterial and venous thrombosis was analyzed. All patients showed characteristic changes in the coagulogram. The patient who, upon admission, had a negative test for COVID-19, and characteristic changes in the coagulogram appeared on the day of recurrent thrombosis, was of greatest interest. All patients received standard treatment and were discharged with improvement after testing negative for COVID-19.Conclusion. Generalization of the clinical course of patients with COVID-19 and thrombosis of various vascular regions allowed us to develop treatment tactics for these groups of patients.

Dynamics of the number of myocardial revascularization operations in some countries in comparison with the Russian Federation in 2000–2018

Aim. To study the dynamics of the number of coronary artery bypass grafting (CABG) and percutaneous coronary interventions (PCI) in some countries and Russia in the 2000–2018..Methods. The data of the official statistics of the Organization for Economic Cooperation and Development on the number of CABG and PCI were used. The countries that have provided data for most of the analyzed years and have more than 30 CABG per 100,000 population (22 countries) were selected. Data on the number of interventions in Russia were obtained from the CNIIOiIZ and Bakulev NMICSSH. The US data are obtained from the literature.Results. In most countries, the number of CABG decreased by 2018.The United States, Denmark, Finland, Israel, and Luxembourg were the most variable in the average indicator. The most expressed decrease occurred in Finland (2.9 times). The number of PCI has increased significantly (in 9 countries by more than 2 times). The exception was the United States, where the number of PCI decreased by 2 times from 2003 to 2016. In Russia, there was an increase in CABG and PCI (by 10.2 and 50.5 times, respectively). The number of CABG and PCI per 100,000 population was 23 and 34 times less, respectively, in Russia than the international average in 2000, and 1.4 and 1.55 times less in 2018. The decrease in CABG is due to the improvement of PCI technologies, as well as the improvement of pharmaceutical treatment of coronary vessels. The number of proceedings, including court ones, on the validity of stent implantation is growing. The crosscountry variability of the use of cardiac surgical methods is influenced by the organizational and financial characteristics of the healthcare system, demographic and clinical characteristics of patients, the knowledge of doctors, etc. The experience of Russia fully confirms this.Conclusion. There is no optimal method for accurately assessing the population's need for certain treatment methods. Each country chooses its own tactics, taking into account its resource capabilities, approaches to decision-making, its values and preferences, but the general trend is a decrease in the number of CABG operations while increasing the PCI. In Russia, there is a multiple increase in the number of CABG and PCI, but it is less than the indicators of most countries.

Remote clinical quality management of endovascular care

Aim. To assess the effectiveness of remote clinical quality management of endovascular care.Methods. The system of clinical quality management of medical care in myocardial infarction (MI) including the quality of remote control of endovascular care was developed and introduced into the health care system of the Moscow Region as a part of the comprehensive study in 2008–2020. The number of people under the study was 8375. The ground for assessing the effectiveness of remote clinical management in 2019–2020 was the health care system of megapolis. Based on the analysis of 2966 endovascular procedures protocols, the treatment tactics effectiveness of intraoperative decisions was studied after an emergency coronary angiography (ECA) had been performed by interventional cardiologists. The system of remote clinical quality management of endovascular care included a complex of audiovisual communications, computer system processes, mentoring and the algorithm for making an intraoperative decision. The effectiveness of remote clinical quality management of endovascular care was investigated on the number of percutaneous coronary interventions (PCI) in MI, mortality of patients with MI in the Regional vascular center in 2019–2020. The T-criteria was used to assess the reliability. The material statistical processing was carried out in the Statistica 6.0 package calculating adequate statistical indicators and their reliability at p≤0.005.Results. Ratio PCI/ECA in 2019, January-March 2020 counted up to 48.95%. In AprilDecember 2020 it increased up to 71.6% (p<0.001). The frequency of performing PCI increased by 1.46 times (p<0.001). Hospital mortality from MI decreased during the following period 2019, April-December 2020 from 9.7% to 8.2% (p = 0.005).Conclusion. Remote clinical management based on telemedicine and mentoring process technologies contributes to improving the quality of endovascular care in MI.

The analysis of in-hospital and long-term results of percutaneous coronary intervention supported by extracorporeal membrane oxygenation in patients with coronary artery disease

Aim. To analyze in-hospital and long-term (12 months) results of percutaneous coronary intervention (PCI) supported by extracorporeal membrane oxygenation (ECMO) in patients with stable coronary heart disease and multivessel coronary artery disease, and to justify the use of such approach in the treatment of this group of patients.Methods. The retrospective analysis included 13 patients with stable coronary artery and multivessel coronary disease. The mean SYNTAX score before the intervention was 31.4±10.8. Between 30 days and 12 months in the postoperative period, the frequency and type of the following major adverse cardiovascular events (MACE) was assessed: all-cause death, myocardial infarction, stroke, repeat revascularization. Twelve months after the event, the data on the frequency and type of adverse cardiovascular events were collected by means of telephone follow-up.Results. Coronary intervention supported by ECMO was performed in all patients. 8 (61.6%) patients required an open surgical approach for ECMO cannula insertion. Door to balloon time was 109.6±79.2 minutes. The mean duration of ECMO support was 101.7±45.4 minutes. Haemodynamic instability, abnormalities in pulmonary gas exchange and rhythm disturbances were not revealed during primary PCI, making it possible to wean off the ECMO post-PCI. The mean residual SYNTAX score was 9.3±11.8. BARC class ≥3 bleeding complications were observed in 6 of 13 patients. Long-term major adverse cardiovascular events with fatal outcomes occurred in 3 (23.1%) patients.Conclusion. Supporting high-risk PCI with ECMO in patients with stable coronary artery disease, multivessel coronary artery disease and low left ventricular ejection fraction made it possible to successfully perform the intervention in all patients. Nevertheless, the long-term (12 months) results show a high percentage of recurrent myocardial infarction, which can be associated with high residual SYNTAX score.

Secondary neurological outcomes in patients with brachiocephalic and coronary artery disease in the early postoperative period after simultaneous and hybrid surgical treatment

Aim. To compare secondary neurological outcomes in patients with brachiocephalic and coronary artery disease in the early postoperative period after different surgical treatment strategies (simultaneous and hybrid).Methods. Secondary neurological outcomes were evaluated in 43 patients with coronary and brachiocephalic artery disease in the early postoperative period after (1) carotid endarterectomy and on-pump coronary artery bypass surgery; (2) percutaneous coronary intervention and carotid endarterectomy. Demographic, clinical, instrumental data were collected. Neuropsychological assessment was performed using the Mini-Mental State Examination and Frontal Assessment Battery. Memory, attention and neurodynamics were measured using the “Status-PF” software at days 2–3 before the surgery and at days 5–7 after it. The presence of postoperative cognitive dysfunction was estimated on the basis of criteria defined as a 20% decline on 20% of the tests. Statistical analysis was performed using the software package “Statistica 10.0”.Results. Patients who underwent hybrid intervention demonstrated improved attention and memory in the early postoperative period. Complex visual-motor reaction significantly increased in patients after simultaneous surgery. Attention differed significantly in both groups. Thus, patients from the hybrid group processed more characters per 1 and 4 minutes while completing the Bourdon proof reading test. The total number of processed characters prevailed in the hybrid group. Cognitive processing speed was higher in the hybrid group according to the brain performance test. The incidence of early postoperative cognitive dysfunction was 60% in patients after simultaneous surgery and 11% in patients after hybrid surgery (p = 0.006, OR±SE 12.5±3.2).Conclusion. Hybrid intervention has shown its superiority over simultaneous intervention in terms of low rate of early cognitive impairment, thereby confirming the necessity to take into account the obtained results while selecting the optimal surgical treatment in patients with coronary and brachiocephalic artery disease present with cognitive deficits at baseline.

Radiomic features of epicardial adipose tissue in coronary atherosclerosis

Aim. To investigate the association of the radiomic characteristics of epicardial adipose tissue (EAT) on contrast-free computed tomography (CT) of the heart with the severity of obstructive coronary lesion and myocardial ischemia.Methods. The study included 68 patients with coronary heart disease (mean age of 63.5±9.4, 45 men and 23 women), and 15 patients (mean age 30±4.8; 14 men and 1 woman) without cardiovascular disease as a control group. All the patients underwent multispiral computed coronary angiography, coronary calcium scores (CCS) determination and stress myocardial perfusion scintigraphy. Radiomic characteristics of EAT (texture analysis by gradations of gray color) were determined on non-contrast computer tomogram images of the heart using 3D-Sliser software and the SliserRadiomics module (version 4.10.2). The obtained indicators were compared between a control and under the study groups as well as between subgroups of patients divided according to the degree of obstruction of the coronary arteries, the size of the perfusion defect, and the value of the CCS.Results. The comparative analysis of radiomic indicators of EAT between patients with coronary artery disease and the control group showed the presence of statistically significant differences between them. At the same time, the correlation analysis in the study group did not reveal any correlations between the radiomic parameters and the size of the perfusion defect, CCS or degree of stenosis of the lumen of the coronary arteries.Conclusion. The textural characteristics of EAT in patients with coronary heart disease differ from those in individuals without cardiovascular pathology. At the same time, these indicators are not associated with the severity of obstructive lesions of the coronary arteries, the value of the CCS, and the size of the perfusion defect according to scintigraphy.

Methodological approach to risk prediction noncompliance in patients with myocardial infarction

Aim. To develop a methodological approach in order to predict the risk of noncompliance in patients with myocardial infarction.Methods. 416 patients were questioned in the single-centered, prospective, non-randomized study using the original author's method. The patients were treated in specialized cardiological departments of the city of Kemerovo with the diagnosed myocardial infarction. The methodological approach to predicting the risk of non-compliance in patients with myocardial infarction covered 29 factors in 6 main blocks: sociodemographic and socio-economic characteristics, health status, medical and pharmaceutical culture of the patient, awareness of medical and pharmaceutical services, patient adherence to medical recommendations.Results. Patients with myocardial infarction were characterized by insufficient adherence to the therapy, low awareness of the disease, which can negatively affect the longterm disease prognosis. The identification of a large number of subjective factors limiting adherence to the therapy is the reason for the widespread use of noncompliance risk measurement among patients with myocardial infarction, which will allow determining the range of the risk group for each individual patient.Conclusion. The adherence to the treatment of patients with myocardial infarction is revealed as 80% which is indicated as low and requires the prophylactic use of educational and psychological programs that increase medical and social awareness and readiness to comply with the doctor's recommendations, and also justifies the need for complex risk measurement of non-compliance patients for personalized identification and addressing risk factors for poor adherence to therapy.

Osteoporosis in patients with coronary artery disease after coronary bypas surgery

Aim. To determine the most significant predictors of an unfavorable progress of osteoporosis (OP) in men with coronary artery disease after coronary artery bypass grafting (CABG) according to long-term (5 years) follow-up data.Methods. The prospective study included 393 patients (men) hospitalized for CABG. All patients underwent multispiral computed tomography of the coronary and carotid arteries to assess the calcium score (CS) and determine the equivalent density of calcium deposits (EDCD), coronary angiography, and dual-energy X-ray absorptiometry. After 5 years (average 59 months) of follow-up, the prognosis (status alive/dead) was assessed in 335 patients. Mortality during follow-up in patients after CABG was 10.7% (36 patients died). 257 patients underwent repeated osteodensitometry, quantitative assessment of coronary and carotid calcification, assessment of the “end points” of bone status (osteoporotic fractures, osteoporosis).Results. During the five-year follow-up an increase in the prevalence of OP was noted from 76.1% to 90.7%, while in 43.6% of cases, the progression of OP was recorded. Fractures occurred in 39 patients (15.2%), and in 34 (13.2%) osteoporosis developed for the first time. OP progression is associated with smoking (OR 5.3, 95% CI 3.1–9.4), 30% or more carotid artery stenosis (OR 5.6, 95% CI 2.9–10.7), baseline severe (more than 400) calcification of the coronary arteries (OR 2.7 at 95% CI 1.3–9.8), low density of (EDCD less than 0.19 g/mm3 ) coronary (OR 1.7 at 95% CI 1.1–8.2) and carotid (OR 2.4, 95% CI 1.4–10.3) calcium deposits. Linear regression analysis made it possible to establish that the reliable predictors of an unfavorable course of OP are coronary CS, EDCD of the carotid arteries, and the absence of statin therapy.Conclusion. OP progression in patients in the long-term period (5 years) after CABG was noted in 43.6%. The predictors of OP progression and the complications are a high level of coronary artery calcification, a low EDCD in the carotid arteries, and 30% or more stenosis of the carotid arteries. Patients receiving statins were associated with a lower risk of osteoporosis.