A study of chemically treated pericardia to manufacture the leaflets of percutaneous heart valves : biomechanical analyses and modelisation

Contexte: En raison de l'utilisation répandue des valvules cardiaques aortiques prothétiques, il est extrêmement important d'en étudier la biofonctionnalité, la biodurabilité et la biocompatibilité. Les valves mécaniques ont une excellente durabilité. Cependant, en raison des traitements anticoagulants, il existe des risques de thromboembolique et hémorragique. Les valves polymériques ont une faible résistance à la calcification et à la thrombose. À cet égard, les valves biologiques sont préférables. Plus récemment, les chirurgiens et les cardiologues ont développe à l'implantation de valves aortiques percutanées, plutôt qu’à la chirurgie ouverte pour traiter les patients âgés et fragiles. Cependant, la durabilité des bioprothèses soulève toujours des questions reliées au sertissage et l’expansion lors de l'implantation. Comme la performance des bioprothèses dépend de l'architecture et du comportement mécanique du tissu sélectionné, il est nécessaire de sélectionner le tissu le plus approprié pour fabriquer ces prothèses. Objectifs: Il s’agit d’identifier le tissu le plus approprié avec la plus longue durabilité pour fabriquer des valvules cardiaques en comparant les propriétés mécaniques et histologiques des péricardes équin, porcin et d’âne par rapport à celles du péricarde bovin et des feuillets de la valve aortique humaine. Hypothèse: La durabilité des valves cardiaques bioprothétiques est largement déterminée par les caractéristiques histologiques et mécaniques des tissus des feuillets. Par conséquent, la sélection du péricarde selon sa structure histologique et ses propriétés mécaniques permettra d’augmenter la durée de vie de ces prothèses. Méthodologie: 1. Étude des structures de collagène des tissus sélectionnés. 2. Étude des propriétés mécaniques des tissus et évaluation de leur durabilité avec différents tests mécaniques. 3. Extraction des propriétés hyperélastiques et viscoélastiques biaxiales à l'aide des modèles appropriés. 4. Application du modèles d'éléments finis est appliqué en utilisant les propriétés mécaniques extraites pour évaluer la déhiscence possible de la valve et le stress sous la charge physiologique. Résultats: Le péricarde d’âne et le péricarde équin ont démontré une architecture ondulée de faisceaux de collagène semblable à celle du péricarde bovin. L’architecture ondulée du péricarde peut convenir aux valves aortiques transcutanées car elles sont moins susceptibles d'être délaminées lors du sertissage. Selon des tests mécaniques, les pourcentages de relaxation des différents péricardes équin (16%), âne (28%) et bovin (21%) étaient supérieurs à ceux du péricarde porcin (11%) et similaires aux feuillets valvulaires aortiques humains natifs (21%). En particulier, le péricarde porcin a démontré un comportement plus rigide (module d'élasticité plus élevé), basé sur sa plus grande amplitude d'énergie de déformation et la pente moyenne des courbes contrainte-étirement. Ce tissu était également moins extensible que les deux autres péricardes et les feuillets humains, en raison de sa souche aréale inférieure. En général, les propriétés mécaniques du péricarde d’âne sont plus proches des feuillets valvulaires humains. De plus, le modèle âne n'a induit que des régions localisées à faible stress pendant les phases systolique et diastolique du cycle cardiaque. En outre, une diminution des contraintes mécaniques sur les feuillets bioprothétiques devrait contribuer à réduire la dégénérescence des tissus et augmenter la durabilité à long terme de la valve. Conclusion: D'après nos observations, les spécimens péricardiques se sont comportés comme des tissus anisotropes et non linéaires - bien caractérisés par des modèles constitutifs. Les résultats indiquent que le péricarde d'âne est mécaniquement et histologiquement plus approprié pour la fabrication de prothèses valvulaires cardiaques que le péricarde bovin. Les résultats de cette étude peuvent être utilisés dans la conception et la fabrication de valvules cardiaques bioprothétiques percutanéei.Background: Due to the widespread use of prosthetic aortic heart valves, investigating these prostheses in terms of biofunctionality, biodurability and biocompatibility is of considerable importance. Mechanical heart valves (MHVs) have excellent durability; however, due to the long-term use of anticoagulants, thromboembolism and hemorrhage remain a possibility. Polymeric valves have a low resistance to calcification and thromboembolism. In this respect, biological valves are preferred. In recent years, surgeons and cardiologists have also used transcatheter aortic valve implantation (TAVI) due to its superiority over the open-heart surgery to treat elderly and frail patients. However, the long-term durability of the commercially available bioprosthesesstill raises questions related to crimping and ballooning at the implantation. The function and performance of the bioprostheses depend on the collagen architecture and mechanical behaviors of the pericardial tissue. Therefore, it is necessary to select the most appropriate pericardia to manufacture these prostheses. Objectives: To identify the most appropriate tissue with a long durability to make bioprosthetic heart valves by analyzing the mechanical and histological properties of the equine, porcine, and donkey pericardia, with respect to those of the bovine pericardium and human aortic valve leaflets. Hypothesis: The long term durability of bioprosthetic heart valves is largely determined by the leaflet tissues. Consequently, selecting the pericardium based on its adequate mechanical property and histological structure will increase the lifetime of these prostheses. Methodologies: 1. Histological analysis was performed to investigate the collagen structures of the selected tissues. 2. Different mechanical tests (uniaxial tests, biaxial tests, and stress relaxation tests) were performed to determine the mechanical properties of the tissues and to evaluate their durability. 3. The biaxial hyperelastic and viscoelastic properties of the selected tissues were extracted using the appropriate models. 4. The finite element model was applied using the extracted mechanical properties to evaluate valve dehiscence and stress under physiological loadings. Results: The donkey and equine pericardia showed a wavy collagen bundle architecture similar to the bovine pericardium. The wavy pericardia may be suitable for the transcatheter aortic valves (TAVs) because they are less likely to be delaminated during crimping. According to the mechanical tests, the relaxation percentages of the equine (16%), donkey (28%), and bovine (21%) pericardia were greater than that of the porcine (11%) pericardium and similar to that of the native human aortic valve leaflets (21%). In particular, the porcine pericardium exhibited a stiffer behavior (higher elastic modulus), based on its greater strain energy magnitude and the average slope of stress-stretch curves. This tissue was also less distensible than the other two pericardia and the native leaflets, due to its lower areal strain. In general, among the pericardia analyzed, the mechanical properties of the donkey pericardium are closer to that of the native leaflets. Furthermore, the donkey model showed low stress regions during the systolic and diastolic phases of the cardiac cycle. Such decreased mechanical stress in the bioprosthetic leaflets should reduce tissue degeneration and increase the long-term durability of the valve. Conclusion: Based on the observations, the pericardial specimens behaved as anisotropic and nonlinear tissues, and their mechanical behaviors were very well characterized by the constitutive models. The results indicate that, compared to the bovine pericardium, the donkey pericardium is mechanically and histologically more appropriate to manufacture heart valve prostheses. Therefore, this study contributes to our understanding of the difference in animal pericardia with respect to human heart leaflets, which is very useful for the design and manufacture of the percutaneous bioprosthetic heart valves

A biomechanical analysis of shear wave elastography in pediatric heart models

Early detection of cardiac disease in children is essential to optimize treatment and follow-up, but also to reduce its associated mortality and morbidity. Various cardiac imaging modalities are available for the cardiologist, mainly providing information on tissue morphology and structure with high temporal and/or spatial resolution. However, none of these imaging methods is able to directly measure stresses or intrinsic mechanical properties of the heart, which are potential key diagnostic markers to distinguish between normal and abnormal physiology. This thesis investigates the potential of a relatively new ultrasound-based technique, called shear wave elastography (SWE), to non-invasively measure myocardial stiffness. The technique generates an internal perturbation inside the tissue of interest, and consequently measures the propagation of the acoustically excited shear wave, of which the propagation speed is directly related to tissue stiffness. This allows SWE to identify regions with higher stiffness, which is associated with pathology. SWE has shown to be successful in detecting tumors in breast tissue and fibrosis in liver tissue, however application of SWE to the heart is more challenging due to the complex mechanical and structural properties of the heart. This thesis provides insights into the acoustically excited shear wave physics in the myocardium by using computer simulations in combination with experiments. Furthermore, these models also allow to assess the performance of currently used SWE-based material characterization algorithms

Viscoelastic Properties of Cardiovascular Tissues

The aims of this chapter are to review the current state of knowledge regarding the viscoelastic behavior of cardiovascular tissues. We begin with a brief, general discussion of measurement and modeling of cardiovascular tissue viscoelasticity. We then review known viscoelastic behavior of arteries, veins, capillaries, blood components, the heart, and lymphatics. For each tissue type, we highlight tissue-specific measurement methods, the cellular and extracellular components responsible for tissue viscoelasticity, and the clinical implications of energy loss due to viscoelasticity. We conclude with a summary and suggestions for future research

Non-Newtonian Rheology in Blood Circulation

Blood is a complex suspension that demonstrates several non-Newtonian rheological characteristics such as deformation-rate dependency, viscoelasticity and yield stress. In this paper we outline some issues related to the non-Newtonian effects in blood circulation system and present modeling approaches based mostly on the past work in this field.Comment: 26 pages, 5 figures, 2 table

Heart Valve Mathematical Models

Nearly 100,000 heart valve replacements or repairs are performed in the US every year. Mathematical models of heart valves are used to improve artificial valve design and to guide surgeons performing valve-repairing surgeries. Models can be used to define the geometry of a valve, predict blood flow dynamics, or demonstrate operating mechanisms of the valve. In this thesis we reviewed features that are typically considered when developing a model of a heart valve. The main modeling methods include representing a heart valve using lumped parameters, finite elements, or isogeometric elements. Examples of a lumped-parameter model and isogeometric analysis are explored. First, we developed a simulation for the lumped-parameter model of Virag and Lulić, and we demonstrated its ability to capture the dynamical behavior of blood pressures, volumes, and flows in the aortic valve region. A Newton-Krylov method was used to estimate periodic solution trajectories, which provide a basis for examining the response to perturbations about initial conditions. Next, an isogeometric model of a heart valve was constructed based on NURBS geometry. The mechanical stiffness of the valve was computed. We discussed how the isogeometric representation could be used in a more complex fluid-structure interaction model to measure surface shear and estimate fatigue failure

Parasternal versus apical view in cardiac natural mechanical wave speed measurements

Shear wave speed measurements can potentially be used to noninvasively measure myocardial stiffness to assess the myocardial function. Several studies showed the feasibility of tracking naturalmechanical waves induced by aortic valve closure in the interventricular septum, but different echocardiographic views have been used. This article systematically studied the wave propagation speedsmeasured in a parasternal long-axis and in an apical four-chamber view in ten healthy volunteers. The apical and parasternal views are predominantly sensitive to longitudinal or transversal tissue motion, respectively, and could, therefore, theoreticallymeasure the speed of different wave modes. We found higher propagation speeds in apical than in the parasternal view (median of 5.1 m/s versus 3.8 m/s, p < 0.01, n = 9). The results in the different views were not correlated (r = 0.26, p = 0.49) and an unexpectedly large variability among healthy volunteers was found in apical view compared with the parasternal view (3.5-8.7 versus 3.2-4.3 m/s, respectively). Complementary finite element simulations of Lamb waves in an elastic plate showed that different propagation speeds can be measured for different particlemotion componentswhen differentwavemodes are induced simultaneously. The in vivo results cannot be fully explained with the theory of Lamb wave modes. Nonetheless, the results suggest that the parasternal long-axis view is amore suitable candidate for clinical diagnosis due to the lower variability in wave speeds

Structure-function relationships in the aortic valve

PhDGlobally, heart valve dysfunction constitutes a large portion of the cardiovascular disease load, causing high rates of mortality in European and industrialized countries. This is reflected in the database of the American Heart Association and the UK Valve Registry, showing a progressive increase in the number and age of patients in need of surgical interventions. Aortic valve (AV) dysfunction is significantly more prevalent than pathologies associated with other heart valves, accounting for approximately 43% of all patients having valvular disease. These statistics highlight the essential need for efficient and long term substitutes. However, the two types of replacement valves currently available in practice, i.e. mechanical and bioprosthetic valves, have only an estimated lifetime of around 10 years, after which the associated problems necessitate re-operation in at least 50-60% of the patients. Moreover, for patients under 35, the failure rate is nearly 100% within 5 years of the valve replacement surgery. The significant numbers of patients suffering from AV dysfunction, shortcomings to currently available valve substitutes, and the market demands for replacement valves has prompted increasing interest in the study of AV biomechanics.A fundamental study of the AV structure-function biomechanics is presented in this thesis. The mechanical behaviour of the AV is characterised at the tissue level, and the associated microstructural mechanisms established. In addition to the experiments, in depth mathematical models are developed and presented, to explain the observed experimental data and elucidate the micromechanics of the AV constituents and their contribution to the tissue behaviour. Tissue-level results indicate that the AV shows ‘shear-thinning’ behaviour, as well as anisotropic time-dependent characteristics. The microstructural experimental data indicates that there is no direct translation of tissue level mechanical stimuli to the ECM, implying that strain transfer is non-affine. Modelling micro-structural mechanics has confirmed that collagen fibres do not need to become fully straight before they contribute to load bearing, while the elastin network has been shown to contribute to load bearing even at high strains, further exacerbating the non-linear stress-strain relationship of the valve. The structural mechanisms underlying time-dependent behaviour of the tissue can be explained at the fibre level, stemming from fibre sliding and the dissipative effects arising due to fibre-fibre and fibre-matrix frictional interactions, suggesting a unified structural mechanism for both the stress-relaxation and creep phenomena. These outcomes contribute to an improved understanding of the physiological biomechanics of the native AV, and may therefore assist in optimising the design processes for substitute valves and selecting appropriate materials to effectively mimic the native valve function. Understanding AV micromechanics also helps quantify the mechanical environment perceived by the residing cells, which can have significant implications for cell-mediated tissue engineering strategies.EPSRC; Discipline Bridging Initiative; MR