Thuy Pham

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

OBJECTIVEnCurrently, 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.nnnMETHODSnThe 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.nnnRESULTSnAged 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.nnnCONCLUSIONSnSignificant 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.

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.

Predictive biomechanical analysis of ascending aortic aneurysm rupture potential.

Aortic aneurysm is a leading cause of death in adults, often taking lives without any premonitory signs or symptoms. Adverse clinical outcomes of aortic aneurysm are preventable by elective surgical repair; however, identifying at-risk individuals is difficult. The objective of this study was to perform a predictive biomechanical analysis of ascending aortic aneurysm (AsAA) tissue to assess rupture risk on a patient-specific level. AsAA tissues, obtained intra-operatively from 50 patients, were subjected to biaxial mechanical and uniaxial failure tests to obtain their passive elastic mechanical properties. A novel analytical method was developed to predict the AsAA pressure-diameter response as well as the aortic wall yield and failure responses. Our results indicated that the mean predicted AsAA diameter at rupture was 5.6 ± 0.7 cm, and the associated blood pressure to induce rupture was 579.4 ± 214.8 mmHg. Statistical analysis showed significant positive correlation between aneurysm tissue compliance and predicted risk of rupture, where patients with a pressure-strain modulus ≥100 kPa may be nearly twice as likely to experience rupture than patients with more compliant aortic tissue. The mechanical analysis of pre-dissection patient tissue properties established in this study could predict the future onset of yielding and rupture in AsAA patients. The analysis results implicate decreased tissue compliance as a risk factor for AsAA rupture. The presented methods may serve as a basis for the development of a pre-operative planning tool for AsAA evaluation, a tool currently unavailable.

Material properties of aged human mitral valve leaflets

This study aimed to characterize the mechanical properties of aged human anterior mitral leaflets (AML) and posterior mitral leaflets (PML). The AML and PML samples from explanted human hearts (n = 21, mean age of 82.62 ± 8.77-years-old) were subjected to planar biaxial mechanical tests. The material stiffness, extensibility, and degree of anisotropy of the leaflet samples were quantified. The microstructure of the samples was assessed through histology. Both the AML and PML samples exhibited a nonlinear and anisotropic behavior with the circumferential direction being stiffer than the radial direction. The AML samples were significantly stiffer than the PML samples in both directions, suggesting that they should be modeled with separate sets of material properties in computational studies. Histological analysis indicated the changes in the tissue elastic constituents, including the fragmented and disorganized elastin network, the presence of fibrosis and proteoglycan/glycosaminoglycan infiltration and calcification, suggesting possible valvular degenerative characteristics in the aged human leaflet samples. Overall, stiffness increased and areal strain decreased with calcification severity. In addition, leaflet tissues from hypertensive individuals also exhibited a higher stiffness and low areal strain than normotensive individuals. There are significant differences in the mechanical properties of the two human mitral valve leaflets from this advanced age group. The morphologic changes in the tissue composition and structure also infer the structural and functional difference between aged human valves and those of animals.

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.

COMPARISON OF BIAXIAL MECHANICAL PROPERTIES OF CORONARY SINUS TISSUES FROM PORCINE, OVINE AND AGED HUMAN SPECIES

Due to its proximity to the mitral valve, the coronary sinus (CS) vessel serves as a conduit for the deployment and implantation of the percutaneous transvenous mitral annuloplasty (PTMA) devices that can potentially reduce the mitral regurgitation. Because CS vessel is a venous tissue and seldom diseased, its mechanical properties have not been well studied. In this study, we performed a multi-axial mechanical test and histological analysis to characterize the mechanical and structural properties of the aged human, porcine and ovine CS tissues. The results showed that the aged human CS tissues exhibited much stiffer and highly anisotropic behaviors compared to the porcine and ovine. Both of the porcine and ovine CS vessel walls were thicker and mainly composed of striated muscle fibers (SMF), whereas the thinner aged human CS had higher collagen, less SMF, and more fragmented elastin fibers, which are possibly due to aging effects. We also observed that the anatomical features of porcine CS vessel might be not suitable for PTMA deployment. These differences between animal and human models raise questions for the validity of using animal models to investigate the biomechanics involved in the PTMA intervention. Therefore, caution must be taken in future studies of PTMA stents using animal models.

Characterization of the mechanical properties of the coronary sinus for percutaneous transvenous mitral annuloplasty

The coronary sinus (CS) vessel serves as a conduit for the deployment of percutaneous transvenous mitral annuloplasty (PTMA) devices for the treatment of functional mitral regurgitation. Characterization of the mechanical response of the CS is an important step towards an understanding of tissue-device interaction in PTMA intervention. The purpose of this study was to investigate the mechanical properties of the porcine CS using the pressure-inflation test and constitutively model the wall behavior using a four fiber family strain energy function (SEF). The results showed that the CS exhibited an S-shaped pressure-radius response and could be dilated up to 88% at a pressure of 80mmHg. Excellent results from model fitting indicated that the four fiber family SEF could capture the experimental data well and could be used in future numerical simulations of tissue-device interaction. In addition, a histological study was performed to identify the micro-structure of the CS wall. We found a high content of striated myocardial fibers (SMFs) surrounding the CS wall, which was also mainly composed of SMFs, while the content of smooth muscle cells was very low. Elastin and collagen fibers were highly concentrated in the luminal and outer layers and sparsely distributed in the medial layer of the CS wall. These structural and mechanical properties of the CS should be taken into consideration in future PTMA device designs.

Tension to passively cinch the mitral annulus through coronary sinus access: an ex vivo study in ovine model

INTRODUCTIONnThe transcatheter mitral valve repair (TMVR) technique utilizes a stent to cinch a segment of the mitral annulus (MA) and reduces mitral regurgitation. The cinching mechanism results in reduction of the septal-lateral distance. However, the mechanism has not been characterized completely. In this study, a method was developed to quantify the relation between cinching tension and MA area in an ex vivo ovine model.nnnMETHODnThe cinching tension was measured from a suture inserted within the coronary sinus (CS) vessel with one end tied to the distal end of the vessel and the other end exited to the CS ostium where it was attached to a force transducer on a linear stage. The cinching tension, MA area, septal-lateral (S-L) and commissure-commissure (C-C) diameters and leakage was simultaneously measured in normal and dilated condition, under a hydrostatic left ventricular pressure of 90 mm Hg.nnnRESULTSnThe MA area was increased up to 22.8% after MA dilation. A mean tension of 2.1 ± 0.5 N reduced the MA area by 21.3 ± 5.6% and S-L diameter by 24.2 ± 5.3%. Thus, leakage was improved by 51.7 ± 16.2% following restoration of normal MA geometry.nnnCONCLUSIONnThe cinching tension generated by the suture acts as a compensation force in MA reduction, implying the maximum tension needed to be generated by annuloplasty device to restore normal annular size. The relationship between cinching tension and the corresponding MA geometry will contribute to the development of future TMVR devices and understanding of myocardial contraction function.

Characterization of biomechanical properties of aged human and ovine mitral valve chordae tendineae.

The mitral valve (MV) is a highly complex cardiac valve consisting of an annulus, anterior and posterior leaflets, chordae tendineae (chords) and two papillary muscles. The chordae tendineae mechanics play a pivotal role in proper MV function: the chords help maintain proper leaflet coaptation and rupture of the chordae tendineae due to disease or aging can lead to mitral valve insufficiency. Therefore, the aim of this study was to characterize the mechanical properties of aged human and ovine mitral chordae tendineae. The human and ovine chordal specimens were categorized by insertion location (i.e., marginal, basal and strut) and leaflet type (i.e., anterior and posterior). The results show that human and ovine chords of differing types vary largely in size but do not have significantly different elastic and failure properties. The excess fibrous tissue layers surrounding the central core of human chords added thickness to the chords but did not contribute to the overall strength of the chords. In general, the thinner marginal chords were stiffer than the thicker basal and strut chords, and the anterior chords were stiffer and weaker than the posterior chords. The human chords of all types were significantly stiffer than the corresponding ovine chords and exhibited much lower failure strains. These findings can be explained by the diminished crimp pattern of collagen fibers of the human mitral chords observed histologically. Moreover, the mechanical testing data was modeled with the nonlinear hyperelastic Ogden strain energy function to facilitate accurate computational modeling of the human MV.