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- Conference Proceeding
5th Biennial Conference on Heart Valve Biology and Tissue Engineering
- Conference date: 18-20 May 2012
- Location: Mykonos Island, Greece
- Volume number: 2012
- Published: 01 May 2012
81 - 86 of 86 results
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A Pulmonary Valved Conduit of Porcine SIS Remodels into Native Tissue in an Ovine Model
Authors: Anna Fallon, Traci Goodchild, Christian Gilbert and Robert MathenyAbstractReconstruction of the pulmonary valve and outflow tract is frequently needed to repair congenital defects. Current substitutes lead to graft failure and reoperation due to calcification, shrinkage, progressive insufficiency or transvalvular gradients, and relative growth of the patient compared to the valve. CorMatrix extracellular matrix (ECM), derived from decellularized, non-crosslinked small intestine submucosa (SIS) is used for general cardiac repairs and regenerates into normal cardiac tissue with growth potential. Previously, we showed that an ECM pulmonary valve leaflet remodeled into a neo-leaflet histologically similar to native valve architecture. In this study we used an ECM valved conduit for pulmonary valve replacement in an ovine model to demonstrate its potential to remodel into native tissue. A trileaflet valved conduit was produced from CorMatrix ECM sutured into a tube then intussuscepted to form a tube within a tube. At three equidistant points the inner tube was sutured to the outer tube forming three leaflets to guide unidirectional flow with physiologic opening and closing mechanics. Under cardiopulmonary bypass the ovine pulmonary valve and pulmonary artery section was removed and replaced with the ECM valved conduit. Valve function was evaluated by echocardiography post-operatively and at bi-monthly intervals until euthanasia at 3, 5, 8, and 12 months. Histological evaluation included H and E, Movat pentachrome, von Kossa, anti-CD31, and anti-eNOS. Our echocardiography results show that a pulmonary valve constructed from ECM opens and closes completely without regurgitation or stenosis for 12 months. Grossly, explanted valves appeared similar to native valves and were remodeling after 3 months with further progression to native morphology after 5, 8 and 12 months. Histological examination showed diffuse cellular infiltration by 3 months. At 5 months, collagen organization was increased and glycosaminoglycans were distributed throughout the middle of the leaflet. At 3 months, SEM and eNOS staining demonstrated a confluent and functional endothelial lining on the pulmonary artery and hinge regions of the valve. At 5 months, this lining extended to the center of the leaflet with confluent areas at the leaflet tip. At 8 and 12 months, a tri-layered structure similar to native valve architecture was demonstrated histologically by a Movat stain with a confluent endothelial lining demonstrated by eNOS and CD31 staining. The von Kossa stain showed an absence of calcific deposits at all time points except occasionally at the suture. These results demonstrate the potential of a CorMatrix ECM pulmonary valve to remodel into endothelialized tissue that is indistinguishable from the host’s native valve both grossly and histologically. Such a regenerated valve would be expected to improve patient outcomes since it remodels into native tissue with growth potential.
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Finite Element Modeling of Transcatheter Aortic Valve Replacement
Authors: Ali N. Azadani, Sam Chitsaz, Andrew Wisneski, Natalie Lui, Julius M. Guccione, Liang Ge and Elaine E. TsengAbstractTranscatheter aortic valve replacement (TAVR) has revolutionized treatment for inoperable and high risk surgical patients with severe symptomatic aortic stenosis. Transcatheter aortic valves (TAVs) are deployed within the native diseased valve without sutures to secure them within the annulus. Oversizing of TAVs with respect to the annulus size is required to achieve appropriate anchoring. Optimal TAV function requires expansion of the frame to its nominal dimension. However, clinically TAVR results routinely in incomplete expansion of the stent frame. We have previously demonstrated that significant under-expansion results in suboptimal TAV function with impaired coaptation of TAV leaflets, but precise characteristics of TAV leaflets and frame after implantation have been poorly studied. The aim of this study was to determine the effect of TAV under-expansion as observed clinically on stress distribution and magnitude in the TAV stent and leaflets using finite element (FE) modeling. A computer aided design (CAD) model of a TAV was developed based on the 23mm Edwards-SAPIEN design and used to create a finite element (FE) model. The 3D model consists of a stent, three pericardial leaflets, a clamp compression unit and an expandable balloon. Large deformation FE simulations were conducted to model the TAVR procedure, including TAV crimping followed by balloon-expansion to 17, 21, and 23mm. Stress distribution on the stent and leaflets were determined. As the post-inflation diameter increased, the von Mises stress on the TAV stent decreased. The maximum von Mises stresses of stent after expansion to 17, 21, and 23mm were 365, 346, and 262 MPa, respectively. However, unlike the stent, the leaflet stress increased as the post-inflation diameter increased. The peak von Mises stresses after expansion were 1.5, 1.3, and 2.4 MPa, respectively. We present the first FE simulation which was developed to model the TAVR procedure from crimping and balloon inflation of the TAV. Stress on stent and leaflets after implantation is dependent on the internal diameter of the inflated stent. While stress on the stent decreases with increasing TAV expansion, stress on the leaflets increases. FE modeling can be further applied evaluate whether a specific TAV size and design is optimal for a specific patient.
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A Completely Biological, Tissue Engineered Valve Leaflet Suitable for TAVI
Authors: Todd McAllister, Nathalie Dusserre, Nicolas Chronos and Nicolas L'HeureuxAbstractClinically available transcatheter aortic valve replacement (TAVR) technologies typically use chemically fixed bovine or equine tissues for the valve leaflets. While these fixed, xenogeneic materials have been used with success in devices placed by open surgical access, the tissue thickness (>500 microns) adds significantly to the overall crossing profile of the delivery device. Complications associated with device diameter are generally reported in at least 10-20% of clinical cases, making a reduced crossing profile one of the most critical targets for second generation TAVR devices. Another limitation associated with pericardium is fatigue induced delamination. Previously we have reported clinical results with a completely autologous tissue engineered vascular graft built using a process termed sheet-based tissue engineering. Using this approach, we were able to build small diameter blood vessels with supraphysiologic burst pressures, and demonstrated clinical durability with time points out to 3 years. Importantly, this tissue engineering approach requires no chemical fixation or exogenous biomaterials. More recently, we reported initial human use with an allogeneic version of the vessel. With time points out to 1 year, the allogeneic tissue engineered material demonstrated no evidence of immune reaction. This transition to an off-the shelf, allogeneic approach enables use the material in a variety of new clinical indications, including valve reconstruction. Valve leaflets built from a single sheet, demonstrated ultimate tensile strength in excess of that for bovine valve leaflets. Of note, the thickness of the sheet was less than 200 microns, roughly 30 percent that of bovine pericardium. The tissue can also be compressed, further reducing the thickness to approximately 75 microns. This thin, durable, single layered tissue can be assembled onto commercially available TAVR devices resulting in a reduction in crossing profile of approximately 2 Fr. The valve leaflets can be sutured easily, coapt normally, and can withstand arterial backpressure. Given the non-laminated structure of the tissue engineered leaflet, the lack of synthetic materials, and the durability demonstrated in other clinical indications, this approach may provide not only a reduced crossing profile, but also improved long term clinical results.
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Imbalance in Extracellular Matrix Synthesis and Degradation as a Mechanism of Leaflet Weakening in Sporadic Mitral Valve Prolapse in Humans
AbstractSporadic mitral valve prolapse (MVP) is a common valvular disorder affecting 2-3% of the humans worldwide. Unlike MVP in Marfan’s and Ehlers-Danlos syndromes, no specific genetic mutations that impact tissue homeostasis are currently identified. Yet, significant degenerative leaflet changes are observed, manifesting as leaflet weakening and billowing. In this study, we hypothesized that assessing the matrix health by investigating the activity of matrix synthetic and degradative markers would provide insights into the leaflet degeneration processes. Mitral leaflets were obtained from eight humans (N =8) undergoing surgical repair for MVP at our institution. Fresh leaflets were rinsed, stored in sterile PBS and divided into annulus, base or edge regions and used for immunohistochemistry(IHC) and western blotting(WB). Matrix synthetic activity was assessed using assays for: prolyl-4-hydroxylase(P4H–collagen synthesis enzyme), heat shock protein-47(HSP47–chaperone for collagen folding), and lysyl oxidase(LOX–collagen cross-linking). Matrix degradation was assessed using assays for matrix metalloproteases: MMP-1(collagen I degradation), MMP-3(collagen III degradation), and MMP-9(collagen V degradation). Tissue sections were imaged and quantitative analysis was performed using an image thresholding technique. Cell viability was confirmed using DAPI, and overall tissue structure assessed using H and E staining. Tissue section closest to the mitral annulus served as the control, against which the belly and edge expressions were compared. In the synthetic pathway, P4H activity decreased from 4±1.5 at the annulus to 2±1.3 at the belly (2X) and increased to 17±12 at the edge (4X). HSP47 activity was 3.2±2 in the annular section that increased to 5.1±2 in the belly (1.6X) and 4±1.3 in the edge (1.2X). LOX expression slightly increased from the annulus to the belly (1.2X), but was significantly higher in the edge (10X). In the degradative pathway, MMP-1 expression was 8.4±6.3 at the annulus, which decreased to 5.6±2.8 in the belly (1.5X), and 6±2 in the edge (1.4X). MMP-3 expression significantly increased from the annulus to the edge, with 2.3±2 at the annulus, 7.7±5 at the belly (3.3X) and 24.5±10.6 at the edge (10.4X). MMP-9 expression decreased from the annulus (1.3±0.4) to the belly (0.7±0.2; 1.7X) and increased to 3±1 in the edge(2.4X). Collagen biosynthesis is adequate in the edge as evident from increased P4H activity, however nominal HSP47 activity indicates poor fibril maturation and folding, resulting in a weak matrix in spite of good cross linking from higher LOX expression. Increased MMP-3 and 9 activities in the edge signify degradation of collagen III and V, which may further weaken the matrix. Studies to investigate the regional differences in genetic, cellular and molecular pathways in MVP and the potential role of the elevated stress in leaflet degradation are necessary.
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A Finite Element Study of Human Pulmonary Autograft Wall Stress after the Ross Procedure
AbstractDilatation of the pulmonary autograft after the Ross procedure can lead to aortic insufficiency and/or aneurysmal pathology requiring reoperation. Autograft remodeling occurs as the autograft wall is exposed to systemic pressure and higher wall stresses, which have not been quantified in humans. The aim of the study was to develop a realistic Finite Element (FE) model of the human pulmonary autograft and to perform simulations at systemic pressure to quantify the increases in autograft wall stress immediately after the Ross procedure. Autograft geometry was generated from high-resolution micro-computed tomography images of an explanted human pulmonary root to create a mesh of hexahedral elements. Constitutive equations were used to describe the regional tissue material properties of the human pulmonary root obtained from bi-axial stretch testing. LS-DYNA (LSTC Inc., Livermore, CA) FE software was used to simulate cardiac cycles at pulmonary and systemic pressure. Autograft dilatation and wall stress distribution were determined. Correlation of LS-DYNA model material properties to actual tissue stress-strain data was performed to ensure model accuracy. Human autograft dilation from pulmonary to systemic pressure was minimal (32.1 to 33.4mm) due to the non-linearity of the material properties. Less compliance was demonstrated at greater wall stresses. Significant increases in autograft wall stresses were found at systemic pressures. Maximal wall stresses increased approximately 10-fold in diastole (12.4 to 122.3 kPa) and 5-fold in systole (48.1 to 234.2 kPa), relative to the wall stresses at pulmonary pressures. Pulmonary autograft wall stress increased by an order of magnitude at systemic pressure. Initial autograft dilation at systemic pressure was minimal as validated by clinical studies. Chronically elevated wall stress may lead to pathologic remodeling and aneurysmal formation over time. The correspondence of this model with future studies of post-dilated autografts will lead to an improved understanding of tissue remodeling, and offer necessary data for developing improvements to the Ross procedure.
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Prevalence of Patients With Severe Aortic Stenosis, Low Flow And Preserved Ejection Fraction: Results From a Cath-Lab Data Base.
Authors: Toniolo Mauro, Rossi Andrea and Cicoira MariantoniettaAbstractRecent echocardiographic studies described that almost 30% of patients with severe aortic valve stenosis on the basis of aortic valve area may paradoxically have a relatively low mean gradient despite a preserved left ventricular ejection fraction (EF). However the existence of this pathologic entity has been questioned mainly for the lack of invasive data. We aimed to describe the prevalence of patients with severely reduced aortic valve area and low gradient from a consecutive series of patients with aortic stenosis and normal EF undergoing cardiac catheterization. Sixty one consecutive patients with invasively measured aortic valve area < 0,6 cmq/mq (AHA/ACC definition for severe aortic stenosis) and EF> 50% formed the study population. Each patient underwent to right and left heart catheterization for a comprehensive invasive hemodynamic evaluation. Aortic valve area was measured by Gorlin formula. Cardiac output was measured by thermodilution or Fick method. Low mean gradient was defined < 30 mmHg. 16 % of patients were characterized by low GM despite severely reduced aortic valve area. Patients with low GM were characterized by significantly higher aortic valve area (0.47±0.09 vs 0.36±0.09 cm2/m2; p=0.0008) but similar left ventricular stroke volume (SV) (65±22 vs 65±17 ml; p=0.9) and cardiac output (4.8±1.1 vs 4.7±1.0; p=0.7). The prevalence of low flow (defined as SV < 35 ml/ m2) was similar between groups (50% vs 43%; p=0.3). There was no difference in term of age (78±10 vs 79±11 years; p=0.6), female gender (50% vs 48%; p=0.5), body surface area (1.79±0.4 vs 1.80±0.4; p=0.8), pulmonary artery systolic pressures (37±9 vs 35±11 mmHg; p=0.8), LV end diastolic pressure (16±4 vs 20±7; p=0.1) and mean wedge pressure (17±7 vs 15±7; p=0.2). Patients with low GM showed a higher mean AO pressure (111±14 vs 93±14; p=0.009) but similar level of aortic distensibility (0.78±0.3 vs 0.9±0.4 ml/mmHg; p=0.3). This invasive study confirms that a substantial percent of patients may have a low GM despite a severely reduced aortic valve area and normal EF. It should be acknowledge that the barely perception of this pathologic entity might have reduced the likelihood of patients to undergo catheterization leading to underestimation of the prevalence of this condition.
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