Development History
Professor Wheatley’s inspiration to design a better heart valve dates back more than twenty years. Research in his laboratory and Glasgow University’s Welcome Surgical Research facility pointed the way towards synthetic leaflet valves as can be read in this article from April 2000 in the European Journal of Cardio-Thoracic Surgery.
Early polyurethane valve
One of the results of the research activities of Professor David Wheatley in the late 1990s was the development of this dip moulded three-leaflet biostable polyurethane valve above.
Polyurethane valve in mitral position
This example of a 6-month explant from growing sheep model in which the above valve was implanted in the mitral position of growing sheep showed unaltered hydrodynamic function and no evidence of thrombo-embolic events. What was even more impressive was the unchanged appearance of the synthetic polymer leaflets on scanning electron microscopy. Results were published in the following two papers.
Wheatley DJ, Bernacca GM, Tolland MM, O’Connor B, Fisher J, Williams DF. Hydrodynamic function of a biostable polyurethane flexible heart valve after 6 months in sheep. Int J Artif Organs 2001; 24:95-101.
Bernacca GM, Straub I, Wheatley DJ. Mechanical and morphological study of biostable polyurethane heart valve leaflets explanted from sheep. J Biomed Mater Research 2002; 61:138-45.
However, subsequent commercialisation of the valve was delayed because of initial concerns over manufacturing and lasting concerns about long-term durability of the polymer leaflets.
Following retirement in 2006 from the University of Glasgow, and a spell of working on pericardial valve designs in South Africa, the concerns about longer-term durability of synthetic alternatives caused Professor Wheatley to consider the potential for enhancing durability of polymer leaflets by re-thinking the design of such valves.
Drawing showing the S-shaped and U-shaped leaflet designs
The above drawing, dating from 2012, illustrates the differences of the novel design that emerged, compared with the conventional valve design (which itself mirrored contemporary glutaraldehyde prepared heterograft leaflet valves, including one of Professor Wheatley’s earlier valves that was withdrawn from a randomised successful clinical trial due to the occurrence of bovine spongiform encephalopathy in British cattle – a stimulus to find a synthetic alternative to bovine pericardium).
Not only would intra-leaflet stresses of ‘a hinge on a curve’ be reduced, but also the excursion at the commissures would be lessened, reducing intra-leaflet stresses during valve opening and closing, with potentially major benefit to valve durability. Additionally, the free leaflet edge that defines the outflow orifice could be made as long as desired allowing inflow and outflow orifices to match, reducing the ‘cone effect’ on flow and reducing shear stress at the blood/surface interface, a potential factor in thrombogenicity. A further advantage soon became apparent as the helical or spiral flow patterns within the heart and ascending aorta gained recognition. It appeared feasible that the novel design could interface synergistically with the normal flow patterns of its environment, both preserving much of this normal physiological flow and also being aided by the spiral flow in valve opening. Furthermore, it might even provide a solution to the longer residence time in the non-coronary sinus that may contribute to the low level of thrombo-embolic complications of biological valve prostheses.
The S-shaped valve design was patented initially in the UK and then in the following countries.
There then followed a substantial period of prototype development, primarily aimed at defining a practical, consistent, cost-effective method of manufacture, during which Wheatley Research Ltd was founded to coordinate efforts, commission work and handle financial aspects.
Dip Moulding
Initially the time-honoured method of dip moulding was tried but was soon shown to result in large variation in thickness of the leaflets, particularly in the lower part of the externally concave leaflet. In spite of many manoeuvres such a rotation of the drying leaflet in different orientation, a consistent, satisfactory leaflet thickness could not be achieved.
Carbothane PC-3585 was used in these initial studies.
Following unsatisfactory production of valves using dip-moulding it was concluded that the asymmetric leaflet shape was the difficulty, since conventional valves were able to be dip-moulded satisfactorily.
Injection Moulding
Injection moulding was considered next and a leading UK firm with an interest in developing the technique was identified (Omega Plastics Group Ltd) who worked with our engineering colleagues (Plunkett Associates Ltd) for translating our design concept into suitable engineering specifications for manufacture of valve frames using sintered titanium and for and designing appropriate over-molds for use by Omega Plastics Group Ltd. They also undertook Moldflow studies to aid in arriving at a suitable design.
Frame design for injection moulding
Moldflow Study (Plunkett Associates)
Injection Moulding Equipment
State-of-the-art injection moulding facilities at Omega Plastic Ltd confirmed the cost effectiveness of injection moulding for valve production but showed the difficulty of obtaining consistent leaflet thickness at 150µ.
25mm and 23mm diameter valves
In practice, it was the result of numerous attempts to achieve uniform, specified leaflet thickness that took considerable time. Pellethane 2363 80A was used for injection moulding.
As this photograph shows there remain difficulties with injection moulding.
Curved Surfaces from Flat Sheets
As a result, attention was turned to the possibilities of manufacture from extruded sheet of polyurethane, using 350µ and 150µ thick sheets supplied by Gerlinger Industries.
This simple model illustrates how to create a curved leaflet surface from a flat polymer sheet
Provided that the shape of the flat polymer sheet is correctly defined and the angle of leaflet restraint at the lateral and lower margins is in correct alignment (tangent to radius of curvature at lateral alignment and in continuity with leaflet slope at lower edge), the leaflets take up a satisfactory shape that accords with the original design concept shape.
In the meantime, preliminary computational studies that Professor Wheatley initiated at Dundee University’s School of Science and Engineering have indicated a high likelihood of the novel design meeting expectations.
These studies suggest that the novel valve, when exposed to clockwise flow (lowest brown line) has lower steady state flow pressure drop than when exposed to anticlockwise flow (blue line), and lower than the control ‘conventional’ design valve.
Further advanced computational flow dynamic studies are currently in preparation.
Meanwhile, the implantation of the first clinical synthetic leaflet valve of recent times, in 2019, is seen as encouragement that others have seen the potential advantages of synthetic leaflet valves.
Our hope is that the novel design would see a further improvement in haemodynamic function, thrombogenic potential and long-term durability. A proposal for a catheter-based version of the valve has been filed but will require further developmental work.
Our company is reaching the limits of its resources, both equipment and access to industrial resource, as well as financial resource. For this reason, it is seeking an arrangement with a centre, or centres, with research facilities and experience in the medical devices field, with particular emphasis on the onerous regulatory hurdles required prior to commercialisation and ultimate clinical application.