Search

The aim of the study was to compare scenarios of numerical modeling of the operation of a heart valve bioprosthesis, identifying their advantages and limitations. Material and methods. Numerical modeling was conducted in the Abaqus/ CAE (Dassault Systèmes, France) engineering analysis environment, simulating two cycles of the valve apparatus’s operation. In total, three different computer models were studied, each providing different levels of detail and complexity of the “UniLine” bioprosthesis. Model No.1 was the most simplified and considered only the geometry of the flap; Model No. 2 incorporated elastic connectors with variable stiffness; Model No. 3 included a composite support frame. Qualitative validation of the modeling results was conducted by comparing with the bench tests data obtained on the hydrodynamic stand (ViVitro Labs, Canada) during tests of the corresponding clinical model of the “UniLine” bioprosthesis. Results. One of the setups, Model No. 2, displayed an artificial stress concentration according to Von Mises in the connector attachment area, reaching 2.695 MPa, which is close to the material’s strength limit. Other setups showed a more moderate stress distribution – up to 0.803 and 0.529 MPa. Moreover, it was demonstrated that only Model No. 2 and Model No. 3 reproduce the key effect of the bioprosthesis operation, the mobility of the commissural posts, ensuring a qualitative match with the work in bench conditions. Conclusions. A methodology is proposed that may be useful for conducting further in silico studies of heart valve bioprostheses. Boundary conditions, methods for linking prosthetic components, and opportunities for large-scale “exploratory” studies based on using simplified models are described. The study results confirm the necessity of including all prosthesis components in the numerical model for a more comprehensive and realistic representation of its biomechanics. Such detail contributes to a more accurate safety and effectiveness assessment of the device and can also serve as a foundation for its further optimization.

Aim. To determine the potential of diagnostic electron microscopy of intraplaque processes (severity of lipid damage, fibrous cap thickness and condition, severity of pathological neovascularization, presence, nature and severity of calcification, ratio and distribution of various cell populations).Material and methods. The study objects were plaques removed during endar­terectomy from the human carotid artery and segments of the human internal mammary artery removed during coronary bypass surgery. Whole specimens were subjected to chemical fixation, staining with heavy metal salts, embedding in epoxy resin followed by layer-by-layer grinding, polishing, contrasting, visualization using back-scattered electron scanning electron microscopy and three-dimensional reconstruction with color mapping (modified EM-BSEM).Results. The use of a modified EM-BSEM made it possible to: 1) visualize the fibrous cap thickness and assess the extracellular matrix; 2) analyze the neointimal lipid distribution; 3) perform three-dimensional reconstruction and analyze the microenvironment of calcifications of various sizes; 4) visualize endothelial cells, defects in interendothelial contacts and the basement membrane of neointimal capillaries with their subsequent three-dimensional reconstruction; 5) perform an analysis of age-dependent defects in the basement membrane and internal elastic membrane of the internal mammary artery. The resolution of the obtained images was significantly superior to intravascular imaging methods (intravascular ultrasound and optical coherence tomography), allowing additional assessment of capillary fluidity, the degree of calcification encapsulation and the condition of elastic fibers. Three-dimensional reconstruction of calcifications, neointimal capillaries and elastic fibers made it possible to assess their spatial density and heterogeneity. Simultaneously with the identification and assessment of these histological structures, objective phenotyping of cell populations was performed, which made it possible to isolate macrophages and foam cells, vascular smooth muscle cells, fibroblasts and endothelial cells in atherosclerotic plaques and automatically identify them through color mapping determined by their electronic contrast distribution signatures.Conclusion. The modified EM-BSEM method allows for universal electron microscopic diagnosis of atherosclerotic and elastolytic lesions of large arteries with high information content about vascular remodeling and high accuracy. Electronic contrast distribution signatures unique for each cell population indicate the possibility of their automated phenotyping using specialized neural network algorithms.

The failure of heart valve bioprostheses, requiring repeated intervention to replace them, is a serious drawback that narrows the scope of such devices. The present study demonstrates the experimental investigation of a medical device designed to partially solve the problem of repeated interventions on heart valves, primarily with an emphasis on reducing the duration and trauma of such procedures due to the sutureless balloon implantation method of the «valvein- valve» method.Material and methods. The paper presents a series of in silico, in vitro and in vivo experiments to evaluate various aspects of the device under development. Numerical modeling of the final shape setting to the supporting frame of the heart valve prosthesis to select the most promising concept for prototyping was carried out in the Abaqus/CAE (Dassault Systèmes, France) based on the finite element method. The selected optimal support frame model was prototyped in the form of a series of prosthesis samples of four standard sizes for hydrodynamic studies of quantitative characteristics in vitro. The study was carried out in the Vivitro Labs unit (Vivitro Labs, Canada), imitating the physiological mode of the heart, the prostheses were examined for the mitral position. The developed prototypes of the device were supplemented with related products, an implant holder and a balloon catheter, after which the proposed method of sutureless fixation was validated in an in vitro implantation procedure on a bovine heart model and a series of in vivo (n = 3) chronic experiments on animals.Results. In the course of numerical simulation, it was shown that in Model No. 3 of the supporting frame of the prosthesis, the smallest stresses occur – with an amplitude of up to 490 MPa. For other concepts (Models No. 1 and No. 2), this indicator was significantly higher, 543 and 514 MPa, respectively. Prototypes obtained on the basis of the selected shape of the support frame demonstrated satisfactory hydrodynamic characteristics: effective hole area 190-261 mm2, regurgitation volume 6–9 ml/cycle, average transprosthetic gradient 4.4–6.4 mmHg, depending on size. The study of the technology of sutureless balloon implantation in an in vitro model of the heart and the subsequent chronic experiment on sheep confirmed the main idea of the system – the possibility of a significant reduction in the duration of repeated prosthetics. It has been shown that the time of suture implantation of the “classic” frame prosthesis of the mitral valve is 23–29 minutes, with a total access time of 41–52 minutes. When implanting the experimental device, the sutureless prosthesis itself took 4–6 minutes, access time 24–29 minutes. At the same time, one-month results of an echocardiographic study of the operation of the prosthesis demonstrated satisfactory hemodynamics.Conclusions. This work demonstrates a consistent series of tests of the system being developed for repeated heart valve replacement, which substantiates some design solutions, confirms the effectiveness and viability of the chosen approach to sutureless minimally invasive implantation.

Background. The study of explanted heart valve bioprostheses is a valuable source of information about the destructive processes in their components that develop as a result of prolonged contact with the recipient’s body. An analysis of the morphology, staging and degree of involvement of various valve prosthesis materials in the prevalence of pathological processes – calcification, mechanical damage, growth of the connective tissue capsule, is the basis for developing potential methods for increasing the service life of these products and reducing the risk of re-interventions. The aim of the study was to evaluate the potential of computed microtomography to analyze the internal structure of a biological prosthetic heart valve explanted due to dysfunction. Material and methods. In this work, we investigated the prevalence of pathological mineralization of the PeriCor bioprosthesis, explanted as a result of the developed dysfunction of the leaflet apparatus with a clinical picture of grade 2B prosthetic insufficiency. The material was described macroscopically, after which it was subjected to high-resolution computed microtomography. In the structure of the sample, X-ray dense areas of pathological mineralization were identified and described, and the volume of the material involved in calcification was assessed. Results. It was shown that the main pathological changes that led to prosthetic dysfunction were degenerative changes in the biomaterial with signs of calcification, thickening and rupture of the leaflets. It was quantitatively determined that the areas of radiologically dense inclusions (calcifications) occupy 11.1 % of the volume of the material. It has been established that the described areas are associated with the sheathing of the frame and with the elements of the suture material used in the production of this bioprosthesis. Conclusion. The method of non-destructive analysis of the internal structure of altered materials of a biological prosthesis studied in this work has demonstrated the possibility of а qualitative and quantitative assessment of areas of pathological mineralization, their distribution and connection with other processes leading to the development of prosthetic dysfunction. The method makes it possible to visualize macro- and microsites of calcification and can become a valuable tool to complement existing approaches to the study of explanted bioprostheses.

Bioprosthetic valve dysfunction represent a serious drawback that limits the wider clinical use of these medical devices for valvular heart disease surgery. Modern studies describe the view of pathophysiologists on this problem as a multifactorial multi-stage process that causes irreversible changes in bioprosthesis components, ultimately leading to its dysfunction. However, in addition to under- standing the causes and manifestations of prosthetic valve dys- function, an applied question arises about the treatment strategies — determining the most attenuated and accessible low-risk method/ device. The aim of this review was to analyze and systematize current literature data on methods and designs used in repeated surgical and transcatheter interventions on heart valves.

Aim. To consider application of convolutional neural networks for processing medical images in various fields of cardiology and cardiac surgery using publications from 2016 to 2019 as an example.Materials and methods. In the study, we used the following scientific databases: PubMed Central, ArXiv, ResearchGate. The cited publications were grouped by the area of interest (heart, aorta, carotid arteries).Results. The general principle of work of the technology under consideration was described, the results were shown, and the main areas of application of this technology in the studies under consideration were described. For most of the studies, sample sizes were given. The author’s view on the development of convolutional neural networks in medicine was presented and some limiting factors for their distribution were listed.Conclusion. A brief overview shows possible areas of application of convolutional neural networks in the fields of cardiology and cardiac surgery. Without denying the existing problems, this type of artificial neural networks may help many doctors and researchers in the future.

Objective: to construct geometric models of carotid bifurcation and build a computer modeling for carotid endarterectomy (CEA) operations with patches of various configurations.Materials and methods. The method uses reconstructed models of a healthy blood vessel obtained from a preoperative computed tomography (CT) study of the affected blood vessel of a particular patient. Flow in the vessel is simulated by computational fluid dynamics using data from the patient's ultrasonic Doppler velocimetry and CT angiography. Risk factors are assessed by hemodynamic indices at the vessel wall associated with Wall Shear Stress (WSS).Results. We used the proposed method to study the hemodynamic results of 10 virtual CEA operations with patches of various shapes on a reconstructed healthy artery of a particular patient. The reason for patch implantation was to ensure that the vessel lumen is not narrowed as a result of the surgery, since closing the incision without a patch can reduce the vessel lumen circumference by 4–5 mm, which adversely affects blood flow. On the other hand, too wide a patch creates aneurysmorphic deformation of the internal carotid artery (ICA) mouth, which is not optimal due to formation of a large recirculation zone. In this case, it was found that the implanted patch width of about 3 mm provides an optimal hemodynamic outcome. Deviations from this median value, both upward and downward, impair hemodynamics. The absence of a patch gives the worst of the results considered.Conclusion: The proposed computer modeling technique is able to provide a personalized patch selection for classical CEA with low risk of restenosis in the long-term follow-up.

The aim of the study was an in vitro hydrodynamic study of the developed prosthetic heart valve of the second generation, designed to carry out an implantation using «valve-in-valve» method. Material and methods. Prototypes of the developed prosthesis were studied under simulated physiological conditions of the heart using a Vivitro Labs pulse duplicator (Canada) in a comparative aspect with «UniLine» clinical commercial aortic valve bioprosthesis (Russia). Samples were tested by simulating sutureless implantation procedure. Results. The developed valves showed satisfactory hydrodynamic characteristics – for all cases of «implantation» from the position of the average trans-prosthetic gradient (6.1–11.1 mm Hg) and the effective orifice area (1.60–1.81 cm2 ). The analysis of the regurgitation fraction allowed us to determine the optimal sizes for implantation using «valvein-valve» method, which subsequently will form the basis of sizing guidelines for size selection. A qualitative analysis of the leaflet’s work demonstrated the presence of slight asymmetry for a number of prostheses – in case of mismatch of sizes when simulating «valve-in-valve» procedure. Conclusion. The tests demonstrate the viability of the developed design from the standpoint of hydrodynamic efficiency and determines the basic rules of selecting a prosthesis for reimplantation relative to the primary valve.

Objective: to investigate dependence of the mechanical properties of mitral annuloplasty rings on heat annealing modes. Materials and methods. The study evaluates the nature of change in stress–strain curves under uniaxial compression of experimental samples processed at varying annealing temperature, duration and pressure. Results. It was noted that higher exposure, temperature, and lower pressure led to increased structural rigidity and strength for small strains. Moreover, the extent of influence of annealing temperature and duration was comparable. A 40% (500–700 °C) change in temperature altered the mechanical properties of the ring – 20% increase in strength. A similar change in heat treatment time (4.5–6.5 min) resulted in a 27% increase in the force required for a 15% compression. Conclusion. The experimental dependences presented in the work allow recommending main parameters for heat treatment mode: temperature range 600–700 °C, 10.5 minutes exposure time, and 0.1–0.5 atm air pressure in the furnace chamber.

Implantation of polymeric heart valves can solve the problems of existing valve substitutes – mechanical and biological. Objective: to comprehensively assess the hemocompatibility of styrene-isobutylene-styrene (SIBS) triblock copolymer, synthesized by controlled cationic polymerization in comparison with expanded polytetrafluoroethylene (ePTFE) used in clinical practice. Materials and methods. SIBS-based films were made by polymer solution casting method; in vitro biocompatibility assessment was performed using cell cultures, determining cell viability, cell adhesion and proliferation; tendency of materials to calcify was determined through in vitro accelerated calcification; in vivo biocompatibility assessment was performed by subcutaneous implantation of rat samples; hemocompatibility was determined ex vivo by assessing the degree of hemolysis, aggregation, and platelet adhesion. Results. The molecular weight of synthesized polymer was 33,000 g/mol with a polydispersity index of 1.3. When studying cell adhesion, no significant differences (p = 0.20) between the properties of the SIBS polymer (588 cells/mm2) and the properties of culture plastics (732 cells/mm2) were discovered. Cell adhesion for the ePTFE material was 212 cells/mm2. Percentage of dead cells on SIBS and ePTFE samples was 4.40 and 4.72% (p = 0.93), respectively, for culture plastic – 1.16% (p < 0.05). Cell proliferation on the ePTFE surface (0.10%) was significantly lower (p < 0.05) than for the same parameters for SIBS and culture plastic (62.04 and 44.00%). Implantation results (60 days) showed the formation of fibrous capsules with average thicknesses of 42 μm (ePTFE) and 58 μm (SIBS). Calcium content in the explanted samples was 0.39 mg/g (SIBS), 1.25 mg/g (ePTFE) and 93.79 mg/g (GA-xenopericardium) (p < 0.05). Hemolysis level of red blood cells after contact with SIBS was 0.35%, ePTFE – 0.40%, which is below positive control (p < 0.05). Maximum platelet aggregation of intact platelet-rich blood plasma was 8.60%, in contact with SIBS polymer – 18.11%, with ePTFE – 22.74%. Conclusion. In terms of hemocompatibility properties, the investigated SIBS polymer is not inferior to ePTFE and can be used as a basis for development of polymeric prosthetic heart valves.

Aim: to assess the contribution of primary tissue failure, calcification, bacterial contamination and pannus to bioprosthetic valve dysfunction.Materials and methods. To evaluate degenerative changes of the «UniLine» bioprosthesis explanted from the mitral position with macroscopic examination, light and scanning electron microscopy, and micro-computed tomography (micro-CT). Light microscopy was used to analyze cell composition, the presence of bacteria, the localization of calcific deposits and recipient cells. Scanning electron microscopy allowed confirming the presence of bacteria. Micro-CT was used to evaluate the deformation of the bioprosthetic elements, the distribution of calcific deposits and their volume in the valve tissue.Results. The presence of pannus, calcification, primary tissue failure and bacterial contamination were found among the causes leading to bioprosthetic dysfunction. Prosthetic leaflets showed pannus growth from the inflow tract. Excessive circumferential pannus extended into outflow tract. Calcific deposits were mostly localized in the commissural zone and the central portion of the leaflets. The total volume of calcification accounted for 1/3 of the bioprosthetic tissue component. The relationship between calcification and stress-strain properties of the bioprosthetic elements has been indicated. The asymmetric deformation of the bioprosthetic stent frame and leaflets with 1.5-fold thickening of the last has been found. The areas with loose and fragmented collagen and elastic fibers contained red blood cells and neutrophils. Endothelial cells and fibroblastic cells were present in the outer surface layers. There were no signs of calcification in the areas accumulating cells and bacteria.Conclusion. We can assume that primary tissue failure, calcification, bacterial contamination and pannus independently contribute to the onset of bioprosthetic heart valve dysfunction.

Bioprosthetic valves are often used to replace diseased heart valves. They differ from mechanical valves by optimal hemodynamic parameters and low thrombogenicity. However, although the durability of modern bioprosthetic valves, their design, and implantation procedures are being improved, the replacement of the native valve does not necessarily lead to favorable outcome, because valvular defect is often replaced by “prosthetic valve disease”. Structural valve degeneration is one of the main causes of bioprosthetic valve failure, but its mechanisms have not been studied in detail. This review summarizes and analyzes current data on mechanisms responsible for bioprosthetic valve structural degeneration. These mechanisms include passive degeneration, inflammation, fibrosis and osteogenesis.

The literature review discusses the studies on developing the polymer membrane of a coronary stent graft. The new generation of coronary stent grafts is designed to increase the hemocompatibility and ensure its delivery to poorly accessible artery regions. Based on the clinical use results, three groups of promising polymers were identified: biostable polyurethanes, polyvinyl alcohol-based cryogels, bioresorbable compositions based on polylactide-caprolactone and lactic acid-glycolic acid copolymer. However, the possibility of their clinical application requires further experimental studying.

Aim. To assess the contribution of pannus and calcification to the development of bioprosthetic valve dysfunction after tricuspid valve replacement in a pediatric patient.Materials and methods. A 3-month-old patient presented with tricuspid valve dysplasia and grade 4 tricuspid insufficiency underwent tricuspid valve replacement with the bioprosthesis «PeriCor» (ZAO «NeoKor», Russian Federation). The patient at the age of 6 years required a redo tricuspid valve replacement 5 years 8 months after initial surgery. Degenerative changes of the dysfunctional bioprosthetic valve explanted from the tricuspid position were assessed using macroscopic description and light microscopy. Cellular composition, the presence of bacteria, colocalization of calcifications with recipient cells were analyzed. The distribution of calcifications and their volume in the biomaterial tissue were estimated using microcomputer tomography imaging (micro-CT).Results. Bioprosthetic valve dysfunction was mainly caused by the pannus formation which was shown to encapsulate the anterior leaflet, resulting in its total failure and severe stenosis (reduced effective orifice area). There were no signs of ruptures and perforations in the valve tissues found. All leaflets were shown to contain predominantly fibroblastic cells and single blood cells, mainly located in the surface layers of the leaflets in the regions without any signs of calcification. Bacteria staining was negative for all types of the studied biomaterials. Calcifications were present in all xeno-tissue elements of the explanted bioprosthesis (i.e. leaflets, aortic segment, and pericardium). In addition, calcifications were also found in pannus growing during a functioning bioprosthetic valve. Calcifications were predominantly located in the co-optation and commissure zones of the leaflets. Importantly, massive calcifications were observed around the bioprosthetic stent frame. The total volume of calcification accounted for 1/3 of the biological component of the bioprosthesis (729 mm3).Conclusion. According to the data obtained in this study, we may conclude that the primary cause of the bioprosthesis failure was the growth of connective tissues, resulting in pannus-related dysfunction, rather than severe calcification of all bioprosthetic components. One may assume that bioprosthetic dysfunction is related to the peculiarity of the inflammatory response of the preschool patient. However, this typeof dysfunctions requires further investigation.

The aim of the study was to perform a series of in vitro tests of a prototype of the developing heart valve prosthesis to evaluate its functional characteristics. Materials and methods. In this work we have used the frames and full prototypes of the prosthesis, consisting of a stent-like stainless steel support frame with mounted biological leaflets and cover. The authors evaluated the calculated and experimental forces necessary for the displacement of the sutureless implanted prosthesis using the test machine under uniaxial tension. The risk of defects and damages to the supporting framework as a result of implantation was evaluated by scanning electron microscopy. The hydrodynamic characteristics of the prosthesis were investigated under physiological conditions and «valvein-valve» implantation. Evaluation of the ergonomics and applicability of the proposed construction on the cadaver heart model of cattle was carried out. Results. As a result of the forces assessment, it was found that the force required to shear the prosthesis was 3.12 ± 0.37 N, while the calculated value was 1.7 N, which is significantly lower than the obtained value. The comparison of the images obtained with small and large magnifications demonstrated the absence of critical surface defects. Additional analysis under the super-large magnifications also did not reveal problem areas. During the hydrodynamic study, it was shown that the average transplant gradient increased slightly from 2.8–3.4 to 3.2–4.5 mm Hg for the initial prosthesis and the «valve-in-valve» complex, respectively. The decrease of the effective orifice area was 6–9% relative to the initial one. Evaluation of the implantation technique demonstrated the consistency of the approach: the use of the developed holder in combination with the balloon implantation system made it possible to position the prosthesis throughout the procedure. Conclusion. The series of tests demonstrates the consistency of the developed design, intended for the replacement of a failed prosthetic valve of the heart with the «valve-in-valve» implantation.

Aim: to evaluate the biomechanical remodeling of polymer grafts modified with vascular endothelial growth factor (VEGF) after implantation into rat abdominal aorta.Materials and methods. Vascular grafts of2 mmdiameter were fabricated by electrospinning from polycaprolactone (PCL) and a mixture of poly (3-hydroxybutyrate-co-3-hydroxyvalerate) and PCL. The grafts were modified with VEGF by biphasic electrospinning. Morphology of the grafts was assessed by scanning electron microscopy. Physico-mechanical properties of PCL and PHBV/PCL grafts were estimated using uniaxial tensile test and physiological circulating system equipped with state-of-theart ultrasound vascular wall tracking system. Physico-mechanical testing of PCL/VEGF and PHBV/PCL/VEGF was performed before and after implantation into rat abdominal aorta for 6 months. The modeling of coronary artery bypass grafting (CABG) was performed by finite element analysis for modified grafts.Results. Durability of PCL and PHBV/PCL grafts did not differ from that of human internal mammary artery; however, elasticity and stiffness of these grafts were higher compared to internal mammary artery. Viscoelastic properties of the grafts were comparable to those of native blood vessels. Modification of the grafts with VEGF reduced material stiffness. Six months postimplantation, PCL/VEGF and PHBV/PCL/VEGF were integrated with aortic tissue that induced changes in the physico-mechanical properties of the grafts similar to the native vessel. Biomechanical modeling confirmed the functioning of modified grafts in bypass position for CABG.Conclusion. PCL/VEGF and PHBV/PCL/VEGF grafts have satisfactory physico-mechanical properties and can be potentially used in the reconstruction of blood vessels.