Patent Publication Number: US-11654019-B2

Title: Replacement heart valves and their methods of use and manufacture

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of U.S. patent application Ser. No. 15/368,312, filed Dec. 2, 2016, which is a divisional application of U.S. patent application Ser. No. 14/611,071, filed Jan. 30, 2015, which claims the benefit of and priority to U.S. Provisional Patent Application Ser. No. 61/991,354, filed May 9, 2014, both of which are incorporated by reference herein in their entirety and for all purposes. 
    
    
     FIELD 
     The subject matter described herein relates generally to improved replacement valves, such as for the aortic and mitral valves of the heart. 
     BACKGROUND 
     The human heart has a number of valves for maintaining the flow of blood through the body in the proper direction. The major valves of the heart are the atrioventricular (AV) valves, including the bicuspid (mitral) and the tricuspid valves, and the semilunar valves, including the aortic and the pulmonary valves. When healthy, each of these valves operates in a similar manner. The valve translates between an open state (that permits the flow of blood) and a closed state (that prevents the flow of blood) in response to pressure differentials that arise on opposite sides of the valve. 
     A patient&#39;s health can be placed at serious risk if any of these valves begin to malfunction. Although the malfunction can be due to a variety of reasons, it typically results in either a blood flow restricting stenosis or a regurgitation, where blood is permitted to flow in the wrong direction. If the deficiency is severe, then the heart valve may require replacement. 
     Substantial effort has been invested in the development of replacement heart valves, most notably replacement aortic and mitral valves. Replacement valves can be implanted percutaneously by way of a transfemorally or transapically introduced catheter, or can be implanted directly through open heart surgery. The replacement valves typically include an arrangement of valve leaflets that are fabricated from porcine tissue or an artificial material such as a polymer. These leaflets are maintained in position by a stent or support structure. 
       FIG.  1 A  is a perspective view depicting a prior art prosthetic heart valve 8 of U.S. Pat. No. 7,682,389 (“Beith”). This valve 8 can be implanted directly and includes a stent 10 and three leaflets 30. When implanted, blood is permitted to flow from the upstream (blood inlet) end 14 towards the downstream (blood outlet) end 12, but is prevented from flowing in the reverse direction by the presence of leaflets 30. Leaflets 30 have free edges 34 located on the downstream end 12. Each leaflet 30 also has a fixed edge (or interface) 32 joined with scalloped edge portions 16a, 16b, and 16c, respectively, of stent 10. A cross-sectional plane “I” is shown that bisects the leaflet 30 joined with fixed edge 16a (located at front right). Cross-sectional plane “I” is parallel to the direction of the flow of blood and thus is vertical in  FIG.  1 A . 
       FIG.  1 B  is a side view of a right-side portion of valve 8 after rotation such that plane “I” is aligned with the page. From the reader&#39;s perspective  FIG.  1 B  is viewed along a normal to plane “I.” From this view, the entirety of fixed edge 32 of leaflet 30 (which is aligned with edge 16a) lies in a flat plane and is straight with no curvature. 
       FIG.  1 C  is a side view of a right-side portion of another prior art valve 8 after rotation such that plane “I” is aligned with the page (like the case with  FIG.  1 B ). Here, fixed edge 32 is fully concave from the perspective exterior to valve 8. In the prior art, this fully concave shape was believed to assist in the movement of the leaflet from the open position to the closed position where the leaflet is pushed or draped into the valve interior, as adequate coaptation in the closed state is essential for the proper functioning of the valve. 
     However, the flat and fully concave shapes of the prior art designs described with respect to  FIGS.  1 A- 1 C  can lead to a valve with compromised hydrodynamic efficiency due to the fact that the local leaflet length at various heights of the valve is not long enough. This can lead to inadequate valve opening. It can also (or alternatively) lead to local bulging and tightness. The flat or fully concave shapes can both result in localized stress concentrations that, in combination with the aforementioned bulging and tightness, can result in reduced durability and premature failure. 
     U.S. Pat. No. 6,613,086 (“Moe”) describes other variations in the shape of the support structure (or valve body) for a directly implantable valve. Moe describes “an attachment curve” that is defined as the position where the leaflets are coupled along the inner wall of the support structure. Moe seeks to increase the durability of each leaflet coupled to the support structure by moving the leaflet&#39;s point of maximum loaded stress along the attachment curve and away from the location of any stress risers. Moe does this by adjusting the radius of the support structure at different heights along the support structure&#39;s axis of flow (see numeral 26 of FIG. 1) and at different radial positions within each cross-sectional plane taken perpendicular to and at different heights along the support structure&#39;s axis of flow. As a result, Moe&#39;s support structures have substantially non-circular or non-cylindrical inner walls along the attachment curve. These support structures can have significantly asymmetric shapes with substantial surface variations, as evidenced by the bulges 58 and 60 described with respect to FIG. 11 of Moe. Moe&#39;s support structures are neither cylindrical nor substantially cylindrical as those terms are used herein. 
     While trying to reduce the localized stress, Moe&#39;s approaches lead to local lengthening of the leaflet at that height in the valve. This local lengthening will lead to an increase in the resistance of the leaflet to open and could compromise the full opening of the valve, leading to local bulging in the leaflet surface. This, in turn, will reduce the hydrodynamic efficiency of the valve and potentially reduce the durability of the valve leaflet. 
     For these and other reasons, needs exist for improved prosthetic valves. 
     SUMMARY 
     Example embodiments of improved prosthetic heart valves and their methods of use and manufacture are provided herein. In some of these example embodiments, the prosthetic heart valve can include: a support structure having a central axis oriented in the direction of blood flow through an interior of the support structure; and a plurality of artificial leaflets, each leaflet having a base along the support structure and a free edge allowed to move independent of the support structure. Each leaflet can also have a central axis extending between the base and the free edge. The support structure can be substantially cylindrical where the base of each leaflet meets the support structure. The artificial leaflets can be adapted to move between a first position, for preventing the flow of blood through an interior of the support structure, and a second position, for allowing the flow of blood through the interior of the support structure. For each leaflet, a profile of the base of the leaflet can be at least partially convex when viewed from an exterior of the support structure along a normal to a plane formed by the central axis of the support structure and the central axis of the leaflet. Additional embodiments are also disclosed. 
     Other systems, methods, features and advantages of the subject matter described herein will be or will become apparent to one with skill in the art upon examination of the following figures and detailed description. It is intended that all such additional systems, methods, features and advantages be included within this description, be within the scope of the subject matter described herein, and be protected by the accompanying claims. In no way should the features of the example embodiments be construed as limiting the appended claims, absent express recitation of those features in the claims. 
    
    
     
       BRIEF DESCRIPTION OF FIGURES 
       The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee. 
       The details of the subject matter set forth herein, both as to its structure and operation, may be apparent by study of the accompanying figures, in which like reference numerals refer to like parts. The components in the figures are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the subject matter. Moreover, all illustrations are intended to convey concepts, where relative sizes, shapes and other detailed attributes may be illustrated schematically rather than literally or precisely. 
         FIG.  1 A  is a perspective view depicting a prior art prosthetic heart valve. 
         FIG.  1 B  is a side view of a right-hand portion of the prior art valve after rotation such that plane “I” is aligned with the page. 
         FIG.  1 C  is a side view of a right-hand portion of another prior art valve after rotation such that plane “I” is aligned with the page. 
         FIGS.  2 A-B  are perspective views of the front half of an example embodiment of a support structure for a prosthetic heart valve. 
         FIGS.  2 C-D  are top down views of an example embodiment of prosthetic valve leaflets in open and closed states, respectively. 
         FIG.  2 E  is an illustrative view depicting a portion of an example embodiment of a prosthetic valve in a laid flat state. 
         FIGS.  2 F-H  are perspective views of an example embodiment of a prosthetic heart valve. 
         FIGS.  2 I-J  are perspective views of an example embodiment of a prosthetic heart valve in line drawing and surface shaded forms, respectively. 
         FIG.  2 K  is a perspective view of an example embodiment of a prosthetic heart valve. 
         FIG.  3 A  is a color top down view comparing the positions of two sets of leaflets in their open states, where the support structure is not shown. 
         FIG.  3 B  is a color perspective view comparing the positions of two sets of leaflets in their open states within the front half of a prosthetic heart valve where the support structure is not shown. 
         FIG.  3 C  is a color top down view comparing the positions of two sets of leaflets in their closed states, where the support structure is not shown. 
         FIG.  3 D  is a color perspective view comparing the positions of two sets of leaflets in their closed states within the front half of a prosthetic heart valve where the support structure is not shown. 
         FIG.  3 E  is a color perspective view depicting an example embodiment of leaflets in their open state with the stress levels experienced at various positions across the surface of the leaflets, where the support structure is not shown. 
         FIG.  3 F  is a color perspective view depicting conventional leaflets in their open state with the stress levels experienced at various positions across the surface of the leaflets, where the support structure is not shown. 
         FIG.  3 G  is a color perspective view depicting an example embodiment of leaflets in their closed state with the stress levels experienced at various positions across the surface of the leaflets, where the support structure is not shown. 
         FIG.  3 H  is a color perspective view depicting conventional leaflets in their closed state with the stress levels experienced at various positions across the surface of the leaflets, where the support structure is not shown. 
         FIG.  3 I  is a color top down view depicting an example embodiment of leaflets in their closed state with the stress levels experienced at various positions across the surface of the leaflets, where the support structure is not shown. 
         FIG.  3 J  is a color top down view depicting conventional leaflets in their closed state with the stress levels experienced at various positions across the surface of the leaflets, where the support structure is not shown. 
         FIG.  3 K  is a color frontal view depicting an example embodiment of a leaflet mapped with the simulated relative degree of vertical strain energy release. 
         FIG.  3 L  is a color frontal view depicting a conventional leaflet mapped with the simulated relative degree of vertical strain energy release. 
         FIG.  3 M  is a color frontal view depicting an example embodiment of a leaflet mapped with the simulated relative degree of lateral strain energy release. 
         FIG.  3 N  is a color frontal view depicting a conventional leaflet mapped with the simulated relative degree of lateral strain energy release. 
         FIGS.  4 A-B  are perspective views depicting the front half of additional example embodiments of a support structure. 
         FIG.  5 A  is a flowchart depicting an example embodiment of a method of manufacturing a prosthetic heart valve. 
         FIG.  5 B  is a photograph depicting an example embodiment of a mandrel for use in a dip casting manufacturing method. 
         FIG.  5 C  is a photograph depicting an example embodiment of a base frame for use in a dip casting manufacturing method. 
     
    
    
     DETAILED DESCRIPTION 
     Before the present subject matter is described in detail, it is to be understood that this disclosure is not limited to the particular embodiments described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. 
     Example embodiments of systems, devices, kits, and methods are provided herein that relate to valve replacement in a patient. These embodiments will be described primarily with respect to replacement of the natural aortic heart valve with a prosthetic heart valve having three artificial (i.e., man-made) leaflets. However, the scope of the present disclosure is not limited to such, and can likewise be applied to prosthetics for replacement of other valves of the heart (e.g., mitral) where those prosthetics have two or more leaflets. These prosthetics may also be used to replace valves in other locations in the patient&#39;s body outside of the heart. 
     The example embodiments of the prosthetic valves disclosed herein are, in many cases, designed in a manner different from those manners taught by the prior art.  FIGS.  2 A-B  are perspective front views and  FIGS.  2 C-D  are top down views of one such example embodiment of a prosthetic valve  100 . Referring to  FIG.  2 A , a support structure  102  meets a plurality of valve leaflets  110 - 1 ,  110 - 2 , and  110 - 3 . Each of leaflets  110  can be discrete from the others (as shown here) or can be portions of one unitary (monolithic) leaflet body. 
     Support structure  102 , which can also be referred to as a stent, is configured to allow blood to flow in direction  101  and has an upstream end  103  and a downstream end  104 . Support structure  102  also includes an annular base portion  105  that can have a planar or flat upstream terminus (not shown) or that can have a curved or scalloped upstream terminus as shown here. Support structure  102  also includes three extensions  106  that project from annular base portion  105  towards downstream end  104 . 
     Extensions  106  include curved interfaces  107 , which are located directly on an edge in this embodiment. Here, each curved interface  107  is the location where support structure  102  meets the operable base  111  of a leaflet  110 . In many embodiments curved interfaces  107  and the leaflet bases  111  will coincide. 
     In the embodiment depicted in  FIG.  2 A , support structure  102  is in the form of a base frame. The leaflets can be integrally formed on this base frame  102 , such as through a casting (e.g., dip casting) or molding process. A dip casting process that is suitable for formation of the leaflets is described with respect to  FIGS.  5 A-C . In an example of a dip casting process, the base frame  102  is placed on a mandrel and dipped in a polymer, which results in the formation of leaflets integrated with a polymeric coating over the base frame. Here, curved interfaces  107  refer to the boundary between support structure  102  and each of the integrated leaflets (i.e., base  111  of each leaflet). Depending on the particular implementation, curved interfaces  107  can coincide with the downstream edge of the base frame itself or the downstream edge of the coating over the base frame. 
     In some embodiments, leaflets  110  (whether they be tissue or artificial) can be physically joined to support structure  102  through a coupling process such as sewing.  FIG.  2 E  is an illustration of an example embodiment of a portion of valve  100  in a laid flat state. Here, leaflet  110 - 1  has been coupled to support structure  102  by a seam  201  created by sewing a suture  202  through leaflet  110 - 1  and support structure  102 . The physical base edge  204  of leaflet  110  can be located upstream from seam  201  (as shown), folded back into a location downstream of seam  201 , or otherwise. In these embodiments, both curved interface  107 - 1  and base  111 - 1  refer to the transition between the secured portion of leaflet  110 - 1  and the operable portion of leaflet  110 - 1  that is free to transition or deflect between the open and closed states, which in the embodiment of  FIG.  2 E  coincides with the upstream edge of support structure  102 . 
     Referring back to  FIG.  2 A , annular base portion  105  also includes flanges  108  and  109  between which a sewing cuff (not shown) can be placed. As an alternative for all of the embodiments described herein, only a single flange  108  may be present, or the flanges  108  and  109  can be omitted altogether. In light of this description, those of ordinary skill in the art will readily understand the design and appearance of a sewing cuff and how it can be coupled with one or more flanges of support structure  102 . 
     In  FIG.  2 A , support structure  102  is positioned according to the perspective depicted by line  2 A- 2 A of  FIG.  2 C . Stated differently, cross-sectional plane “I” of  FIG.  2 C  is parallel to the page of  FIG.  2 A  such that the viewer views  FIG.  2 A  along a normal “N” to plane “I”. Plane “I” can also be described as extending through a central axis of valve  100  oriented in the direction of blood flow (indicated by the solid circle at the tip of the normal “N” arrow in  FIG.  2 C ) and a central axis of the respective leaflet extending between base  111  and free edge  112 . An example of the central axis is where plane “I” intersects leaflet  110 - 1  in  FIGS.  2 C-D . There, plane I is a center plane or mid-plane to leaflet  110 - 1 . 
       FIG.  2 B  depicts the embodiment of  FIG.  2 A  in an annotated form to allow comparison with the flat downstream edges  70 - 1  and  70 - 2  that would be present if support structure  102  was shaped according to the prior art approach of  FIGS.  1 A-B . Here, interfaces  107 - 1  and  107 - 2  can be seen to bulge in a pronounced fashion from flat edges  70 - 1  and  70 - 2 . Note that edge  70 - 2  is referred to as flat because it would appear flat if support structure  102  were rotated to place edge  70 - 2  in the position of edge  70 - 1  in  FIG.  2 B . The bulges of interface  107 - 1  and  107 - 2  would be even more pronounced if compared to the prior art concave edge approach of  FIG.  1 C . Although interface  107 - 3  and  70 - 3  are not shown, the same relationships would present for those as well. 
       FIG.  2 C  depicts leaflets  103  in their open positions with support structure  102  omitted. However, were support structure  102  to be shown, apex A 1  of extension  106 - 1  and apex A 2  of extension  106 - 2  (both shown in  FIG.  2 A ) would be positioned as noted in  FIG.  2 C . 
     Leaflets  103  each have a free edge  112  that moves independent of support structure  102 .  FIG.  2 D  depicts leaflets  110  after movement to their closed positions. In the closed position, in many embodiments the majority of free edges  112  will be in contact with each other. In some embodiments, the entirety of free edges  112  will be in contact with each other. 
     As seen in  FIG.  2 A , interface  107 - 1  is partially convex and concave from the perspective exterior to valve  100 . Interface  107 - 1  coincides with base  111 - 1  of leaflet  130 - 1  (see  FIGS.  2 I-K ). The convex portion  120  is midway along interface  107 - 1 . Convex portion  120  is convex in two dimensions, e.g., like a portion of the border of a two-dimensional ellipse from the perspective of outside the ellipse. 
     Concave portions  121 - 1  and  121 - 2  can be present on both sides of the convex middle portion  120 . As seen in  FIG.  2 A , concave portion  121 - 1  has a significantly lower degree of curvature than convex middle portion  120 . The combination of a convex portion with one or more concave portions gives interface  107 - 1  an undulating appearance when viewed from this perspective. This appearance can also be referred to as S-shaped or multi-curved if there is at least one concave portion and at least one convex portion (e.g., two concave portions and two convex portions qualifies as S-shaped), and those portions can vary in height and degree of curvature. In some embodiments, interface  107 - 1  can be convex along its entire height (or length). In other embodiments, interface  107 - 1  can include a convex portion with a flat (or linear) portion on one or both sides. In still other embodiments, interface  107 - 1  can include a convex portion in combination with any number of flat portions and concave portions. 
       FIG.  2 F  is a perspective front view of another example embodiment of a support structure  102  for a prosthetic valve  100 . In this embodiment, the degree of curvature present in convex portion  120  and concave portions  121 - 1  and  121 - 2  is relatively less than in the embodiment described with respect to  FIG.  2 A .  FIG.  2 G  is a perspective front view of the embodiment of  FIG.  2 F  annotated to allow comparison of interfaces  107 - 1  and  107 - 2  with prior art edges  70 - 1  and  70 - 2  (described with respect to  FIG.  2 B ). 
     In  FIGS.  2 F-G , only the front half of support structure  102  is shown (i.e., forward of plane “I”), with the back half and valve leaflets  110  omitted for ease of illustration. The entire support structure  102  is depicted in the perspective view of  FIG.  2 H .  FIGS.  2 I- 2 J  are a line drawing perspective view and surface shaded perspective view, respectively, of the embodiment of  FIG.  2 F  with leaflets  110  included.  FIG.  2 K  is a line drawing perspective view of the embodiment of  FIG.  2 F  taken from a different perspective than that of  FIG.  2 I . 
     In addition to being described as “convex,” certain convex portions of interface  107 - 1  can be described as tapering at an increasing rate as the distance increases from upstream end  103 . Characterized in yet another manner, the convex curve may be regarded as “concave down” with respect to a straight line reference similar to edge  70 - 1  described with respect to  FIG.  2 B . The convexity may change in direction to “concave up” (i.e., change in mathematical sign considering a second derivative of interface  107 - 1 ) and/or may change in magnitude (i.e., in terms of degree of curvature) along the length of interface  107 - 1 . 
     For all of the embodiments described herein, any of the aforementioned shapes can likewise be present on interfaces  107 - 2  and  107 - 3  when those interfaces  107 - 2  and  107 - 3  are viewed from the same perspective as interface  107 - 1  in  FIG.  2 A . Preferably, each of interfaces  107 - 1 ,  107 - 2  and  107 - 3  has the same shape to maximize the synchronous motion of leaflets  110 , as significantly asynchronous motion can negatively impact the durability of valve  100 . However, each interface  107  can vary in shape with respect to the others provided that the durability of valve  100  remains acceptable. 
     While support structure  102  can take various shapes, in all embodiments, support structure  102  can be substantially cylindrical or cylindrical. As those of ordinary skill in the art understand, being “cylindrical” does not require support structure  102  to be in the form of a full geometric cylinder (e.g., vertical walls oriented at a right angle to a circular cross-section), but rather requires support structure  102  to lie along a part of a hypothetical geometric cylinder (with only minor deviation). For example, the entire inner lumen surface (the surface directly adjacent the flow of blood) of support structure  102  as depicted in  FIG.  2 D  is cylindrical as that term is used herein. Similarly, those of ordinary skill in the art understand that a support structure  102  that is “substantially cylindrical” is permitted greater deviation from a mathematical cylinder than simply “a cylindrical support structure” and would readily recognize those support structures that qualify as being substantially cylindrical. 
     While the entirety of support structure  102  can be cylindrical or substantially cylindrical, it is also the case that only part of support structure  102  can be cylindrical or substantially cylindrical, with the remaining part of support structure  102  being non-cylindrical. For instance, in the embodiment described with respect to  FIG.  2 D , although the entire inner lumen surface of support structure  102  is cylindrical, the opposite outer surface has flanges  108  and  109  that are not cylindrical. 
     In other embodiments, only the portion of support structure  102  along curved interfaces  107  (e.g., along base  111  of leaflets  110 ) may be cylindrical or substantially cylindrical. Such a configuration distinguishes over the subject matter of U.S. Pat. No. 6,613,086 (“Moe”) described herein. 
     When support structure  102  is formed from a base frame coated in polymer, then in some embodiments, only the base frame (either the entirety or a portion thereof) can be cylindrical or substantially cylindrical, while the outer surface of the polymer coating is not cylindrical or not substantially cylindrical. For example, in some embodiments the inner lumen surface of a base frame is cylindrical and the outer surface of the polymer coating (along the inner lumen of the base frame) is substantially cylindrical (or even non-cylindrical) due to variations in the coating thickness. 
     In the embodiments of  FIGS.  2 A-B  and  2 F-K, valve  100  is sized to fit a 23 millimeter (mm) aortic tissue annulus, although this embodiment can be sized at other standard dimensions as well, such as 17 mm, 18 mm, 19 mm, 20 mm, 21 mm, 22 mm, 24 mm, 25 mm, 26 mm, 27 mm, 28 mm, and 29 mm, as well as dimensions that lie in between. These dimensions are commonly referred to as the inner diameter or “ID” of valve  100 , which is the lateral dimension of the valve at a position commensurate with leaflets  110 . The valve may have an even larger lateral dimension elsewhere, such as the location of the sewing cuff. 
       FIG.  4 A  depicts another embodiment of valve  100  (in a view similar to that of  FIG.  2 A ). In this embodiment, valve  100  is sized for a 19 mm tissue annulus. Interface  107 - 1  includes a convex portion  401  with a smaller flat or concave portion  402  near apex A 1  of extension  106 - 1 . Interface  107 - 1  of valve  100  can again be seen to bulge in a pronounced convex fashion from the overlaid flat edge  70 - 1 . Interface  107 - 2  and  107 - 3  (not shown) have similar shapes. 
       FIG.  4 B  depicts another embodiment of valve  100  (again in a view similar to that of  FIG.  2 A ). In this embodiment, valve  100  is sized for a 27 mm tissue annulus. Interface  107 - 1  is S-shaped with a first slightly convex portion  403  adjacent apex A 1 , a concave portion  404  immediately upstream (below), and a second slightly convex portion  405  upstream from (below) concave portion  404 . Overlaid flat edge  70 - 1  is again present to further illustrate the differences with interface  107 - 1  of this embodiment of valve  100 . Interface  107 - 2  and  107 - 3  (not shown) have similar shapes. 
     The embodiments of valve  100  described herein are suitable for implantation in the body of a patient using any number of medical procedures. Preferably, these embodiments of valve  100  are for direct implantation to the aortic annulus using open heart surgery. Such embodiments of valve  100  are not radially collapsible for insertion into an intravascular delivery device (e.g., a catheter) or a transapical delivery device. However, in other embodiments, valve  100  can be configured with a radially collapsible support structure  102  that allows the lateral dimension of valve  100  to be reduced by a degree sufficient to permit the insertion into an appropriately sized intravascular or transapical delivery device. 
     All of the embodiments of valve  100  described herein can also be provided to a medical professional (or retained by a medical professional) as part of a kit (or a set) of prosthetic valves being sized for various tissue annulus dimensions. The sizes can include any combination of two or more of the following: 17 mm, 18 mm, 19 mm, 20 mm, 21 mm, 22 mm, 23 mm, 24 mm, 25 mm, 26 mm, 27 mm, 28 mm, and 29 mm. In one embodiment, the kit includes at least one valve  100  configured with an at least partially convex interface  107  as described herein, along with one or more valves having different configurations. In another embodiment, for each labeled size, the kit includes at least one of the embodiments of a valve  100  described herein. In still another embodiment, the kit includes a 19 mm valve  100  in the form of the embodiment described with respect to  FIG.  4 A , a 23 mm valve  100  in the form of the embodiment described with respect to  FIG.  2 F , and a 27 mm valve  100  in the form of the embodiment described with respect to  FIG.  4 B . 
     Support structure  102  can be fabricated from any desired material, such as polymers (e.g., polyether ether ketones (PEEK), polyurethanes, etc.), metals (e.g., nitinol, stainless steel, etc.), and others. Leaflets  110  are fabricated from an artificial polymeric material, including any biostable polyurethanes and polyurethane compositions (e.g., polysiloxane-containing polyurethanes, etc.) known in the art. Examples of polyurethane containing leaflets are described in U.S. Pat. Nos. 6,984,700, 7,262,260, 7,365,134, and Yilgor et al., “Silicone containing copolymers: Synthesis, properties and applications,” Prog. Polym. Sci. (2013), all of which are incorporated by reference herein in their entirety for all purposes. Materials that approach ideal isotropic non-creeping characteristics are particularly suitable for use in many embodiments. While many materials can be used, it is preferable that the selected material have the appropriate modulus of elasticity to allow leaflets  110  to readily and repeatedly transition between the open and closed states without succumbing to fatigue or stress related failure. In many example embodiments, the modulus of elasticity for leaflets  110  is in the range of 10-45 MegaPascals (MPa). In certain other example embodiments, the modulus of elasticity for leaflets  110  is in the range of 20-30 MPa. 
     Valves  100  designed in accordance with the embodiments described herein exhibited superior performance over previous valves in a number of respects. For example,  FIGS.  3 A-N  are a series of simulation outputs that compare the performance of leaflets of an embodiment of a 23 mm valve  100  having leaflets  110  (similar to that described with respect to  FIGS.  2 F-K ) as compared to a valve having a flat edge  70  with leaflets  72  similar to the prior art approach described with respect to  FIGS.  1 A-B  as well as  FIGS.  2 B,  2 G, and  4 A -B. Such comparisons demonstrate the improved performance of the at least partially convex edge embodiments over the prior art flat edge approach (as well as the prior art concave edge approach described with respect to  FIG.  1 C ). 
       FIG.  3 A  is a top down view of leaflets  110  (blue) in their open position as compared to leaflets  72  (red) each having a base that would be attached to flat edge  70 . It is seen here that the free edges of leaflets  110  approach the wall of support structure  102  (not shown) much more closely than the free edges of leaflets  72  and thus provide significantly less resistance to blood flow through the interior of valve  100 . This is shown further in  FIG.  3 B , which is a view of open leaflets  110  in an orientation corresponding to that of  FIG.  2 F  but without showing support structure  102 . The visible surfaces are those that are closest to the viewer. Almost the entirety of leaflets  110  are closer to the viewer than leaflets  72 , resulting in a larger interior space through which blood can flow. 
       FIG.  3 C  is a top down view of leaflets  110  (blue) in their closed position as compared to leaflets  72  (red). Visible surfaces indicate those that are closest to the viewer looking into valve  100  from the downstream end. Leaflets  110  extend further into the interior of valve  100  than leaflets  72 , and achieve a higher degree of coaptation and thus a better seal against backflow and regurgitation, particularly in the center where all three of leaflets  110  meet. Leaflets  110  also eliminate the buckled or dimpled portion that is present in each of leaflets  72  and seen as the circular spots. Leaflets  110  of  FIG.  3 C  is shown from a different perspective in  FIG.  3 D . 
       FIG.  3 E  is a perspective of leaflets  110  in the open position showing the stress levels experienced at various positions across the surface of leaflets  110 . In  FIGS.  3 E-N , increasing relative stress is indicated by color in the following order: dark blue (lowest relative stress), light blue, green, yellow, orange, and red (highest relative stress). The maximum principal stress experienced by leaflets  110  was calculated to be 2.64 (MPa). This is compared to leaflets  72  of  FIG.  3 F , which is shown on the same scale as  FIG.  3 E  and indicates that leaflets  72  generally experience higher stress, particularly across the center region of leaflets  72  and along the mid-region of the bases. The maximum principal stress experienced by leaflets  72  was calculated to be 2.75 MPa. 
       FIG.  3 G  is a perspective of leaflets  110  in the closed position showing the stress levels experienced at various positions across the surface of leaflets  110 . The maximum principal stress experienced by leaflets  110  in this position was calculated to be 2.75 MPa.  FIG.  3 H , which is shown on the same scale as  FIG.  3 G , indicates that leaflets  72  experience higher stress in pockets positioned on both sides of each leaflet  72  near the junction of the free edge and base. The maximum principal stress for leaflet  72  was 3.005 MPa, which is again higher than for leaflets  110 . 
       FIG.  3 I  is a top down view of the simulation of leaflets  110  in  FIG.  3 G  and  FIG.  3 J  is a top down view of the simulation of leaflets  72  in  FIG.  3 H . This comparison shows the higher degree of coaptation achieved by leaflets  110 , particularly at the center of valve  100  and where adjacent free edges meet in proximity to the support structure (not shown). 
       FIG.  3 K  is a front view of leaflet  110  mapped with the simulated relative degree of vertical strain energy release.  FIG.  3 L  is a front view of leaflet  72  showing the simulated relative degree of vertical strain energy release according to the same scale as  FIG.  3 K .  FIG.  3 M  is a front view of leaflet  110  mapped with the simulated relative degree of lateral strain energy release.  FIG.  3 N  is a front view of leaflet  72  showing the simulated relative degree of lateral strain energy release according to the same scale as  FIG.  3 M . 
     Strain energy release is determined by an integral across the entire cycle of motion of the leaflet, i.e., movement between the open and closed positions and back. Vertical strain energy release is a measurement of how much energy is present at each position on the leaflet to drive the growth of a defect in the vertical direction, i.e., between bottom and top as shown in  FIGS.  3 K-L . Lateral strain energy release is a measurement of how much energy is present at each position on the leaflet to drive the growth of a defect in the lateral direction, i.e., between left and right sides as shown in  FIGS.  3 M-N . 
     As can be seen in  FIGS.  3 K-L , leaflet  110  experiences significantly reduced vertical strain energy release, which was calculated to be 110.331 joules per mm squared (J/mm2), as compared to 132.151 J/mm2 for leaflet  72 . The most significantly reduced regions are shown in the lower center portion of leaflet  110  and in the upper corners of leaflet  110  where the free edge and base come together. 
     With respect to the lateral strain energy releases depicted in  FIGS.  3 M-N , leaflet  110  again experiences significant reductions as compared to leaflet  72 . In this example, the lateral strain energy release for leaflet  110  was determined to be 61.315 J/mm2 and the lateral strain energy release for leaflet  72  was determined to be 71.097 J/mm2. 
     These significant reductions in strain energy release allows for the use of a wider range of materials in leaflets  110 , such as those having lower cut-growth thresholds that may exhibit superior overall performance as compared to those having higher cut-growth thresholds. Alternatively, the same materials with high cut growth thresholds may be employed but with prospects for longer lifetime in use. 
     Leaflets  110  are coupled to support structure  102  in a number of ways, such as adhesives, molding, casting, sewing, fasteners, and others known to those of ordinary skill in the art.  FIG.  5 A  is a flow diagram depicting an example embodiment of a method  500  of manufacturing certain embodiments of prosthetic heart valve  100  using a dip casting process. At  502 , a base frame is fabricated from a rigid material such as a polyether ether ketone (PEEK), a polyetherimide (PEI) such as ULTEM, and the like. This can be done by machining or injection molding. At  504 , the base frame is placed on a dipping mandrel that has the shape of the interior surface of the support structure and leaflets. An example embodiment of a base frame  501  is depicted in the photograph of  FIG.  5 B . An example embodiment of a dipping mandrel  503 , without the base frame, is depicted in the photograph of  FIG.  5 C . Mandrel  503  can be inserted into a polymeric solution with forming equipment that envelops the base frame and casts the leaflets in the desired form. 
     At  506 , the base frame and mandrel is dipped in a polymeric solution under both high temperature and humidity and then withdrawn. Although the methods disclosed herein are not limited to such, in some example embodiments, the relative humidity (RH) can be in the range of 20-80% and the temperature can be in the range of 20-50 degrees C. Step  506  can result in a manifestation of support structure  102  and leaflets  111  together in an integrally formed but unfinished state. 
     Dipping step  506  can be performed only once to arrive at the fully formed (but unfinished) valve, or can be performed multiple times (e.g., two times, three times, or as many times as desired). In one embodiment, the base frame is fabricated from a first material (e.g., PEEK) different than the polymeric material from which the leaflets are fabricated. In that case it may be desirable to form the leaflets to the base frame only after the base frame has been pre-coated by the leaflet polymer to provide for greater cohesion. The base frame can be pre-coated by first dipping the base frame in the leaflet polymer having a first viscosity. This can be done with or without the mandrel. If done with the mandrel, the resulting leaflets can be removed. The pre-coated base frame can then be placed on the mandrel and dipped again, this time in the leaflet polymer with the same or a relatively higher viscosity. This second dipping can result in the formation of the full leaflet bodies integrally formed with the support structure. Use of a low viscosity followed by a higher viscosity can allow for formation of a thin pre-coating that does not significantly distort the shape of the underlying base frame followed by formation of the leaflets having the desired thickness. 
     At  508 , support structure  102  and leaflets  111  can be trimmed and otherwise finished to achieve accurate and precise edges and surface smoothness. This can occur, for example, through laser cutting, ultrasonic trimming, water knife, a mechanical clam shell cutter, and the like. Finally, at  510 , a sewing cuff can be coupled with support structure  102  and the final device can be packaged in the desired sterile container. 
     Those of ordinary skill in the art will readily recognize, in light of this description, the many variations of suitable dip casting procedures, pressures, and temperatures that are not stated here yet are suitable to fabricate the prosthetic heart valves described herein. Likewise, those of ordinary skill in the art will also recognize, in light of this description, the alternatives to dip casting that can be used to fabricate the prosthetic heart valves described herein. 
     As already mentioned, the embodiments of prosthetic heart valve  100  described herein can be directly implanted into the heart of the patient. In one such example procedure, the appropriate size replacement valve can be determined and then an open heart access procedure is performed by a surgeon to gain access to the malfunctioning valve of the heart that will be replaced. The surgeon can then position the selected prosthetic heart valve  100  in position over the malfunctioning valve and attach valve  100  to the surrounding tissue. The attachment can occur, for instance, by fastening the sewing cuff to the tissue with one or more sutures. Prior to attachment, if the surgeon determines that the selected valve size is not optimal, then a different valve having a different size can be selected and placed in position within the heart. In some other embodiments, the malfunctioning valve can be removed prior to positioning valve  100  in the intended location. Once valve  100  is attached, the open heart cavity is closed and the procedure is ended. 
     As used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise. 
     It should be noted that all features, elements, components, functions, and steps described with respect to any embodiment provided herein are intended to be freely combinable and substitutable with those from any other embodiment. If a certain feature, element, component, function, or step is described with respect to only one embodiment, then it should be understood that that feature, element, component, function, or step can be used with every other embodiment described herein unless explicitly stated otherwise. This paragraph therefore serves as antecedent basis and written support for the introduction of claims, at any time, that combine features, elements, components, functions, and steps from different embodiments, or that substitute features, elements, components, functions, and steps from one embodiment with those of another, even if the following description does not explicitly state, in a particular instance, that such combinations or substitutions are possible. It is explicitly acknowledged that express recitation of every possible combination and substitution is overly burdensome, especially given that the permissibility of each and every such combination and substitution will be readily recognized by those of ordinary skill in the art. 
     While the embodiments are susceptible to various modifications and alternative forms, specific examples thereof have been shown in the drawings and are herein described in detail. It should be understood, however, that these embodiments are not to be limited to the particular form disclosed, but to the contrary, these embodiments are to cover all modifications, equivalents, and alternatives falling within the spirit of the disclosure. Furthermore, any features, functions, steps, or elements of the embodiments may be recited in or added to the claims, as well as negative limitations that define the inventive scope of the claims by features, functions, steps, or elements that are not within that scope. 
     Other systems, devices, methods, features and advantages of the subject matter described herein will be or will become apparent to one with skill in the art upon examination of the following figures and detailed description. It is intended that all such additional systems, devices, methods, features and advantages be included within this description, be within the scope of the subject matter described herein, and be protected by the accompanying claims. In no way should the features of the example embodiments be construed as limiting the appended claims, absent express recitation of those features in the claims.