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Percutaneous coronary intervention, a common treatment for atherosclerotic coronary artery lesions, occasionally results in perforations associated with increased mortality rates. Stents coated with a bioresorbable polymer membrane may offer an effective solution for sealing coronary artery perforations. Additionally, such coatings could be effective in mitigating neointimal hyperplasia within the vascular lumen and correcting symptomatic aneurysms. This study examines polymer membranes fabricated by electrospinning of polycaprolactone, polydioxanone, polylactide-co-caprolactone, and polylactide-co-glycolide. In uniaxial tensile tests, all the materials appear to surpass theoretically derived elongation thresholds necessary for stent deployment, albeit polydioxanone membranes are found to disintegrate during the experimental balloon expansion. As revealed by in vitro hemocompatibility testing, polylactide-co-caprolactone membranes exhibit higher thrombogenicity compared to other evaluated polymers, while polylactide-co-glycolide samples fail within the first day post-implantation into the abdominal aorta in rats. The PCL membrane exhibited significant water leakage in the permeability test. Comprehensive evaluation of mechanical testing, bio- and hemocompatibility, as well as biodegradation dynamics shows the advantage of membranes based on and the mixture of polylactide-co-caprolactone and polydioxanone over other polymer groups. These findings lay a foundational framework for conducting preclinical studies on stent configurations in large laboratory animals, emphasizing that further investigations under conditions closely mimicking clinical use are imperative for making definitive conclusions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rezvova, Ovcharenko, Klyshnikov, Glushkova, Kostyunin, Shishkova, Matveeva, Velikanova, Shabaev and Kudryavtseva.)

Introduction: The development of next-generation tissue-engineered medical devices such as tissue-engineered vascular grafts (TEVGs) is a leading trend in translational medicine. Microscopic examination is an indispensable part of animal experimentation, and histopathological analysis of regenerated tissue is crucial for assessing the outcomes of implanted medical devices. However, the objective quantification of regenerated tissues can be challenging due to their unusual and complex architecture. To address these challenges, research and development of advanced ML-driven tools for performing adequate histological analysis appears to be an extremely promising direction., Methods: We compiled a dataset of 104 representative whole slide images (WSIs) of TEVGs which were collected after a 6-month implantation into the sheep carotid artery. The histological examination aimed to analyze the patterns of vascular tissue regeneration in TEVGs in situ . Having performed an automated slicing of these WSIs by the Entropy Masker algorithm, we filtered and then manually annotated 1,401 patches to identify 9 histological features: arteriole lumen, arteriole media, arteriole adventitia, venule lumen, venule wall, capillary lumen, capillary wall, immune cells, and nerve trunks. To segment and quantify these features, we rigorously tuned and evaluated the performance of six deep learning models (U-Net, LinkNet, FPN, PSPNet, DeepLabV3, and MA-Net)., Results: After rigorous hyperparameter optimization, all six deep learning models achieved mean Dice Similarity Coefficients (DSC) exceeding 0.823. Notably, FPN and PSPNet exhibited the fastest convergence rates. MA-Net stood out with the highest mean DSC of 0.875, demonstrating superior performance in arteriole segmentation. DeepLabV3 performed well in segmenting venous and capillary structures, while FPN exhibited proficiency in identifying immune cells and nerve trunks. An ensemble of these three models attained an average DSC of 0.889, surpassing their individual performances., Conclusion: This study showcases the potential of ML-driven segmentation in the analysis of histological images of tissue-engineered vascular grafts. Through the creation of a unique dataset and the optimization of deep neural network hyperparameters, we developed and validated an ensemble model, establishing an effective tool for detecting key histological features essential for understanding vascular tissue regeneration. These advances herald a significant improvement in ML-assisted workflows for tissue engineering research and development., Competing Interests: VD was employed by Quantori. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Danilov, Laptev, Klyshnikov, Stepanov, Bogdanov, Antonova, Krivkina, Kutikhin and Ovcharenko.)

Background: Decellularized xenogenic scaffolds represent a promising substrate for tissue-engineered vascular prostheses, particularly those with smaller diameters (<6 mm). Despite their benefits, a notable limitation presents itself during decellularization, namely, the diminished mechanical strength that introduces the risk of aneurysmal dilations in the early post-implantation period. This study introduces a strategy for modification the mechanical properties of these biological scaffolds through the forming of an external polymeric reinforcement via thermal extrusion., Methods: The study utilized scaffolds fabricated from bovine internal mammary arteries through decellularization and preservation. The scaffolds were divided into subgroups and reinforced with polymeric helices made of Polyvinylidene fluoride (PVDF) and Polycaprolactone (PCL), n  = 5 for each. An experimental setup for external reinforcement coating was designed. Computed microtomography was employed to obtain accurate 3D models of the scaffolds. Mechanical properties were evaluated through in vitro uniaxial tension tests (Z50, Zwick/Roell, Germany), compliance evaluation and numerical simulations (Abaqus/CAE, Dassault Systemes, France) to investigate the effect of external reinforcement on aneurysm growth., Results: Using a double-layer helix for the reinforcement significantly enhanced the radial tensile strength of the scaffolds, increasing it up to 2.26 times. Yet, the comparison of vessel's compliance between two reinforced and the Control scaffolds within the physiological pressures range did not reveal any significant differences. Numerical simulation of aneurysm growth showed that thin-walled regions of the Control scaffold developed aneurysmal-type protrusions, bulging up to 0.7 mm, with a substantial degradation of mechanical properties. In contrast, both PVDF and PCL reinforced scaffolds did not exhibit significant property degradation, with deformations ranging 0.1-0.13 mm depending on the model, and a maximum decrease in the modulus of elasticity of 23%., Conclusion: The results of the study demonstrated that the external polymer helical reinforcement of decellularized scaffolds via thermal extrusion enables a controlled modification of mechanical properties, notably enhancing radial strength while maintaining sufficient compliance within the physiological pressure range. A series of in vitro tests demonstrated the consistency and potential of this approach for decellularized xenogenic scaffolds, a concept that had not been explored before., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Klyshnikov, Rezvova, Belikov, Glushkova and Ovcharenko.)

Majority of modern techniques for creating and optimizing the geometry of medical devices are based on a combination of computer-aided designs and the utility of the finite element method This approach, however, is limited by the number of geometries that can be investigated and by the time required for design optimization. To address this issue, we propose a generative design approach that combines machine learning (ML) methods and optimization algorithms. We evaluate eight different machine learning methods, including decision tree-based and boosting algorithms, neural networks, and ensembles. For optimal design, we investigate six state-of-the-art optimization algorithms, including Random Search, Tree-structured Parzen Estimator, CMA-ES-based algorithm, Nondominated Sorting Genetic Algorithm, Multiobjective Tree-structured Parzen Estimator, and Quasi-Monte Carlo Algorithm. In our study, we apply the proposed approach to study the generative design of a prosthetic heart valve (PHV). The design constraints of the prosthetic heart valve, including spatial requirements, materials, and manufacturing methods, are used as inputs, and the proposed approach produces a final design and a corresponding score to determine if the design is effective. Extensive testing leads to the conclusion that utilizing a combination of ensemble methods in conjunction with a Tree-structured Parzen Estimator or a Nondominated Sorting Genetic Algorithm is the most effective method in generating new designs with a relatively low error rate. Specifically, the Mean Absolute Percentage Error was found to be 11.8% and 10.2% for lumen and peak stress prediction respectively. Furthermore, it was observed that both optimization techniques result in design scores of approximately 95%. From both a scientific and applied perspective, this approach aims to select the most efficient geometry with given input parameters, which can then be prototyped and used for subsequent in vitro experiments. By proposing this approach, we believe it will replace or complement CAD-FEM-based modeling, thereby accelerating the design process and finding better designs within given constraints. The repository, which contains the essential components of the study, including curated source code, dataset, and trained models, is publicly available at https://github.com/ViacheslavDanilov/generative&#95;design., Competing Interests: VD, AP, and YG were employed by the Company Quantori. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Danilov, Klyshnikov, Onishenko, Proutski, Gankin, Melgani and Ovcharenko.)

The development of a novel artificial heart valve with outstanding durability and safety has remained a challenge since the first mechanical heart valve entered the market 65 years ago. Recent progress in high-molecular compounds opened new horizons in overcoming major drawbacks of mechanical and tissue heart valves (dysfunction and failure, tissue degradation, calcification, high immunogenic potential, and high risk of thrombosis), providing new insights into the development of an ideal artificial heart valve. Polymeric heart valves can best mimic the tissue-level mechanical behavior of the native valves. This review summarizes the evolution of polymeric heart valves and the state-of-the-art approaches to their development, fabrication, and manufacturing. The review discusses the biocompatibility and durability testing of previously investigated polymeric materials and presents the most recent developments, including the first human clinical trials of LifePolymer. New promising functional polymers, nanocomposite biomaterials, and valve designs are discussed in terms of their potential application in the development of an ideal polymeric heart valve. The superiority and inferiority of nanocomposite and hybrid materials to non-modified polymers are reported. The review proposes several concepts potentially suitable to address the above-mentioned challenges arising in the R&D of polymeric heart valves from the properties, structure, and surface of polymeric materials. Additive manufacturing, nanotechnology, anisotropy control, machine learning, and advanced modeling tools have given the green light to set new directions for polymeric heart valves.

Background Whereas the risk factors for structural valve degeneration (SVD) of glutaraldehyde-treated bioprosthetic heart valves (BHVs) are well studied, those responsible for the failure of BHVs fixed with alternative next-generation chemicals remain largely unknown. This study aimed to investigate the reasons behind the development of SVD in ethylene glycol diglycidyl ether-treated BHVs. Methods and Results Ten ethylene glycol diglycidyl ether-treated BHVs excised because of SVD, and 5 calcified aortic valves (AVs) replaced with BHVs because of calcific AV disease were collected and their proteomic profile was deciphered. Then, BHVs and AVs were interrogated for immune cell infiltration, microbial contamination, distribution of matrix-degrading enzymes and their tissue inhibitors, lipid deposition, and calcification. In contrast with dysfunctional AVs, failing BHVs suffered from complement-driven neutrophil invasion, excessive proteolysis, unwanted coagulation, and lipid deposition. Neutrophil infiltration was triggered by an asymptomatic bacterial colonization of the prosthetic tissue. Neutrophil elastase, myeloblastin/proteinase 3, cathepsin G, and matrix metalloproteinases (MMPs; neutrophil-derived MMP-8 and plasma-derived MMP-9), were significantly overexpressed, while tissue inhibitors of metalloproteinases 1/2 were downregulated in the BHVs as compared with AVs, together indicative of unbalanced proteolysis in the failing BHVs. As opposed to other proteases, MMP-9 was mostly expressed in the disorganized prosthetic extracellular matrix, suggesting plasma-derived proteases as the primary culprit of SVD in ethylene glycol diglycidyl ether-treated BHVs. Hence, hemodynamic stress and progressive accumulation of proteases led to the extracellular matrix degeneration and dystrophic calcification, ultimately resulting in SVD. Conclusions Neutrophil- and plasma-derived proteases are responsible for the loss of BHV mechanical competence and need to be thwarted to prevent SVD.

Nanocomposites based on poly(styrene- block -isobutylene- block -styrene) (SIBS) and single-walled carbon nanotubes (CNTs) were prepared and characterized in terms of tensile strength as well as bio- and hemocompatibility. It was shown that modification of CNTs using dodecylamine (DDA), featured by a long non-polar alkane chain, provided much better dispersion of nanotubes in SIBS as compared to unmodified CNTs. As a result of such modification, the tensile strength of the nanocomposite based on SIBS with low molecular weight (M n = 40,000 g mol -1 ) containing 4% of functionalized CNTs was increased up to 5.51 ± 0.50 MPa in comparison with composites with unmodified CNTs (3.81 ± 0.11 MPa). However, the addition of CNTs had no significant effect on SIBS with high molecular weight (M n ~70,000 g mol -1 ) with ultimate tensile stress of pure polymer of 11.62 MPa and 14.45 MPa in case of its modification with 1 wt% of CNT-DDA. Enhanced biocompatibility of nanocomposites as compared to neat SIBS has been demonstrated in experiment with EA.hy 926 cells. However, the platelet aggregation observed at high CNT concentrations can cause thrombosis. Therefore, SIBS with higher molecular weight (M n ~70,000 g mol -1 ) reinforced by 1-2 wt% of CNTs is the most promising material for the development of cardiovascular implants such as heart valve prostheses.

Objective: To describe geometric models of carotid artery bifurcation and computer modeling of carotid endarterectomy (CEA) with patches of various configurations., Material and Methods: The method was demonstrated on a reconstructed model of intact vessel based on preoperative CT of the affected vessel in a certain patient. Blood flow is modeled by computational fluid dynamics using Doppler ultrasound data. Risk factors were assessed considering hemodynamic parameters of vascular wall associated with WSS., Results: We studied hemodynamic results of 10 virtual CEA with patches of various shapes on the example of a reconstructed intact artery in a particular patient. Patch implantation is aimed at prevention of carotid artery narrowing since simple suture without a patch can reduce circumference of the artery by 4-5 mm. This result adversely affects blood flow. On the other hand, too wide a patch creates aneurysm-like deformation of internal carotid artery bulb. It is not optimal due to a large recirculation zone. It was found that patch width approximately equal to 3 mm ensures an optimal hemodynamic result. Deviations from this median value, both upward and downward, impair hemodynamics while the absence of a patch results the worst result., Conclusion: The proposed computer modeling technique is able to provide a personalized patch selection for CEA with low risk of restenosis in long-term follow-up period.

Bioprosthetic heart valves (BHVs) are known for their lower thrombogenicity rates and excellent hemodynamic parameters similar to native valves. However, the lifespan of these medical devices is limited to 15 years due to the structural valve degeneration. One of the mechanisms underlying functional impairment and calcification of BHVs includes proteolytic degradation of biomaterials. However, proteases found in xenogeneic BHVs tissue remain poorly studied. In this study using the dot blot assay, we have performed a screening analysis of proteolytic enzymes and their inhibitors in the leaflets of five BHVs explanted due to their dysfunction. Five aortic valves (AVs) explanted due to calcific aortic valve disease were studied as a comparison group. The results of the study have demonstrated that at least 17 proteases and 19 of their inhibitors can be found in BHVs. In the AVs 20 proteases and 21 their inhibitors were identified. Small quantitative differences were noted between proteomic profiles of the BHVs and AVs. Matrix metalloproteinases (MMPs) were expressed in BHVs and AVs at comparable levels, but the level of tissue inhibitors of metalloproteinases-1/-2 and RECK protein in implant tissues was lower than in natural valves. Probably, excessive activity of MMPs cannot be counterbalanced by their inhibitors in BHVs and therefore MMPs can degrade prosthetic biomaterial. Moreover, the detection of a wide range of proteolytic enzymes and their inhibitors in the degenerated BHVs suggests the existence of several pathophysiological pathways that can lead to structural valve degeneration.

Currently, transcatheter aortic valve implantation (TAVI) represents the most efficient treatment option for patients with aortic stenosis, yet its clinical outcomes largely depend on the accuracy of valve positioning that is frequently complicated when routine imaging modalities are applied. Therefore, existing limitations of perioperative imaging underscore the need for the development of novel visual assistance systems enabling accurate procedures. In this paper, we propose an original multi-task learning-based algorithm for tracking the location of anatomical landmarks and labeling critical keypoints on both aortic valve and delivery system during TAVI. In order to optimize the speed and precision of labeling, we designed nine neural networks and then tested them to predict 11 keypoints of interest. These models were based on a variety of neural network architectures, namely MobileNet V2, ResNet V2, Inception V3, Inception ResNet V2 and EfficientNet B5. During training and validation, ResNet V2 and MobileNet V2 architectures showed the best prediction accuracy/time ratio, predicting keypoint labels and coordinates with 97/96% accuracy and 4.7/5.6% mean absolute error, respectively. Our study provides evidence that neural networks with these architectures are capable to perform real-time predictions of aortic valve and delivery system location, thereby contributing to the proper valve positioning during TAVI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Danilov, Klyshnikov, Gerget, Skirnevsky, Kutikhin, Shilov, Ganyukov and Ovcharenko.)

Invasive coronary angiography remains the gold standard for diagnosing coronary artery disease, which may be complicated by both, patient-specific anatomy and image quality. Deep learning techniques aimed at detecting coronary artery stenoses may facilitate the diagnosis. However, previous studies have failed to achieve superior accuracy and performance for real-time labeling. Our study is aimed at confirming the feasibility of real-time coronary artery stenosis detection using deep learning methods. To reach this goal we trained and tested eight promising detectors based on different neural network architectures (MobileNet, ResNet-50, ResNet-101, Inception ResNet, NASNet) using clinical angiography data of 100 patients. Three neural networks have demonstrated superior results. The network based on Faster-RCNN Inception ResNet V2 is the most accurate and it achieved the mean Average Precision of 0.95, F1-score 0.96 and the slowest prediction rate of 3 fps on the validation subset. The relatively lightweight SSD MobileNet V2 network proved itself as the fastest one with a low mAP of 0.83, F1-score of 0.80 and a mean prediction rate of 38 fps. The model based on RFCN ResNet-101 V2 has demonstrated an optimal accuracy-to-speed ratio. Its mAP makes up 0.94, F1-score 0.96 while the prediction speed is 10 fps. The resultant performance-accuracy balance of the modern neural networks has confirmed the feasibility of real-time coronary artery stenosis detection supporting the decision-making process of the Heart Team interpreting coronary angiography findings.

The aim of the study was to determine the potential mechanism of vascular complications due to "catheter-vascular wall" interaction in transcatheter aortic valve replacement using experimental and numerical analysis., Materials and Methods: A series of full-scale bench tests and numerical simulations were carried out using the CoreValve commercial transfemoral delivery system for aortic valve bioprosthesis (Medtronic Inc., USA). Full-scale tests were carried out using a phantom of the vascular system (a polymeric silicone model of Transcatheter Aortic Valve; Trandomed 3D Inc., China) with simulation of all stages of delivery system movement along the vascular bed. They involved introduction into the common femoral artery, movement along the abdominal and thoracic parts of the aorta, the aortic arch, and positioning the system to the implantation site. The force arising from the passage of the delivery system was assessed using sensors of a Z50 universal testing machine (Zwick/Roell, Germany). Numerical simulation of transcatheter valve replacement procedure was carried out in a similar way with allowance for the patient-specific anatomy of the recipient's aorta using the finite element method in the Abaqus/CAE environment (Dassault Systèmes, France)., Results: It was found that in the process of the delivery system passing through the vascular system, there occurred force fluctuations associated with catheter bending and its interaction with the aortic wall in the region of its arch. For example, in the initial straight portions, the pushing force was 3.8-7.9 N; the force increased to the maximum (11.1 and 14.4 N with and without the prosthesis) with bending of the distal portion of the catheter. A similar increase was observed when performing numerical simulation with high-quality graphic visualization of stress on the "spots" of contact between the catheter and the vascular wall with an increase in stress to 0.8 MPa., Conclusion: Numerical and full-scale bench tests prove the significant effect of the properties of delivery system catheter for transcatheter aortic valve replacement on the interaction with the aortic walls., Competing Interests: Conflicts of interest. There are no conflicts of interest related to this study.

The implantation of bioprosthetic heart valves (BHVs) is increasingly becoming the treatment of choice in patients requiring heart valve replacement surgery. Unlike mechanical heart valves, BHVs are less thrombogenic and exhibit superior hemodynamic properties. However, BHVs are prone to structural valve degeneration (SVD), an unavoidable condition limiting graft durability. Mechanisms underlying SVD are incompletely understood, and early concepts suggesting the purely degenerative nature of this process are now considered oversimplified. Recent studies implicate the host immune response as a major modality of SVD pathogenesis, manifested by a combination of processes phenocopying the long-term transplant rejection, atherosclerosis, and calcification of native aortic valves. In this review, we summarize and critically analyze relevant studies on (1) SVD triggers and pathogenesis, (2) current approaches to protect BHVs from calcification, (3) obtaining low immunogenic BHV tissue from genetically modified animals, and (4) potential strategies for SVD prevention in the clinical setting.

In this study, we incorporated carbon nanotubes (CNTs) into poly(styrene- block -isobutylene- block -styrene) (SIBS) to investigate the physical characteristics of the resulting nanocomposite and its cytotoxicity to endothelial cells. CNTs were dispersed in chloroform using sonication following the addition of a SIBS solution at different ratios. The resultant nanocomposite films were analyzed by X-ray microtomography, optical and scanning electron microscopy; tensile strength was examined by uniaxial tension testing; hydrophobicity was evaluated using a sessile drop technique; for cytotoxicity analysis, human umbilical vein endothelial cells were cultured on SIBS-CNTs for 3 days. We observed an uneven distribution of CNTs in the polymer matrix with sporadic bundles of interwoven nanotubes. Increasing the CNT content from 0 wt% to 8 wt% led to an increase in the tensile strength of SIBS films from 4.69 to 16.48 MPa. The engineering normal strain significantly decreased in 1 wt% SIBS-CNT films in comparison with the unmodified samples, whereas a further increase in the CNT content did not significantly affect this parameter. The incorporation of CNT into the SIBS matrix resulted in increased hydrophilicity, whereas no cytotoxicity towards endothelial cells was noted. We suggest that SIBS-CNT may become a promising material for the manufacture of implantable devices, such as cardiovascular patches or cusps of the polymer heart valve.

Sutureless implantation of the mitral valve bioprosthesis using the valve-in-valve method was performed on a large animal (sheep). According to the results of a two-stage implantation (primary implantation of a xenopericardial 26-mm framed bioprosthesis and reimplantation of the developed 23-mm bioprosthesis), minor changes in quantitative indicators were revealed: an increase in the transprosthetic gradient by 1.3 mm Hg and a decrease in the area of the mitral orifice by 21.6%. Considerable reduction in the intervention time by 18 min was achieved (by 40% in comparison with the primary prosthesis). The absence of adverse events in the animal and complications in the post-operative period, as well as physiological hemodynamic indicators indicate the safety of the developed medical device.

Polymeric heart valves seem to be an attractive alternative to mechanical and biological prostheses as they are more durable, due to the superior properties of novel polymers, and have the biocompatibility and hemodynamics comparable to tissue substitutes. This study reports a comprehensive assessment of a nanocomposite based on the functionalised graphene oxide and poly(carbonate-urea)urethane with the trade name "Hastalex" in comparison with GORE-TEX, a commercial polymer routinely used for cardiovascular medical devices. Experimental data have proved that GORE-TEX has a 2.5-fold (longitudinal direction) and 3.5-fold (transverse direction) lower ultimate tensile strength in comparison with Hastalex (p < 0.05). The contact angles of Hastalex surfaces (85.2 ± 1.1°) significantly (p < 0.05) are lower than those of GORE-TEX (127.1 ± 6.8°). The highest number of viable cells Ea.hy 926 is on the Hastalex surface exceeding 7.5-fold when compared with the GORE-TEX surface (p < 0.001). The platelet deformation index for GORE-TEX is 2-fold higher than that of Hastalex polymer (p < 0.05). Calcium content is greater for GORE-TEX (8.4 mg/g) in comparison with Hastalex (0.55 mg/g). The results of this study have proven that Hastalex meets the main standards required for manufacturing artificial heart valves and has superior mechanical, hemocompatibility and calcific resistance properties in comparison with GORE-TEX.

The aim of the study was to develop a prognostic model based on statistical discriminant analysis to assess the risk of postoperative disturbance of cardiac conduction and paraprosthetic regurgitation after transcatheter aortic valve replacement., Materials and Methods: Clinical data of 10 patients implanted with CoreValve TM prostheses (Medtronic Inc., USA) were used to develop prognostic models. To that end, we analyzed changes in hemodynamic and functional parameters provided by echocardiography in the pre- and postoperative periods., Results: We observed significant positive changes in the severity of left ventricular myocardial hypertrophy; on the contrary, volume indicators did not significantly change, which might be associated with the concentric type of left ventricular hypertrophy. The discriminant analysis made it possible to determine major (preoperative) morphological and functional indicators associated with the two most common complications of the procedure: left bundle branch block and paraprosthetic regurgitation. Left ventricular posterior wall thickness, interventricular septal thickness, left atrium dimension, and myocardial mass are the critical factors that determine the development of these complications., Conclusion: In the prognostic model, the proposed weighting coefficients allow one to assess the risk of postoperative complications; however, the presence of false-positive results requires further refinement of these coefficients within the linear equation., Competing Interests: Conflict of interest. The authors declare no conflict of interest.

Calcific aortic valve stenosis (CAVS) is a serious socio-economic problem in developed countries because this disease is the most common indication for aortic valve replacement. Currently, there are no methods for non-invasive treatment of CAVS. Nevertheless, it is assumed that effective drug therapy for CAVS can be developed on the basis of modulators of the renin-angiotensin-aldosterone system (RAAS), which is involved in the pathogenesis of this disease. The purpose of this paper is to compile and analyze current information on the role of RAAS in the CAVS pathophysiology. Recent data on the effectiveness of RAAS inhibition are reviewed.

Calcific aortic valve disease (CAVD), previously thought to represent a passive degeneration of the valvular extracellular matrix (VECM), is now regarded as an intricate multistage disorder with sequential yet intertangled and interacting underlying processes. Endothelial dysfunction and injury, initiated by disturbed blood flow and metabolic disorders, lead to the deposition of low-density lipoprotein cholesterol in the VECM further provoking macrophage infiltration, oxidative stress, and release of pro-inflammatory cytokines. Such changes in the valvular homeostasis induce differentiation of normally quiescent valvular interstitial cells (VICs) into synthetically active myofibroblasts producing excessive quantities of the VECM and proteins responsible for its remodeling. As a result of constantly ongoing degradation and re-deposition, VECM becomes disorganised and rigid, additionally potentiating myofibroblastic differentiation of VICs and worsening adaptation of the valve to the blood flow. Moreover, disrupted and excessively vascularised VECM is susceptible to the dystrophic calcification caused by calcium and phosphate precipitating on damaged collagen fibers and concurrently accompanied by osteogenic differentiation of VICs. Being combined, passive calcification and biomineralisation synergistically induce ossification of the aortic valve ultimately resulting in its mechanical incompetence requiring surgical replacement. Unfortunately, multiple attempts have failed to find an efficient conservative treatment of CAVD; however, therapeutic regimens and clinical settings have also been far from the optimal. In this review, we focused on interactions and transitions between aforementioned mechanisms demarcating ascending stages of CAVD, suggesting a predisposing condition (bicuspid aortic valve) and drug combination (lipid-lowering drugs combined with angiotensin II antagonists and cytokine inhibitors) for the further testing in both preclinical and clinical trials., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Infective endocarditis (IE) is the disease that has high inhospital mortality. Heart valves dysfunction - both native and prosthetic - is the primary IE complication requiring a surgical intervention. The IE causes and its course have been discussed in this review. In particular, the role of concomitant infectious foci in the formation and development of IE have been considered, the mechanisms of mutual transition of subacute and acute clinical forms have been described. Modern diagnostic principles and methods based on the Duke criteria system have been mentioned, as well as the difficulties that follow the patient's clinical status evaluation. The normobiotic microbiota participation, as well as the possibilities for their identification using blood culture and PCR technique, have been closely reviewed. According to modern researches and publications, there have been made the conclusion about the contribution of obligate anaerobic bacteria, fungi and viruses to the development of endocarditis. There have been described the hypothesis about the presumptive strategy for the cardiac dysfunction formation as a result of the IE causative agents cells metabolic activity based on a literature data analysis in the article: vegetation formed by Staphylococcus aureus can lead to the heart valve stenosis, and the influence of hyaluronidases, collagenases on a heart valve structure can lead to regurgitation. The pathogens cells ability to avoid the human immune system response is caused by the biofilms, fibrin vegetations formation and the enzymes production - cytotoxins (streptolysins, leukocidin, etc.). It has been suggested that the mediators of inflammation and leukocyte cells participate in the destruction of native and prosthetic tissues due to an IE pathogens inaccessibility for immunocompetent cells.

Since its introduction in 2002, transcatheter aortic valve implantation (TAVI) has evolved dramatically and is now standard of care for intermediate risk patients with aortic stenosis. The development of innovative transcatheter heart valves and refinement of technical skills have contributed to the decrease in complication rates associated with TAVI. Increased experience, smaller sheaths, rigorous pre-procedural planning and improved vascular closing techniques have resulted in markedly lower rates of vascular complications. The next step was the simplification of the procedure, which contributed to a further decrease in complications, reduced procedural time, and shorter hospital stay. Change-over from general anaesthesia to conscious sedation, refusal from predilatation, and use of the radial approach instead of the contralateral femoral approach are all instrumental in achieving optimal results. Prospects for development include visual assist systems and robotic systems that can potentially optimize the transcatheter aortic valve implantation process, improve safety and effectiveness of the procedure.

Postoperative complications in vascular surgery may be partly provoked by suture material. Analysis of the mechanisms of these complications may be useful for their prevention. Mechanisms of suture-induced thrombosis and neointimal hyperplasia, possible strategies for prevention of postoperative complications including those allowing drug deliveries directly to the vascular anastomosis area are discussed in the article. According to the literature data, heparin is the most optimal drug for modifying suture material and prevention of thrombosis and neointimal hyperplasia. Heparin delivery to the vascular anastomosis site will reduce the risk of thrombosis by inhibiting the activity of thrombin. Complex of heparin and antithrombin III increases inhibitory effect of antithrombin against thrombin. In addition, heparin is able to reduce proliferation of vascular smooth muscle cells through inhibition of the synthesis of extracellular matrix proteases involved in migration and proliferation of cells. Thus, heparin delivery to the vascular injury site may be used to prevent thrombosis and myoproliferative response. Moreover, this strategy prevents complications associated with systemic administration of anticoagulants.

Calcification of cardiovascular tissues and biological substitutes results in abnormal biomechanics, causing stenosis or tissues ruptures. Therefore, the understanding of calcification pathways will facilitate the development of strategies for calcification risk reduction. Even though calcification pathways have been studied since the mid-80s and are widely described in the medical literature, there is no consensus on the cause-and-effect relationships in this pathological process. The current review covers the composition, structural aspects and specific localization of calcific deposits in native heart valves and blood vessels, bioprosthetic heart valves treated with glutaraldehyde. Moreover, experimental data on the composition of in vivo and in vitro calcification are presented. These characteristics of calcific deposits provide new insights in the calcification pathways. According to the results of the literature review, one may conclude that cell death, microfracture of the surrounding tissues with the overall biochemical imbalance may potentiate the calcification process. Moreover, the progression of calcification process is associated with the accumulation of mechanical stress.

Background: There are two main methods used for transcatheter aortic valve replacement (TAVR) FEA modeling for medical devices development: patient specific and general approaches. Advantages and disadvantages of both approaches have never been compared in a single study., Method: Here we propose a bioinformatic algorithm to evaluate the accuracy of patient specific and generalized FEA approaches with regards to proximity configuration of the implanted stent reconstructed by computed tomography. In addition, in this study we also assessed the impact of the level of detail on FEA accuracy in the patient specific approach., Results: Our results demonstrate that in certain cases, the generalized approach can ensure the same accuracy as the patient specific approach. Therefore, considering high cost effectiveness of the generalized approach, we identify it as more feasible in the context of TAVR. Furthermore, we suggest that high level of detail can improve the reproducibility of modeling results in the patient specific approach., Conclusions: Our findings may help medical engineers to better understand the peculiarities of both approaches and therefore make the right decision when choosing a particular approach for computer modeling. Future studies are required to validate our observations., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

This paper presents the analysis of relationships between geometrical parameters of the tubular leaflet apparatus and its functional characteristics. In addition, the degree of the influence of deformation of different zones of leaflets on its ability to perform its function is evaluated in this work. The outcomes of this study could be helpful in developing new models of the transcatheter prosthetic heart valves leaflet apparatus or analyzing existing in-clinical transcatheter aortic valve implantation prostheses.

The development of computer-based 3D models of the aortic root is one of the most important problems in constructing the prostheses for transcatheter aortic valve implantation. In the current study, we analyzed data from 117 patients with and without aortic valve disease and computed tomography data from 20 patients without aortic valvular diseases in order to estimate the average values of the diameter of the aortic annulus and other aortic root parameters. Based on these data, we developed a 3D model of human aortic root with unique geometry. Furthermore, in this study we show that by applying different material properties to the aortic annulus zone in our model, we can significantly improve the quality of the results of finite element analysis. To summarize, here we present four 3D models of human aortic root with unique geometry based on computational analysis of ECHO and CT data. We suggest that our models can be utilized for the development of better prostheses for transcatheter aortic valve implantation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)