Introduction
Transcatheter aortic valve implantation (TAVI) has evolved to become the standard treatment for inoperable and high-risk patients with severe aortic stenosis [
1‐
3], accounting for more than 20% of global aortic valve replacement procedures [
4,
5]. In intermediate-risk patients, TAVI has shown clinical outcomes and survival rates similar or superior to surgical aortic valve replacement [
6‐
8]. However, further developments are still necessary to overcome technical and procedural challenges such as secure deployment and correct positioning of the prosthesis, common presence of paravalvular leakage [
9,
10], frequent changes in atrioventricular conduction [
11], difficulties in vascular access, embolization, and risk of stroke [
12,
13]. More recently, there have been reports concerning possible subclinical leaflet thrombosis and reduced leaflet motion [
14].
Chemically treated bovine and porcine pericardium are commonly used as leaflet material for TAVI valves, based on their broad and successful clinical history in surgical bioprostheses [
15]. Nevertheless, the durability of bioprosthetic leaflets is still a matter of debate [
16‐
18]. The nonphysiological stresses, applied to the leaflets of TAVI prostheses during crimping and deployment, cause tissue dehydration and are believed to increase the risk of structural damage [
19‐
21], affecting adversely the durability of the pericardial valves [
22‐
26]. Polymeric heart valves could represent an attractive alternative to xenograft tissues, addressing these limitations. Although no polymeric valve has reached the market yet, mainly due to their limited durability and hemocompatibility [
27], recent advances in biomaterial science, surface modification techniques, prosthetic design, and fabrication methods have contributed to the development of new synthetic materials more suitable for valvular applications [
28‐
30].
This study describes the in vitro hydrodynamic assessment of a new transcatheter heart valve concept, recently developed at UCL. The TRISKELE is a self-expanding valve with polymeric leaflets, aiming to mitigate complications related to imprecise valve positioning and provide a more reliable solution for both high risk patients with severe aortic stenosis and additionally the lower risk patient demographics at a lower cost.
Discussion
This study provided important data on the function and flow characteristics of the TRISKELE valves, as well as the reference devices. The valves were implanted in the mock aortic roots following their intended loading and deployment steps (the reference valves were implanted in accordance with their manufacturer’s instructions for use), and tested in pulsatile setup simulating a wide range of flow conditions over increasing cardiac output of 2–7 l/min. The self-expanding valves, the TRISKELE and the CoreValve, experienced some flow-induced self-readjustment from their initial implantation position while reaching physiologic pressure and flow conditions.
In general, the TRISKELE valves had comparable performance with the control valves during systole, with exception for the 21-mm annulus aortic root, where our study device exhibited appreciably higher levels of ∆P and worse EOA than the controls (Fig.
4a). This can be attributed to the adopted anchoring approach, designed to reduce the radial forces while enhancing anchoring, which may produce some overconstraint of the leaflets commissures at the smallest implantation sizes, compared to the reference valves. Nevertheless, this limitation could be corrected by expanding the available sizes for the valve to lower diameters.
The SAPIEN valves demonstrated comparatively better performance in small implantation sizes (21 and 23 mm), probably due to the fact that this prosthesis, being balloon expandable, has a stiffer stent which retains a larger EOA after inflation of the balloon and successive partial recoil. TAVI prostheses typically operate at a configuration that is smaller than their fully expanded forms. Once implanted, the functional orifice area of a these valves may be limited by the stenotic native valve leaflets and/or the inner diameter of the diseased bioprostheses (in the case of valve-in-valve procedure) [
46‐
48]. The self-expanding stents may be associated with a relatively smaller EOA, as they are often deformed under the radial anchoring forces [
49].
Common recurrence of paravalvular regurgitation is a major drawback of current TAVI valves [
9,
10,
50,
51]. The TRISKELE demonstrated superior performance during diastole, achieving major reduction in paravalvular leakage in all aortic roots. The sealing cuff incorporated into the TRISKELE design minimizes the paravalvular leakage by covering the gaps between the prosthetic and native tissue. Almost all sizes of the TRISKELE valves achieved a significantly lower total regurgitation (closing regurgitation and leaking volume) compared to the control valves.
The systolic hydrodynamic function of TAVI valves may be as good as or even exceed the performance of surgically implanted bioprostheses [
52]; however, their diastolic performance is often compromised by paravalvular leakage and transvalvular regurgitation, resulting in increased energy loss during diastole [
53]. Energy loss measurements provide a comprehensive criteria to evaluate and compare the overall hydrodynamic performance of the valves during an entire cardiac cycle, based on their effect on the ventricular workload [
45]. Higher paravalvular leakage and central regurgitation have an adverse impact upon valve performance. The lower total energy loss achieved by the TRISKELE indicates a lesser fraction of the ventricular workload to operate, when compared to the reference valves.
Both reference valves experienced some form of dislodgement during the tests, which compromised their performance within the recommended implantation ranges, with the CoreValves having more frequent migrations at CO higher than 3 l/min. In these cases, it was only possible to determine the hydrodynamic performance of the functional components by “artificially” constraining the valves in their initial axial position, although this was not ideal. These premature migrations may be, to some extent, associated with the absence of calcific or fibrotic lesions in the in vitro test model and the smooth surface of the silicone leaflets in the mock aortic roots. Similar observations have been reported previously in animal studies [
54,
55].
No migration was observed for the TRISKELE valves, which contrary to the reference devices is secured to the implantation site by applying mainly counteracting axial forces, rather than radial actions [
49]. The lower protrusions of the frame (inflow portion) project into the left ventricle and the upper petal-like ribs (outflow portion) expand radially on top of the valve annulus, into the leaflets of the native valve (Fig.
1). The valve anchoring is achieved by constraining the aortic annulus and not by dilating it, thus avoiding the application of high levels of distributed radial forces which might perturb the atrioventricular node and the left bundle branch. This approach is suitable for application in patients with calcific stenosis, as well as for uncalcified anatomies, as confirmed by the successful implants in healthy and compliant native ovine aortic valve [
31].
In an attempt to replicate the presence of stiffened native cusps, the mock aortic roots used in this study were made with the same thickness as the root wall. This is, necessarily, an approximation, as it does not incorporate the surface irregularities produced by the presence of calcific nodules, which possibly contribute, in vivo, to a more effective retention of the reference valves. However, the model provides an idealized configuration, which allows direct comparison of different valves under identical anatomical and operating conditions.
Polymeric leaflets provide more design freedom compared to industry standard xenografts. Biostable polymers can be used to produce leaflets two to three times thinner than pericardial tissues, which can potentially result in smaller collapsible valve profile and minimize complications related to vascular access. The thinner polymeric leaflets also improve the hemodynamics of the valve, making it easier to open and achieve a larger orifice area [
56].
Biostable polymers can be engineered to exhibit a tailored range of physical, chemical, and biological characteristics. The α-Gal-free nature of biostable polymers means lower risks of calcification compared to porcine and bovine tissues and may lead to potential advantages in terms of long-term performance and durability [
38,
57,
58]. Moreover, there is no suturing involved in the manufacturing process, hence no stitch hole in the leaflets which could cause tissue tear in the flexion zones. Pericardial tissues are reported to be prone to dehydration and collagen fiber impairment [
22‐
26]. Polymeric leaflets are less susceptible to physical damage induced as a result of collapsing/crimping, hence can be preloaded in air long before the operation, without causing any observable harm to the valve [
31].
While new TAVI devices with improved delivery strategies are being developed, there are both hopes and concerns on expanding the application of TAVI to less risky patient demographics [
6,
59]. The future of transcatheter heart valve replacement and its expansion to lower risk patients depends on technological advances in biomaterials, anticalcification treatment, and development of collapsible valves for optimal delivery and deployment.
Conclusion
An in vitro study was performed to evaluate the hydrodynamic function of a new transcatheter heart valve concept, with polymeric leaflets, an adaptive sealing cuff, and a novel fully retrievable self-expanding frame. The TRISKELE prototypes of 23, 26, and 29 nominal diameter were manufactured using a new automated technique which allows manufacturing of highly reproducible polymeric valves. The TRISKELE valves exhibited comparable or superior hydrodynamic performance compared to the SAPIEN XT (Edwards Lifesciences) and the CoreValve (Medtronic) devices, when tested in appropriate annuli (21-, 23-, 25-, and 27-mm diameter). The TRISKELE valve demonstrated significant reduction in paravalvular leakage (independently on the presence of calcification). The satisfactory results from this study encourage the possibility for further development and refinement. The TRISKELE valve is currently under preclinical investigation for its durability and function in chronic animal studies.