Caitlin Martin

Significant differences in the material properties between aged human and porcine aortic tissues

OBJECTIVE Currently, percutaneous aortic valve (PAV) replacement devices are being investigated to treat aortic stenosis in patients deemed to be of too high a risk for conventional open-chest surgery. Successful PAV deployment and function are heavily reliant on the tissue-stent interaction. Many PAV feasibility trials have been conducted with porcine models under the assumption that these tissues are similar to human; however, this assumption may not be valid. The goal of this study was to characterize and compare the biomechanical properties of aged human and porcine aortic tissues. METHODS The biaxial mechanical properties of the left coronary sinus, right coronary sinus, non-coronary sinus, and ascending aorta of eight aged human (90.1 ± 6.8 years) and 10 porcine (6-9 months) hearts were quantified. Tissue structure was analyzed via histological techniques. RESULTS Aged human aortic tissues were significantly stiffer than the corresponding porcine tissues in both the circumferential and longitudinal directions (p < 0.001). In addition, the nearly linear stress-strain behavior of the porcine tissues, compared with the highly nonlinear response of the human tissues at a low strain range, suggested structural differences between the aortic tissues from these two species. Histological analysis revealed that porcine samples were composed of more elastin and less collagen fibers than the respective human samples. CONCLUSIONS Significant material and structural differences were observed between the human and porcine tissues, which raise questions on the validity of using porcine models to investigate the biomechanics involved in PAV intervention.

Biomechanical characterization of ascending aortic aneurysm with concomitant bicuspid aortic valve and bovine aortic arch.

Studies have shown that patients harboring bicuspid aortic valve (BAV) or bovine aortic arch (BAA) are more likely than the general population to develop ascending aortic aneurysm (AsAA). A thorough quantification of the AsAA tissue properties for these patient groups may offer insights into the underlying mechanisms of AsAA development. Thus, the objective of this study was to investigate and compare the mechanical and microstructural properties of aortic tissues from AsAA patients with and without concomitant BAV or BAA. AsAA (n=20), BAV (n=20) and BAA (n=15) human tissues were obtained from patients who underwent elective AsAA surgery. Planar biaxial and uniaxial failure tests were used to characterize the mechanical and failure properties of the tissues, respectively. Histological analysis was performed to detect medial degenerative characteristics of aortic aneurysm. Individual layer thickness and composition were quantified for each patient group. The circumferential stress-strain response of the BAV samples was stiffer than both AsAA (p=0.473) and BAA (p=0.152) tissues at a low load. The BAV samples were nearly isotropic, while AsAA and BAA samples were anisotropic. The areal strain of BAV samples was significantly less than that of AsAA (p=0.041) and BAA (p=0.004) samples at a low load. The BAA samples were similar to the AsAA samples in both mechanical and failure properties. On the microstructural level, all samples displayed moderate medial degeneration, characterized by elastin fragmentation, cell loss, mucoid accumulation and fibrosis. The ultimate tensile strength of BAV and BAA sampleswere also found to decrease with age. Overall, the BAV samples were stiffer than both AsAA and BAA samples, and the BAA samples were similar to the AsAA samples. The BAV samples were thinnest, with less elastin than AsAA and BAA samples, which may be attributed to the loss of extensibility of these tissues at a low load. No apparent difference in failure mechanics among the tissue groups suggests that each of the patient groups may have a similar risk of rupture.

Biomechanical characterization of aortic valve tissue in humans and common animal models.

Aortic valve disease develops in an escalating fashion in elderly patients. Current treatments including total valve replacement and valve repair techniques are still suboptimal. A thorough understanding of the animal and human valve tissue properties, particularly their differences, is crucial for the establishment of preclinical animal models and strategies for evaluating new valve treatment techniques, such as transcatheter valve intervention and tissue engineered valves. The goal of this study was to characterize and compare the biomechanical properties and histological structure of healthy ovine, porcine, and human aortic valve leaflets. The biaxial mechanical properties of the aortic valve leaflets of 10 ovine (∼1 year), 10 porcine (6-9 months), and 10 aged human (80.6 ± 8.34) hearts were quantified. Tissue microstructure was analyzed via histological techniques. Aged human aortic valve leaflets were significantly less compliant than both ovine and porcine leaflets, with the ovine leaflets being the most compliant. Histological analysis revealed structural differences between the species: the human and porcine leaflets contained more collagen and elastin than the ovine leaflets. Significant mechanical and structural differences in the aortic valve tissues of 6- to 9-month-old porcine models and 1-year-old ovine models with respect to those of aged humans, suggest that these animal models may not be representative of the typical patient undergoing aortic valve replacement.

Computational Modeling of Cardiac Valve Function and Intervention

In the past two decades, major advances have been made in the clinical evaluation and treatment of valvular heart disease owing to the advent of noninvasive cardiac imaging modalities. In clinical practice, valvular disease evaluation is typically performed on two-dimensional (2D) images, even though most imaging modalities offer three-dimensional (3D) volumetric, time-resolved data. Such 3D data offer researchers the possibility to reconstruct the 3D geometry of heart valves at a patient-specific level. When these data are integrated with computational models, native heart valve biomechanical function can be investigated, and preoperative planning tools can be developed. In this review, we outline the advances in valve geometry reconstruction, tissue property modeling, and loading and boundary definitions for the purpose of realistic computational structural analysis of cardiac valve function and intervention.

Comparison of transcatheter aortic valve and surgical bioprosthetic valve durability: A fatigue simulation study

Transcatheter aortic valve (TAV) intervention is now the standard-of-care treatment for inoperable patients and a viable alternative treatment option for high-risk patients with symptomatic aortic stenosis. While the procedure is associated with lower operative risk and shorter recovery times than traditional surgical aortic valve (SAV) replacement, TAV intervention is still not considered for lower-risk patients due in part to concerns about device durability. It is well known that bioprosthetic SAVs have limited durability, and TAVs are generally assumed to have even worse durability, yet there is little long-term data to confirm this suspicion. In this study, TAV and SAV leaflet fatigue due to cyclic loading was investigated through finite element analysis by implementing a computational soft tissue fatigue damage model to describe the behavior of the pericardial leaflets. Under identical loading conditions and with identical leaflet tissue properties, the TAV leaflets sustained higher stresses, strains, and fatigue damage compared to the SAV leaflets. The simulation results suggest that the durability of TAVs may be significantly reduced compared to SAVs to about 7.8 years. The developed computational framework may be useful in optimizing TAV design parameters to improve leaflet durability, and assessing the effects of underexpanded, elliptical, or non-uniformly expanded stent deployment on TAV durability.

Simulation of long-term fatigue damage in bioprosthetic heart valves: effects of leaflet and stent elastic properties.

One of the major failure modes of bioprosthetic heart valves (BHVs) is noncalcific structural deterioration due to fatigue of the tissue leaflets; yet, the mechanisms of fatigue are not well understood. BHV durability is primarily assessed based on visual inspection of the leaflets following accelerated wear testing. In this study, we developed a computational framework to simulate BHV leaflet fatigue, which is both efficient and quantitative, making it an attractive alternative to traditional accelerated wear testing. We utilize a phenomenological soft tissue fatigue damage model developed previously to describe the stress softening and permanent set of the glutaraldehyde-treated bovine pericardium leaflets in BHVs subjected to cyclic loading. A parametric study was conducted to determine the effects of altered leaflet and stent elastic properties on the fatigue of the leaflets. The simulation results show that heterogeneity of the leaflet elastic properties, poor leaflet coaptation, and little stent-tip deflection may accelerate leaflet fatigue, which agrees with clinical findings. Therefore, the developed framework may be an invaluable tool for evaluating leaflet durability in new tissue valve designs, including traditional BHVs as well as new transcatheter valves.

On the Mechanics of Transcatheter Aortic Valve Replacement.

Transcatheter aortic valves (TAVs) represent the latest advances in prosthetic heart valve technology. TAVs are truly transformational as they bring the benefit of heart valve replacement to patients that would otherwise not be operated on. Nevertheless, like any new device technology, the high expectations are dampened with growing concerns arising from frequent complications that develop in patients, indicating that the technology is far from being mature. Some of the most common complications that plague current TAV devices include malpositioning, crimp-induced leaflet damage, paravalvular leak, thrombosis, conduction abnormalities and prosthesis-patient mismatch. In this article, we provide an in-depth review of the current state-of-the-art pertaining the mechanics of TAVs while highlighting various studies guiding clinicians, regulatory agencies, and next-generation device designers.

Patient-specific finite element analysis of ascending aorta aneurysms

Catastrophic ascending aorta aneurysm (AsAA) dissection and rupture can be prevented by elective surgical repair, but identifying individuals at risk remains a challenge. Typically the decision to operate is based primarily on the overall aneurysm size, which may not be a reliable indicator of risk. In this study, AsAA inflation and rupture was simulated in 27 patient-specific finite element models constructed from clinical CT imaging data and tissue mechanical testing data from matching patients. These patients included n = 8 with concomitant bicuspid aortic valve (BAV), n = 10 with bovine aortic arch (BAA), and n = 10 with neither BAV nor BAA. AsAA rupture risk was found to increase with elevated systolic wall stress and tissue stiffness. The aortic size index was sufficient for identifying the patients with the lowest risk of rupture, but unsuitable for delineating between patients at moderate and high risk. There was no correlation between BAV or BAA and AsAA rupture risk; however, the AsAA morphology was different among these patients. These results support the use of mechanical parameters such as vessel wall stress and tissue stiffness for AsAA presurgical evaluation.

Modeling of long-term fatigue damage of soft tissue with stress softening and permanent set effects.

One of the major failure modes of bioprosthetic heart valves is non-calcific structural deterioration due to fatigue of the tissue leaflets. Experimental methods to characterize tissue fatigue properties are complex and time-consuming. A constitutive fatigue model that could be calibrated by isolated material tests would be ideal for investigating the effects of more complex loading conditions. However, there is a lack of tissue fatigue damage models in the literature. To address these limitations, in this study, a phenomenological constitutive model was developed to describe the stress softening and permanent set effects of tissue subjected to long-term cyclic loading. The model was used to capture characteristic uniaxial fatigue data for glutaraldehyde-treated bovine pericardium and was then implemented into finite element software. The simulated fatigue response agreed well with the experimental data and thus demonstrates feasibility of this approach.

Evaluation of transcatheter heart valve biomaterials: Biomechanical characterization of bovine and porcine pericardium

OBJECTIVE Bovine pericardium (BP) has been identified as a choice biomaterial for the development of surgical bioprosthetic heart valves (BHV) and transcatheter aortic valves (TAV). Porcine pericardium (PP) and younger BP have been suggested as candidates TAV leaflet biomaterials for smaller-profile devices due to their reduced thickness; however, their mechanical and structural properties remain to be fully characterized. This study characterized the material properties of chemically treated thick (PPK) and thin (PPN) PP, as well as fetal (FBP), calf (CBP) and adult (ABP) BP tissues in order to better understand their mechanical behavior. METHODS Planar biaxial testing and uniaxial failure testing methods were employed to quantify tissue mechanical responses and failure properties. Fiber characteristics were examined using histological analysis. RESULTS ABP and CBP tissues were significantly stiffer and stronger than the younger FBP tissues. Histological analysis revealed a significantly larger concentration of thin immature collagen fibers in the FBP tissues than in the ABP and CBP tissues. While PP tissues were thinnest, they were stiffer and less extensible than the BP tissues. CONCLUSIONS Due to comparable mechanical properties but significantly reduced thickness, CBP tissue may be a more suitable material for TAV manufacturing than ABP tissue. FBP tissue, despite its reduced thickness and higher flexibility, was weaker and should be studied in more detail. Although PP tissues are the thinnest, they were least extensible and failed at earlier strain than BP tissues. The differences between PP and BP tissues should be further investigated and suggest that they should not be used interchangeably in the manufacturing of TAV.