Patent Application
20240033077
Heart valve disease affects upwards of 5 million Americans. Annually, 150,000 heart valve transplants are performed using either a mechanical valve or a bovine or porcine xenograft. Mechanical valve recipients have a lifespan of 20-30 years and require lifelong anticoagulant therapy. Xenografts are treated to prevent transplant rejection, limiting their lifespan to 20 years. Currently, many xenograft-based prosthetic heart valves are made using a handsewn construction. This process is time-consuming and costly.
The ideal transplant is a living valve made from the patient's own tissues. Researchers are attempting to grow cells into a valve shape using an extracellular matrix (“ECM”) scaffold, but to date none are fully functional.
Thus, there is a need to develop a method for valve fabrication that is simpler in construction than using ECM scaffolds, but still allows for flexible sheets of material to be used.
The present disclosure addresses the aforementioned drawbacks by providing a prosthetic heart valve that is composed from a flexible substrate having a plurality of leaflet-defining regions and a plurality of outer wall-defining regions. When the flexible membrane is folded into a folded configuration the plurality of outer wall-defining regions form a cylindrical outer wall and the plurality of leaflet-defining regions form a corresponding plurality of flexible leaflets arranged within a lumen of the cylindrical outer wall.
It is another aspect of the present disclosure to provide a prosthetic heart valve device that includes a flexible substrate having an annular shape, where the flexible substrate includes an outer periphery that circumscribes the flexible substrate, an inner periphery that defines an aperture of the annular shape, a plurality of leaflet-defining regions, and a plurality of wall-defining regions. Each leaflet-defining region is defined by an arcuate segment extending along the outer periphery from a first point to a second point, a first edge line extending from the first point to a nadir point on the inner periphery, and a second edge line extending from the second point to the nadir point on the inner periphery. Each wall-defining region is defined as a portion of the flexible substrate opposed by the first edge line of a first leaflet-defining region and the second edge line of a second leaflet-defining region that is adjacent the first leaflet-defining region. When in a folded configuration, the first edge line and the second edge line of each leaflet-defining portion meet in a seam region such that the plurality of wall-defining regions circumscribe a cylindrical volume and define an outer wall, and such that each leaflet-defining region extends from its nadir point at an inflow end of cylindrical volume to at least a free edge lying in a transverse plane at an outflow end of the cylindrical volume.
The foregoing and other aspects and advantages of the present disclosure will appear from the following description. In the description, reference is made to the accompanying drawings that form a part hereof, and in which there is shown by way of illustration a preferred embodiment. This embodiment does not necessarily represent the full scope of the invention, however, and reference is therefore made to the claims and herein for interpreting the scope of the invention.
Described here are prosthetic heart valves that can be designed to replace damaged or diseased native heart valves. Advantageously, the prosthetic heart valves are constructed from a flexible substrate that can be folded from an unfolded configuration to a folded configuration, in which the prosthesis is operable as a prosthetic heart valve. The prosthetic heart valves can be designed as atrioventricular valves (e.g., tricuspid valve, mitral valve) or as semilunar valves (e.g., aortic valve, pulmonary valve).
In general, the prosthetic heart valves described in the present disclosure are constructed from a single flexible substrate that is folded to create a prosthetic heart valve. A suitable flexible substrate can start in one of two forms: a flat two-dimensional sheet, or a three-dimensional shape (e.g., a curved sheet). As one example, the three-dimensional shape may be similar to a hollow conical frustum. In the case of a flat sheet, a specific shape can be cut from the sheet, folded around, and the ends secured in a way that produces the three-dimensional shape. Alternatively, the three-dimensional shape can be fabricated directly.
The three-dimensional shape is then folded in a manner that produces two or three leaflets within a hollow cylinder, similar to the configuration of the leaflets and root of a native heart valve. In some configurations, the two-dimensional shape may be directly folded to form the prosthetic heart valve. In either instance, the folded shape can be maintained by attaching adjacent portions of the material by any suitable means (e.g. sutures). The valve can be implanted surgically (with or without a support frame) or affixed to a stent and implanted via a catheter. In some embodiments, a support frame can be provided at the inflow end 12 of the prosthetic heart valve 10, at the outflow end 14 of the prosthetic heart valve 10, or at both the inflow end 12 and the outflow end 14 of the prosthetic heart valve 10. Advantageously, the support frame at the inflow end 12 can be made rigid in order to provide more stability and improved functioning of the prosthetic heart valve 10. When a support frame is provided at both the inflow end 12 and the outflow end 14, the support frame at the inflow end 12 can be made more rigid than the support frame at the outflow end 14, or the support frames at both the inflow end 12 and outflow end 14 can be made with substantially similar rigidities.
The construction of the prosthetic heart valves 10 described in the present disclosure offers several advantages over conventional prosthetic heart valve designs. Generally, because the entire prosthetic heart valve (leaflets and root) can be produced from one continuous piece of biomaterial, failure points and stress concentrations that are associated with current prosthetic valves can be significantly reduced or otherwise eliminated. Further, the most vulnerable regions of the valve, the leaflet commissures, are generally eliminated and instead replaced with leaflets that gently fold inward and outward during each cardiac cycle with no areas of stress concentration. The vulnerable sutures are all located in the root behind the center of the leaflets, where minimal stress is located.
Furthermore, overlapping folds of the material or an appropriate suturing strategy during implantation can be used to accommodate somatic growth in pediatric patients. For example, the material can be secured to the native root rather than to itself at the adjacent folding sites to allow for circumferential expansion.
The foldable construction of the prosthetic heart valves described in the present disclosure allows for straightforward fabrication. The lower material demands also allow for a wider range of biocompatible materials, biomaterials, and/or tissues to be utilized in the construction of the prosthetic heart valve.
The prosthetic heart valves described in the present disclosure can be deployed using conventional surgical procedures, including both retrograde and antegrade approaches. In addition, the prosthetic heart valves described in the present disclosure can be deployed using minimally invasive procedures, such as a transcatheter aortic valve replacement (“TAVR”) procedure.
The prosthetic heart valve 10 generally includes a plurality of outer wall portions 16 and a plurality of leaflet portions 18. The outer wall portions 16 collectively define an outer wall, or frame, of the prosthetic heart valve 10, and the leaflet portions 18 collectively define leaflets, or cusps, of the prosthetic heart valve 10, as illustrated in
In
The prosthetic heart valve 10 is generally operable as follows. When in the closed state, blood will flow into the central lumen of the prosthetic heart valve 10 at the inflow end 12. The blood will then impinge upon and thus apply pressure to the lower surface of the leaflet portions 18. The force of the blood on the leaflet portions 18 pushes the leaflet portions 18 outward to open the valve. Generally, the leaflet portions 18 are pressed outward from the flow axis and towards the outer wall portions 16 of the prosthetic heart valve 10. In this way, the prosthetic heart valve 10 is opened from its closed state shown in
The flexible substrate 20 may have a generally annular shape defined by an outer periphery 24 and an inner periphery 26 that circumscribes a central aperture 28 of the flexible substrate 20. As one example, the flexible substrate 20 can have a generally triangular annular shape, as shown in
The flexible substrate 20 contains a plurality of leaflet-defining regions 30 and a plurality of wall-defining regions 32. When the flexible substrate 20 is folded into the folded configuration of the prosthetic heart valve 10, the leaflet-defining regions 30 form the leaflet portions 18 of the prosthetic heart valve 10. These leaflet portions 18 are shaped and operable as pliable heart valve leaflets, or cusps. Likewise, when the flexible substrate 20 is folded into the folded configuration of the prosthetic heart valve 10, the wall-defining regions 32 will form the outer wall portions 16 of the foldable heart valve 10.
In general, the flexible substrate 20 includes the same number of leaflet-defining regions 30 as wall-defining regions 32. As one non-limiting example, the foldable heart valve 10 can include three leaflet-defining regions 30 and three wall-defining regions 32. In other configurations, the flexible substrate 20 can contain more or fewer than three leaflet-defining regions 30 and/or wall-defining regions 32.
Each leaflet-defining region 30 is bounded by an arcuate segment 34 of the outer periphery 24 of the flexible substrate, a two edges 36 defined as line segments, which may be linear or arcuate segments, extending from the outer periphery 24 to the inner periphery 26. For instance one of the two edges 36a can extend from a first end of the arcuate segment 34 to a point on the inner periphery 26 of the flexible substrate 22. This point 38 may be, for example, a corner or vertex on the inner periphery 26. Similarly, the other of the two edges 36b can extend from the other end of the arcuate segment 34 to the same point 38 on the inner periphery 26. When the flexible substrate 20 is folded from the unfolded configuration to its folded configuration, thereby forming the prosthetic heart valve 10, these points 38 on the inner periphery 26 will correspond to the nadir points 22 of the respective leaflet portions 18.
When folding the flexible substrate 20 from its unfolded configuration to its folded configuration, the leaflet-defining regions 30 can be folded along the fold line 42 while bringing edges 36a and 36b into contact with each other. In doing so, the flexible substrate 20 is further folded along each edge 36a and 36b such that the leaflet-defining regions 30 are folded towards the inner surface of the prosthetic heart valve 10 at each edge 36. Likewise, the wall-defining regions 32 are folded towards the outer surface of the prosthetic heart valve 10 at each edge 36. Further, folding the leaflet-defining regions 30 along the fold line 42 forms the central edge 44 of each leaflet portion 18 on its lower surface (i.e., the inflow side surface) and the central crease 46 of each leaflet portion 18 on its upper surface (i.e., the outflow side surface). The central edge 44 and/or central crease 46 of each leaflet portion 18 extends from the nadir point 22 at the inflow end 12 of the prosthetic heart valve 10 to the central point of the free edge 40 for a given leaflet portion 18. An example of this folding process is shown in
The region where the end of the free edge 40 of one leaflet region 18 abuts the end of the free edge 40 of an adjacent leaflet region 18 defines a commissure 48. Advantageously, the commissures 48 of the prosthetic heart valves 10 described in the present disclosure do not experience high stresses based on the simple, folded construction of the prosthetic heart valve 10.
The region where edges 36 and 36b are brought into contact will form a seam 50 where the adjacent leaflet portions 18 and outer wall portions 16 can be coupled together in order to form the functional prosthetic heart valve 10. For instance, the seams can be joined or otherwise coupled via adhesive, sutures, or the like. Advantageously, this construction allows for vulnerable sutures to be located behind the leaflet portions 18 of the prosthetic heart valve 10 and, thus, away from stresses. As an added advantage, by using two suture lines along the opposed vertical edges of the seam 50 and directly to the native root, circumferential expansion of the prosthetic heart valve 10 is capable, thereby accommodating somatic growth of a pediatric heart. This advantage can be realized even if the valve material is inert because the shape changes to accommodate the expanding annulus. A tissue engineered (i.e., living) valve with this design may also allow the prosthetic heart valve 10 itself to grow along with the expanding annulus.
In some instances, the flexible substrate 20 can be folded in such a way that the leaflet-defining regions 30 are folded towards the inner lumen of the prosthetic heart valve 10 when in its folded configuration. In other instances, the flexible substrate 20 can be folded in such a way that the leaflet-defining regions 30 will be on the outside of the central lumen of the prosthetic heart valve 10. The prosthetic heart valve 10 can then be inverted, such that the leaflet portions 18 will be contained within the central lumen of the prosthetic heart valve 10. An example of this folding and inversion is shown in FIG.
Although the flexible substrates 20 shown in
In this way, the flexible substrate 20 can be manufactured as a flat substrate, which may simplify the manufacturing process, and then made into an annular shape with a curved surface to facilitate folding of the flexible substrate 20 into the prosthetic heart valve 10. For instance, the flexible substrate 20 can be easily manufactured by cutting a flat sheet of material according to a pattern that defines the shape of the flexible substrate 20. The two cut ends 52 and 54 of the flexible substrate 20 can then be joined (e.g., via adhesive, sutures, or otherwise) in order to form an annular shape with a curved surface.
Alternatively, the flexible substrate 20 can be manufactured as an annular shape with a curved surface. As one example, the flexible substrate 20 can be manufactured on the surface of an appropriately shaped form, mold, or the like. For instance, as shown in
In some alternative configurations, the flexible substrate 20 can have a generally conical annular shape, such as shown in
When constructed for use as an aortic heart valve, the prosthetic heart valve 10 can be modified to include openings for the coronary ostia. For example, holes can be made in the outer wall portions 16 and/or outer surface of the leaflet portions 18 such that when the prosthetic heart valve 10 is deployed the holes will align with the coronary ostia.
In some configurations, a sewing cuff and/or extension can be added on to the prosthetic heart valve 10 to allow for suturing above and/or below the prosthetic heart valve 10.
The flexible substrate 20 can be composed of any suitable biocompatible material, biomaterial, engineered tissue, and/or natural tissue that can be formed into a flat sheet or around a form, such as a conical frustum. Because of the ease of fabrication and less demanding durability requirements of the prosthetic heart valves described in the present disclosure, the types of materials that can be used to make the valves can be greatly expanded relative to other prosthetic heart valve designs. For example, tissue engineering approaches can be implemented, whereby living materials capable of remodeling, repair, and growth are used to fabricate the valve. Similarly, blood compatible materials that do not require lifelong compliance with anticoagulation therapy can also be used. As non-limiting examples, blood compatible materials such as polydimethylsiloxane, expanded polytetrafluoroethylene, polyethylene terephthalate, and/or polyurethane can be used.
The material type, flexible substrate thickness, and other dimensions can be adjusted in order to fine tune or otherwise alter the valve mechanics and/or functionality. For example, in some embodiments the flexible substrate 20 can have a thickness of not more than 0.6 mm. As one advantageous example, the flexible substrate can have a thickness of 0.4 mm. In other examples, the flexible substrate 20 can have a thickness in a range of about 0.1 mm to about 0.6 mm (e.g., 0.1 mm, 0.15 mm, 0.2 mm, mm, 0.3 mm, 0.35 mm, 0.4 mm, 0.45 mm, 0.5 mm, 0.55 mm, or 0.6 mm, or other thicknesses in the range of about 0.1 mm to about 0.6 mm). In general, as the flexible substrate 20 is made thicker, a less stiff material can be used, and as the flexible substrate is made thinner, a more stiff material can be used.
As one example, the flexible substrate 20 can be composed of biocompatible materials, such as vinyl, nylon, polydimethylsiloxane, expanded polytetrafluoroethylene, polyethylene terephthalate, polyethylene glycol, poly(lactic acid), poly(glycolic acid), poly(lactic-co-glycolic acid), polycaprolactone, poly(glycerol sebacate), or polyurethane.
As another example, the flexible substrate 20 can be composed of biomaterials, such as gelatin, collagen, elastin, alginate, collagen gel. Biomaterials may include tissue-engineered materials, such as cells on a scaffold, or decellularized membranes and/or polymers. For instance, decellularized porcine small intestinal submucosa, decellularized porcine pericardium, decellularized bovine pericardium, and/or decellularized amniotic membrane can be used.
As still another example, the flexible substrate 20 can be composed of tissues, such as bovine pericardium, porcine pericardium, small intestinal submucosa, amniotic membrane.
In one non-limiting example, the flexible substrate 20, and thus the resulting prosthetic heart valve 20, can be composed of electrospun polyurethane. Referring now to
Advantageously, when using an electrospinning process the resulting flexible substrate can be made thicker in regions that correspond to the free edge 40 of the leaflet portions 18 when the flexible substrate 20 is folded into the folded configuration of the prosthetic heart valve 10, as shown in
The present disclosure has described one or more preferred embodiments, and it should be appreciated that many equivalents, alternatives, variations, and modifications, aside from those expressly stated, are possible and within the scope of the invention.
This application claims the benefit of U.S. Provisional Patent Application Ser. No. 63/086,564, filed on Oct. 1, 2020, and entitled “FOLDABLE PROSTHETIC HEART VALVE,” which is herein incorporated by reference in its entirety.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US2021/053164 | 10/1/2021 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 63086564 | Oct 2020 | US |
