Hemodynamic and thrombogenic analysis of a trileaflet polymeric valve using a fluid-structure interaction approach.

Surgical valve replacement in patients with severe calcific aortic valve disease using either bioprosthetic or mechanical heart valves is still limited by structural valve deterioration for the former and thrombosis risk mandating anticoagulant therapy for the latter. Prosthetic polymeric heart valves have the potential to overcome the inherent material and design limitations of these valves, but their development is still ongoing. The aim of this study was to characterize the hemodynamics and thrombogenic potential of the Polynova polymeric trileaflet valve prototype using a fluid-structure interaction (FSI) approach. The FSI model replicated experimental conditions of the valve as tested in a left heart simulator. Hemodynamic parameters (transvalvular pressure gradient, flow rate, maximum velocity, and effective orifice area) were compared to assess the validity of the FSI model. The thrombogenic footprint of the polymeric valve was evaluated using a Lagrangian approach to calculate the stress accumulation (SA) values along multiple platelet trajectories and their statistical distribution. In the commissural regions, platelets were exposed to the highest SA values because of highest stress levels combined with local reverse flow patterns and vortices. Stress-loading waveforms from representative trajectories in regions of interest were emulated in our hemodynamic shearing device (HSD). Platelet activity was measured using our platelet activation state (PAS) assay and the results confirmed the higher thrombogenic potential of the commissural hotspots. In conclusion, the proposed method provides an in depth analysis of the hemodynamic and thrombogenic performance of the polymer valve prototype and identifies locations for further design optimization.

Physical Characterization and Platelet Interactions under Shear Flows of a Novel Thermoset Polyisobutylene-based Co-polymer.

Over the years, several polymers have been developed for use in prosthetic heart valves as alternatives to xenografts. However, most of these materials are beset with a variety of issues, including low material strength, biodegradation, high dynamic creep, calcification, and poor hemocompatibility. We studied the mechanical, surface, and flow-mediated thrombogenic response of poly(styrene-coblock-4-vinylbenzocyclobutene)-polyisobutylene-poly(styrene-coblock-4-vinylbenzocylcobutene) (xSIBS), a thermoset version of the thermoplastic elastomeric polyolefin poly(styrene-block-isobutylene-block-styrene) (SIBS), which has been shown to be resistant to in vivo hydrolysis, oxidation, and enzymolysis. Uniaxial tensile testing yielded an ultimate tensile strength of 35 MPa, 24.5 times greater than that of SIBS. Surface analysis yielded a mean contact angle of 82.05° and surface roughness of 144 nm, which was greater than for poly(ε-caprolactone) (PCL) and poly(methyl methacrylate) (PMMA). However, the change in platelet activation state, a predictor of thrombogenicity, was not significantly different from PCL and PMMA after fluid exposure to 1 dyn/cm(2) and 20 dyn/cm(2). In addition, the number of adherent platelets after 10 dyn/cm(2) flow exposure was on the same order of magnitude as PCL and PMMA. The mechanical strength and low thrombogenicity of xSIBS therefore suggest it as a viable polymeric substrate for fabrication of prosthetic heart valves and other cardiovascular devices.

Toward optimization of a novel trileaflet polymeric prosthetic heart valve via device thrombogenicity emulation.

Aortic stenosis is the most prevalent and life-threatening form of valvular heart disease. It is primarily treated via open-heart surgical valve replacement with either a tissue or a mechanical prosthetic heart valve (PHV), each prone to degradation and thrombosis, respectively. Polymeric PHVs may be optimized to eliminate these complications, and they may be more suitable for the new transcatheter aortic valve replacement procedure and in devices like the total artificial heart. However, the development of polymer PHVs has been hampered by persistent in vivo calcification, degradation, and thrombosis. To address these issues, we have developed a novel surgically implantable polymer PHV composed of a new thermoset polyolefin called cross-linked poly(styrene-block-isobutylene-block-styrene), or xSIBS, in which key parameters were optimized for superior functionality via our device thrombogenicity emulation methodology. In this parametric study, we compared our homogeneous optimized polcymer PHV to a prior composite polymer PHV and to a benchmark tissue valve. Our results show significantly improved hemodynamics and reduced thrombogenicity in the optimized polymer PHV compared to the other valves. These results indicate that our new design may not require anticoagulants and may be more durable than its predecessor, and validate the improvement, toward optimization, of this novel polymeric PHV design.

In vitro evaluation of a novel hemodynamically optimized trileaflet polymeric prosthetic heart valve.

Calcific aortic valve disease is the most common and life threatening form of valvular heart disease, characterized by stenosis and regurgitation, which is currently treated at the symptomatic end-stages via open-heart surgical replacement of the diseased valve with, typically, either a xenograft tissue valve or a pyrolytic carbon mechanical heart valve. These options offer the clinician a choice between structural valve deterioration and chronic anticoagulant therapy, respectively, effectively replacing one disease with another. Polymeric prosthetic heart valves (PHV) offer the promise of reducing or eliminating these complications, and they may be better suited for the new transcatheter aortic valve replacement (TAVR) procedure, which currently utilizes tissue valves. New evidence indicates that the latter may incur damage during implantation. Polymer PHVs may also be incorporated into pulsatile circulatory support devices such as total artificial heart and ventricular assist devices that currently employ mechanical PHVs. Development of polymer PHVs, however, has been slow due to the lack of sufficiently durable and biocompatible polymers. We have designed a new trileaflet polymer PHV for surgical implantation employing a novel polymer-xSIBS-that offers superior bio-stability and durability. The design of this polymer PHV was optimized for reduced stresses, improved hemodynamic performance, and reduced thrombogenicity using our device thrombogenicity emulation (DTE) methodology, the results of which have been published separately. Here we present our new design, prototype fabrication methods, hydrodynamics performance testing, and platelet activation measurements performed in the optimized valve prototype and compare it to the performance of a gold standard tissue valve. The hydrodynamic performance of the two valves was comparable in all measures, with a certain advantage to our valve during regurgitation. There was no significant difference between the platelet activation rates of our polymer valve and the tissue valve, indicating that similar to the latter, its recipients may not require anticoagulation. This work proves the feasibility of our optimized polymer PHV design and brings polymeric valves closer to clinical viability.

Polymeric trileaflet prosthetic heart valves: evolution and path to clinical reality.

Present prosthetic heart valves, while hemodynamically effective, remain limited by progressive structural deterioration of tissue valves or the burden of chronic anticoagulation for mechanical valves. An idealized valve prosthesis would eliminate these limitations. Polymeric heart valves (PHVs), fabricated from advanced polymeric materials, offer the potential of durability and hemocompatibility. Unfortunately, the clinical realization of PHVs to date has been hampered by findings of in vivo calcification, degradation and thrombosis. Here, the authors review the evolution of PHVs, evaluate the state of the art of this technology and propose a pathway towards clinical reality. In particular, the authors discuss the development of a novel aortic PHV that may be deployed via transcatheter implantation, as well as its optimization via device thrombogenicity emulation.

Thrombogenic potential of Innovia polymer valves versus Carpentier-Edwards Perimount Magna aortic bioprosthetic valves.

Trileaflet polymeric prosthetic aortic valves (AVs) produce hemodynamic characteristics akin to the natural AV and may be most suitable for applications such as transcatheter implantation and mechanical circulatory support (MCS) devices. Their success has not yet been realized due to problems of calcification, durability, and thrombosis. We address the latter by comparing the platelet activation rates (PARs) of an improved polymer valve design (Innovia LLC) made from poly(styrene-block-isobutylene-block-styrene) (SIBS) with the commercially available Carpentier-Edwards Perimount Magna Aortic Bioprosthetic Valve. We used our modified prothrombinase platelet activity state (PAS) assay and flow cytometry methods to measure platelet activation of a pair of 19 mm valves mounted inside a pulsatile Berlin left ventricular assist device (LVAD). The PAR of the polymer valve measured with the PAS assay was fivefold lower than that of the tissue valve (p = 0.005) and fourfold lower with flow cytometry measurements (p = 0.007). In vitro hydrodynamic tests showed clinically similar performance of the Innovia and Magna valves. These results demonstrate a significant improvement in thrombogenic performance of the polymer valve compared with our previous study of the former valve design and encourage further development of SIBS for use in heart valve prostheses.

Development and evaluation of a novel artificial catheter-deliverable prosthetic heart valve and method for in vitro testing.

BACKGROUND: This work presents a novel artificial prosthetic heart valve designed to be catheter or percutaneously deliverable, and a method for in vitro testing of the device. The device is intended to create superior characteristics in comparison to tissue-based percutaneous valves. METHODS: The percutaneous heart valve (PhV) was constructed from state-of-the-art polymers, metals and fabrics. It was tested hydrodynamically using a modified left heart simulator (Lhs) and statically using a tensile testing device. RESULTS: The PhV exhibited a mean transvalvular pressure gradient of less than 15 mmhg and a mean regurgitant fraction of less than 5 percent. It also demonstrated a resistance to migration of up to 6 N and a resistance to crushing of up to 25 N at a diameter of 19 mm. The PhV was crimpable to less than 24 F and was delivered into the operating Lhs via a 24 F catheter. CONCLUSION: An artificial PhV was designed and optimized, and an in vitro methodology was developed for testing the valve. The artificial PhV compared favorably to existing tissue-based PhVs. The in vitro test methods proved to be reliable and reproducible. The PhV design proved the feasibility of an artificial alternative to tissue based PhVs, which in their traditional open-heart implantable form are known to have limited in vivo durability.