Artificial heart valves with a sealing layer or valve structure to reduce the risk of blood clots.

Abstract

The prosthetic heart valve may have one or more sealing layers. The inner skirt and / or outer skirt may include one or more sealing layers, or the entire valve frame may be encapsulated within one or more sealing layers. Each sealing layer may be substantially non-porous or may have pores therein sized to inhibit cellular in-growth. The sealing layer may prevent ingrowth of surrounding native tissue, thereby reducing pannus formation on the prosthetic valve leaflets. Alternatively or additionally, the shape of the leaflets of the prosthetic valve's valvular structure and / or the coupling of the leaflets to the valve frame may be selected to avoid the occurrence of stasis when implanted in a hemodynamic position with a relatively low pressure gradient. Such a prosthetic heart valve may reduce the risk of thrombosis.

Description

Technical Field

[0001] Cross - References to Related Applications This application claims the benefit of U.S. Provisional Application No. 63 / 112,080, filed on November 10, 2020, and U.S. Provisional Application No. 63 / 240,766, filed on September 3, 2021, which are hereby incorporated by reference herein.

[0002] The present disclosure relates to an artificial heart valve, and more particularly to a sealing layer and / or its valve leaflet structure that can reduce the risk of thrombus from an implanted artificial heart valve.

Background Art

[0003] The human heart can suffer from various valvular diseases, resulting in significant heart dysfunction, and ultimately requiring repair of the original valve or replacement of the original valve with an artificial valve. There are many well - known repair devices (e.g., stents) and artificial valves, as well as many well - known methods for implanting these devices and valves into humans. Percutaneous and minimally invasive surgical approaches are used in various procedures to deliver artificial medical devices to locations inside the body where surgical access is not easily achievable or where access without surgery is desirable. In one particular example, an artificial heart valve is attached in a crimped configuration to the end of a delivery device and can advance through the patient's vasculature until the artificial valve reaches the transplant site in the heart. Thereafter, the artificial valve is expanded to its functional size, for example, by inflating a balloon on which the artificial valve is mounted and actuating a mechanical actuator that applies an expanding force to the artificial valve, or by deploying the artificial valve from the sheath of the delivery device such that the artificial valve can self - expand to its functional size.

[0004] These expandable transcatheter heart valves have an annular metal frame, a valve structure with multiple leaflets supported within the frame, an inner skirt coupled to the inside of the metal frame, and an outer skirt coupled to the outside of the metal frame. The inner and outer skirts are often made of porous material, such as polyethylene terephthalate (PET) fabric. The porous nature of the skirt material (e.g., having pores larger than 30 μm to 50 μm) is designed to promote intracellular proliferation from the surrounding native tissue or from surrounding overgrown structures. This tissue proliferation into the skirt can integrate the implanted heart valve into the patient's native anatomical structure and further reduce paravalvular leakage (PVL). However, such proliferation can also occur from the porous skirt onto the leaflets of the implanted artificial heart valve. Indeed, tissue and pannus growth has been observed on the leaflets of implanted artificial heart valves, which can later act as a substrate for thrombus deposition.

[0005] Furthermore, at certain implant locations, the prosthetic heart valve may be exposed to a relatively low-pressure hemodynamic environment (for example, the driving pressure that causes the implanted valve to open is less than 30 mmHg, for example, at the mitral or tricuspid location). In conventional prosthetic heart valves, low pressure gradients can cause abnormal movement as the valve leaflets transition between the open and closed configurations of the valve structure. Abnormal leaflet movement can lead to stasis, thereby making the leaflets less resistant to chronic thrombosis, thickening (which further restricts leaflet movement), or both.

[0006] Therefore, there is a need for artificial heart valves that reduce the risk of thrombosis associated with artificial heart valve implantation, and for methods for implanting and constructing such artificial heart valves. [Overview of the project]

[0007] In one embodiment, an artificial heart valve can be summarized as comprising an annular frame, a valve structure, and an inner skirt. The annular frame may be radially foldable and expandable between a radially compressed configuration and a radially expanded configuration. The annular frame may have an inlet end and an outlet end separated from the inlet end along the axial direction of the frame. The valve structure may be supported within the annular frame. The valve structure may include a plurality of leaflets. Each leaflet may have a pointed rim and a tab on both sides with respect to the leaflet's centerline. The pointed rim may curve along at least a portion thereof to form a apex at the leaflet's centerline. The valve structure may be coupled to the frame via a plurality of commissure assemblies formed by paired tabs of adjacent leaflets. An inner skirt may be positioned on the radially inner surface of the annular frame and coupled thereto. The inner skirt may include a sealing layer configured to prevent infiltration of cells from the patient's surrounding native tissue into the sealing layer when the artificial heart valve is implanted in the patient. An inner skirt may be positioned along the radial direction of the annular frame, between the annular frame and the pointed edge of each valve leaflet. The inner skirt may extend along the axial direction of the frame, at least from the apex of the pointed edge of the valve leaflet to at least a number of commissure assemblies.

[0008] In another embodiment, the artificial heart valve can be summarized as comprising an annular frame and a valve structure. The annular frame may be radially foldable and expandable between a radially compressed configuration and a radially expanded configuration. The annular frame may have an inlet end and an outlet end separated from the inlet end along the axial direction of the frame. The valve structure may be supported within the annular frame and may comprise a plurality of leaflets. Each leaflet may have a pointed rim and a tab on both sides with respect to the leaflet's centerline. The pointed rim may curve along at least a portion thereof to form a apex at the leaflet's centerline. The valve structure may be coupled to the frame via a plurality of commissure assemblies formed by paired tabs of adjacent leaflets. The annular frame may be sealed by a sealing layer constructed to prevent cell infiltration from the patient's surrounding native tissue into the sealing layer when the artificial heart valve is implanted in the patient.

[0009] In another embodiment, the artificial heart valve may include an annular frame, a valve structure, and means for preventing cell proliferation from the patient's original tissue on the leaflets of the valve structure. The annular frame may have an inlet end and an outlet end separated from the inlet end along the axial direction of the frame. The valve structure may be supported within the annular frame and may include a plurality of leaflets. Each leaflet may have a pointed rim and a tab on both sides with respect to the leaflet's centerline. The pointed rim may be curved along at least a portion thereof. The valve structure may be coupled to the frame via a plurality of commissure assemblies formed by paired tabs of adjacent leaflets.

[0010] In another embodiment, the artificial heart valve can be summarized as comprising a frame, a valve structure, and means for preventing cell proliferation from the patient's original tissues on the leaflets of the valve structure. The valve structure may be coupled to the frame and may include multiple leaflets.

[0011] In another embodiment, the assembly can be summarized as including a delivery device and an artificial heart valve. The delivery device may include an elongated shaft. The artificial heart valve may follow any of the embodiments described above. The artificial heart valve may be mounted on an elongated shaft in a radially compressed configuration for delivery into the patient's body.

[0012] In another embodiment, a method for implanting an artificial heart valve in a patient's body can be summarized as including inserting the distal end of a delivery device into the patient's vascular structure. The delivery device may include an elongated shaft. The artificial heart valve may be detachably mounted to a radially compressed configuration on the elongated shaft of the delivery device, according to any of the embodiments described above.

[0013] In another embodiment, a method for assembling an artificial heart valve can be summarized as including providing an inner skirt on the radially inner surface of an annular frame. The annular frame may be radially foldable and expandable between a radially compressed configuration and a radially expanded configuration. The annular frame may have an inlet end and an outlet end separated from the inlet end along the axial direction of the frame. The inner skirt may include a sealing layer. The sealing layer may include a layer formed directly on the radially inner surface of the annular frame. When the artificial heart valve is implanted in a patient, the sealing layer may be constructed in such a way that infiltration of cells from the patient's surrounding native tissue into the sealing layer is prevented.

[0014] In another embodiment, a method for assembling an artificial heart valve can be summarized as comprising bonding an inner skirt to the radially inner surface of an annular frame. The annular frame may be radially foldable and expandable between a radially compressed configuration and a radially expanded configuration. The annular frame may have an inlet end and an outlet end separated from the inlet end along the axial direction of the frame. The inner skirt may include a sealing layer configured to prevent infiltration of cells from the patient's surrounding native tissue into the sealing layer when the artificial heart valve is implanted in the patient.

[0015] In another embodiment, a method for assembling an artificial heart valve can be summarized as comprising sealing an annular frame with a sealing layer. The annular frame may be radially foldable and expandable between a radially compressed configuration and a radially expanded configuration. The annular frame may have an inlet end and an outlet end separated from the inlet end along the axial direction of the frame. When the artificial heart valve is implanted in a patient, the sealing layer may be constructed in such a way that infiltration of cells from the patient's surrounding native tissue into the sealing layer is prevented.

[0016] In another embodiment, the valve leaflets for the valvular structure of an artificial heart valve can be summarized as comprising a first portion, a second portion, and first and second tabs. The first and second tabs may be located on either side of the first portion with respect to the centerline of the first portion. Each tab may have a base edge and an outer edge. The outer edges of the first and second tabs may be substantially parallel to each other. The second portion may have a semi-elliptical or semi-elliptical shape defining a pointed edge. The pointed edge may extend from the base edge of the first tab to the base edge of the second tab. The pointed edge may curve along its entire length between the base edges of the first tab and the base edge of the second tab.

[0017] In another embodiment, an artificial heart valve can be summarized as comprising an annular frame, a valve structure, and an inner skirt. The annular frame may be radially foldable and expandable between a radially compressed configuration and a radially expanded configuration. The annular frame may have an inlet end and an outlet end separated from the inlet end along the axial direction of the frame. The valve structure may be supported within the annular frame and may comprise a plurality of leaflets. Each leaflet may conform to any of the examples described above. The valve structure may be coupled to the frame via a plurality of commissure assemblies formed by pairs of tabs from adjacent leaflets. An inner skirt may be located on the radially inner surface of the annular frame and may be coupled to it. The pointed edges of the second portion of each leaflet at each pointed edge may be coupled to the inner skirt. One or more sutures may be coupled to the inner skirt and the pointed edges of each leaflet, and the suture line formed by one or more sutures may follow the curvature of the pointed edge. A suture line formed by one or more sutures may be continuous from the apex of the pointed edge to the substantial commissure assembly.

[0018] In another embodiment, an artificial heart valve can be summarized as comprising one or more frames and a valve structure supported within one or more frames. One or more frames may be radially foldable and expandable between a radially compressed configuration and a radially expanded configuration. One or more frames may define the inlet and outlet ends of the artificial heart valve, with the outlet end separated from the inlet end along the axial direction of one or more frames. The valve structure may include a plurality of leaflets. Each leaflet may have a first portion, a second portion, a first tab, and a second tab. The first and second tabs may be on either side of the first portion with respect to the centerline of the first portion. Each tab may have a base edge and an outer edge. The outer edges of the first and second tabs may be substantially parallel to each other (e.g., when in a planar view before mounting to one or more frames, when the tabs are mounted to one or more frames, or both). The second portion may have a semi-elliptical or semi-elliptical shape defining a pointed edge. The pointed edge may extend from the base edge of the first tab to the base edge of the second tab. The pointed edge may curve along its entire length between the base edges of the first tab and the base edge of the second tab. The valve structure may be joined to the frame via multiple commissure assemblies formed by pairs of tabs from adjacent leaflets. The pointed portion of the second part of each leaflet at each pointed edge may be joined directly or indirectly to one or more frames via one or more sutures, and the suture line formed by one or more sutures may follow the curvature of the pointed edge. The suture line formed by one or more sutures may be continuous from the apex of the pointed edge to a substantial commissure assembly.

[0019] In another embodiment, the artificial heart valve can be summarized as comprising an annular frame and valve means for regulating blood flow through the artificial heart valve in hemodynamic conditions at the implanted site in a patient experiencing relatively low pressure gradients. The annular frame may have an inlet end and an outlet end separated from the inlet end along the axial direction of the frame.

[0020] In another embodiment, the assembly can be summarized as including a delivery device and an artificial heart valve. The delivery device may include an elongated shaft. The artificial heart valve may follow any of the embodiments described above. The artificial heart valve may be mounted on an elongated shaft in a radially compressed configuration for delivery into the patient's body.

[0021] In another embodiment, a method for implanting an artificial heart valve in a patient's body can be summarized as including inserting the distal end of a delivery device into the patient's vascular structure. The delivery device may include an elongated shaft. The artificial heart valve may be detachably mounted to a radially compressed configuration on the elongated shaft of the delivery device, according to any of the embodiments described above.

[0022] In another embodiment, a method for assembling an artificial heart valve can be summarized as including providing an inner skirt on the radially inner surface of an annular frame. The annular frame may be radially foldable and expandable between a radially compressed configuration and a radially expanded configuration. The annular frame may have an inlet end and an outlet end separated from the inlet end along the axial direction of the frame. The method may further include forming a plurality of commissure assemblies with a plurality of leaflets. Each leaflet may have a first portion, first and second tabs, and a second portion. The first and second tabs may be on either side of the first portion with respect to the centerline of the first portion. Each tab may have a base edge and an outer edge. The outer edges of the tabs may be substantially parallel to each other. The second portion of each leaflet may have a semi-elliptical or semi-elliptical shape defining a pointed edge. The pointed edge of each leaflet may extend from the base edge of the first tab to the base edge of the second tab. The pointed edge of each leaflet can be curved along its entire length between the base edge of the first tab and the base edge of the second tab. Each commissure assembly may be formed by a pair of tabs of adjacent leaflets. The method may also include connecting each commissure assembly to an annular frame and connecting the pointed edges of the second portion of each leaflet to the inner skirt at each pointed edge via one or more sutures. The suture line formed by one or more sutures may follow the curvature of the pointed edge.

[0023] In another embodiment, an artificial heart valve can be summarized as comprising an annular frame, a valve structure, an inner skirt, and an outer skirt. The annular frame may be radially foldable and expandable between a radially compressed configuration and a radially expanded configuration. The annular frame may have an inlet end and an outlet end separated from the inlet end along the axial direction of the frame. The valve structure may be supported within the annular frame and may include a plurality of leaflets. Each leaflet may have a first portion, a second portion, and first and second tabs. The first and second tabs may be on either side of the first portion with respect to the centerline of the first portion. Each tab may have a base edge and an outer edge. The outer edges of the first and second tabs may be substantially parallel to each other. The second portion may have a semi-elliptical or semi-elliptical shape defining a pointed edge extending from the base edge of the first tab to the base edge of the second tab. The pointed edge may curve along its entire length between the base edge of the first tab and the base edge of the second tab. An inner skirt may be positioned on and bonded to the radially inner surface of the annular frame. The inner skirt may include a sealing layer configured to prevent cell infiltration into the sealing layer from the patient's natural tissue when the artificial heart valve is implanted in the patient. An outer skirt may be positioned on the radially outer surface of the annular frame. The outer skirt may cover substantially the entire radially outer surface of the annular frame between the inlet and outlet ends. The valve structure may be bonded to the frame via a plurality of commissure assemblies formed by pairs of tabs from adjacent leaflets. The inner skirt may be positioned along the radial direction of the annular frame between the annular frame and the second portion of each leaflet. The inner skirt may extend along the axial direction of the frame, at least from the apex of the pointed edge of the leaflet to at least a plurality of commissure assemblies. The pointed edge of the second portion of each leaflet at each pointed edge may be bonded to the inner skirt by one or more sutures. The suture line formed by one or more sutures may follow the curvature of the pointed edge. The suture line can be substantially continuous or partially continuous from the apex of the pointed edge to substantially the commissure assembly.

[0024] In another embodiment, an artificial heart valve can be summarized as comprising an annular frame and a valve structure. The annular frame may be radially foldable and expandable between a radially compressed configuration and a radially expanded configuration. The annular frame may have an inlet end and an outlet end separated from the inlet end along the axial direction of the frame. The valve structure may be supported within the annular frame and may include a plurality of leaflets. Each leaflet may have a first portion, a second portion, and first and second tabs. The first and second tabs may be on either side of the first portion with respect to the centerline of the first portion. Each tab may have a base edge and an outer edge. The outer edges of the first and second tabs may be substantially parallel to each other. The second portion may have a semi-elliptical or semi-elliptical shape defining a pointed edge extending from the base edge of the first tab to the base edge of the second tab. The pointed edge may curve along its entire length between the base edge of the first tab and the base edge of the second tab. The annular frame may be enclosed by a sealing layer constructed to prevent cell proliferation from the patient's natural tissue into the sealing layer when the artificial heart valve is implanted in the patient. The valve structure may be joined to the frame via a plurality of commissure assemblies formed by pairs of tabs from adjacent leaflets. The pointed edges of the second portion of each leaflet at each pointed edge may be joined to the sealing layer by one or more sutures. The suture line formed by one or more sutures may follow the curvature of the pointed edge. The suture line may be substantially continuous or partially continuous from the apex of the pointed edge to substantially the commissure assembly.

[0025] In another aspect, an artificial heart valve can be summarized as including an annular frame, valve leaflet means for regulating blood flow through the artificial heart valve in the hemodynamic situation at the implanted position in a patient experiencing a relatively low pressure gradient, and means for preventing ingrowth of cells from the native tissue surrounding the patient on the valve leaflets of the valve leaflet means. The annular frame can be foldable radially and expandable between a radially compressed configuration and a radially expanded configuration. The annular frame can have an inflow end and an outflow end separated from the inflow end along the axial direction of the frame.

[0026] In another aspect, an assembly can be summarized as including a delivery device and an artificial heart valve. The delivery device can include an elongated shaft. The artificial heart valve can follow any of the above-described embodiments. The artificial heart valve may be attached onto the elongated shaft in a radially compressed configuration for delivery into the patient's body.

[0027] In another aspect, a method of implanting an artificial heart valve into a patient's body can be summarized as including inserting the distal end of a delivery device into the patient's vasculature. The delivery device can include an elongated shaft. The artificial heart valve can follow any of the above-described embodiments and may be removably attached in a radially compressed configuration on the elongated shaft of the delivery device.

[0028] In another embodiment, a method for assembling an artificial heart valve can be summarized as comprising providing an inner skirt on the radially inner surface of an annular frame. The annular frame may be radially foldable and expandable between a radially compressed configuration and a radially expanded configuration. The annular frame may have an inlet end and an outlet end separated from the inlet end along the axial direction of the frame. The inner skirt may include a sealing layer configured to prevent infiltration of cells from the patient's natural tissues into the sealing layer when the artificial heart valve is implanted in the patient. The sealing layer may include a layer formed directly on the radially inner surface of the annular frame. The method may further include forming a plurality of commissure assemblies with a plurality of leaflets. Each leaflet may have a first portion, first and second tabs, and a second portion. The first and second tabs may be on either side of the first portion with respect to the centerline of the first portion. Each tab may have a base edge and an outer edge. The outer edges of the tabs may be substantially parallel to each other. The second portion of each leaflet may have a semi-elliptical or semi-elliptical shape defining a pointed edge. The pointed edge of each leaflet may extend from the base edge of the first tab to the base edge of the second tab. The pointed edge of each leaflet may curve along its entire length between the base edge of the first tab and the base edge of the second tab. Each commissure assembly may be formed by a pair of tabs of adjacent leaflets. The method may further include connecting each commissure assembly to an annular frame. An inner skirt may be positioned between the annular frame and the second portion of each leaflet along the radial direction of the annular frame, and the inner skirt may extend along the axial direction of the frame, at least from the apex of the leaflet's pointed edge to at least a number of commissure assemblies. The method may also include connecting the pointed edges of the second portions of each leaflet to the inner skirt at each pointed edge via one or more sutures. The suture line formed by one or more sutures may follow the curvature of the pointed edge. The suture line may be substantially continuous or partially continuous from the apex of the pointed edge to substantially the commissure assembly.

[0029] In another embodiment, a method for assembling an artificial heart valve can be summarized as comprising bonding an inner skirt to the radially inner surface of an annular frame. The annular frame may be radially foldable and expandable between a radially compressed configuration and a radially expanded configuration. The annular frame may have an inlet end and an outlet end separated from the inlet end along the axial direction of the frame. The inner skirt may include a sealing layer configured to prevent infiltration of cells from the patient's natural tissues into the sealing layer when the artificial heart valve is implanted in the patient. The method may further include forming a plurality of commissure assemblies with a plurality of leaflets. Each leaflet may have a first portion, first and second tabs, and a second portion. The first and second tabs may be on either side of the first portion with respect to the centerline of the first portion. Each tab may have a base edge and an outer edge. The outer edges of the tabs may be substantially parallel to each other. The second portion of each leaflet may have a semi-elliptical or semi-elliptical shape defining a pointed edge. The pointed edge of each leaflet may extend from the base edge of the first tab to the base edge of the second tab. The pointed edge of each leaflet may curve along its entire length between the base edge of the first tab and the base edge of the second tab. Each commissure assembly may be formed by a pair of tabs of adjacent leaflets. The method may also include connecting each commissure assembly to an annular frame. An inner skirt may be positioned between the annular frame and the second portion of each leaflet along the radial direction of the annular frame, and the inner skirt may extend along the axial direction of the frame, at least from the apex of the leaflet's pointed edge to at least a number of commissure assemblies. The method may further include connecting the pointed edges of the second portion of each leaflet to the inner skirt at each pointed edge via one or more sutures. The suture line formed by one or more sutures may follow the curvature of the pointed edge, and the suture line may be substantially continuous or partially continuous from the apex of the pointed edge to substantially the commissure assembly.

[0030] In another aspect, a method of assembling an artificial heart valve can be summarized as including enclosing an annular frame with a sealing layer. The annular frame can be foldable in the radial direction and expandable between a radially compressed configuration and a radially expanded configuration. The annular frame can have an inflow end and an outflow end separated from the inflow end along the axial direction of the frame. The sealing layer can be constructed such that when the artificial heart valve is implanted in a patient, ingrowth of cells from the patient's native tissue around into the sealing layer is prevented. The method can further include forming a plurality of commissure assemblies at a plurality of valve leaflets. Each valve leaflet can have a first portion, first and second tabs, and a second portion. The first and second tabs can be on opposite sides of the first portion with respect to a centerline of the first portion. Each tab can have a base edge and an outer edge. The outer edges of the tabs can be substantially parallel to each other. The second portion of each valve leaflet can have a semi-elliptical or semi-oval shape defining a leading edge. The leading edge of each valve leaflet can extend from the base edge of the first tab to the base edge of the second tab. The leading edge of each valve leaflet can curve along the entire length between the base edge of the first tab and the base edge of the second tab. Each commissure assembly can be formed by tabs of a pair of adjacent valve leaflets. The method can further include coupling each commissure assembly to the annular frame and coupling the leading edge portions of the second portions of each valve leaflet to the sealing layer at their respective leading edges via one or more sutures. A suture line formed by the one or more sutures can follow the curvature of the leading edge. The suture line can be substantially continuous or partially continuous from the apex of the leading edge to substantially the commissure assembly.

Brief Description of the Drawings

[0031] [Figure 1] FIG. 1 shows a schematic cross-sectional view of a human heart in which an artificial heart valve can be attached, according to one or more embodiments of the disclosed subject matter. [Figure 2A] FIG. 2A shows a partial cross-sectional view of an exemplary artificial heart valve attached at the aortic position of a human heart. [Figure 2B]Figure 2B shows the valve structure of the implanted artificial heart valve in the closed configuration of Figure 2A, as viewed from the outflow end of the artificial heart valve. [Figure 2C] Figure 2C shows the valve structure of the implanted artificial heart valve in the open configuration shown in Figure 2A, viewed from the outflow end of the artificial heart valve. [Figure 2D] Figure 2D is a simplified cross-sectional view of the implanted artificial heart valve shown in Figure 2C. [Figure 3A] Figure 3A is a simplified cross-sectional view of an implanted artificial heart valve, according to one or more embodiments of the disclosed subject, which uses an inner sealing layer to prevent cell proliferation from the surrounding intrinsic tissue. [Figure 3B] Figure 3B is a simplified cross-sectional view of an implanted artificial heart valve, according to one or more embodiments of the disclosed subject, which uses an inner sealing layer to prevent cell proliferation from the surrounding intrinsic tissue. [Figure 3C] Figure 3C is a simplified cross-sectional view of an implanted artificial heart valve, according to one or more embodiments of the disclosed subject, which uses an inner sealing layer to prevent cell proliferation from the surrounding intrinsic tissue. [Figure 3D] Figure 3D is a simplified cross-sectional view of an implanted artificial heart valve, according to one or more embodiments of the disclosed subject, which uses an inner sealing layer to prevent cell proliferation from the surrounding intrinsic tissue. [Figure 3E] Figure 3E is a simplified, enlarged perspective view showing an exemplary connection of the crossover assembly to the inner skirt, corresponding to the configuration in Figure 3D. [Figure 4A] Figure 4A is a simplified cross-sectional view of an implanted artificial heart valve, according to one or more embodiments of the disclosed subject, which uses inner and outer sealing layers to prevent cell proliferation from the surrounding intrinsic tissue. [Figure 4B] Figure 4B is a simplified cross-sectional view of an implanted artificial heart valve, according to one or more embodiments of the disclosed subject, which uses inner and outer sealing layers to prevent cell proliferation from the surrounding intrinsic tissue. [Figure 4C]Figure 4C is a simplified cross-sectional view of an implanted artificial heart valve, according to one or more embodiments of the disclosed subject, which uses inner and outer sealing layers to prevent cell proliferation from the surrounding intrinsic tissue. [Figure 4D] Figure 4D is a simplified cross-sectional view of an implanted artificial heart valve, according to one or more embodiments of the disclosed subject, which uses inner and outer sealing layers to prevent cell proliferation from the surrounding intrinsic tissue. [Figure 5A] Figure 5A is a side view of a first exemplary artificial heart valve having an inner skirt with a sealing layer to prevent cell proliferation from the surrounding intrinsic tissue, according to one or more embodiments of the disclosed subject. [Figure 5B] Figure 5B is a perspective view of the inside of the artificial heart valve shown in Figure 5A, as seen from the valve's inlet end. [Figure 5C] Figure 5C is a perspective view of the first exemplary artificial heart valve in Figure 5A, with the outer skirt attached, as seen from the outflow end. [Figure 5D] Figure 5D is a perspective view of the annular frame of the first exemplary artificial heart valve in Figure 5A, viewed from the outflow end. [Figure 5E] Figure 5E is an enlarged perspective view of the commissure attached to the annular frame of the first exemplary artificial heart valve in Figure 5A. [Figure 6A] Figure 6A is a side view of a second exemplary artificial heart valve having an inner and outer skirt with a sealing layer to prevent cell intrinsic proliferation from the surrounding intrinsic tissue, according to one or more embodiments of the disclosed subject. [Figure 6B] Figure 6B is a perspective view from the outflow end of a second exemplary artificial heart valve having an inner and outer skirt containing a sealing layer to prevent cell intrinsic proliferation from the surrounding intrinsic tissue, according to one or more embodiments of the disclosed subject. [Figure 6C] Figure 6C is a simplified cross-sectional view of the commissure attached to the annular frame of the second exemplary artificial heart valve in Figure 6A. [Figure 7A]Figure 7A is a side view of a third exemplary artificial heart valve having an inner skirt with a sealing layer to prevent cell proliferation from the surrounding intrinsic tissue, according to one or more embodiments of the disclosed subject. [Figure 7B] Figure 7B is a perspective view of the inside of the artificial heart valve shown in Figure 7A, as seen from the inlet end of the valve. [Figure 7C] Figure 7C is a simplified cross-sectional view showing the arrangement of the inner and outer skirts of the third exemplary artificial heart valve in Figure 7A. [Figure 8A] Figure 8A is a perspective view from the outflow end of a fourth exemplary artificial heart valve having an inner skirt containing a sealing layer to prevent cell proliferation from the surrounding intrinsic tissue, according to one or more embodiments of the disclosed subject matter. [Figure 8B] Figure 8B is a translucent view of the fourth exemplary artificial heart valve in Figure 8A, showing the underlying structural features of the valve frame. [Figure 9A] Figure 9A is a side view of a fifth exemplary artificial heart valve, according to one or more embodiments of the disclosed subject, having a frame enclosed in a sealing layer to prevent cell proliferation from the surrounding intrinsic tissue. [Figure 9B] Figure 9B is a perspective view from the outflow end of a fifth exemplary artificial heart valve having a frame enclosed in a sealing layer to prevent cell proliferation from surrounding intrinsic tissue, according to one or more embodiments of the disclosed subject. [Figure 10A] Figure 10A is a side view of a sixth exemplary artificial heart valve having a sealing layer to prevent cell proliferation from surrounding intrinsic tissue, according to one or more embodiments of the disclosed subject. [Figure 10B] Figure 10B is a perspective view from the outflow end of a sixth exemplary artificial heart valve having a sealing layer to prevent cell proliferation from surrounding intrinsic tissue, according to one or more embodiments of the disclosed subject. [Figure 10C] Figure 10C is a simplified cross-sectional view of the sixth exemplary artificial heart valve shown in Figure 10A. [Figure 11A]Figure 11A is a perspective view from the outflow end of a seventh exemplary artificial heart valve having a sealing layer to prevent cell proliferation from surrounding intrinsic tissue, according to one or more embodiments of the disclosed subject. [Figure 11B] Figure 11B is a partial cross-sectional view of the seventh exemplary artificial heart valve in Figure 11A, showing the underlying structural features of the valve frame.

[0032] [Figure 12A] Figure 12A is a simplified cross-sectional view of an implanted artificial heart valve at a low-pressure gradient position. [Figure 12B] Figure 12B shows the view from the outflow end of the implanted artificial heart valve at a low-pressure gradient position. [Figure 13A] Figure 13A is a simplified leaflet plan view for use in one or more embodiments of the disclosed subject matter, of an exemplary valve structure for regulating blood flow in hemodynamic conditions of a low pressure gradient. [Figure 13B] Figure 13B is an enlarged external view of an exemplary valve structure coupled to an annular frame and inner skirt of an artificial heart valve according to one or more embodiments of the disclosed subject. [Figure 13C] Figure 13C is an enlarged internal view of an exemplary valve structure coupled to an annular frame and inner skirt of an artificial heart valve according to one or more embodiments of the disclosed subject. [Figure 14A] Figure 14A is a side view of a first exemplary artificial heart valve having a valve structure for regulating blood flow in low-pressure gradient hemodynamic conditions, according to one or more embodiments of the disclosed subject matter. [Figure 14B] Figure 14B is a perspective view of the annular frame of the first exemplary artificial heart valve shown in Figure 14A, viewed from the outflow end. [Figure 14C] Figure 14C is a simplified plan view of a single leaflet from the valve structure of the first exemplary artificial heart valve in Figure 14A. [Figure 14D] Figure 14D is an enlarged perspective view of the commissure attached to the annular frame of the first exemplary artificial heart valve in Figure 14A. [Figure 14E]Figure 14E is a view from the outflow end of the valve structure of the first exemplary artificial heart valve in the open configuration of Figure 14A. [Figure 15A] Figure 15A is a simplified plan view of a single valve leaflet from the valve structure of a comparative example of an artificial heart valve. [Figure 15B] Figure 15B is a view from the outflow end of the valve structure of a comparative example of the artificial heart valve in the open configuration shown in Figure 15A. [Figure 16A] Figure 16A is a side view of an exemplary docking station for an artificial heart valve having a valve structure for regulating blood flow in low-pressure gradient hemodynamic conditions, according to one or more embodiments of the disclosed subject. [Figure 16B] Figure 16B is a partial cross-sectional view of the docking station in Figure 16A with the artificial heart valve installed. [Figure 17A] Figure 17A is a simplified cross-sectional view of an exemplary artificial mitral valve having an annular frame enclosed in a sealing layer to prevent cell proliferation from surrounding intrinsic tissue, according to one or more embodiments of the disclosed subject. [Figure 17B] Figure 17B is a perspective view from the outflow end of the exemplary artificial mitral valve shown in Figure 17A. [Figure 17C] Figure 17C is a translucent side view of an exemplary artificial mitral valve from Figure 17B with the outer skirt removed to show its basic features. [Figure 17D] Figure 17D is a translucent perspective view from the outflow end of an exemplary artificial mitral valve shown in Figure 17B, with the outer skirt removed to illustrate its basic features. [Figure 18] Figure 18 is a simplified diagram of an exemplary delivery system for implanting one of the exemplary artificial heart valves into a patient, according to one or more embodiments of the disclosed subject matter. [Figure 19] Figure 19 is a simplified diagram of an exemplary docking station on which an exemplary artificial mitral valve can be implanted in a patient according to one or more embodiments of the disclosed subject. [Figure 20A]Figure 20A is a partial cross-sectional view of the initial stage of an exemplary docking station from Figure 19 within the patient's original mitral valve. [Figure 20B] Figure 20B shows an example of the docking station from Figure 19 in the initial stages of implantation, viewed from the inflow end, within the patient's original mitral valve. [Figure 20C] Figure 20C is a partial cross-sectional view of the post-implantation stage of the exemplary docking station of Figure 19 within the patient's original mitral valve. [Figure 20D] Figure 20D is a view from the inflow end of the docking station from Figure 19 in the patient's original mitral valve, in a post-implantation stage. [Figure 21A] Figure 21A is a partial cross-sectional view of an exemplary implant of the exemplary artificial mitral valve of Figure 17B in a previously implanted docking station. [Figure 21B] Figure 21B is a simplified diagram of the example artificial mitral valve shown in Figure 17B, as viewed from the left ventricle, after implantation into the patient's original mitral valve. [Figure 22] Figure 22 is a perspective view of the outer skirt for an artificial heart valve, depicted as an axially elongated shape. [Figure 23] Figure 23 shows the outer skirt of Figure 22 in a radially extended state. [Figure 24A] Figure 24A is an exemplary plan view of the woven fabric for the first fabric layer of the outer skirt in Figures 22 and 23, depicted in an elongated form. [Figure 24B] Figure 24B shows a detailed view of the area 24B circled in Figure 24A. [Figure 25] Figure 25 shows the woven fabric from Figure 24 in a radially expanded state. [Figure 26] Figure 26 shows the basic leno weave structure. [Figure 27A] Figure 27A shows the formation of the first fabric layer of the outer skirt in Figure 22. [Figure 27B] Figure 27B shows the formation of the first fabric layer of the outer skirt in Figure 23. [Figure 28] Figure 28 shows a basic plain weave structure. [Figure 29] Figure 29A shows the formation of the second fabric layer of the outer skirt in Figure 22. [Figure 29] Figure 29B shows the formation of the second fabric layer of the outer skirt in Figure 22. [Figure 30] Figure 30 shows the formation of the second fabric layer of the outer skirt in Figure 23. [Figure 31] Figure 31 is an elevation view showing the outer skirt of Figure 23, which is positioned around the radially extended artificial heart valve. [Figure 32] Figure 32 is an elevation view showing the inner fabric layer of the outer skirt of Figure 23, which is positioned around the frame of the artificial heart valve. [Figure 33] Figure 33 is a cross-sectional view of the outer skirt of Figure 23, which is positioned around the artificial heart valve. [Figure 34] Figure 34 shows the outer skirt of Figure 23, which is positioned around the artificial heart valve and has a flap of inner fabric layer folded around the outer layer. [Modes for carrying out the invention]

[0033] General Considerations

[0034] All features described herein are independent of each other and can be used in combination with any other features described herein, unless structurally impossible. For example, the delivery device 1800 shown in Figure 18 can be used in combination with any artificial heart valve described herein. In another embodiment, the valve structure described with respect to Figures 13A to 14E can be used in combination with any of the artificial valves shown in Figures 3A to 9B. In yet another embodiment, various exemplary configurations of the sealing layer of the artificial heart valve frame, protective cover, and / or coupling member, as discussed with respect to Figures 3A to 11B, can be used with any of the disclosed artificial valves or their modifications thereof.

[0035] For the purpose of this explanation, this specification describes specific aspects, advantages, and novel features of the subject matter. The disclosed methods, apparatus, and systems should not be construed as limiting in any way. Rather, this disclosure covers all novel and non-obvious features and aspects of the various disclosed implementations and implementations, both individually and in various combinations and subcombinations with one another. The methods, apparatus, and systems are not limited to any particular aspect or feature, or any combination thereof, nor do the disclosed implementations and implementations require the existence of any one or more particular advantages or the resolution of any problem. The techniques of any example or implementation can be combined with the techniques described in one or more other examples or implementations.

[0036] The disclosed implementation examples and some of the operations of the implementations are described in a specific sequential order for convenience of presentation, but it should be understood that this method of description is inclusive of reordering unless a specific order is required by the specific terms described below. For example, operations described sequentially may, in some cases, be reordered or performed simultaneously. Furthermore, for the sake of simplification, the accompanying drawings cannot show the various ways in which the disclosed methods may be used in combination with other methods. In addition, this description may use terms such as “provide” or “achieve” to describe the disclosed methods. These terms are high-level abstractions of the actual operations performed. The actual operations corresponding to these terms may vary depending on the specific implementation and will be readily recognizable to those skilled in the art.

[0037] As used herein in relation to artificial heart valve assemblies, and the implantation and construction of artificial heart valves, “proximal” refers to the location, orientation, or portion of a component closer to the handle of the delivery system or device, which is outside the user and the patient, while “distal” refers to the location, orientation, or portion of a component further away from the user and the handle, and closer to the implantation site. The terms “longitudinal” and “axial” refer to axes extending in the proximal and distal directions, respectively, unless otherwise expressly defined.

[0038] The terms “axial,” “radial,” and “circumferential” are used herein to describe the arrangement and assembly of components relative to the geometric shape of the frame of an artificial heart valve. While such terms are used for explanatory convenience, the disclosed examples and implementations are not strictly limited to these descriptions. Specifically, when a component or action is described with respect to a particular direction, this includes directions parallel to the specified direction as well as slight deviations therefrom. Thus, a description of a component extending along the axial direction of the frame does not require the component to be aligned with the center of the frame; rather, the component may extend substantially along a direction parallel to the central axis of the frame.

[0039] As used herein, the terms “integrally formed” and “single structure” refer to a structure that does not involve any welding, fasteners, or other means for fastening separately formed material pieces together.

[0040] As used herein, actions occurring "simultaneously" or "concurrently" generally occur at the same time as each other, but delays in the occurrence of an action relative to another, for example, due to the interval between components, are explicitly within the scope of the above terms unless a specific opposite term is used.

[0041] In this application and claims, the singular forms "a," "an," and "the" include the plural form unless the context otherwise explicitly indicates. Furthermore, the term "includes" means "comprises." Furthermore, the term "combined" generally means being combined or joined physically, mechanically, chemically, magnetically, and / or electrically, and does not preclude the existence of intermediate elements between combined or related items unless otherwise specified. As used herein, "and / or" means "and" or "or," as well as "and" and "or."

[0042] Directions and other relative references may be used to facilitate, but are not intended to limit, the consideration of the drawings and principles herein. For example, certain terms such as “inside,” “outside,” “upper,” “lower,” “inside,” “outside,” “top,” “bottom,” “internal,” “external,” “left,” and “right” may be used. Such terms are used to provide some degree of clarity of explanation, particularly with respect to illustrated embodiments, when dealing with relative relationships, where applicable. However, such terms are not intended to imply absolute relationships, positions, and / or orientations. For example, with respect to an object, an “upper” part can become a “lower” part simply by inverting the object. Nevertheless, these are still the same part, and the object remains the same.

[0043] Overview of Disclosure Technology

[0044] This specification describes artificial heart valves designed to reduce the risk of thrombosis. In some implementations, the artificial heart valve may have one or more sealing layers configured to prevent ingrafting of surrounding intrinsic tissue. For example, the inner and / or outer skirts may contain one or more sealing layers, or the entire valve frame may be encapsulated within one or more sealing layers. Conventional materials used for the inner and outer skirts may have pores therein that allow ingrafting of surrounding intrinsic tissue, while the sealing layers disclosed herein may be formed from hydrophobic materials, may be substantially non-porous, or otherwise may have pores small enough to prevent intracellular growth. Thus, the disclosed sealing layers can prevent or at least reduce ingrafting of surrounding intrinsic tissue, thereby avoiding or at least reducing pannus formation on the artificial valve leaflets that may otherwise arise from such ingrafting. Alternatively or additionally, in some implementations, the shape of the valve leaflets of the artificial valve's valve structure and / or the bonding of the leaflets to the frame may be selected to avoid or at least reduce the occurrence of stasis when implanted in a hemodynamic position with a relatively low pressure gradient.

[0045] Examples of the disclosed technology Exemplary sealing layer to prevent internal migration within the organization

[0046] Referring to Figure 1, a schematic cross-section of a human heart 10 is shown. The mitral valve 16 separates the left ventricle 14 from the left atrium 12, and the tricuspid valve 26 separates the right ventricle 28 from the right atrium 24. The aortic valve 20 further separates the left ventricle 14 from the ascending aorta 22, and the pulmonary valve 30 further separates the right ventricle 28 from the pulmonary artery 32. Deoxygenated blood is delivered to the right atrium 24 by the superior vena cava 34, the inferior vena cava 36, ​​and the coronary sinus. During diastole, as the right ventricle 28 expands, the deoxygenated blood in the right atrium 24 is guided into the right ventricle 28 through the tricuspid valve 26. During the subsequent systole, the contraction of the right ventricle 28 pushes the deoxygenated blood into it through the pulmonary valve 30 into the pulmonary artery 32. In addition to forcing blood through the unidirectional pulmonary valve 30, the contraction pressure from the right ventricle 28 also closes the unidirectional tricuspid valve 26, thereby preventing blood from the right ventricle 28 from re-entering the right atrium 24.

[0047] Oxygenated blood is delivered to the left atrium 12 by the pulmonary veins. During diastole, as the left ventricle 14 expands, the oxygenated blood from the left atrium 12 is guided to the left ventricle 14 through the mitral valve 16. During the subsequent systole, the contraction by the left ventricle 14 pushes the oxygenated blood through the aortic valve 20 into the ascending aorta 22, where it circulates throughout the body. Furthermore, forcing blood through the unidirectional aortic valve 20, the pressure of the contraction by the left ventricle 14 also facilitates the closing of the unidirectional mitral valve 16, thereby preventing blood from the left ventricle 14 from re-entering the left atrium 12. The contraction by the left ventricle 14 creates a significant pressure difference between the left ventricle 14 and the left atrium 12. A series of chordae tendineae 18 connect the leaflets of the mitral valve 16 to the papillary muscles located on the wall of the left ventricle 14. During diastole, both the chordae tendineae 18 and the papillary muscles are stretched to hold the mitral valve leaflets 16 in a closed position and prevent them from extending posteriorly into the left atrium 12.

[0048] None of the original heart valves described above may function properly, for example, by allowing blood to flow backward through them or into upstream cardiac chambers or blood vessels. In some implementations, an artificial heart valve may be implanted within the original heart valve to prevent or inhibit such backflow and / or to address any other dysfunction of the original heart valve. In other implementations, an artificial heart valve may be implanted in a blood vessel leading to a cardiac chamber, such as the inferior or superior vena cava, to prevent or inhibit backflow within it during systole. Generally, an artificial heart valve implanted in the aortic location (e.g., within the original aortic valve 20) can typically experience relatively high pressure gradients (e.g., a drive pressure of approximately 125 mmHg). In contrast, artificial heart valves implanted in the lungs (e.g., within the original pulmonary valve 30), the tricuspid location (e.g., within the original tricuspid valve 26), the mitral valve location (e.g., within the original mitral valve 16), or in blood vessels leading to the heart chambers (e.g., within the inferior vena cava 36 or superior vena cava 34) can typically encounter relatively low pressure gradients (e.g., drive pressures of approximately 30 mmHg or less).

[0049] Figures 2A–2D show an artificial heart valve 100 implanted in the aortic location (e.g., within the leaflets 40 of the original aortic valve 20). The artificial heart valve 100 includes a valve structure comprising an annular frame 102 and three leaflets 106. The valve structure is coupled to the annular frame 102 near the outflow end 110 of the artificial valve 100 by a plurality of commissures 112 formed by tabs of adjacent leaflets 106. The artificial heart valve 100 also includes an inner skirt 114 covering the inner circumferential surface of the annular frame 102 near the inflow end 108 of the artificial valve 100. The artificial valve 100 further includes an outer skirt 104 covering the outer circumferential surface of the annular frame 102 near the inflow end 108. Each leaflet 106 has a pointed edge that attaches to the inner skirt 114. Further details of the artificial heart valve 100 are disclosed in U.S. Patent Application Publication No. 2019 / 0365530, which is incorporated herein by reference.

[0050] In conventional artificial heart valves, the inner skirt 114 and outer skirt 104 are composed of porous materials such as fabrics, knitted fibers, or knitted fabrics formed from synthetic fibers such as polyethylene terephthalate (PET) fibers. The porous nature of the skirt material (e.g., having pores larger than 30 μm to 50 μm) is designed to be substantially impermeable to blood cells in the blood flow through the heart valve, while promoting intracellular proliferation of the surrounding innate tissue. For example, tissue or cells from the valve leaflets 40 in contact with the outer skirt 104 can grow into the outer skirt 104 and thereby into the inner skirt 114 on the opposite side of the annular frame 102. This innate tissue proliferation into the skirts 104, 114 can further secure the heart valve 100, which has been implanted within the patient's original anatomical structure, and reduce paravalvular leakage (PVL).

[0051] However, tissue infiltration into the prosthetic heart valve 100 can extend beyond the outer skirt 104 and inner skirt 114. Since the leaflets 106 of the prosthetic valve 100 are attached to the inner skirt 114, tissue infiltration into the inner skirt 114 can migrate onto the leaflets 106, as shown by route 122 in Figure 2D. Furthermore, since the commissure 112 of the valve structure of the prosthetic valve 100 has a portion located outside the annular frame 102, the commissure 112 is more likely to come into contact with the original anatomical structure (e.g., the leaflets 40), thus providing an additional pathway 124 for tissue growth on the leaflets. Tissue infiltration into the valve structure can result in the formation of a pannus on the surface of the leaflets 106, which can impair the functionality of the valve structure. Furthermore, the pannus on the leaflets 106 can function as a substrate to which thrombi can later be deposited. When implanted in a location with a relatively low pressure gradient, the lower flow conditions experienced by the artificial valve 100 may allow for easier propagation of tissue over the valve leaflet 106 via pathways 122 and 124.

[0052] Accordingly, in some implementations, the artificial heart valve is provided with one or more sealing layers to prevent or at least reduce intrinsic tissue proliferation via pathways 122 and / or 124. As used herein, “sealing layer” refers to a layer constructed such that, when implanted in a patient, intrinsic cell proliferation into the layer is prevented or at least inhibited. In some implementations, such sealing layers are substantially non-porous or otherwise have pores therein that are small enough to inhibit cell proliferation. The size and characteristics of the pores within the sealing layer (e.g., porous, flexible) may be adapted to prevent intracellular proliferation, which may also depend on the implant location (e.g., pressure gradient, blood flow conditions), the desired implant lifespan, the thickness of the sealing layer, and / or other factors.

[0053] In some implementations, the sealing layer may have pores within it, for example, each with a size of 8 μm or less (e.g., diameter or maximum lateral dimension in the case of non-circular shapes). Alternatively or additionally, in some implementations, the size of each pore in the sealing layer may be, for example, 20 μm or less, 10 μm or less, or 5 μm or less. In some implementations, the sealing layer may have a range of different pore sizes, such that at least 90% of the pores have a size of 8 μm or less. Or or additionally, in some implementations, the pore size distribution of the sealing layer may be such that at least 90% of the pores have a size of 20 μm or less, 10 μm or less, or 5 μm or less.

[0054] In some implementations, pores opening on the outer diameter side of the sealing layer (e.g., the side facing outward toward the surrounding natural tissue) may be larger in size than pores opening on the inner diameter side of the sealing layer (e.g., the side facing inward toward the valve structure of the artificial valve). In such implementations, each pore opening to the inner diameter side of the sealing layer may be, for example, 8 μm or less in size. Alternatively or additionally, in some implementations, the size of each individual pore opening to the inner diameter side of the sealing layer may be, for example, 20 μm or less, 10 μm or less, or 5 μm or less. Alternatively or additionally, in some implementations, the inner diameter side of the sealing layer may have a pore size distribution having at least 90% of pores being 20 μm or less, 10 μm or less, 8 μm or less, or 5 μm or less.

[0055] In some implementations, the pore size of the sealing layer can be characterized by imaging the pores of a portion or the entire sealing layer. Alternatively or additionally, in some implementations, the pore size of the sealing layer can be characterized by imaging the pores of at least a portion of the inner diameter side of the sealing layer. For example, the pore size of the sealing layer may be characterized by optical microscopy, electron microscopy (e.g., scanning electron microscopy), or X-ray microcomputed tomography (micro-CT) imaging (e.g., American Society for Testing and Materials (ASTM) F2450-18, “Standard Guide for Evaluating the Microstructure of Polymer Scaffolds Used in Tissue Engineering Medical Products,” ASTM International, West Conshohocken, PA, 2018, which is incorporated herein by reference). Alternatively or additionally, in some implementations, the pore size of the sealing layer can be characterized by performing one or more porometry or porosimetry tests on the sealing layer. For example, the pore size of a sealed layer can be determined by capillary flow porometry or bubble point testing (e.g., ASTM F316-03 (2019), "Standard Test Method for Pore Size Characteristics of Membrane Filters by Bubble Point and Mean Flow Pore Test," ASTM International, West Conshohocken, PA, 2019, which is incorporated herein by reference), or mercury intrusion porosimetry (e.g., UOP578-11, "Automated Pore Volume and Pore Size Distribution of Porous Materials by Mercury Intrusion," ASTM International, West Conshohocken, PA, 2011, or US Pharmaceutical Convention for Micromeritics and Particulate Systems Instruments). <267> This can be characterized by "Porous Measurement by Mercury Intrusion," US Pharmaceutical Convention, Rockville, MD, 2012 (both incorporated herein by reference).

[0056] In some implementations, the pore size of the sealing layer may be characterized by the size of particles that are restricted from passing through the sealing layer. The nominal pore size of the sealing layer may be defined as the particle size (e.g., cross-sectional dimensions) that restricts 90% of particles from passing through the sealing layer, while the absolute pore size of the sealing layer may be defined as the maximum particle size that a particle cannot pass through the sealing layer under given test conditions (e.g., pressure induced across the sealing layer). In some implementations, the sealing layer may have nominal pore sizes of 20 μm or less, 10 μm or less, 8 μm or less, or even 5 μm or less. Alternatively or additionally, in some implementations, the sealing layer may have absolute pore sizes of 20 μm or less, 10 μm or less, 8 μm or less, or even 5 μm or less when subjected to a pressure difference similar to the pressure difference experienced at the desired implant location (e.g., in the range of 20 mmHg to 250 mmHg).

[0057] In some implementations, the sealing layer includes a hydrophobic polymer material. Examples of hydrophobic polymer materials, but not limited to, include polytetrafluoroethylene (PTFE), expanded PTFE (ePTFE), urethane, polyurethane (PU), thermoplastic PU (TPU), silicone, or combinations or copolymers thereof. In one embodiment, the hydrophobic polymer material includes an electrospin urethane layer having ePTFE (e.g., Bioweb®, sold by Zeus Industrial Products Inc., Orangeburg, SC). In another embodiment, the hydrophobic polymer material includes a copolymer of silicone and TPU (e.g., Quadrasil®, sold by Biomerics, Salt Lake City, Utah, USA). Other hydrophobic polymer materials or combinations thereof, not specifically listed above, that can later form a seal that is substantially non-porous or has pores small enough to inhibit intracellular proliferation, are also possible in some implementations.

[0058] In some implementations, the sealing layer may be a single layer of hydrophobic polymer material. Alternatively, the sealing layer may be a laminated structure of multiple sublayers, one or more of which are formed from hydrophobic polymer material. In one embodiment, the sealing layer may have a layer of hydrophobic polymer material bonded to a substrate layer (e.g., a fabric or knitted material such as PET) or formed on the substrate layer. In another embodiment, the hydrophobic polymer material may cover the substrate layer on at least two sides (e.g., by using separate sublayers of hydrophobic polymer material sandwiching the substrate layer between them, or by encapsulating the substrate layer within the hydrophobic polymer material). Alternatively, the hydrophobic polymer material may be provided on only one side of the substrate layer, for example, on the surface of the substrate layer facing the frame of an artificial heart valve. The substrate layer may be porous or otherwise have a structure that allows for cell proliferation, but the addition of a hydrophobic polymer material can impart properties to the substrate layer that prevent cell proliferation, for example, by at least partially filling the pores of the substrate layer or otherwise preventing cells from entering or leaving the substrate layer, thereby enabling the combination to function as a sealing layer.

[0059] In some implementations, the sealing layer may be formed directly on or above the target barrier surface (e.g., the surface of the artificial valve frame or the substrate layer) (e.g., together with one or more intervening layers). For example, the sealing layer may be formed on or above the target barrier surface of the frame by electrospinning, dip coating, or spray coating. In dip coating or spray coating, a hydrophobic polymer material or its precursor can be dissolved in a reagent or dissolved to form a liquid. The resulting liquid is coated on or above the target barrier surface of the frame (e.g., by immersing the frame or substrate layer in the liquid or by spraying the liquid onto the frame or substrate). The sealing layer can be formed in situ by drying or otherwise solidifying the coating. In electrospinning, a hydrophobic polymer material or its precursor is dissolved or provided in a solution. The molten material or solution is then released and extruded through a spinneret under a high-voltage electric field. The extruded molten material or solution solidifies or coagulates to form ultrafine filaments that can be deposited directly on or above the target barrier surface. In some implementations, a sealing layer may be formed and then attached to or on the target barrier surface (for example, together with one or more intervening layers). For example, the sealing layer may be formed by extrusion or casting and then attached to or on the target barrier surface (for example, by partially embedding the frame or base layer within the sealing layer using one or more sutures, or by any other attachment means).

[0060] Alternatively, or additionally, in some implementations, the annular frame may be encapsulated by a sealing layer such that the inner and outer surfaces of the frame are covered by the sealing layer. For example, the frame may be encapsulated by providing separate polymer layers on the radially inner and radially outer surfaces of the annular frame, and then the polymer layers may be pressed or melted together to embed the frame. In another embodiment, the frame may be encapsulated by coating (e.g., dipping or spraying) or electrospinning the sealing layer over all surfaces of the annular frame. Alternatively, or additionally, the substrate layer may be encapsulated with a hydrophobic polymer material to form a sealing layer such that opposing surfaces of the substrate layer are covered by the hydrophobic polymer material. For example, the substrate layer may be encapsulated by providing separate polymer layers on opposing surfaces of the substrate layer, and then the polymer layers may be pressed or melted together to embed the substrate layer. In another embodiment, the substrate layer may be encapsulated by coating (e.g., dipping or spraying) or electrospinning the hydrophobic polymer material over all surfaces of the substrate layer. Further details regarding options and techniques for manufacturing layers that may be used to form a sealing layer can be found in U.S. Patent Application Publication No. 2020 / 0155306 and U.S. Patent No. 10,232,564, both of which are incorporated herein by reference in their entirety.

[0061] In some implementations, at least the inner skirt of the artificial heart valve includes a sealing layer. For example, Figure 3A shows an exemplary configuration of an artificial heart valve 200 in which the inner skirt 214 includes a sealing layer. The leaflets 106 of the valve structure of the artificial heart valve 200 may be coupled to the inner skirt 214 (e.g., via one or more sutures), which can then be coupled to the frame 102 (e.g., on the frame or by being formed via one or more sutures). Thus, the inner skirt 214 helps to secure the valve structure to the frame and provides a seal between the valve and the original annulus by blocking blood flow through the opening cell of the frame below the lower edge of the leaflets 106. The outer skirt 104 may also be coupled to the frame 102, for example, via an opposing portion at the inlet end 202 of the valve 200, or optionally coupled to the inner skirt 214, as described below for other exemplary configurations.

[0062] In some implementations, the inner skirt 214 with a sealing layer extends at least to the commissure 112 (as shown in 206), thereby providing a barrier on the radially inner side of the annular frame from which surrounding native tissue growth is likely to occur due to contact with the native valve leaflets 40. In the illustrated embodiment of Figure 3A, the outer skirt 104 may be formed from a conventional material (e.g., PET), and therefore tissue growth may occur within the outer skirt 104. However, the provision of a sealing layer on the radially inner side of the annular frame 102 may prevent, or at least inhibit, tissue growth from reaching the valve leaflets 106 of the artificial heart valve 200.

[0063] In some implementations, the inner skirt, including a sealing layer, may extend further to the outflow end of the artificial heart valve. For example, Figure 3B shows an exemplary configuration of an artificial heart valve 220 in which the inner skirt 224 with a sealing layer extends from the inflow end 222 to the outflow end 226 of the valve, thereby providing a continuous barrier against tissue ingrafting across the entire radial inner surface of the annular frame 102. One or more openings may be formed in the inner skirt 224 at positions corresponding to the commissure window of the annular frame 102 for attaching the commissure 112 to the annular frame 102. The commissure 112 may extend radially through the openings in the inner skirt 224 and through the commissure window for joining (e.g., via one or more sutures) on the radially outer side of the annular frame 102.

[0064] Similar to the configuration in Figure 3A, the artificial heart valve 220 in Figure 3B may include an outer skirt 104 formed from a conventional material and attached to the radially outer surface of the annular frame 102. The outer skirt 104 may also be joined to the inner skirt 224 by, for example, wrapping the outer skirt 104 around the inlet end 222 of the frame 102 and bringing it into contact with the inner skirt 224, as shown in Figure 3B, and the overlapping portions of the skirts may be sutured together. Alternatively, the inner skirt 224 and the outer skirt 104 may be joined at the inlet end 222 in a manner similar to that shown in Figure 3A. Alternatively, the inner skirt 224 may be wrapped around the inlet end 222 of the frame 102 so as to be in contact with the outer skirt 104, and the overlapping portions of the skirts may be sutured together.

[0065] In some implementations, the artificial heart valve may include one or more protective covers on the radially outer surface of the annular frame to protect the commissure portion 112 of the valve structure extending radially outward from each inner skirt, for example. For example, Figure 3C shows an exemplary configuration of an artificial heart valve 240 in which a protective cover 242a is positioned on the commissure portion 112 on the radially outer surface of the annular frame 102. The protective cover 242a includes a sealing layer that prevents or at least reduces tissue intrusion into the portion of the leaflet 106 forming the commissure portion 112, for example, via the original leaflet 40. In some implementations, the protective cover 242a may be provided only in the area where the commissure portion 112 is located. For example, the protective cover 242a may be integrated with the commissure portion 112, such as a coupling member that wraps around other exposed surfaces of the leaflet tabs. Optionally, the protective cover may be configured as an annular member wrapped around the radially outer circumference of the annular frame 102, thereby providing a protective cover portion 242b in areas that do not have the connecting portion 112.

[0066] Alternatively, in some implementations, the artificial heart valve can be mounted with the commissure 112 radially inward of the sealing layer. In such configurations, a separate protective cover 242a may not be necessary. For example, Figure 3D shows an exemplary configuration of an artificial heart valve 260 in which the commissure 112 is directly bonded to the inner skirt 224, for example, using one or more sutures. Along the radial direction of the annular frame 102, the sealing layer of the inner skirt 224 provides a space between the surrounding natural tissue (e.g., the valve leaflet 40) and the valve leaflet 106 of the artificial valve 100, thereby separating the valve leaflet 106 from potential tissue ingrafts. Figure 3E shows an exemplary attachment of the commissure assembly 112 to the inner skirt 224, viewed from the radially inward side of the frame 102 of the artificial heart valve 260. The inner skirt 224 may be attached to the studs 262 of the frame 102 via one or more sutures 272. The interconnected supports 262 of the frame 102 can form an opening cell 264 covered by an inner skirt 224 to which the commissar 112 can be attached. The tabs 268 of adjacent valve leaflets 106 can rotate in opposite directions along the circumferential direction to form a T-shape and can be attached to the inner skirt 224 using one or more sutures 270. In this way, the commissar tab assembly can be attached to the frame without requiring a separate commissar window.

[0067] In some implementations, both the inner and outer skirts may include a sealing layer. For example, Figure 4A shows an exemplary configuration of an artificial heart valve 300 having an inner skirt 224 and an outer skirt 304, each including a sealing layer. In Figure 3B, the inner skirt 224 may extend from the inlet end 302 to the outlet end 306 of the valve, thereby providing a continuous barrier to tissue infiltration across the entire radially inner surface of the annular frame 102. Alternatively, in some implementations, the inner skirt may extend along the axial direction of the frame 102 from the inlet end 302 to the commissure 112, similar to the configuration shown in Figure 3A. The leaflets 106 of the valve structure of the artificial heart valve 200 may be coupled to the inner skirt 224 (e.g., via one or more sutures), and the commissure 112 may extend through the respective openings of the inner skirt 224 and be attached to the annular frame. In contrast to the configurations shown in Figures 3A to 3D, the outer skirt 304 with a sealing layer provides an additional barrier against endografts, thereby further inhibiting the native tissue from reaching the leaflets 106 of the artificial valve 300. The outer skirt 304 may be bonded to the frame 102 (e.g., via one or more sutures) and may be bonded to the inner skirt 224 at the inlet end 302 via opposing portions (e.g., by one or more sutures, or by fusing, melting, or otherwise joining the sealing layers of the skirts 224, 304) or as optional as described for the other exemplary configurations described above. Alternatively or additionally, the inner skirt 224 may be fused or melted to the outer skirt 304 at the annular frame 102 in order to attach the skirts 224, 304 to the frame 102.

[0068] In some implementations, the outer skirt, including the sealing layer, may extend further to the outflow end of the artificial heart valve. For example, Figure 4B shows an exemplary configuration of an artificial heart valve 340 in which both an inner skirt 224 with a sealing layer and an outer skirt 342 with a sealing layer extend from the inflow end 344 to the outflow end 346, thereby providing a further continuous barrier against tissue ingrafting across the entire radial outer surface of the annular frame 102. To attach the commissure 112 to the annular frame 102, one or more openings may be formed in the inner skirt 224 at locations corresponding to the commissure window of the annular frame 102. Corresponding openings may be formed in the outer skirt 342. The commissure 112 may extend radially through the openings in the inner skirt 224, through the commissure window, and through the openings in the outer skirt 342 for bonding on the radially outer side of the outer skirt 342 (e.g., via one or more sutures).

[0069] Both the inner skirt 224 and the outer skirt 342 can be joined to the frame 102, for example, using one or more sutures. The outer skirt 342 can also be joined to the inner skirt 222 by wrapping the outer skirt 342 around the inlet end 344 of the frame 102 and bringing it into contact with the inner skirt 224, as shown in Figure 4B, and the overlapping portions of the skirts can be joined together (for example, by suturing, fusing, melting, or other joining methods). Alternatively, the inner skirt 224 and the outer skirt 342 can be joined at the inlet end 344 in a manner similar to that shown in Figure 4A. Alternatively, the inner skirt 224 may be wrapped around the inlet end 344 of the frame 102 so as to be in contact with the outer skirt 342, and the overlapping portions of the skirts can be joined together (for example, by suturing, fusing, melting, or other joining methods). Alternatively, or additionally, the inner skirt 224 may be fused or melted to the outer skirt 342 in the annular frame 102 in order to attach the skirts 224, 342 to the frame 102.

[0070] In some implementations, the inner and outer skirts can share the same sealing layer. For example, Figure 4C shows an exemplary configuration of an artificial heart valve 320 having a continuous skirt layer 322 containing a sealing layer. The continuous skirt layer 322 is positioned over the entire radially inner surface of the annular frame 102, thereby providing an inner skirt portion 328. Alternatively, in some implementations, the skirt layer 322 can extend over the radially inner surface of the annular frame 102 from the inlet end 324 to the commissar 112, similar to the configuration shown in Figure 3A. A portion of the skirt layer 322 can be wound around the inlet end 324 and positioned over at least a portion (and optionally all) of the radially outer surface of the annular frame 102, thereby providing an outer skirt portion 326. Similar to the configuration described above, the leaflets 106 of the valve structure of the artificial heart valve 320 may be coupled to the inner skirt portion 328 (for example, via one or more sutures), and the commissures 112 may extend through each opening of the inner skirt portion 328 and be attached to the annular frame. In some implementations, the continuous skirt layer 322 may be fixed to the annular frame using one or more sutures. Alternatively or additionally, the inner skirt portion 328 may be fused or melted to the outer skirt portion 326 in the annular frame 102 in order to fix the continuous skirt layer 322 to the frame 102.

[0071] In some implementations, the inner and outer skirts, which share the same sealing layer, can be further extended to cover all surfaces of the artificial heart valve frame, thereby sealing the frame within the sealing layer. For example, Figure 4D shows an exemplary configuration of an artificial heart valve 360 ​​having an annular frame 102 sealed within a sealing layer 362. The sealing layer 362 may be positioned on all surfaces of the annular frame 102, thereby providing both an inner skirt portion 366 and an outer skirt portion 364 that functions as a barrier against tissue ingrafting. In some implementations, the sealing layer 362 is formed by positioning separate sealing sublayers on the radially inner and radially outer surfaces of the annular frame 102, and then fusing, dissolving, or otherwise joining the sealing sublayers together with the annular frame 102. Alternatively, in some implementations, the sealing layer 362 may be formed directly on the annular frame 102, for example, via dip coating, spray coating, electric spinning, etc. Further details regarding the materials and techniques for encapsulation and attachment of the skirt to the artificial valve frame can be found in U.S. Patent No. 8,945,209 and U.S. Patent Application Publication No. 2020 / 0155306, both of which are incorporated in their entirety by reference. In addition to providing a desired barrier to tissue growth, the encapsulation process can avoid or at least reduce the time-consuming assembly associated with suturing the skirt to the annular frame.

[0072] In some implementations, the sealing layers of the inner skirt, outer skirt, and / or encapsulation layer may have sufficient strength and elasticity to avoid yielding or tearing, particularly during the transition of the artificial valve between a fully expanded configuration and a crimped configuration, where the valve may be subjected to a change in longitudinal dimension of up to 30% (e.g., at the suture hole). Alternatively, or additionally, the inner skirt may include a scrim layer (e.g., a woven or cloth such as PET fabric) in addition to the sealing layer. The scrim layer may be positioned along the axial direction of the frame to which the valve leaflets of the valve diaphragm structure are attached to the inner skirt. For example, in the illustrated embodiments of Figures 3A to 4C, the inner skirt may have a scrim layer either between the sealing layer and the annular frame, or on the radially inner side of the sealing layer. Alternatively, or additionally, the scrim layer may be encapsulated in the frame by the sealing layer. The scrim layer may be positioned along the axial direction of the frame to which the valve leaflets of the valve diaphragm structure are attached to the encapsulation sealing layer. For example, in the embodiment illustrated in Figure 4D, the scrim layer can be enclosed in the frame 102 by an inclusion skirt layer 322. The scrim layer can improve the suture retention strength of the inner skirt or inclusion layer.

[0073] Exemplary artificial heart valve with sealing layer Figures 5A–5E show various features of an exemplary artificial heart valve 400 having an inner skirt including a sealing layer. The artificial heart valve 400 may be crimped or held by an implant delivery device in a radially compressed configuration, or the artificial heart valve may be routed to the patient's heart through the patient's anatomical structure and then expanded into a radially expanded configuration when the artificial heart valve reaches the desired implantation site in the heart. In certain examples, it may also be implanted in other locations in the heart, including within the original mitral valve (e.g., mitral valve 16 in Figure 1), the original pulmonary valve (e.g., pulmonary valve 30 in Figure 1), or the original tricuspid valve (e.g., tricuspid valve 26 in Figure 1), but the artificial heart valve 400 can be implanted within the original aortic annulus. The artificial heart valve 400 can be implanted using any known delivery device, e.g., the delivery device shown in Figure 18.

[0074] The artificial heart valve 400 may include an annular stent or frame 402 having a first axial end 416 and a second axial end 418. In the illustrated example, the first axial end 416 may be the outflow end and the second axial end 418 may be the inflow end. The outflow end 416 is the nearest end of the artificial valve when attached to a delivery device for delivering and implanting the artificial heart valve 400 into the original aortic valve using a transfemoral retrograde delivery approach. In other implementations, the inflow end 418 may be the nearest end of the artificial valve when attached to a delivery device, depending on the specific original valve being replaced and the delivery technique used (e.g., transseptal, transapical).

[0075] In some implementations, the frame 402 or its components (e.g., the struts 430) can be fabricated from any of the various suitable plastically expandable or self-expanding materials known in the art. Plastically expandable materials that can be used to form the frame 402 include, but are not limited to, stainless steel, biocompatible high-strength alloys (e.g., cobalt-chromium or nickel-cobalt-chromium alloys), polymers, or combinations thereof. In certain embodiments, the frame 402 is fabricated from a nickel-cobalt-chromium-molybdenum alloy such as MP35N® alloy (SPS Technologies, Jenkintown, Pennsylvania), which is equivalent to UNS R30035 alloy (ASTM F562-13, "Standard Specification for Forged 35 Cobalt-35 Nickel-20 Chromium-10 Molybdenum Alloys for Surgical Implant Applications", (UNS R30035), ASTM International, West Conshohocken, PA, 2013, which are incorporated herein by reference). MP35N® alloy / UNS R30035 alloy contains 35% nickel, 35% cobalt, 20% chromium, and 10% molybdenum by weight. Self-expanding materials that may be used to form frame 402 may include, but are not limited to, nickel-titanium alloys (NiTi) such as Nitinol.

[0076] If composed of a plastically expandable material, the frame 402 (and thus the artificial heart valve 400) can be crimped into a radially compressed configuration on a delivery catheter and then expanded in the patient's body by an inflatable balloon or equivalent inflation mechanism. A delivery device having an inflatable balloon for delivering an artificial valve having a plastically expandable frame is disclosed in U.S. Patent Application Publication 2013 / 0030519, which is incorporated herein by reference. Alternatively, if composed of a self-expanding material, the frame 402 (and thus the artificial heart valve 400) can be crimped into a radially compressed configuration and constrained to the compressed configuration by insertion into a delivery catheter sheath or equivalent mechanism. Once advanced to the desired implantation site, the artificial heart valve can be advanced from the delivery sheath, thereby expanding the artificial heart valve to its functional size. Further details of delivery devices that may be used to deliver and implant self-expandable artificial valves (including any of the artificial valves disclosed herein, when the frame is composed of a self-expandable material such as nitinol) are disclosed in U.S. Patent Applications Publications 2014 / 0343670 and 2010 / 0049313, which are incorporated herein by reference.

[0077] In some implementations, the struts 430 of frame 402 are pivotable or bendable relative to each other to allow radial expansion and contraction of frame 102. For example, frame 402 may be formed from a single piece of material (e.g., a metal tube) (e.g., via laser cutting, electroforming, or physical vapor deposition). In other implementations, frame 402 may be constructed by forming individual components (e.g., struts and fasteners of the frame) and then mechanically assembling and connecting the individual components together. For example, instead of the strut structure illustrated in Figures 5A–5E, the frame may have individual diagonally extending struts, pivotably connected to each other by one or more swivel joints along the length of each strut, as described in U.S. Patent Application Publications 2018 / 0153689, 2018 / 0344456, and 2019 / 0060057 (all of which are incorporated herein by reference).

[0078] In Figure 5D, the frame 402 can be formed by multiple circumferentially spaced commissure windows 414. The valve structure 406 can be coupled to the frame 402 by the commissure windows 414. For example, the valve structure 406 may have multiple commissure assemblies 412, each corresponding to one of the commissure windows 414 of the frame 402. In the illustrated embodiments of Figures 5A to 5C, the valve structure 406 includes three valve leaflets 410 (e.g., a tricuspid structure), and the commissure windows 414 are equally spaced along the circumference of the frame 402 at 120-degree intervals (i.e., 0 degrees, 120 degrees, and 240 degrees). However, other spacings and numbers of commissure windows 414 are also possible. For example, in some implementations, the valve structure includes two valve leaflets (e.g., a bicuspid structure), and the commissure windows are located on both sides of the frame (e.g., aligned on the same diameter of the frame).

[0079] In Figures 5A to 5C, the artificial heart valve 400 includes an inner skirt 408 containing one or more sealing layers. The inner skirt 408 may be mounted on the interior of the frame 402 (for example, on the radially inner circumferential wall formed by the lattice structure of the frame's struts). The inner skirt 408 may extend around the entire circumference of the interior of the frame 402, for example, along the axial direction of the frame 402 from a position adjacent to the commissure window 414 to the position of the inlet end 418 of the frame 402, or immediately after it. The inner skirt 408 can function as a sealing member to prevent or at least reduce leakage around the valve (for example, when the valve is placed in the implantation site) and as a mounting surface for fixing a portion of the valve leaflets 410 to the frame 402. For example, the pointed edges of the valve leaflets 410 may be attached to the inner skirt 408 via one or more sutures along the suture line 420. The inner skirt can be attached to selected struts of the frame 402 as shown in Figures 5A and 5C. In some implementations, the valve leaflet 410 may have a reinforcing member (e.g., fabric strip 454) along the inner surface of the pointed edge of the valve leaflet, to which the valve leaflet 410 is attached to the inner skirt 408, as shown in Figure 5B.

[0080] In Figure 5C, the artificial heart valve 400 may also include an outer skirt 404. The outer skirt 404 may be mounted on the outside of the frame 402 (for example, on the radially outer circumferential wall formed by the lattice structure of the frame's supports). The outer skirt 404 may extend around the entire circumference of the outside of the frame 402, for example, extending along the axial direction of the frame from the position of the inlet end 418 of the frame or just after it to about half the axial height of the frame 402. The outer skirt 404 can function as a sealing member by sealing against the tissue of the original valve annulus, and can help reduce paravalvular leakage past the artificial heart valve 400.

[0081] The inner and outer skirts 408, 404 may be mounted to the frame 402 by means of sutures, adhesives, welding, and / or other means for attaching the skirts to the frame. Further details relating to the frame structure, the inner and outer skirts, the technique for assembling the valve leaflets to the inner skirt, and the technique for assembling the skirts onto the frame (which may be employed in valve 400 or any other exemplary valve) are disclosed in U.S. Patent No. 9,393,110, U.S. Patent Application Publication No. 2019 / 0192296, International Publication No. WO / 2020 / 159783, and International Patent Application No. PCT / US2020 / 024559, each of which is incorporated herein by reference.

[0082] The outer skirt 404 may be formed from any of a variety of suitable biocompatible materials, including either various synthetic materials (e.g., polyethylene terephthalate (PET)) or intrinsic tissue (e.g., pericardial tissue). Since the outer skirt 404 does not contain a sealing layer, intrinsic tissue may grow within the outer skirt 404 and invade the leaflets of the valve structure. However, as discussed in detail above, the sealing layer of the inner skirt 408 may act as a barrier against further intrinsic tissue growth on the leaflets, thereby avoiding or at least reducing pannus formation on the leaflets 410 and reducing the associated risk of thrombosis.

[0083] The valve structure 406 may be configured to allow blood flow through the frame 402 in only one direction in order to regulate the flow of blood from the inlet end 418 to the outlet end 416 through the artificial heart valve 400. The valve structure 406 may include, for example, a leaflet assembly formed by a plurality of leaflets 410, each made of a flexible material. The leaflets 410 can transition between an open configuration in which blood flows through the valve 400 via a flow channel formed by the leaflets, and a closed configuration in which the leaflets obstruct blood flow through the valve 400. The leaflets 410 may be made in whole or in part from a biological material, a biocompatible synthetic material, or other similar material. A suitable biological material may be, for example, bovine pericardium (or pericardium from other sources).

[0084] In Figure 5D, each intersection window 414 may be formed within or part of a grid structure formed by axial supports 438 and angled supports 430. The supports 430, 438 of the frame may form rows extending circumferentially around the opening cells 444, 446, 448, 450, with the row of cells 450 closest to the outflow end 416 having a larger open area than the other cells. In the illustrated embodiment of Figure 5D, each intersection window 414 may have a rectangular structure with a central opening defined by a pair of side supports 432 (e.g., mainly extending axially along the frame 402) and a pair of crossbars (e.g., at both ends of the supports 432, mainly extending circumferentially along the frame 402). Other shapes and configurations of the intersection windows 414 are also possible. For example, instead of a rectangular opening, the interlocking window may define an opening that is square, elliptical, square-elliptical, triangular, L-shaped, T-shaped, C-shaped, H-shaped, or any other shape.

[0085] Figure 5E shows an exemplary approach for securing a commissure assembly 412 of a valve structure to a commissure window 414 of an annular frame 402. The commissure assembly 412 may include a first tab portion 428 extending through the window 414 and rotated along the circumferential direction of the frame 402 to form a T-shape. The first tab portion 428 may be wrapped in or at least partially covered by a connecting member 452 (e.g., flexible cloth). The commissure assembly 412 may include a second tab portion 422 folded against the inner surface of each valve leaflet 410, and a third tab portion 424 extending along the circumferential direction of the frame 402 and facing the first tab portion 428. The third tab portion 424 may be connected to the connecting member 452 and / or each of the first tab portions 428 via one or more sutures 426. The second tab portion 422 can form a multilayer structure of the leaflet material just inside the commissure window 414. The multilayer structure is more resistant to bending or articulation than the leaflet portion bending radially inward, thereby the leaflet 410 mainly articulates with the inner edge 455 of the second tab portion 422. The second tab portion 422 can therefore help the leaflet avoid contact with or damage from the frame 402 during the normal operation of the valve structure 406.

[0086] After all three commissure tab assemblies are secured to their respective window frames 414, the lower edges of the leaflets 410 between the commissure assemblies 412 can be sutured to the inner skirt 408. For example, in Figures 5A–5B, each leaflet 410 can be sutured to the inner skirt 408 along the suture line 420, for example, using Ethibond thread. The suture may be an in-and-out suture extending through each leaflet 410, the skirt 408, and an optional reinforcing strip 454. In this way, the lower edges of the leaflets 410 can be secured to the frame 402 via the inner skirt 408. Further details relating to the frame 402, the valve structure 406, and exemplary techniques for connecting the valve structure to the frame are described in U.S. Patent No. 9,393,110, which is incorporated herein by reference.

[0087] The above discussion relating to Figures 5A to 5E identifies a specific configuration of the artificial heart valve 400, but other examples of artificial heart valves disclosed herein or otherwise may include any of the innovations and modifications discussed above with respect to Figures 3A to 4D, or described below with respect to Figures 6A to 21B.

[0088] Figures 6A–6C illustrate various features of another exemplary artificial heart valve 500. Similar to the artificial heart valve 400 shown in Figures 5A–5E, the exemplary artificial heart valve 500 of Figures 6A–6C has an annular frame 402, a valve structure 406 including a plurality of valve leaflets 410, an inner skirt 508 including one or more sealing layers, and an outer skirt 504. Similar to valve 400, the artificial heart valve 500 may be crimped or held in a radially compressed configuration by an implant delivery device (e.g., the delivery device illustrated in Figure 18, or any other delivery device), while the artificial heart valve is routed to the patient's heart through the patient's anatomical structure and then expands to a radially expanded configuration once the artificial heart valve reaches the desired implantation site in the heart. In certain cases, the artificial heart valve 500 can be implanted in other locations in the heart, including within the original mitral valve (e.g., mitral valve 16 in Figure 1), the original pulmonary valve (e.g., pulmonary valve 30 in Figure 1), or the original tricuspid valve (e.g., tricuspid valve 26 in Figure 1), but it can also be implanted within the original aortic annulus.

[0089] However, in contrast to the configurations shown in Figures 5A to 5E, the inner skirt 508 of the valve 500 in Figures 6A to 6C extends along its axial direction from the inlet end 418 to the outlet end 416 on the radially inner surface of the annular frame 402, and the outer skirt 504 includes one or more sealing layers. The extension of the inner skirt 508 to the outlet end 416 may provide additional protection from intrinsic tissue infiltration, which may occur, for example, through a portion of the commissure assembly 412, which is located on the radially outer side of the annular frame and may come into contact with the intrinsic tissue surrounding the patient (e.g., the intrinsic valve leaflets). The outer skirt 504 may extend along its axial direction from the inlet end 418 to a remote intermediate portion from the outlet end 416 on the radially outer surface of the frame 402. In addition to the barrier provided by the sealing layer of the inner skirt 508, the provision of a sealing layer on the outside of the frame 402 (e.g., as part of the outer skirt 504) provides an additional barrier against intrinsic tissue infiltration, thereby further reducing the possibility of pannus formation and the resulting risk of thrombosis.

[0090] Figures 6A and 6B show the inner skirt 508 terminating at the end of the axial support 438, but the inner skirt 508 can also extend along the axial direction of the frame 402 to the apex 460 formed by the angled support 430 at the inlet end 418 of the frame 402 (for example, as shown in Figure 8A). In either configuration, one or more sealing layers of the inner skirt 508 can provide a substantially continuous barrier against tissue ingrafting across the entire inner surface in the radial direction of the annular frame 402. Figures 6A and 6B show the outer skirt 504 terminating at the apex formed by the angled support 430 tangent to the opening cell 444, but the outer skirt can extend along the axial direction of the frame 402 to a position close to the outlet end 416, for example, to a position covering the suture line 420, an adjacent position, and a position exposing the commissure window 414, or a position encompassing the commissure window 414 (for example, as shown in Figure 4) (for example, as shown in Figure 8A).

[0091] The inner and outer skirts 508, 504 may be attached to the frame 402 by means of sutures, adhesives, welding, and / or other means for attaching the skirts to the frame. For example, a portion of the outer skirt 504 may be wrapped around the inlet end 418 of the frame 402 and in contact with the inner skirt 508, and the contact portions of the skirts 504, 508 may be joined together using one or more sutures. Alternatively, or additionally, the inner skirt 508 and the outer skirt 504 may be joined together with the support of the frame 402 trapped between them by, for example, melting or fusing together the portions of the skirts extending through the opening cells 444, 446. Similar to the valve 400, the lower edge of the valve leaflet 410 of the valve 500 may be joined to the inner skirt 508 by one or more sutures along a suture line 420, for example. Further details relating to the inner and outer skirts, techniques for assembling the valve leaflets to the inner skirt, and techniques for assembling the skirts to the frame (which may be employed in valve 500 or other exemplary valves) are disclosed in U.S. Patent No. 9,393,110, U.S. Patent Application Publications 2019 / 0192296 and 2019 / 0365530, International Publication No. WO / 2020 / 159783 and International Patent Application No. PCT / US2020 / 024559, each of which is incorporated herein by reference.

[0092] To allow the commissure assembly 412 of the valve structure 406 to be mounted through the commissure window 414, an opening 520 can be formed in the inner skirt 508 corresponding to the window 414, for example, as shown in Figure 6C. The opening 520 may have dimensions along the circumferential direction of the frame that are slightly larger than the width of the commissure assembly 412 mounted to the window 414. Thus, the first tab portion 428 and the third tab portion 424 of the commissure assembly 412 can be joined to each other using sutures 426 in a manner similar to that shown, for example, in Figure 5E. Alternatively, the opening 520 may have dimensions along the circumferential direction of the frame that are smaller than the width of the commissure assembly 412. For example, the opening in the inner skirt 508 may be slightly smaller than the width of the pair of first tab portions 428 that pass through the window 414. In this configuration, the suture 426 for the first tab portion 428 and the third tab portion 424 may also pass through a portion of the inner skirt 508 adjacent opening 520, or sutures may be provided to separately join each of the first tab portion 428 and the third tab portion 424 to a portion of the inner skirt 508 adjacent opening 520.

[0093] The above discussion relating to Figures 6A to 6C identifies a specific configuration of the artificial heart valve 500, but other examples of artificial heart valves disclosed herein or otherwise may include any of the innovations and modifications discussed above relating to Figures 3A to 5E, or described below relating to Figures 7A to 21B.

[0094] Figures 7A–7C show various features of another exemplary artificial heart valve 600. Similar to the artificial heart valve 500 shown in Figures 6A–6C, the exemplary artificial heart valve 600 in Figures 7A–7C has an annular frame 402, a valve structure 406 including a plurality of valve leaflets 410, an inner skirt 508 including one or more sealing layers, and an outer skirt 604. Similar to valve 500, the artificial heart valve 600 may be crimped or held in a radially compressed configuration by an implant delivery device (e.g., the delivery device shown in Figure 18, or any other delivery device), while the artificial heart valve is routed to the patient's heart through the patient's anatomical structure and then expands to a radially expanded configuration once the artificial heart valve reaches the desired implantation site in the heart. In certain cases, the artificial heart valve 600 can be implanted in other locations in the heart, including within the original mitral valve (e.g., mitral valve 16 in Figure 1), the original pulmonary valve (e.g., pulmonary valve 30 in Figure 1), or the original tricuspid valve (e.g., tricuspid valve 26 in Figure 1), but it can also be implanted within the original aortic annulus.

[0095] However, in contrast to the configurations shown in Figures 6A to 6C, the outer skirt 604 can be formed of a non-airtight material and can extend along the axial direction on the radial outer surface of the frame 402 from the inlet end 418 to the apex formed by the angled support 430 adjacent to the opening cell 446. Alternatively, the outer skirt 604 can also extend along the axial direction of the frame 402 to a position close to the outlet end 416, for example, at a position covering the suture line 420, at a position exposed adjacent to the commissure window 414, or at a position covering the commissure window 414. Since the outer skirt 604 does not include a sealing layer, the original tissue can grow within the outer skirt 404 and invade the leaflets of the valve structure. However, as discussed in detail above, the sealing layer of the inner skirt 508 can act as a barrier against further infiltration of the original tissue on the leaflets, thereby avoiding or at least reducing pannus formation on the leaflets 410 and reducing the associated risk of thrombosis.

[0096] The outer skirt 604 may include at least one soft plush surface oriented radially outward to buffer and seal against the original structure surrounding the valve 600. For example, the outer skirt 604 may be made from any of the fibers of various fabrics, knits, or crochet fabrics, and the radially outward surface is the plush nap or pile of the fabric. Exemplary fibers with pile include velour, velvet, velour, corduroy, terrycloth, fleece, and the like. Alternatively or additionally, the outer skirt 604 may include a nonwoven fabric (e.g., felt) or fiber (e.g., nonwoven cotton fiber). Alternatively or additionally, the outer skirt 604 may be formed as or constructed from a porous or spongy material, such as any of the various suitable polymer foam materials or woven fabrics such as woven PET. In some implementations, the material selected for the outer skirt 604 may contribute to improved compressibility and shape memory properties of the outer skirt. For example, a pile layer can be compressed under load (e.g., when in contact with natural tissue, other implants, etc.), but otherwise conform to return to its original size and / or shape when the load is removed.

[0097] The outer skirt 604 can be secured to the frame 402 and / or the inner skirt 508 using a variety of techniques and configurations. For example, as shown in Figures 7B-7C, the first edge 606 of the outer skirt 604 can be wrapped around the inlet end 418 of the frame 402, and the first edge 606 of the outer skirt 604 can be attached to the contact edge 610 of the inner skirt 508 and / or frame 402 by one or more sutures 608 and / or adhesive. Instead of, or in addition to, sutures, the outer skirt 604 can be attached to the inner skirt 508 by, for example, ultrasonic welding or any other bonding means. Alternatively, the edge of the inner skirt 508 may be wrapped around the radially outer surface of the outer skirt 604 and the inlet end 418 of the frame 402 that contacts the contact portion of the skirt 508, 604, which is attached together using one or more sutures, adhesive, welding, or any other bonding means. Further details relating to the outer skirt and techniques for assembling the skirt onto the frame (which may be employed in valve 600 or any other exemplary valve) are disclosed in U.S. Patent No. 9,393,110, U.S. Patent Application Publications 2019 / 0192296 and 2019 / 0365530, International Publication No. WO / 2020 / 159783, and International Patent Application No. PCT / US2020 / 024559, each of which is incorporated herein by reference.

[0098] The above discussion relating to Figures 7A to 7C identifies a specific configuration of the artificial heart valve 600, but other examples of artificial heart valves disclosed herein or otherwise may include any of the innovations and modifications discussed above relating to Figures 3A to 6C, or described below relating to Figures 8A to 21B.

[0099] Figures 8A–8B illustrate the features of another exemplary artificial heart valve 700. Similar to the artificial heart valve 500 shown in Figures 6A–6C, the exemplary artificial heart valve 700 in Figures 8A–8B has an annular frame 402, a valve structure 406 including a plurality of valve leaflets 410, an inner skirt 708 including one or more sealing layers, and an outer skirt 704 including one or more sealing layers. Similar to valve 500, the artificial heart valve 700 may be crimped or held in a radially compressed configuration by an implant delivery device (e.g., the delivery device shown in Figure 18, or any other delivery device), while the artificial heart valve is routed to the patient's heart through the patient's anatomical structure and then expands to a radially expanded configuration once the artificial heart valve reaches the desired implantation site in the heart. In certain cases, the artificial heart valve 700 can be implanted in other locations in the heart, including within the original aortic valve (e.g., the aortic valve 20 in Figure 1), the original pulmonary valve (e.g., the pulmonary valve 30 in Figure 1), or the original tricuspid valve (e.g., the tricuspid valve 26 in Figure 1), but it can also be implanted within the original mitral valve.

[0100] However, in contrast to the configurations shown in Figures 6A-6C, the inner skirt 708 of the valve 700 in Figures 8A-8B extends from the inlet end 418 to the outlet end 416 over the entire radially inner surface of the annular frame 402, and the outer skirt 704 extends from the inlet end 418 to the outlet end over the entire radially outer surface of the annular frame 402. In some implementations, in addition to one or more sealing layers therein, the outer skirt 704 may further include a radially outer layer that provides a soft plush surface and is formed from a nonwoven fabric or fiber and / or from a porous or spongy material. Thus, the outer skirt 704 can retain buffering and sealing functions against the intrinsic tissue surrounding the valve (similar to the above for the outer skirt 604 in Figures 7A-7C) and at the same time provide a barrier against tissue infestation (similar to the above for the outer skirt 504 in Figures 6A-6C).

[0101] Additionally, or alternatively, the radially lateral layer may be designed and / or configured to prevent paravalvular leakage between the prosthetic valve 700 and the original valve in order to protect the original anatomical structure (e.g., to allow the original valve leaflets to smoothly join to the valve) and / or to promote tissue endografting (e.g., for when the valve frame is smaller than the corresponding original annulus into which it is implanted). While such radially lateral layers of the outer skirt 704 may allow endografting, the sealing layer of the outer skirt 704 acts as a barrier against further endografting. Furthermore, by extending the sealing layers of the inner skirt 708 and outer skirt 704 across the entire inner and outer surfaces of the frame, potential pathways for tissue endografting can be eliminated or at least further reduced, thereby further reducing the possibility of pannus formation and the resulting risk of thrombosis.

[0102] In some embodiments, the inlet protection cap 706 may be formed from or positioned on the inner skirt 708 and / or the outer skirt 704 at the inlet end 418 of the valve 700, and / or the outlet protection cap 702 may be formed from or positioned on the inner skirt 708 and / or the outer skirt 704 at the outlet end 416 of the valve 700. When formed from the inner or outer skirt, the protection caps 702, 706 may be formed from the same material as one or more layers of the constituent skirt. For example, the protection caps 702 and / or 706 may be extensions of the sealing layer of the outer skirt 704, which is wrapped around each end of the annular frame 402. Alternatively, when formed separately and positioned on the inner or outer skirt, the protection caps 702, 706 may include another sealing layer that acts as an additional barrier against tissue endoplasia, for example. Alternatively, when formed separately on the inner or outer skirt and positioned thereon, the protective caps 702, 706 may include a biocompatible thermoplastic polymer such as PET, nylon, or ePTFE, or other suitable intrinsic or synthetic fibers, or a soft monolithic material. In such configurations, the sealing layers of the inner and outer skirts may act to separate the protective caps 702, 706 otherwise, thereby preventing any tissue grafts from propagating to the leaflets of the valve structure 406.

[0103] The inner and outer skirts 708, 704 may be joined to the frame 402 by means of sutures, adhesives, welding, and / or other means for attaching the skirts to the frame. For example, each of the inner skirt 708 and the outer skirt 704 may be sutured to face the support of the frame 402. Alternatively or additionally, the inner skirt 708 and the outer skirt 704 may be joined together with the support of the frame 402 captured between them, for example, by suturing them together, or by melting or fusing together the portions of the skirts extending through the opening cells 444-450 of the frame. Similar to the valve 400, the lower edge of the valve leaflet 410 of the valve 500 may be joined to the inner skirt 508 by one or more sutures along the suture line 420. Further details relating to the structure of the outer skirt, the inlet / outlet protection portion, and the technique for assembling the skirt to the frame (which may be employed in valve 700 or any other exemplary valve) are disclosed in U.S. Patent Nos. 9,393,110 and 10,195,025, U.S. Patent Application Publications 2018 / 0206982, 2019 / 0192296, 2019 / 0365530, 2019 / 0374337, and 2019 / 0046314, International Publication No. WO / 2020 / 159783, and International Patent Application Nos. PCT / US2020 / 024559 and PCT / US2020 / 036577, each of which is incorporated herein by reference.

[0104] To ensure that the commissure assembly 412 of the valve structure 406 is coupled to the commissure window of the frame 402, an opening may be formed in at least the inner skirt 708 and optionally in the outer skirt 704 at a position corresponding to the window 414. Alternatively, the outer skirt 704 may be attached to the valve frame 402 after the commissure assembly 412 has been attached to each window 414 of the frame 402, in order to avoid forming any openings in the commissure assembly of the outer skirt 704. The commissure assembly 412 may be attached to the window 414 in another manner, similar to that described above for Figures 5E and 6C, and the valve leaflets may be sutured to the inner skirt 708 in the same manner as described above for Figures 5A and 5B.

[0105] The above discussion relating to Figures 8A to 8B identifies a specific configuration of the artificial heart valve 700, but other examples of artificial heart valves disclosed herein or otherwise may include any of the innovations and modifications discussed above with respect to Figures 3A to 7C, or described below with respect to Figures 9A to 21B.

[0106] Figures 9A–9B illustrate the features of another exemplary artificial heart valve 800. Similar to the artificial heart valve 700 shown in Figures 8A–8B, the artificial heart valve 800 of Figures 9A–9B has an annular frame 402, a valve structure 406 including a plurality of valve leaflets 410, and one or more sealing layers. Similar to valve 700, the artificial heart valve 800 may be crimped or held in a radially compressed configuration by an implant delivery device (e.g., the delivery device shown in Figure 18, or any other delivery device), while the artificial heart valve is routed to the patient's heart through the patient's anatomical structure and then expands to a radially expanded configuration once the artificial heart valve reaches the desired implantation site in the heart. In certain cases, the artificial heart valve 800 can be implanted in other locations in the heart, including within the original aortic valve (e.g., the aortic valve 20 in Figure 1), the original pulmonary valve (e.g., the pulmonary valve 30 in Figure 1), or the original tricuspid valve (e.g., the tricuspid valve 26 in Figure 1), but it can also be implanted within the original mitral valve.

[0107] However, in contrast to the configurations shown in Figures 8A and 8B, the inner and outer skirts are replaced by an inclusion layer 804 comprising one or more sealing layers. The inclusion layer 804 fills the open cells 444-450 of the frame 402, surrounds the pillars 430 and 438 of the frame 402, and the inclusion layer 804 encloses the entire annular frame 402 on all sides, thereby enclosing the annular frame 402 within the layer 804. The inclusion layer 804 forms a radially inner surface that functions as an airtight inner skirt and a radially outer surface that functions as an airtight outer skirt. Thus, the inclusion layer 804 provides both internal and external barriers to tissue endoplasia of the frame 402, and therefore reduces the possibility of pannus formation.

[0108] The encapsulation layer 804 can be formed by pre-forming sublayers, placing the sublayers on both sides of the frame 402, and then joining the sublayers to embed the annular frame 402 within them. For example, the first extruded sublayer may be placed on the radially inner surface of the annular frame 402, and the second extruded sublayer may be placed on the radially outer surface of the annular frame 402. The first and second sublayers can then be joined to the supports of the frame 402 between them, for example, by fusion, melting, welding, etc. Alternatively, the encapsulation layer 804, or a portion thereof, can be formed directly on the frame, for example, by dip coating, spray coating, electric spinning, or similar methods. In addition to providing a barrier to tissue endografting, encapsulating the encapsulation layer 804 can avoid or at least reduce the time-consuming assembly associated with suturing the skirt to the annular frame.

[0109] In some implementations, a separate outer skirt may be provided in addition to the encapsulation layer 804. For example, the separate outer skirt may be positioned on the radially outer surface of the encapsulation layer 804 and bonded to it (e.g., by sutures or other arbitrary bonding means). Similar to the outer skirt 604 in Figures 7A-7C, the separate outer skirt bonded to the encapsulation layer 804 may provide a soft, plush surface and include a radially outer layer formed from a nonwoven fabric or fiber and / or from a porous or spongy material. The separate outer skirt can provide a buffer and seal to the intrinsic tissue around the valve, while the encapsulation layer 804 acts as a barrier to prevent tissue infiltration from reaching the valve leaflets 410 of the valve membrane structure 406.

[0110] In some implementations, a separate inner skirt or scrim layer may be provided in addition to the encapsulation layer 804. For example, the separate inner skirt may be positioned on the radially inner surface of the encapsulation layer 804 and bonded to it (e.g., by sutures or other arbitrary bonding means). Alternatively or additionally, a scrim layer (e.g., woven fabric or cloth) may be positioned on the radially inner surface of the annular frame 402 before encapsulation, and the encapsulation layer 804 may surround both the annular frame 402 and the scrim layer. The separate inner skirt and / or scrim layer can increase the suture retention strength for the attachment of the valve leaflets 410 to it, while the encapsulation layer 804 acts as a barrier to prevent tissue ingrafting from reaching the valve leaflets 410 of the valve structure 406.

[0111] An opening may be created within the encapsulation layer 804 at a position corresponding to the window 414, so that the commissar assembly 412 of the valve structure 406 can pass through and be attached to the commissar window 414. In some implementations, the opening is created after the encapsulation layer 804 is formed on the annular frame 402, for example by cutting the layer 804 in the region surrounding the window 414 and / or by puncturing through the layer 804 covering the opening of the window 414. Alternatively, in some implementations, the opening may be created during the formation of the encapsulation layer 804 on the annular frame 402, for example by covering the window 414 during the encapsulation process, by inserting a temporary sacrificial member into the window opening during the encapsulation process, or otherwise by preventing material from being on and obstructing the window 414 during the encapsulation process. Alternatively, in some implementations, the opening may be created in one or more of the sublayers used to form the encapsulation layer 804 before the encapsulation of the annular frame 402. The commissure assembly 412 can be attached to the window 414 in an alternative manner, similar to that described above with respect to Figures 5E and 6C, and the valve leaflets can be sutured to the encapsulation layer 804 in the same manner as described above with respect to Figures 5A and 5B.

[0112] Further details relating to the replacement of the inner or outer skirt using an encapsulation layer, the materials for the encapsulation layer, and techniques for encapsulation and attachment of the valve leaflets to the encapsulation layer (which may be employed in valve 800 or any other exemplary valve) can be found in U.S. Patent No. 8,945,209 and U.S. Patent Application Publication No. 2020 / 0155306, both of which are incorporated in whole by reference. The above discussion relating to Figures 9A–9B identifies a particular configuration of the artificial heart valve 800, but other examples of artificial heart valves disclosed herein or otherwise may include any of the innovations and variations discussed above relating to Figures 3A–8B or described below relating to Figures 10A–21B.

[0113] Figures 10A–10C illustrate various features of another exemplary artificial heart valve 900 having a dual-frame structure and primarily intended for implantation into a genuine mitral valve or genuine tricuspid valve. First, Figure 10C shows a cross-sectional view of the artificial heart valve 900 in an extended configuration. The artificial valve 900 may include an inner frame 908, an outer frame 902, a valve structure 918 consisting of multiple valve leaflets 922, and one or more skirts such as an outer skirt 904 and an inner skirt 906. The inner frame may have a substantially spherical shape such that the diameter of the region near the inlet end 916 and the outlet end 914 is smaller than the diameter of the intermediate region between the inlet end region and the outlet end region. The outer frame 902 can be coupled to the inner frame 908 using any suitable fasteners and / or techniques. Alternatively, the inner frame 908 and the outer frame 902 may be formed as a single or monolithic structure.

[0114] The valve structure 918 may include a plurality of leaflets 922, for example, three leaflets joined at a commissure. The valve structure 918 may also include one or more intermediate components 912 (which may be made of fiber) positioned between a portion or all of the leaflets 922 and the inner frame 908. Thus, at least a portion of each leaflet 922 may be joined to the inner frame 908 via the intermediate components 912, and as a result, parts or all of each portion of the leaflet 922 at the commissure and / or the pointed edge of the leaflet 922 are not directly joined to the inner frame 908. Rather, the leaflets 922 may be considered to be indirectly joined to the inner frame 908 or to be floating within the inner frame 908. For example, parts or all of each portion of the leaflet 922 adjacent to the commissure and / or the pointed edge of the leaflet 922 may be spaced radially inward from the inner surface of the inner frame. Such configurations can allow for greater flexibility in the selection of the valve frame's geometric shape (e.g., a non-cylindrical frame that better fits the original valve ring) and / or the size of the valve frame (e.g., a frame with a larger diameter than that of the valve membrane structure).

[0115] The outer skirt 904 of the artificial heart valve 900 may be coupled to the inner frame 908 and / or the outer frame 902. In the illustrated embodiment of Figure 10C, the outer skirt 904 is positioned and fixed to the outside of the outer frame 902. The outer skirt 904 may also be fixed to a portion of the valve structure 918, for example, a portion of the intermediate component 912 near the inlet end 916. The inner skirt 906 of the artificial heart valve 900 may be coupled to the valve structure 918 and the outer skirt 904. In the illustrated embodiment of Figure 10C, the first end of the inner skirt 906 is coupled to the valve structure 918 along the portion adjacent to the inner frame 908, and the second end of the inner skirt 906 is coupled to the lower region of the outer skirt 904. Thus, a smooth surface may be formed beneath each of the valve leaflets 922, which may beneficially enhance hemodynamics while reducing the area of ​​retention.

[0116] The outer frame 902 may include multiple struts, at least a portion of which form each cell 924. Any number and configuration of struts can be used, such as oval, egg-shaped, rounded polygonal, teardrop, chevron, diamond, curved, or any other shape formed by the undulating strut rings. The outer frame 902 may be used to engage with the original annulus, the original valve leaflets, or any other tissue or body cavity, while spacing the inflow end 916 of the valve 900 from the heart or blood vessel wall. The inner frame 908 may include one or more anchor projections 910 which may be configured to contact or engage with the original mitral valve annulus on the ventricular side, tissue beyond the original annulus on the ventricular side, the original valve leaflets on the ventricular side, and / or other tissue at or around the implant site during one or more stages of the cardiac cycle, such as systole and / or diastole. In certain embodiments, the anchor projection 910 may extend behind the original valve leaflets (e.g., the original mitral valve leaflets or the original tricuspid valve leaflets). When positioned within the original mitral valve (or tricuspid valve), the anchor projection 910 can advantageously eliminate, inhibit, or limit the movement of the implanted prosthetic valve 900 when subjected to forces directed, for example, from the outflow end 914 to the inflow end 916 during systole.

[0117] The intermediate component 912, the inner skirt 906, and the outer skirt 904 may each include one or more sealing layers. For example, at least the intermediate component 912 includes one or more sealing layers, while the inner skirt 906 and the outer skirt 904 are formed of an impermeable but porous material. In such a configuration, the original tissue can grow within the outer and inner skirts, but further infiltration of the original tissue on the valve leaflet 922 is blocked by the sealing layer of the intermediate component 912 to which the valve leaflet 922 is attached. Alternatively, at least the inner skirt 906 and the intermediate component 912 include one or more sealing layers, thereby providing multiple barriers against the intrinsic tissue infiltration. In yet another alternative, each of the intermediate component 912, the inner skirt 906, and the outer skirt 904 includes one or more sealing layers, thereby further insulating the valve leaflet 922 from potential infiltration of the original tissue and potential pannus formation. In some implementations, other components of the artificial valve 900 that come into contact with the original tissue may include one or more sealing layers, such as part or all of the anchor projection 910. In some implementations, the sealing layers of the intermediate component 912, inner skirt 906, outer skirt 904, and / or anchor projection 910 are formed separately (e.g., by extrusion, casting, etc.) and then joined to the inner frame 908 or outer frame 902 (e.g., by suturing, welding, fusion, etc.). Alternatively or additionally, the sealing layers of the intermediate component 912, inner skirt 906, outer skirt 904, and / or anchor projection 910 may be formed directly on the inner frame 908 or outer frame 902, for example, by coating or encapsulation (e.g., electrospinning, dip coating, or spray coating).

[0118] In certain cases, the artificial heart valve 900 can be implanted in other locations of the heart, including within the original aortic valve (e.g., the aortic valve 20 in Figure 1), the original pulmonary valve (e.g., the pulmonary valve 30 in Figure 1), or the original tricuspid valve (e.g., the tricuspid valve 26 in Figure 1), but it can also be implanted within the original mitral valve. Further details relating to the construction and operation of the medial and lateral frames, the configuration of the intermediate portion and the medial and lateral skirts, implantation, and the delivery system for implantation (which may be employed in valve 900 or any other exemplary valve) are disclosed in U.S. Patent No. 10,350,062 and U.S. Patent Application Publications 2018 / 0055629 and 2019 / 0262129, respectively, which are incorporated herein by reference.

[0119] The above discussion relating to Figures 10A to 10C identifies a specific configuration of the artificial heart valve 900, but other examples of artificial heart valves disclosed herein or otherwise may include any of the innovations and modifications discussed above relating to Figures 3A to 9B, or described below relating to Figures 11A to 21B.

[0120] Figures 11A and 11B illustrate various features of another exemplary artificial heart valve, in particular showing a surgical valve 1000 having components including one or more sealing layers. The surgical valve 1000 generally includes a wire morphology assembly 1002, a sewing ring assembly 1004, a stent assembly 1006, and a valve structure 1008. The valve structure 1008 may include three valve leaflets 1010 in a tricuspid arrangement. The wire morphology assembly 1002 may include a wire morphology, a fabric cover surrounding the wire morphology, and one or more sealing layers surrounding the fabric cover. The sealing layers include one or more sealing layers, thereby providing a barrier against tissue infiltration into the wire morphology assembly 1002. The wire form may be formed from one or more wire pieces such as stainless steel or a Co-Cr-Ni alloy such as Elgiloy (e.g., 39-41% cobalt, 19-21% chromium, 14-16% nickel, 11.3-20.5% iron, 6-8% molybdenum, and 1.5-2.5% manganese). The fabric cover may be formed from any biocompatible fiber, such as PET. The fabric cover comprises elongated strips of material having opposing ends that come together to form a butt joint. The opposing longitudinal edges of the fabric cover can then be wrapped around the wire form and joined together (e.g., via stitching). Alternatively, an inclusion layer formed around the fabric cover can be used to secure the fabric cover to the wire form instead of sewing the edges of the fabric cover separately.

[0121] The sewing ring assembly 1004 may include a sewing ring insert, a second fabric cover (e.g., PET) surrounding the insert, and one or more second inclusion layers surrounding the second fabric cover. The second inclusion layers include one or more sealing layers, thereby providing a barrier against tissue infiltration into the sewing ring assembly 1004. The sewing ring insert may have a conventional structure and may be made from a suture-permeable material for suturing the valve to the original valve annulus. For example, the sewing ring insert may be formed from a silicone-based material, although other suture-permeable materials may be used. Similar to the wire morphological assembly 1002, the second fabric cover may be fixed to the sewing ring insert using a second inclusion layer formed around the second fabric cover, instead of sewing the edges of the fabric cover separately.

[0122] The stent assembly 1006 may include an inner support and an outer band positioned around the inner support. The inner support may include cup portions extending between upright commissar portions. The outer band can be molded to conform to the curvature of the pointed portion of the inner support. For example, the inner support may be formed from a polymer material such as polyester, and the outer band may be formed from a relatively rigid metal such as a Co-Cr-Ni alloy (e.g., Elgiloy) or stainless steel. A third fabric cover may completely cover the inner support and the outer band. One or more third encapsulation layers may surround the third fabric cover. The third encapsulation layer includes one or more sealing layers, thereby providing a barrier against tissue infiltration into the stent assembly 1006. Similar to the wire morphological assembly 1002, the third fabric cover may be secured to the inner support and the outer band using a third encapsulation layer formed around the third fabric cover, instead of sewing the edges of the fabric cover separately.

[0123] Once the wire-shaped assembly 1002, the sewing ring assembly 1004, and the stent assembly 1006 are formed, these components can be assembled together with the valve leaflets 1010 to form the assembled valve 1000. For example, three valve leaflets 1010 may be positioned together with the wire-shaped assembly 1002. Each valve leaflet 1010 may include two tabs positioned on the opposing ends of the leaflet. Each tab can be aligned with the tabs of adjacent valve leaflets to form a commissure assembly 1060. The lower edge of each valve leaflet 1010 extending between the tabs can be sutured to the wire-shaped assembly 1002, for example, to an encapsulation layer and / or its fabric cover. Each commissure assembly 1060 can be inserted between adjacent upright extensions 1064 and wrapped around each commissure post 1066 of the stent assembly 1006. The tabs of the commissure assembly 1060 may be sutured together or otherwise joined to each other and / or to the commissure post 1066.

[0124] Next, the wire morphology assembly 1002 may be fixed to the upper inner portion of the stent assembly 1006, and the sewing ring assembly 1004 may be fixed to the lower outer portion of the stent assembly 1006. The stent assembly 1006 can be fitted or engaged with the corresponding contour of the wire morphology assembly 1002. Thus, the commissar post 1066 and the pointed portion extending between the commissar posts may be sized and shaped to correspond to the curvature of the wire morphology assembly. The wire morphology assembly 1002 may be fixed to the stent assembly 1006 via sutures extending through the fabric cover of the wire morphology assembly and the openings of the inner support and outer band of the stent assembly 1006. The sewing ring assembly 1004 may be fixed to the stent assembly 1006 via the sewing ring assembly and sutures extending through the openings of the inner support and outer band of the stent assembly. The protective cover 1062 is positioned over the exposed portion of the commissure assembly 1060 (e.g., the tab of the valve leaflet 1010) and can be secured in place by sutures. In some implementations, the cover 1062 includes one or more sealing layers.

[0125] Similar to the other embodiments described above, the provision of sealing layers in the wire-shaped assembly 1002, the sewing ring assembly 1004, and the stent assembly 1006 provides a barrier against tissue infiltration reaching the valve leaflet 1010 of the valve structure 1008. As a result, the incidence of pannus formation on the valve leaflet 1010 can be reduced, and the risk of thrombosis resulting from such pannus can be reduced. In some implementations, some parts of the assembly or its components may be designed to promote tissue infiltration, while the remaining assembly or components include sealing layers that prevent tissue infiltration from reaching the valve leaflet 1010. For example, the sewing ring assembly 1004 may be constructed without a sealing layer to allow tissue infiltration, while the wire-shaped assembly 1002 and stent assembly 1006, which would otherwise be directly coupled to the part of the valve leaflet 1010, may have their respective sealing layers that inhibit further tissue propagation from the sewing ring assembly 1004 to the valve leaflet 1010. Further details relating to various assemblies and the construction of their sealing layers (which may be employed in valve 1000 or any other exemplary valve) are disclosed in U.S. Patent Application Publication No. 2020 / 0155306 and are incorporated herein by reference.

[0126] The above discussion relating to Figures 11A to 11B identifies a specific configuration of the artificial heart valve 1000, but other examples of artificial heart valves disclosed herein or otherwise may include any of the innovations and modifications discussed above relating to Figures 3A to 10B, or described below relating to Figures 12A to 21B. Furthermore, although specific examples of artificial heart valves are described above, the provision of one or more sealing layers to prevent the intrusion of tissue endothelium into the valve leaflets is applicable to a wide variety of artificial valves. For example, an existing inner or outer skirt of an artificial heart valve disclosed in any of U.S. Patent Nos. 6,730,118, 7,101,396, 7,393,360, 7,510,575, 7,993,394, 8,652,202, 8,992,608, 9,339,382, and 10,603,165, U.S. Patent Application Publication Nos. 2018 / 0325665, 2018 / 0344456, and 2019 / 0060057, and International Publication No. WO / 2020 / 081893 (all of which are incorporated herein by reference) can be replaced or at least complemented by one or more sealing layers. Alternatively or additionally, U.S. Patent Nos. 6,730,118, 7,101,396, 7,393,360, 7,510,575, 7,993,394, 8,652,202, 8,992,608, 9,339,382, and 10,603,165, U.S. Patent Application Publication Nos. 2018 / 0325665, 2018 / 0 Any of the artificial heart valves disclosed in Publication No. 344456, and Publication No. 2019 / 0060057, and International Publication No. WO / 2020 / 081893 may be modified in accordance with the teachings of this disclosure to include one or more sealing layers between the surrounding original tissue and the attachment point of the artificial heart valve leaflets, for example, between at least the radially inner surface of the valve frame and the leaflets.

[0127] Low opening pressure valve membrane structure

[0128] As mentioned above with respect to Figure 1, an artificial heart valve implanted in the aortic location (e.g., within the original aortic valve 20) can typically experience relatively high pressure gradients (e.g., drive pressure of approximately 125 mmHg). In contrast, an artificial heart valve implanted in the lung location (e.g., within the original pulmonary valve 30), tricuspid location (e.g., within the original tricuspid valve 26), mitral valve location (e.g., within the original mitral valve 16), or in a blood vessel leading to a cardiac chamber (e.g., within the inferior vena cava 36 or superior vena cava 34) can typically encounter relatively low pressure gradients (e.g., drive pressure of approximately 30 mmHg or less).

[0129] For example, Figures 12A and 12B show an exemplary artificial heart valve 1100 implanted between the leaflets 40 of the original mitral valve. The artificial heart valve 1100 may have a valve structure 1122 including a frame 1102, an inner skirt 1114, an outer skirt 1104, and a plurality of leaflets 1106. The leaflets 1106 may be attached to the frame via commissure assemblies 1112 attached to each window of the frame 1102, as described above, and via pointed edges (e.g., via one or more sutures) attached to the inner skirt 1114. One or more protective caps or cover layers 1116 may be positioned on the struts of the frame 1102 at their inlet end 1124 and / or outlet end 1126, as shown in Figure 12A. Accordingly, the artificial heart valve 1100 may have a configuration similar to that described in any of U.S. Patent Applications Publication Nos. 2018 / 0206982, 2019 / 0192296, and 2019 / 0374337, which are incorporated herein by reference and for further details. Alternatively or additionally, the artificial heart valve 1100 may have a configuration similar to that described in U.S. Patent No. 10,350,062 and U.S. Patent Applications Publication Nos. 2018 / 0055629 and 2019 / 0262129, each of which is incorporated herein by reference.

[0130] Since the movement of the valve leaflets of the valve structure is driven by the pressure across the valve, such low-pressure implant positions can lead to abnormal leaflet movement, such as stasis and / or delayed or slow opening of the valve structure, which can contribute to chronic thrombosis and / or thickening of the leaflets. Under low-pressure flow conditions associated with such implant positions, the new cavity region 1118 formed between the leaflet 1106 and the annular frame 1102 may be subjected to insufficient flushing, thereby making the valve structure 1122 more susceptible to thrombus formation 1120, as shown in Figure 12B.

[0131] Therefore, in some implementations, the valve structure of the artificial heart valve can be modified to facilitate the transition of the valve leaflets between open and closed configurations and to promote proper irrigation of the new sinus region when implanted in a low-pressure position. In some implementations, the shape of the valve leaflets can be modified, for example, the shape and arrangement of the curved pointed edge that connects to the valve frame via the inner skirt, relative to the leaflet tabs that form the commissure assembly attached to each window of the valve frame. In some implementations, the suture line used to attach the pointed edge of the valve leaflet to the inner skirt extends to a substantial location on or near the commissure assembly to which it is attached. In some implementations, the shape of the curved pointed edge can be made shallower than conventional leaflet designs, for example, to promote irrigation of the new sinus region.

[0132] For example, Figures 13A to 13C show an exemplary embodiment of an artificial heart valve having a modified valve structure including a plurality of valve leaflets 1200. The valve leaflets 1200 of the valve structure may be made in whole or in part from a biological material, a biocompatible synthetic material, or other such material. A preferred biological material may be, for example, bovine pericardium (or pericardium from other sources). As shown in Figure 13A, at the free edge (or joint edge) (upper edge in the figure) of the valve leaflet 1200, a first portion 1204 may extend between a pair of tabs 1208 (also referred to herein as valve leaflet tabs or commissure stubs) at both ends of the valve leaflet 1200 with respect to the centerline 1202 of the first portion 1204. As used herein, “upper” and “lower” may be relative to the central longitudinal axis of the artificial heart valve when the valve structure is mounted and coupled to the frame 1302, with the upper being closer to the outflow end of the valve and the lower being closer to the inflow end of the valve. The first portion 1204 defines a first edge 1206 (also called the upper edge) which may extend between the tabs 1208. Each tab 1208 may have at least an outer edge 1210 and a base edge 1212. In some implementations, the outer edges 1210 of the tabs 1208 are substantially parallel to each other, for example, both edges 1210 extend along a direction 1226. In some implementations, the outer edges 1210 (and direction 1226) may be parallel to the centerline 1202 of the first portion 1204.

[0133] At the lower edge of the valve leaflet 1200, a second portion 1214 (also referred to herein as a pointed edge) is provided on the side surface of the first portion opposite to the first edge portion 1206. The second portion 1214 can define a pointed edge 1216 that extends between the base ends 1212 of the tab 1208 and curves along its entire length (or substantially along its entire length) between the base edges 1212 of the tab 1208. Thus, the curvature of the pointed edge 1216 can continue to a substantial position at each base edge 1212 of the tab 1208, or to an adjacent position 1222, as shown in Figure 13A. The curvature of the pointed edge 1216 can also be such that the tangent 1224 of the pointed edge 1216 at position 1222 is substantially parallel to the outer edge 1210 of the tab 1208 (for example, parallel to direction 1226). Conversely, the curvature of the pointed edge 1216 may be such that the fold line at any other position along the pointed edge other than 1222 is not parallel to the outer edge 1210 of the tab 1208 (for example, the fold line intersects direction 1226). In some implementations, the curvature of the pointed edge 1216 may define a vertex 1230 that may coincide with the center line 1202 of the first portion 1204.

[0134] In some implementations, the second portion 1214 may have a semi-elliptical or semi-elliptical shape, with a pointed edge 1216 following a curve defined by a semi-elliptical or semi-elliptical shape. The semi-elliptical or semi-elliptical shape may lie on the major axis 1228 (where the foci of the ellipse 1218 are located), substantially parallel to the base edge 1212 of the tab 1208 and / or substantially perpendicular to the centerline 1202 of the first portion 1204. In some implementations, the major axis 1228 substantially coincides with the base edge 1212, as shown in Figure 13A.

[0135] The tabs 1208 of adjacent valve leaflets 1200 may be paired together to form a commissure assembly 1304, which is coupled (directly or indirectly) to the respective commissure windows 1312 of the frame 1302, as shown in Figure 13B. For example, the coupling of the commissure assembly to the frame window is as shown in Figure 5E, or separately described in U.S. Patent No. 9,393,110, incorporated by the above reference. The outer edge 1210 of the tab 1208 may therefore be located outside the valve frame 1302 and positioned to extend along a direction substantially parallel to the axial direction of the frame 1302. In some implementations, the suture line 1220 used to attach the second portion 1214 of each valve leaflet 1200 to the inner skirt 1314 may extend to a substantial position or adjacent position 1324 on the commissure assembly 1304 to which it is attached (e.g., the base edge 1212 of the corresponding tab 1208). In some implementations, the presence of the struts 1308 of the frame 1302 and / or the crossbar 1306 of the window 1312 may cause position 1324 to be spaced away from the base edge 1212 along the axial direction of the frame 1302, for example, to allow access during suturing of the valve leaflet 1200 to the inner skirt 1314 and / or to avoid the area where the inner skirt 1314 is sutured to the struts 1308 of the frame 1302. Nevertheless, it is preferable that the suture line position 1324 be as close to the base edge 1212 as possible.

[0136] The combination of the semi-elliptical or semi-elliptical shape of the second portion 1214, the parallel arrangement of the outer edge 1210 of the tab 1208 and the tangent 1224 of the pointed edge 1216, and the continuous suture line 1220 extending (or extending as close as possible) to the base edge 1212 of the tab 1208, allows the valve structure formed by the leaflets to transition more easily between open and closed configurations, thereby avoiding abnormal leaflet movement at low-pressure gradient implant locations. Furthermore, the relatively shallow new cavity region generated by the semi-elliptical or semi-elliptical shape of the second portion 1214 allows for more thorough cleaning of the new cavity, thereby minimizing the risk of thrombus formation within it. In some implementations, the shape of the leaflets 1200 described above and their attachment to the frame 1302 allows the valve structure to have a larger diameter outlet in the open configuration than that provided by conventional valve structures using the same annular frame. In the open configuration, the valve leaflets of the valve structure may be positioned near the radially inner surface of the frame, such that the centerline of the first portion is substantially parallel to the axial direction of the frame. Exemplary artificial heart valve with low-opening pressure valve structure

[0137] Figures 14A–14E illustrate various features of an exemplary artificial heart valve 1400 having a low-opening pressure valve structure. The artificial heart valve 1400 may be crimped or held by an implant delivery device in a radially compressed configuration, or the artificial heart valve may be routed to the patient's heart through the patient's anatomical structure, and then expanded to a radially expanded configuration after reaching the desired implantation site in the heart. In certain embodiments, the artificial heart valve 1400 may be implanted in the original pulmonary valve (e.g., pulmonary valve 30 in Figure 1), the original tricuspid valve (e.g., tricuspid valve 26 in Figure 1), or in one of the cardiac chambers or in blood vessels leading from them, including in a docking station (e.g., docking station 1600 in Figures 16A–16B), or in the original mitral valve (e.g., mitral valve 16 in Figure 1). For implantation within the original mitral or tricuspid valve, in some implementations, the artificial heart valve 1400 can be implanted within a docking station (e.g., docking station 1900 in Figures 19-21B) that is implanted within the original valve. The artificial heart valve 1400 can be implanted using any known delivery device, for example, the delivery device shown in Figure 18.

[0138] The artificial heart valve 1400 may include an annular stent or frame 402 having a first axial end 1416 and a second axial end 1418. In the illustrated example, the first axial end 1416 may be the outflow end, and the second axial end 1418 may be the inflow end. The outflow end 1416 is the nearest end of the artificial valve when attached to a delivery device for delivering and implanting the artificial heart valve 1400 into the original aortic valve using a transfemoral retrograde delivery approach. In other implementations, the inflow end 1418 may be the nearest end of the artificial valve when attached to the delivery device, depending on the specific original valve being replaced and the delivery technique used (e.g., transseptal, transapical).

[0139] In some implementations, the frame 402 or its components (e.g., angled supports 430, axial supports 438, windows 414) can be made from any of the various suitable plastically expandable or self-expanding materials known in the art. Plastically expandable materials that can be used to form the frame 402 include, but are not limited to, stainless steel, biocompatible high-strength alloys (e.g., cobalt-chromium or nickel-cobalt-chromium alloys), polymers, or combinations thereof. In certain embodiments, frame 402 is made from a nickel-cobalt-chromium-molybdenum alloy such as MP35N® alloy (SPS Technologies, Jenkintown, Pennsylvania), which is equivalent to UNS R30035 alloy (covered by ASTM F562-13, “Standard Specification for Forged 35 Cobalt-35 Nickel-20 Chromium-10 Molybdenum Alloys for Surgical Implant Applications”, (UNS R30035), ASTM International, West Conshohocken, PA, 2013, which are incorporated herein by reference). MP35N® alloy / UNS R30035 alloy contains 35% nickel, 35% cobalt, 20% chromium, and 10% molybdenum by weight. Self-expanding materials that may be used to form frame 402 may include, but are not limited to, nickel-titanium alloys (NiTi) such as Nitinol.

[0140] When composed of a plastically expandable material, the frame 402 (and thus the artificial heart valve 1400) is crimped into a radially compressed configuration on a delivery catheter and can then be expanded in the patient's body by an inflatable balloon or equivalent inflation mechanism. Alternatively, when composed of a self-expanding material, the frame 402 (and thus the artificial heart valve 1400) is crimped into a radially compressed configuration and can be constrained to the compressed configuration by insertion into the sheath of a delivery catheter or equivalent mechanism. Once advanced to the desired implantation site, the artificial heart valve can be advanced from the delivery sheath, thereby expanding the artificial heart valve to its functional size. Further details of delivery devices that can be used to deliver and implant self-expandable artificial valves (including any of the artificial valves disclosed herein when the frame is composed of a self-expandable material such as nitinol) are disclosed in U.S. Patent Applications Publications 2014 / 0343670 and 2010 / 0049313, which are incorporated herein by reference.

[0141] In some implementations, the struts 430 of frame 402 are pivotable or bendable relative to each other to allow radial expansion and contraction of frame 102. For example, frame 402 may be formed from a single piece of material (e.g., a metal tube) (e.g., via laser cutting, electroforming, or physical vapor deposition). In other implementations, frame 402 may be constructed by forming individual components (e.g., struts and fasteners of the frame) and then mechanically assembling and connecting the individual components together. For example, instead of the strut structure illustrated in Figures 14–14B, the frame may have individual diagonally extending struts, pivotably connected to each other by one or more swivel joints along the length of each strut, as described in U.S. Patent Application Publications 2018 / 0153689, 2018 / 0344456, and 2019 / 0060057 (all of which are incorporated herein by reference).

[0142] In Figure 14B, the frame 402 can be formed by multiple circumferentially spaced commissure windows 414. The valve structure can be coupled to the frame 402 at the commissure windows 414. For example, the valve structure may have multiple commissure assemblies 1412, each corresponding to one of the commissure windows 414 of the frame 402. In the illustrated embodiments of Figures 14A to 14E, the valve structure includes three valve leaflets 1410 (e.g., a tricuspid structure), and the commissure windows 414 are arranged at equal intervals of 120 degrees along the circumference of the frame 402 (i.e., 0 degrees, 120 degrees, and 240 degrees). However, other intervals and numbers of commissure windows 414 are also possible. For example, in some implementations, the valve structure includes two valve leaflets (e.g., a bicuspid structure), and the commissure windows are arranged on both sides of the frame (e.g., aligned on the same diameter of the frame).

[0143] As shown in Figures 14A and 14D, the artificial heart valve 1400 may also include one or more skirts or sealing members. For example, the artificial heart valve 1400 may include an inner skirt 1408 mounted inside the frame 402 (e.g., radially inward of the frustoconical wall formed by the lattice structure of the frame's supports). The inner skirt 1408 may be a circumferential inner skirt extending around the entire circumference inside the frame 402. The inner skirt 1408 can function as a sealing member to prevent or at least reduce leakage around the valve (e.g., when the valve is placed in the implantation site) and as a mounting surface for securing a portion of the valve leaflets 1410 to the frame 402.

[0144] Although not shown in Figures 14A to 14E, the artificial heart valve 1400 may include an outer skirt attached to the outside of the frame 402 in a manner similar to that described above with respect to any of Figures 5A to 9B (e.g., radially outside the frustoconical wall formed by the lattice structure of the frame's supports). The outer skirt may function as a sealing member by sealing the tissue of the original annular valve, which may help reduce paravalvular leakage passing through the artificial heart valve 1400. The inner and outer skirts may be formed from any of a variety of suitable biocompatible materials, including a variety of synthetic materials (e.g., polyethylene terephthalate (PET)) or original tissue (e.g., pericardial tissue). The inner and / or outer skirts may be bonded to the frame 402 using sutures, adhesives, welding, and / or other means for attaching the skirts to the frame. Further details relating to the inner and outer skirts, techniques for assembling the valve leaflets to the inner skirt, and techniques for assembling the skirts to the frame are disclosed in U.S. Patent No. 9,393,110, U.S. Patent Application Publication No. 2019 / 0192296, International Publication No. WO / 2020 / 159783, and International Patent Application No. PCT / US2020 / 024559, which are incorporated herein by reference, respectively.

[0145] The valve structure may be configured to allow blood flow through the frame 402 in only one direction, for example, to regulate blood flow from the inlet end 1418 to the outlet end 1416 through the artificial heart valve 1400. The valve structure may include a plurality of leaflets 1410, each made from a flexible material. The leaflets 1410 can transition between an open configuration in which blood flows through the valve 1400 via a flow channel formed by the leaflet, and a closed configuration in which the leaflet obstructs blood flow through the valve 1400. The leaflets 1410 may be made in whole or in part from a biological material, a biocompatible synthetic material, or other such material. A preferred biological material may be, for example, bovine pericardium (or pericardium from other sources). In some implementations, the leaflets 1410 may have a reinforcing member (e.g., a fabric strip) on the pointed edge 1466 to which the leaflet 1410 is attached to the inner skirt 1408.

[0146] Similar to the configuration shown in Figure 13A, the valve leaflet 1410 has a first portion 1454, a pair of first tabs 1458 at both ends of the valve leaflet 1410 with respect to the centerline 1452 of the first portion 1454, and a second portion 1494, as best shown in Figure 14C. The first portion 1454 defines a first edge 1456 which may extend between the first tabs 1458. Each first tab 1458 may have at least an outer edge 1460 and a base edge 1462. The outer edges 1460 of the first tabs 1458 may be substantially parallel to each other, for example, both edges 1460 extending along a direction 1490. The outer edges 1460 (and direction 1490) may also be parallel to the centerline 1452 of the first portion 1454. The valve leaflet 1410 may also have a pair of second tabs 1494 on both ends of the leaflet 1410 with respect to the centerline 1452. Each second tab 1494 may be separated from the corresponding first tab 1458 by a gap or cutout 1493. The second tabs 1494 may also have outer edges 1492 that are substantially parallel to each other. The outer edges 1492 of the second tabs 1494 may also be substantially parallel to the outer edge 1460 and / or the centerline 1452.

[0147] The second portion 1464 defines a pointed edge 1466 that extends between the base edges 1462 of the first tab 1458 and curves along its entire length (or substantially along its entire length) between the base edges 1462. The pointed edge 1466 may have a vertex 1480 that coincides with the centerline 1452 of the first portion 1454. The second portion 1464 has a semi-elliptical shape, having a pointed edge 1466 that follows a semi-elliptical curve along the entire length from one base edge 1462 of the first tab 1458 to the corresponding base edge 1462 of the other tab 1458. The major axis 1468 of the semi-ellipse is positioned to substantially coincide with the base edge 1462, as shown in Figure 14C. Therefore, at position 1472, where the pointed edge 1466 intersects the base edge 1462 of the first tab 1458, the tangent 1474 to the pointed edge 1466 is substantially parallel to the outer edge 1460 of the tab 1458 (for example, parallel to direction 1490) and substantially perpendicular to the base edge 1462.

[0148] The pointed edge 1466 of each leaflet 1410 can be sutured to the medial skirt 1408, for example, along a suture line 1420. The suture may be an in-and-out suture, positioned over each leaflet 410, the skirt 408, and the pointed edge 1466, or extending through any reinforcing strip positioned adjacent to the pointed edge 1466 (e.g., using Ethibond thread or similar). As discussed in Figures 13A–13C, the suture line 1420 can extend continuously from the apex 1480 of the pointed edge to a substantial position at the base edge 1462 of the first tab 1458 forming the commissure assembly 1412, or adjacent to them.

[0149] In Figures 14B and 14D, each interlocking window 414 may be formed within or part of a grid structure formed by axial supports 438 and angled supports 430. The supports 430, 438 of the frame may form rows extending circumferentially around the opening cells 444, 446, 448, 450, with the row of cells 450 closest to the outflow end 416 having a larger open area than the other cells. In the illustrated embodiment of Figure 14B, each interlocking window 414 may have a rectangular structure with a central opening defined by a pair of side supports 432 (e.g., mainly extending axially along the frame 402) and a pair of crossbars (e.g., at both ends of the supports 432, mainly extending circumferentially along the frame 402). Other shapes and configurations of the interlocking windows 414 are also possible. For example, instead of a rectangular opening, the interlocking window may define an opening that is square, elliptical, square-elliptical, triangular, L-shaped, T-shaped, C-shaped, H-shaped, or any other shape.

[0150] Figure 14D shows an exemplary approach for securing a commissure assembly 1412 of a valve structure to a commissure window 414 of an annular frame 402. The commissure assembly 1412 includes a part of a first tab 1458 that extends through the window 414 and rotates along the circumferential direction of the frame 402 to form a T-shape. The first tab 1458 can be wrapped in or at least partially covered by a connecting member 1486 (e.g., flexible cloth). A first part 1494a of a second tab 1494 is folded against the inner surface of each valve leaflet 1410, and a second part 1494b of the second tab 1494 may extend along the circumferential direction of the frame 402 and be folded to face the first tab portion 1458. The second part 1494b can be connected to the connecting member 1486 and / or each of the first tabs 1458 via one or more sutures 1484.

[0151] The first part 1494a of the second tab 1494 can form a multilayer structure of the leaflet material just inside the commissure window 414, and this structure is more resistant to bending or articulation than the radially inward leaflet portion, thereby causing the leaflet 410 to primarily articulate with the inner edge 1482 of the first part 1494a of the second tab 1494. Thus, the first part 1494a of the second tab 1494 can help the leaflet avoid contact with or damage from the frame 402 during the normal operation of the valve structure. Detailed instructions for folding the second tab 1494 to produce the arrangement of the first part 1494a and the second part 1494b, as shown in Figure 14D, can be found, for example, in U.S. Patent No. 9,393,110, which is incorporated herein by reference.

[0152] For comparison, Figure 15A shows a conventional design of a valve leaflet 1510 having an upper free edge portion 1554 that extends between a pair of first tabs 1558 on both ends of the valve leaflet 1510 with respect to the centerline 1552 of the leaflet. At the lower edge of the valve leaflet 1510, a lower edge portion 1564 extends between the respective ends of the tabs 1558. However, in contrast to the second portion 1464 in Figure 14C, the lower edge portion 1564 in Figure 15A is not curved along its entire length. Rather, the lower edge portion 1564 includes a substantially straight edge portion 1512 extending from the base edge 1562 of the first tabs 1558, and a substantially V-shaped intermediate edge portion 1566 between the straight edge portions 1512. The substantially V-shaped intermediate edge portion may have a smoothly curved apex portion 1580 and oblique portions connecting the apex portions 1580 to each of the straight edge portions 1512. The slanted portion may have a larger radius of curvature than the vertex portion of 1580.

[0153] Similar to the valve leaflet 1410 in Figure 14C, the valve leaflet 1510 may have a pair of second tabs 1594 separated from the first tab 1558 by a gap or cutout 1593. However, the outer edges 1560 of the first tab 1558 extending along direction 1590 are not parallel to each other, nor are they parallel to the centerline 1552. Furthermore, the tangent 1582 to the lower edge portion 1564, where the lower edge portion 1564 intersects with the base edge 1562 of the first tab 1558, is not parallel to the outer edge 1560 of the first tab 1558, nor is it perpendicular to the base edge 1562 of the first tab 1558. Finally, the suture line used to attach the lower edge portion 1564 to the inner skirt of the valve may extend only from the apex 1580 to the lower end of the straight edge portion 1512, and the straight edge portion 1512 may be joined separately to the straight edge portion 1512 of the adjacent valve leaflet, for example, using a comb stitch. As a result of the shape of the valve leaflet 1510, the construction and attachment of the commissure assembly to the frame 402, and the suture line joining the lower edge portion 1564 to the inner skirt, the valve structure may have a more difficult transition time between the open and closed configurations at low pressure gradient positions. The valve structure formed by the conventional valve leaflet 1510 may also result in an outlet opening area 1588 in the open configuration that is significantly smaller than the inlet area of ​​the frame.

[0154] In contrast, the embodiments in Figures 14A–14E provide a valve structure that transitions more easily between open and closed configurations, thereby avoiding abnormal leaflet movement at low-pressure gradient implant locations. For example, the combination of the semi-elliptical shape of the second portion 1464, the parallel arrangement of the tangents 1474 to the outer edge 1460 and pointed edge 1466 of the first tab 1458, and the continuous suture line 1420 extending (or as close as possible) to the base edge 1462 of the first tab 1458 allows for such easier transitions, thereby reducing the possibility of abnormal leaflet movement due to lower pressure gradients. Compared to conventional leaflets 1510, the shallower, more rounded new sinus region formed by the semi-elliptical shape of the edge 1466 of the leaflet 1410 attached to the inner skirt can help facilitate effective irrigation of the new sinus region. Irrigation of the new sinus and avoidance of leaflet stasis in low-pressure implant environments can further reduce the risk of thrombosis. In some implementations, the outlet opening area 1488 may be larger, as shown in Figure 14E, due to an easier transition to the open configuration. Accordingly, the size of the first part 1494a protruding inward in Figure 14D can be reduced compared to the first part 1594a protruding inward in Figure 15B, or they can be eliminated together so that the valve membrane structure formed by the valve leaflet 1410 can make full use of the larger outlet opening area 1488. In some implementations, for example, the thickness of the valve leaflet 1410 can be reduced compared to a conventional valve leaflet so that the valve leaflet is more fitted and therefore easier to transition between the open and closed configurations. For example, the thickness of a conventional valve leaflet 1510 is 0.016 inches to 0.020 inches (406 μm to 508 μm), while the thickness of the valve leaflet 1410 may be approximately 0.012 inches (305 μm).

[0155] The above discussion relating to Figures 14A to 14E identifies a specific configuration of the artificial heart valve 1400, but other examples of artificial heart valves disclosed herein or otherwise may include any of the innovations and modifications discussed above relating to Figures 3A to 13C, or described below relating to Figures 16A to 21B. For example, a modified valve structure formed by the valve leaflets 1410 is adapted to replace the valve structure 918 of the artificial heart valve 900 in Figures 10A to 10C, thereby avoiding abnormal leaflet movement when the artificial heart valve 900 is installed in a low-pressure gradient implant position.

[0156] Figures 16A and 16B illustrate various features of a docking station (also referred to herein as a valve dock or docking device) that can be used with an artificial heart valve such as valve 1400 at a low-pressure implant position. The docking station 1600 can be fabricated from an elastic or conforming material and can be designed to accommodate large variations in anatomical structure. For example, the docking station 1600 can be fabricated from a highly flexible metal (e.g., Nitinol), a metal alloy, a polymer, or an open-cell foam. The docking station 1600 may be self-expanding (e.g., by being formed from a shape memory alloy), manually expandable (e.g., expandable via a balloon), or mechanically expandable.

[0157] In Figure 16A, the docking station 1600 may include a frame 1602 that forms one or more cells. The band 1606 may extend around the waist or narrow portion 1608, or be integrated with the waist to form a non-expandable or substantially non-expandable valve seat. The band 1606 can stiffen the waist, and when the docking station is deployed and expanded, the waist / valve seat becomes relatively non-expandable in the deployed configuration. As shown in Figure 16B, the valve 1610 (e.g., an artificial heart valve 1400, or any other valve disclosed herein or known in the art) may be secured to the docking station 1600 by extending the frame of the artificial valve 1610 into the narrow portion 1608 that forms the valve seat. The band 1606 may be made from PET, one or more sutures, fibers, metals, polymers, biocompatible tapes, or any relatively non-expandable material known in the art that can restrict the shape of the valve seat and hold the valve 1610 installed therein.

[0158] The docking station 1600 can be implanted in a blood vessel within the patient's vascular system, for example, into or from the atria of the heart (e.g., the pulmonary artery, inferior vena cava, or superior vena cava). The frame 1602 may include one or more retaining portions 1620, which may have outwardly curved flares designed to help secure the docking station 1600 within the blood vessel. Thus, the docking station 1600 can provide an installation site for an artificial heart valve within a blood vessel, rather than within one of the original heart valves. The docking station may have an impermeable material 1604 bonded to the frame 1602, forming a sealing portion. For example, the sealing portion may include a radially outwardly extending portion 1612, and the impermeable material 1604 may extend at least from portion 1612 to the valve seat, thereby making the docking station 1600 impermeable to blood flow and directing blood into the inlet end 1614 of the docking station to the valve 1610 provided in the valve seat.

[0159] Although the impermeable material 1604 may be impermeable to blood flow, it may still allow tissue infiltration from the original tissue surrounding the blood vessel. In some implementations, the impermeable material 1604 can replace a sealing layer, for example, as described above with respect to Figures 3A to 11B. Alternatively, or additionally, the inner skirt, outer skirt, or both of the artificial heart valve 1610 can fold with one or more sealing layers to act as a barrier against further tissue infiltration from the docking station to the leaflets of the artificial valve 1610. Furthermore, since the valve attached to the docking station 1600 may experience a relatively low pressure gradient, the artificial heart valve 1610 preferably includes a valve structure designed to more easily transition between open and closed configurations, for example, as described above with respect to Figures 13A to 14E.

[0160] Further details relating to the construction and use of a docking system adapted to docking station 1600 and / or to be used with the artificial valve 1610 or any other exemplary valve are disclosed in U.S. Patent No. 10,363,130 and U.S. Patent Application Publication 2019 / 0000615, each incorporated herein by reference. The above discussion with respect to Figures 16A–16B identifies specific configurations of docking station 1600 and artificial heart valve 1610, but other examples of docking stations and / or artificial heart valves disclosed herein or otherwise may include any of the innovations and variations discussed above with respect to Figures 3A–14E or below with respect to Figures 17A–21B.

[0161] Furthermore, while specific examples of docking stations and artificial heart valves are described above, the provision of low-pressure open valve structures is applicable to a wide variety of artificial valves and / or associated docking stations. For example, existing valve structures for artificial heart valves disclosed in any of U.S. Patent Nos. 6,730,118, 7,101,396, 7,393,360, 7,510,575, 7,993,394, 8,652,202, 8,992,608, 9,339,382, and 10,603,165, U.S. Patent Application Publication Nos. 2018 / 0325665, 2018 / 0344456, and 2019 / 0060057, and International Publication No. WO / 2020 / 081893, can replace the disclosed valve structures, all of which are incorporated herein by reference. Alternatively, or in addition, any of the artificial heart valves disclosed in any of U.S. Patent Nos. 6,730,118, 7,101,396, 7,393,360, 7,510,575, 7,993,394, 8,652,202, 8,992,608, 9,339,382, and 10,603,165, U.S. Patent Application Publications 2018 / 0325665, 2018 / 0344456, and 2019 / 0060057, and International Publication No. WO / 2020 / 081893 may be modified to operate at a low-pressure gradient implant position in accordance with the teachings of this disclosure. Exemplary prosthetic valve having a sealing layer and a low-opening pressure valve membrane structure

[0162] Figures 17A to 17D show various features of an exemplary artificial heart valve 1700 having one or more sealing layers and a low-opening pressure valve structure for implantation, for example, at the mitral valve location. Similar to the artificial heart valve 800 shown in Figures 9A to 9B, the exemplary artificial heart valve 1700 of Figures 17A to 17D has an annular frame 1702, a valve structure including a plurality of valve leaflets 1706, and an encapsulation layer 1704 including one or more sealing layers. The encapsulation layer 1704 fills the opening cells of the frame 1702 and surrounds the studs of the frame 1702, so that the encapsulation layer 1704 encloses the entire annular frame 1702 on all sides, thereby allowing the annular frame 1702 to be encapsulated or embedded within the layer 1704. The encapsulation layer 1704 forms a radially inner surface that functions as an airtight inner skirt 1710 and a radially outer surface that functions as an airtight outer skirt 1708. Therefore, the inclusion layer 1704 provides both internal and external barriers to tissue endoproliferation, thus reducing the possibility of pannus formation.

[0163] The encapsulation layer 1704 can be formed by pre-forming sublayers, arranging the sublayers on both sides of the frame 1702, and then joining the sublayers to embed the annular frame 1702 within them. For example, the first extruded sublayer may be placed on the radially inner surface of the annular frame 1702, and the second extruded sublayer may be placed on the radially outer surface of the annular frame 1702. The first and second sublayers can then be joined to the supports of the frame 1702 and between them, for example, by fusion, melting, welding, etc. Alternatively, the encapsulation layer 1704, or a portion thereof, can be formed directly on the frame 1702, for example, by dip coating, spray coating, electric spinning, or similar methods.

[0164] In some implementations, the encapsulation layer 1704 includes a sealing layer as described in detail in the section above. For example, the encapsulation layer 1704 may be formed from a hydrophobic polymer material and have pores of a sufficiently small size (e.g., 20 μm or less, 10 μm or less, 8 μm or less, or even 5 μm or less) that are substantially non-porous or inhibit intracellular proliferation. Exemplary materials for the sealing layer include PTFE, ePTFE, urethane, PU, ​​TPU, silicone, or combinations or copolymers thereof. For example, in an exemplary implementation, the frame 1702 is encapsulated by a urethane layer electrospinned with ePTFE. In another exemplary implementation, the frame 1702 is encapsulated by a copolymer of silicone and TPU, and the copolymer may be coated onto the frame 1702. Further details of the materials for the encapsulation layer, and the techniques for encapsulation and attachment of the valve leaflets to the encapsulation layer (which may be employed in valve 1700 or any other exemplary valve) can be found in U.S. Patent No. 8,945,209 and U.S. Patent Application Publication No. 2020 / 0155306, both of which are incorporated in their entirety by reference.

[0165] In the illustrated embodiments of Figures 17A and 17B, a separate outer skirt 1712 is provided on top of the encapsulation layer 1704. The outer skirt 1712 is positioned on the radially outer surface of the encapsulation layer 1704 and may be joined thereto by stitching or any other binding means. For example, the outer skirt 1712 may be made from any of a variety of fabrics, knits, or crochet fabrics, the radially outer surface of which may be the plush nap or pile of the fabric. Exemplary fibers with pile include velour, velvet, velour, corduroy, terrycloth, fleece, and the like. Alternatively or additionally, the outer skirt 1712 may include nonwoven fabrics (e.g., felt) or fibers (e.g., nonwoven cotton fibers). Alternatively or additionally, the outer skirt 1712 may be formed as or constructed from a porous or spongy material, such as any of a variety of suitable polymer foam materials or woven fabrics such as woven PET. The material selected for the outer skirt 1712 may contribute to improving the compressibility and shape memory properties of the outer skirt. For example, the pile layer may be able to conform to compress under load (e.g., when in contact with original tissue, other implants, etc.) but otherwise return to its original size and / or shape when the load is removed. Thus, the material selected for the outer skirt 1712 may allow, and even encourage, tissue ingrafting. However, the inclusion layer 1704 acts as a barrier to prevent tissue ingrafting from reaching the leaflets 1706 of the valve structure.

[0166] The valve leaflets 1706 of the valve structure are coupled to the frame 1702 via commissure assemblies 1714 that are coupled to each commissure window of the frame. In the embodiments illustrated in Figures 17B to 17D, the valve structure includes three valve leaflets 1706 (e.g., a tricuspid structure), and the commissure windows are equally spaced at 120-degree intervals (i.e., 0, 120, and 240 degrees) along the circumference of the frame 1702. However, other intervals and numbers of commissure windows are also possible. The valve structure can be configured to allow blood flow through the frame 1702 in only one direction, for example, to regulate blood flow from the inlet to the outlet end through the artificial heart valve 1700. The valve leaflets 1706 transition between an open configuration in which blood flows through the valve 1700 through the flow channels formed by the leaflets, and a closed configuration in which the leaflets 1706 obstruct blood flow through the valve 1700. The valve leaflet 1706 may be made in whole or in part from a biological material, a biocompatible synthetic material, or other such material. A preferred biological material may be, for example, bovine pericardium (or pericardium from other sources). The valve leaflet 1706 may have a shape and arrangement similar to the valve leaflet 1410 described above with respect to Figures 14C-14E, for example, with the outer edge of the tab being substantially parallel, the pointed edge having a semi-elliptical or semi-elliptical shape, and the base edge of the tab having a tangent to the pointed edge substantially parallel to the outer edge of the tab.

[0167] An opening may be created within the encapsulation layer 1704 at a location corresponding to the window, so that the commissural assembly of the valve structure can pass through and be mounted in the commissural window of the frame 1702. In some implementations, the opening may be created after the encapsulation layer 1704 is formed on the annular frame 1702, for example by cutting the layer 1704 in the region surrounding the window and / or by puncturing through the layer 1704 covering the window opening. Alternatively, in some implementations, the opening may be created during the formation of the encapsulation layer 1704 on the annular frame 1702, for example by covering the window during the encapsulation process, by inserting a temporary sacrificial member into the window opening during the encapsulation process, or otherwise by preventing the window from being formed by the material during the encapsulation process. Alternatively, in some implementations, the opening may be created in one or more of the sublayers used to form the encapsulation layer 1704 before the encapsulation of the annular frame 1702. The connecting assembly can be attached to the window of frame 1702 in an alternative manner, similar to that described above for Figures 5E and 6C.

[0168] The valve leaflets can be sutured to the encapsulation layer 1704, for example, on the radially medial surface 1710, in the same manner as described above for Figures 5A and 5B. However, in contrast to the valves of Figures 5A and 5B, the prosthetic valve 1700 has a suture line 1716 that attaches the pointed edge of the valve leaflet 1706 to the encapsulation layer 1704 and extends continuously from the apex of the pointed edge to a substantial position in the commissure assembly, or an adjacent position, which is attached to the commissure window (for example, to the base edge of the valve leaflet tab inserted into the window, or as close to it as possible). Similar to the configurations of Figures 14A and 14E, the valve structure of the prosthetic valve 1700 transitions more easily between open and closed configurations, thereby avoiding abnormal valve leaflet movement at low-pressure gradient implant locations. Furthermore, the valve leaflet 1706 can form a shallower, more rounded new sinus region, which can facilitate the irrigation of the new sinus region. Cleaning the new sacrum and avoiding leaflet stasis in a low-pressure graft environment can further reduce the risk of thrombosis.

[0169] The above discussion relating to Figures 17A–17D identifies a specific configuration of the artificial mitral valve 1700, but other examples of artificial heart valves disclosed herein or otherwise may include any of the innovations and modifications discussed above with respect to Figures 3A–17D, or described below with respect to Figures 18–21B.

[0170] Figure 18 shows an exemplary delivery device 1800 that can be used to deliver and implant an artificial heart valve 1700, or any other exemplary artificial heart valve. The delivery device 1800 includes a handle 1802 that can be positioned outside the patient and used to articulate the distal end portion 1806 of an elongated shaft 1812 within the patient. The artificial heart valve 1700 may be positioned on the distal end portion 1806 in a radially compressed state. For example, the artificial valve 1700 may be crimped onto an inflatable balloon 1804 or another type of expansion member that can be used to radially expand the artificial valve 1700. The distal end portion 1806, including the artificial valve 1700, can be advanced through the vascular structure to a selected implantation site (e.g., within the original mitral valve and / or within a previously implanted host valve). Although not specifically shown in Figure 18, it will be understood that the delivery device 1800 can advance along the guidewire, and that the delivery device 1800 may include an innermost shaft defining the lumen of the guidewire, as is known in the art. The prosthetic valve 1700 can then be deployed to the implantation site, for example, by inflating the balloon 1804. Further details of a delivery device that may be used to deliver and implant a plastically expandable prosthetic heart valve such as the prosthetic valve 1700 (or any other prosthetic heart valve disclosed herein) are disclosed in U.S. Patent Applications Publication Nos. 2017 / 0065415, 2016 / 0158497, and 2013 / 0030519, which are incorporated herein by reference.

[0171] If the prosthetic valve 1700 to be implanted is a self-expanding prosthetic valve, the prosthetic valve may be held in a radially compressed state within a delivery capsule or sheath of a delivery device 1800 as it is inserted through the patient's vascular structure to the desired implantation site and advanced. Once positioned at the desired implantation site, the prosthetic valve can be unfolded from the delivery capsule, allowing it to self-expand to its radially expanded functional size within the original valve or a previously implanted host valve. Further details of delivery devices that may be used to deliver and implant self-expanding prosthetic valves (including any of the prosthetic valves disclosed herein when the frame is composed of a self-expanding material such as nitinol) are disclosed in U.S. Patent Applications Publication Nos. 2014 / 0343670 and 2010 / 0049313, which are incorporated herein by reference.

[0172] When the artificial valve 1700 is implanted at the mitral valve location, an anchoring device or docking device (e.g., a docking station or valve dock) can be used. For example, Figure 19 shows an exemplary docking device 1900 having a coil or coiled portion having multiple windings extending along the central axis of the docking device. The coil or coiled portion may be continuous and may extend in a substantially helical manner, having sections of various different sizes and shapes. For example, the docking device 1900 may be configured to fit the mitral valve location, but in other implementations, it may be shaped similarly or differently and / or adapted for better housing at other intrinsic valve locations, such as the tricuspid valve. Advantageously, the geometric shape of the docking device 1900 can provide engagement with the intrinsic anatomical structure, increasing stability and reducing relative movement between the docking device 1900, the artificial valve 1700 docked within it, and the intrinsic anatomical structure. This reduction in relative motion can prevent material degradation of the components of the docking device 1900 and / or the artificial valve 1700 docked therein, thus preventing damage / injury to the original tissue.

[0173] The docking device 1900 may include a central region 1902 having a coil, a coiled portion, or multiple coils. The coiled portion or coil of the central region 1902 may be of similar size and shape, or may vary in size and / or shape. For example, the central region 1902 may have 3 or approximately 3 coil turns having substantially equal inner diameters. The central region 1902 of the docking device 1900 functions as the primary landing area or retaining area for holding the expandable prosthetic valve when the docking device 1900 and the prosthetic valve are implanted in the patient's body. The coiled portion or coil of the central region 1902 may also be called a “functional coil” or “functional turn,” as the properties of these coils contribute most to the amount of retaining force generated between the prosthetic valve, the docking device 1900, and the original mitral valve leaflets and / or other anatomical structures.

[0174] In the illustrated embodiment of Figure 19, the docking device 1900 may also have a distal or lower region 1904. The distal region 1904 may have a lead coil / wound (also called a circumferential coil / wound) which may have a larger diameter than the functional coil / wound or the coil / wound of the central region 1902. The diameter or width of the circumferential coil / wound or lead coil / wound (e.g., ventricular coil / wound) of the lower region 1904 may be selected to be larger to more easily navigate the distal or lead tip 1906 of the docking device 1900 and to surround the features of the original anatomical structure (e.g., valve leaflets and / or chordae tendineae).

[0175] Once the distal tip 1906 is navigated around the desired original anatomical structure, the remaining coils of the docking device 1900 may also be guided around the same feature. In some implementations, the size of the other coils can be reduced sufficiently to pull the damaged anatomical feature radially inward or slightly radially inward. In the illustrated embodiment of Figure 19, the docking device 1900 further includes an enlarged proximal or upper region 1908 having a stabilizing coil / winding (which may be, for example, an atrial coil / winding) of the docking device 1900. During the transition or intermediate stages of the implantation procedure, for example, during the time between the deployment and undeployment of the docking device 1900 and the final delivery of the prosthetic valve, the coils may shift and / or deviate from their desired position or orientation, for example, by normal cardiac function. Stabilizing mechanisms or coils may be used to help stabilize the docking device in the desired position during the intermediate stages. For example, the docking device 1900 includes an upper region 1908 having an expandable stabilizing coil / winding, which is intended to be positioned within the circulatory system (e.g., the left atrium) so as to stabilize the docking device 1900. For example, the upper region 1908 or the stabilizing coil / winding may be configured to abut against or press against the wall of the circulatory system (e.g., against the wall of the left atrium) to maintain the desired position of the docking device 1900 before implantation of the prosthetic valve.

[0176] The stabilizing coil / winding (e.g., atrial coil / winding) in the upper region 1908 of the docking device 1900 may extend up to approximately one turn or rotation and terminate at the proximal tip 1910. The radial size of the stabilizing coil / winding (e.g., atrial coil) in the upper region 1908 may be significantly larger than the size of the functional coil in the central region 1902, so that the stabilizing coil / winding flares or extends sufficiently outward to contact the wall of the circulatory system (e.g., the wall of the left atrial region). The proximal tip 1910 of the upper region 1908 may include, for example, an eyelet or eyehole for securing the docking device 1900 to the delivery system.

[0177] In an implementation where the docking device 1900 is used at the mitral valve position, the docking device may first advance and be delivered to the original mitral valve annulus, and then set to the desired position before implantation of the artificial heart valve. In some implementations, the docking device 1900 is flexible and / or made from a shape memory material, so that the coil of the docking device 1900 can be straightened for delivery via a transcatheter approach. In some implementations, the coil is made from another biocompatible material such as stainless steel. Some of the same catheter and other delivery tools can be used for the delivery of both the docking device 1900 and the artificial valve 1700 without performing separate preparation steps, simplifying the end-user implantation procedure. Further details of the docking station and its implantation (which may be employed for the artificial valve 1700 or any other exemplary valve) are disclosed in U.S. Patent No. 10,463,479 and International Application No. PCT / US2020 / 036577, both of which are incorporated herein by reference.

[0178] Figures 20A to 21B illustrate the various stages of implanting the docking device and artificial heart valve into the original mitral valve. First, referring to Figures 20A to 20B, the initial stages of delivering the docking device 1900 to the mitral valve position and implanting the docking device 1900 into the original mitral valve 16 are shown. The distal end portion of the delivery system 2002 advances to the original mitral valve 16 in the patient's heart. The docking device can be positioned in the original mitral valve 16 such that its distal tip 1906 extends through the mitral valve 16 into the left ventricle. The sleeve shaft of the delivery system 2002 can be retracted proximal to expose the docking device 1900 and / or pushed out of the delivery system, thereby allowing the shape-memory material of the docking device 1900 to adopt a coiled shape in the central region 1902, which can surround the chordae tendineae 18 in the left ventricle, as shown in Figures 20C to 20D. Once fully deployed within the mitral valve 16, the docking device 1900 can be separated from the delivery system 2002. The artificial heart valve 1700 may then be delivered between the original valve leaflets 2004 of the mitral valve 16 using the same or a different delivery system (e.g., delivery device 1800), as shown in Figures 21A-21B, and the artificial heart valve 1700 may be expanded and attached within the docking device 1900. Example of an outer skirt for an artificial heart valve

[0179] Figures 22 and 23 show an outer skirt 2200 that can be attached to the outer surface of the prosthetic heart valve according to a different implementation. The outer skirt 2200 provides a cushion that can come into contact with the surrounding tissue after the prosthetic heart valve has been implanted within the original anatomical structure. The cushion can reduce damage to the surrounding tissue due to movement or friction between the tissue and the surface of the prosthetic heart valve. The outer skirt 2200 can also reduce paravalvular leakage. While prosthetic valves with the skirt 2200 can also be implanted in other locations with or without a docking device, the skirt 2200 is particularly applicable to prosthetic heart valves implanted within a docking device 1900 of the original mitral valve, such as the prosthetic heart valve 1700 shown in Figure 21B.

[0180] In the implementations illustrated in Figures 22 and 23, the outer skirt 2200 includes an outer fabric layer 2202 and an inner fabric layer 2204. Each of the outer fabric layer 2202 and the inner fabric layer 2204 may have a tubular shape. The inner fabric layer 2204 is positioned on the inner surface of the outer fabric layer 2202. In some embodiments, the inner fabric layer 2204 may be attached to the outer fabric layer 2202 (e.g., by suture, ultrasonic welding, adhesive, or lamination techniques). The outer skirt 2200 is positioned around the frame of the artificial heart valve so that the inner fabric layer 2204 is interposed between the frame and the outer fabric layer 2202 during use. The outer fabric layer 2202 includes a cushion that can protect the surrounding tissue from damage after valve implantation.

[0181] In one embodiment, the outer skirt 2200 is elastic between an elongated state corresponding to a radially compressed configuration of the artificial heart valve and a radially expanded state corresponding to a radially expanded configuration of the artificial heart valve. In the elongated state, the outer skirt 2200 is relatively long and has a relatively narrow diameter (as shown in Figure 22). In the expanded state, the outer skirt 2200 is relatively short and has a relatively wide diameter (as shown in Figure 23).

[0182] In one embodiment, the outer fabric layer 2202 can be made of a woven fabric consisting of sections having different structures. Figures 24A and 24B show an exemplary woven fabric 2206 having different sections, which may include one or more first fabric sections 2208, one or more second fabric sections 2210, and fabric edge sections 2212, 2214. The first fabric section 2208 may have a woven structure, the second fabric section 2210 may have a floating structure, and the fabric edge sections 2212, 2214 may have a woven structure. The woven structures of the first fabric section 2208 and the fabric edge sections 2212, 2214 may be the same or different. The different sections 2208, 2210, 2212, and 2214 may be formed as rows or stripes extending in the circumferential direction. The stripes of the first fabric section 2208 may be arranged alternately with the stripes of the second fabric section 2210 along the x-axis.

[0183] The woven fabric 2206 can be constructed using warp and weft threads, as is known in weaving techniques. In some embodiments, the fabric 2206 may be woven so that the warp threads run longitudinally along the fabric, while the weft threads are interlaced with the warp threads transversely. In Figure 24A, the y-axis may represent the longitudinal direction (or longitudinal threads) of the fabric, and the x-axis may represent the transverse direction (or transverse threads) of the fabric. Individual warp threads may be called “warp ends,” and a single weft thread extending transversely to the warp threads may be called a “pick” or “fill.”

[0184] In the illustrated embodiment of Figure 24A, the first fabric section 2208 and fabric edge sections 2212, 2214 have a woven structure, meaning that the weft threads are interlaced with the warp ends in a pattern defined in these sections. The second fabric section 2210 has a floating structure, meaning that the weft threads are not interlaced with the warp ends in these sections. The floating structure can consist of floating threads. In the embodiment shown in Figure 24A, the floating threads are floating weft threads (i.e., threads extending transversely or along the x-axis of the fabric) that can allow the fabric to be stretched transversely or along the x-axis. In an alternative embodiment, it is possible to weave the fabric such that the floating threads are floating warp threads (i.e., threads extending longitudinally or along the y-axis of the fabric), and the stripes of the first fabric section 2208 may alternate with the stripes of the second fabric section 2210 along the y-axis.

[0185] In one embodiment, the woven fabric 2206 can have an axially expanded state with a length L1 (shown in Figure 24A) corresponding to the radially compressed state of the artificial valve, and an axially shortened state with a length L2 (shown in Figure 25) corresponding to the radially expanded state of the artificial valve, where L1 > L2. A second fabric section 2210 having a floating structure allows for adjustment of the length of the woven fabric 2206 between L1 and L2. In the elongated state of the fabric, the floating threads constituting the floating structure of the second fabric section 2210 may be substantially parallel to the y-axis. In the shortened state, the floating threads of the second fabric section 2210 can twist and kink in many directions to form a compressible mass that can provide cushioning.

[0186] In one embodiment, the woven structure of the first fabric section 2208 (as well as the fabric edge sections 2212, 2214) can be a leno weave structure. In a leno weave, at least some of the warp ends do not lie parallel to the other warp ends. Instead, some of the warp ends are partially twisted around the other warp ends, forming gaps for the passage of the weft. A leno weave structure uses two types of warp threads known as leno and ground threads. The leno and ground threads intersect alternately, resulting in the twisted structure of the leno weave. The leno weave forms a rigid, open mesh structure, allowing the first fabric section 2208 to serve as a support for the second fabric section 2210, which has a floating structure. The leno weave can also allow the first section 2210 to stretch transversely (which is circumferential when the fabric is used as the outer fabric layer of an outer skirt).

[0187] Figure 26 shows three picks 2216a, 2216b, and 2216c of a pure leno weave. For illustrative purposes, four pairs of warp ends 2218a, 2218b, 2218c, and 2218d are shown. A pair of warp ends 2218a contains a leno yarn 2220a and a ground yarn 2222a, a pair of warp ends 2218b contains a leno yarn 2220b and a ground yarn 2222b, a pair of warp ends 2218c contains a leno yarn 2220c and a ground yarn 2222c, and a pair of warp ends 2218d contains a leno yarn 2220d and a ground yarn 2222d. The leno and ground yarns of each pair of warp ends cross each other between the picks. The basic building blocks of a leno weave are completed with two picks. A woven section of the desired length can be constructed by repeating these two picks.

[0188] The woven structure of the first fabric section 2208 is not limited to the pure leno weave structure shown in Figure 26. Other leno weave structures different from the pure leno weave shown in Figure 26 can also be constructed. Other embodiments of leno weave structures that may be used for the fabric for the outer skirt, and further details of the structure of the outer fabric layer 2202 can be found in U.S. Patent Application Publication No. 2019 / 0374337 and U.S. Patent No. 11,013,600, which are incorporated herein by reference.

[0189] In one embodiment, as shown in Figure 27A (for simplification, the structure of the woven fabric 2206 is not shown in Figure 27A), the woven fabric 2206 may have a width W and length L in a spread-out or flat configuration (before being attached to the artificial valve frame). For the woven fabric structure and floating yarn orientation shown in Figures 24A and 24B, the width W may be along the longitudinal threads of the woven fabric (y-axis in Figure 24A), and the length L may be along the transverse threads of the woven fabric (x-axis in Figure 24A). In the finished tube formed from the woven fabric 2206, the length L may be along the longitudinal direction of the tube, and the width W may be along the circumferential direction of the tube. The width W and length L can be selected based on the desired dimensions of the outer skirt, which may be based on the dimensions of the artificial heart valve in a radially compressed configuration and a radially expanded configuration. The width W and length L may be further selected based on the material of the fabric (e.g., how much elasticity the fabric has along the longitudinal and transverse threads). The woven fabric 2206 can be folded such that the longitudinal edges 2226a and 2226b of the fabric overlap each other, as shown in Figure 27B. The overlapping edges 2226a and 2226b can be fixed together (for example, by a stitch 2228) to form a tube corresponding to the first fabric layer of the outer skirt.

[0190] In one embodiment, the inner fabric layer 2204 can be constructed from a fabric having a woven structure (e.g., plain weave, including variants). Plain weave (also called tabby weave) is a weave in which all wefts alternately pass over and under the warp threads, forming a cross pattern. The warp threads lie parallel to each other across the warp threads. Figure 28 shows a plain weave with wefts 2227 intersecting warp threads 2229. Plain weave produces the largest number of intersections per unit space compared to other weave patterns, which can result in a strong and durable fabric. Variations of plain weave include rib weave, where either the warp or weft is thicker, and basket weave, where two or more wefts alternately pass over and under two or more warp threads. The numerous intersections in the plain weave may allow the inner fabric layer 2204 to function as an effective barrier between the floating structure of the outer fabric layer 2202 and the frame of the artificial valve. The numerous crosses also allow the fabric to be relatively thin yet strong, enabling the outer skirt 2200 to be sutured to the frame 402 and allowing the artificial heart valve to be crimped without tearing the inner fabric layer 2204. The inner fabric layer 2204 is also designed to provide additional structure to the outer fabric layer 2202 to help distribute the load of the frame cells to the original anatomical structure. The inner fabric layer 2204 may be thinner than the outer fabric layer 2202. In one embodiment, the thickness of the inner fabric layer 2204 may be about 50 microns, and the thickness of the outer fabric layer 2202 may be about 750 microns.

[0191] In one embodiment, the inner fabric layer 2204 can be made by providing a fabric 2230 as shown in Figure 29A. Strips 2230a of the fabric 2230 can be cut along bias lines 2235a, 2235b (for example, lines at a 45-degree angle to the longitudinal threads 2234 and transverse threads 2236 of the fabric 2230). The fabric 2230 has higher elasticity along the bias compared to along the longitudinal threads 2234 and transverse threads 2236. As shown in Figure 29B, by cutting the fabric strip 2230a along the bias of the fabric 2230 and orienting the fabric strip 2230a so that the cut bias edges 2235a and 2235b become the upper and lower edges of the inner fabric layer 2204, respectively, the fabric or yarn of the inner fabric layer 2204 extends at an angle of 0 to 90 degrees with respect to the upper edge 2235a and lower edge 2235b of the inner fabric layer 2204 and the central longitudinal axis of the artificial valve frame. Alternatively, the inner fabric layer 2204 can be woven so that the warp and weft threads or their fibers extend at an angle of 0 to 90 degrees with respect to the upper and lower edges of the fabric. Preferably, the warp and weft threads or their fibers of layer 2204 extend at an angle of 45 degrees with respect to the upper and lower edges 2235a, 2235b of layer 2204 and the central longitudinal axis of the artificial valve frame. This allows the final inner fabric layer 2204 to have relatively high axial elasticity when the artificial valve frame is compressed radially for delivery to the patient. The fabric strip 2230a can be folded (e.g., along lines 2231a, 2231b) to overlap with the lateral edge portions 2236b, 2236b as shown in Figure 30. The overlapping lateral edge portions 2236a, 2236b can be fixed together (e.g., by sutures 2238) to form a tube corresponding to the inner fabric layer 2204. In some cases, stabilizing tape can be attached to the overlapping lateral edge portions 2236a, 2236b. In this case, the overlapping lateral edge portions 2236a, 2236b and the stabilizing tape can be fixed together (e.g., by sutures) to form a tube.

[0192] In another embodiment, the fabric 2230 can be woven in a tubular shape (for example, using a double weave) with a desired diameter for the inner fabric layer 2204. The inner fabric layer 2204 can be provided by cutting the woven tube to a desired length.

[0193] The outer fabric layer 2202 fabric 2206 and the inner fabric layer 2204 fabric 2230 can be made from a variety of biocompatible thermoplastic polymers such as polyethylene terephthalate (PET), expanded polytetrafluoroethylene (ePTFE), and nylon, or from other suitable synthetic or natural fibers. In certain embodiments, both fabrics 2206 and 2230 are made from PET fibers. In some embodiments, the inner fiber layer 2204 may be substantially porous, or may have a pore structure that inhibits intracellular proliferation, as described for the sealing layer herein.

[0194] Figure 31 shows an artificial heart valve 400 in a radially extended configuration, with an outer skirt 2200 wrapped around the aforementioned artificial heart valve 400 (as an example). The outer skirt 2200 is assembled on the frame 402 of the artificial heart valve 400 such that an inner fabric layer 2204 extends around the outer surface of the frame 402 (clearly shown in Figure 32), and an outer fabric layer 2202 extends around the inner fabric layer 2204. The inner fabric layer 2204 at its position between the outer fabric layer 2202 and the frame 402 (see Figure 33) separates at least a portion of the outer fabric layer 2202 from the frame 402. In one embodiment, the inner fabric layer 2204 is sized and positioned such that it separates at least a second fabric section 2210 of the outer fabric layer 2202, including a floating structure from the frame 402.

[0195] The floating structure (e.g., floating threads) of the second fabric section 2210 of the outer fabric layer 2202 provides cushioning that can prevent trauma to surrounding tissues after the implantation of the artificial heart valve. To optimize the cushioning effect of the buffer layer, it is preferable that the floating structure protrudes radially outward so that tissues can come into contact with the floating structure. However, the floating structure is compressible and easily maneuverable. When the artificial valve is implanted, if the inner fabric layer 2204 is not present, the floating structure may be compressed against the struts 430 of the frame 402, and the joints formed between the struts and a portion of the floating structure may protrude into the frame 402, which is not very effective in providing cushioning. This phenomenon can occur when the artificial valve is implanted in a relatively rigid docking device, such as the docking device 1900. In some cases, a docking device that exerts an inward force on the outer skirt may cause permanent deformation of the floating structure. To prevent this scenario, the inner fabric layer 2204 is provided as a separating layer between the frame 402 and the outer fabric layer 2202. The inner fabric layer 2204 prevents direct contact between the outer fabric layer 2202 and the relatively rigid metal surface of the frame 402, thereby maintaining the elasticity of the floating structure. The inner fabric layer 2204 also maintains the floating structure on the outside of the frame 402 and maximizes contact between the floating structure and the surrounding original tissue.

[0196] The outer skirt 2200 is configured to allow the frame 402 to move between a radially compressed configuration and a radially expanded configuration. In the illustrated embodiment, a first fabric section 2208 of the outer fabric layer 2202 is circumferentially positioned around the frame 402, and a second fabric section 2210 of the outer fabric layer 2202 is circumferentially positioned around the frame 402. The first fabric section 2208 can expand (e.g., expand or stretch) circumferentially (e.g., due to the elasticity of the leno structure in this direction) of the outer skirt 2200 / frame 402 when the frame 402 is expanded from a radially compressed configuration to a radially expanded configuration. The circumferential expansion of the first fabric section 2208 increases the diameter of the outer fabric layer 2202, allowing the outer fabric layer 2202 to accommodate the expanded frame. The second fabric section 2210 can be contracted in the axial direction of the outer skirt 2200 / frame 402 (for example, by twisting and torsion of the floating threads in these sections) when the frame 402 is expanded from a radially compressed configuration to a radially expanded configuration.

[0197] The inner fabric layer 2204 and the outer fabric layer 2202 may substantially extend along the axial length of the frame 402 so as to substantially cover the outer circumferential surface of the frame 402, as shown in Figures 31 to 33. In other embodiments, the inner fabric layer 2204 and the outer fabric layer 2202 may only partially extend along the axial length of the frame 402 (for example, from the inlet end 418 to about the midpoint of the axial length of the frame 402) so as to cover a portion of the outer circumferential surface of the frame 402. In some cases, the inner fabric layer 2204 may be longer than the outer fabric layer 2202, and the inner fabric layer 2204 may substantially extend along the axial length of the frame 402, while the outer fabric layer 2202 may only partially extend along the axial length of the inner fabric layer 2204.

[0198] In another embodiment, as shown in Figure 34, the inner fabric layer 2204 may have extra material (or flaps) 2204a, 2204b at its ends, which can be folded over the end sections of the outer fabric layer 2202. The flaps can be secured to the outer fabric layer 2202 and to a portion of the inner fabric layer 2204 between the outer fabric layer 2202 and the frame 402 (e.g., by sutures 2241 or adhesive). The flaps can prevent direct contact between the apex 460 formed by the support 430 of the frame 402 at the inlet end 418 and outlet end 416 of the frame 402 and the surrounding tissue.

[0199] The outer skirt 2200 can be coupled to the frame 402 using a variety of methods. In one embodiment, the outer fabric layer 2202 may be fixed to the inner fabric layer 2204, which can be fixed to a selected support 430 of the frame 402 (for example, by sutures 2240 as shown in Figure 32). Reinforcement material 2205 may be used at the base of the inner fabric layer 2204, attached to the apex 460 of the inlet end 418 of the frame 402. In another embodiment, the outer fabric layer 2202 can be fixed to the inner fabric layer 2204, which can be fixed to the inner skirt 408 located within the artificial heart valve. Other implementations of coupling the outer skirt to the artificial heart valve disclosed in other implementations herein can be applied to coupling the outer skirt 2200 to the artificial heart valve.

[0200] The outer skirt 2200 is illustrated as covering the frame 402 of the artificial heart valve 400, but it should be understood that the outer skirt 2200 may be applicable to any other artificial heart valves disclosed herein. Furthermore, the outer skirt 2200 may be used with or without an inner skirt located within the frame of the artificial heart valve. If the outer skirt 2200 is used without an inner skirt within the artificial heart valve, or if the inner skirt within the artificial heart valve is not airtight, the inner fabric layer 2204 may be airtight. Additional examples

[0201] Additional embodiments based on the principles described herein are described below. Further embodiments within the scope may be, for example, taken by taking one feature of one embodiment alone, taking multiple features of one embodiment in combination, or combining one or more features of one embodiment with one or more features of one or more other embodiments. [Examples]

[0202] Example 1 The artificial heart valve comprises: an annular frame that can be folded radially and expandable between a radially compressed configuration and a radially expanded configuration, the annular frame having an inlet end and an outlet end away from the inlet end along the axial direction of the frame; a valve structure supported within the annular frame and comprising a plurality of leaflets, each leaflet having a pointed rim and tabs on both sides with respect to the leaflet's centerline, the pointed rim curving along at least a portion thereof to form a apex on the leaflet's centerline, the valve structure being coupled to the frame via a plurality of commissure assemblies formed by a pair of tabs of adjacent leaflets; and an inner skirt disposed on and coupled to the radially inner surface of the annular frame, the inner skirt comprising a sealing layer configured such that, when the artificial heart valve is implanted in the patient, cell proliferation from the patient's natural tissue into the sealing layer is prevented. An inner skirt is positioned radially along the annular frame between the annular frame and the pointed edge of each valve leaflet, and the inner skirt extends axially along the frame from at least the apex of the pointed edge of the valve leaflet to at least a plurality of commissure assemblies.

[0203] Example 2 Any embodiment of this specification, in particular the artificial heart valve described in Example 1, wherein the sealing layer is substantially non-porous or has pores therein that are sized to inhibit intracellular proliferation.

[0204] Example 3 An artificial heart valve according to any embodiment of this specification, particularly the one of Examples 1 and 2, wherein the sealing layer is formed from a hydrophobic polymer material comprising polytetrafluoroethylene (PTFE), expanded PTFE (ePTFE), urethane, polyurethane (PU), thermoplastic PU (TPU), silicone, or a combination or copolymer thereof.

[0205] Example 4 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 1 to 3, wherein the pointed edges of each valve leaflet are attached to the inner skirt.

[0206] Example 5 Any embodiment of this specification, particularly the artificial heart valve described in Embodiment 4, wherein the pointed edges of each valve leaflet are attached to the inner skirt via one or more sutures.

[0207] Example 6 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 4 to 5, wherein the inner skirt further comprises a scrim layer whose pointed edge is located in a region along the axial direction to which the inner skirt is attached.

[0208] Example 7 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 1 to 6, wherein the inner skirt substantially covers the entire radial inner surface of the annular frame between the inlet and outlet ends.

[0209] Example 8 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 1 to 7, wherein the commissure assembly extends radially through each opening in the inner skirt and through each commissure window in the annular frame.

[0210] Example 9 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 1 to 8, further comprising one or more protective covers, each protective cover comprising a second sealing layer of a hydrophobic polymer material, the second sealing layer being substantially non-porous or having pores therein sized to prevent cell ingratification, and one or more protective covers being positioned on each radially outer surface portion of the annular frame, with the commissure assembly extending through the commissure window.

[0211] Example 10 Any embodiment of this specification, in particular the artificial heart valve described in Example 9, is a single annular cover in which one or more protective covers are wrapped around a portion of the radially outer surface of the annular frame.

[0212] Example 11 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 1 to 8, wherein the inner skirt is coupled to the frame, and the commissure assembly extends radially to each radially inner surface portion of the inner skirt and is coupled thereto by one or more sutures, thereby indirectly coupling the valve structure to the frame.

[0213] Example 12 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 1 to 11, wherein the sealing layer includes lamination of sublayers.

[0214] Example 13 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 1 to 12, wherein the sealing layer includes a layer formed directly on the radially inner circumferential surface of the annular frame.

[0215] Example 14 Any embodiment of this specification, particularly the artificial heart valve described in Example 13, wherein the sealing layer comprises an electrospin layer, a dip coating layer, or a spray coating layer on the radially inner surface of the annular frame.

[0216] Example 15 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 13 to 14, wherein a sealing layer is formed on the frame so as to be joined thereto without sutures.

[0217] Example 16 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 1 to 12, wherein the sealing layer includes a layer that is formed separately from the frame and subsequently attached to the frame.

[0218] Example 17 Any embodiment of this specification, particularly the artificial heart valve according to Example 16, wherein the sealing layer is an extruded or cast layer attached to the annular frame by one or more sutures.

[0219] Example 18 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 1 to 17, further comprising an outer skirt positioned on a portion of the radially outer surface of an annular frame, wherein the outer skirt extends axially from the inlet end of the frame.

[0220] Example 19 An artificial heart valve according to any embodiment of this specification, particularly the one described in Embodiment 18, wherein the outer skirt is coupled to a support for an annular frame, an inner skirt, or a combination thereof.

[0221] Example 20 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 18 to 19, wherein the outer skirt is connected to an annular frame or an inner skirt by one or more sutures.

[0222] Example 21 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 18-20, wherein the outer skirt is positioned on and bonded to the radially outer surface portion of an annular frame, and the outer skirt comprises a third sealing layer of a hydrophobic polymer material, the third sealing layer being substantially non-porous or having pores therein that are sized to inhibit intracellular proliferation.

[0223] Example 22 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 18 to 21, wherein the outer skirt extends axially from at least the inlet end of the frame to at least a plurality of commissure assemblies.

[0224] Example 23 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 18 to 22, wherein the outer skirt substantially covers the entire radial outer surface of the annular frame between the inlet and outlet ends.

[0225] Example 24 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 21 to 23, wherein the inner skirt and the outer skirt are part of the same single skirt structure wrapped around the inlet end of the annular frame, and the sealing layer and the third sealing layer are the same sealing layer.

[0226] Example 25 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 18 to 23, wherein a portion of the outer skirt faces or overlaps with a portion of the inner skirt at the inlet end of the annular frame and is coupled to the portion of the inner skirt.

[0227] Example 26 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 18 to 25, wherein the third sealing layer includes lamination of sublayers.

[0228] Example 27 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 18 to 26, wherein the third sealing layer includes a layer formed directly on the radial outer surface of the annular frame.

[0229] Example 28 An artificial heart valve according to any embodiment herein, particularly embodiment 27, wherein the third sealing layer includes an electrospinning layer, a dip coating layer, or a spray coating layer on the radially outer peripheral surface of the annular frame.

[0230] Embodiment 29 An artificial heart valve according to any embodiment herein, particularly any one of embodiments 27 - 28, wherein the third sealing layer is formed on the frame so as to be coupled thereto without sutures.

[0231] Embodiment 30 An artificial heart valve according to any embodiment herein, particularly any one of embodiments 18 - 26, wherein the third sealing layer includes a layer formed separately from the frame and then attached to the frame.

[0232] Embodiment 31 An artificial heart valve according to any embodiment herein, particularly embodiment 30, wherein the third sealing layer is an extruded layer or a cast layer attached to the annular frame by one or more sutures.

[0233] Embodiment 32 An artificial heart valve according to any embodiment herein, particularly any one of embodiments 18 - 20, wherein the outer skirt includes polyethylene terephthalate (PET).

[0234] Embodiment 33 For each cross - link assembly, the tabs are separated and folded to form a T - shape such that each tab includes a first portion that extends along the circumferential direction of the frame and contacts the coupling member, and a second portion that extends along the radial direction of the frame, contacts the corresponding second portion of the other tab of the pair, and connects the first portion to the central portion of the valve tip, according to any embodiment herein, particularly any one of embodiments 1 - 32.

[0235] Embodiment 34 An artificial heart valve according to any embodiment herein, particularly embodiment 33, wherein the coupling member includes a flexible cloth or fabric.

[0236] Example 35 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 33 to 34, wherein the binding member comprises a fourth sealing layer of a hydrophobic polymer material, the fourth sealing layer being substantially non-porous or having pores sized to inhibit intracellular proliferation.

[0237] Example 36 The artificial heart valve comprises an annular frame that can be folded radially and expandable between a radially compressed configuration and a radially expanded configuration, the annular frame having an inlet end and an outlet end away from the inlet end along the axial direction of the frame, and a valve structure supported within the annular frame and comprising a plurality of leaflets, each leaflet having a pointed rim and tabs on both sides with respect to the leaflet's centerline, the pointed rim being curved along at least a portion thereof to form a apex on the leaflet's centerline, and the valve structure being coupled to the frame via a plurality of commissure assemblies formed by paired tabs of adjacent leaflets. The annular frame is sealed by a sealing layer constructed to prevent cell infiltration into the sealing layer from the patient's natural tissues when the artificial heart valve is implanted in the patient.

[0238] Example 37 Any embodiment of this specification, in particular the artificial heart valve described in Example 36, wherein the sealing layer is substantially non-porous or has pores therein that are sized to inhibit intracellular proliferation.

[0239] Example 38 An artificial heart valve according to any embodiment of this specification, particularly any one of Examples 36 to 37, wherein the sealing layer is formed from a hydrophobic polymer material comprising polytetrafluoroethylene (PTFE), expanded PTFE (ePTFE), urethane, polyurethane (PU), thermoplastic PU (TPU), silicone, or a combination or copolymer thereof.

[0240] Example 39 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 36 to 38, wherein the pointed edges of each valve leaflet are attached to a sealing layer.

[0241] Example 40 An artificial heart valve according to any embodiment of this specification, particularly the embodiment 39, wherein the pointed edges of each valve leaflet are attached to a sealing layer via one or more sutures.

[0242] Example 41 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 39 to 40, comprising a scrim layer disposed between an annular frame and an encasing sealing layer, wherein the scrim layer has a pointed edge in a region along the axial direction to which it is attached to the sealing layer.

[0243] Example 42 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 36 to 41, wherein the commissure assembly extends radially through each commissure window of the annular frame through each opening in the sealing layer, and the commissure assembly is joined to the commissure window by one or more sutures.

[0244] Example 43 An artificial heart valve according to any embodiment of this specification, particularly the one described in Example 42, further comprising one or more protective covers, each protective cover comprising a second sealing layer of a hydrophobic polymer material, the second sealing layer being substantially non-porous or having pores therein sized to prevent cell ingratification, and one or more protective covers being positioned on the respective radially outer surface portions of the annular frame, with the commissure assembly extending through the commissure window.

[0245] Example 44 An artificial heart valve according to any embodiment herein, particularly the one in Example 43, which is a single annular cover wrapped around a portion of the radially outer surface of an annular frame, with one or more protective covers.

[0246] Example 45 The commissure assembly extends radially within each radially inner surface portion of the encapsulating sealing layer and is coupled thereto by one or more sutures, thereby coupling the valve leaflet structure to the frame, of any example herein, particularly any one of Examples 36 - 44 of an artificial heart valve.

[0247] Example 46 An artificial heart valve according to any example herein, particularly any one of Examples 36 - 45, wherein the sealing layer comprises a lamination of sub - layers.

[0248] Example 47 An artificial heart valve according to any example herein, particularly any one of Examples 36 - 46, wherein the sealing layer comprises an electrospun layer, a dip - coating layer, or a spray - coating layer.

[0249] Example 48 For each commissure assembly, each tab is separated and folded to form a folded T - shape such that each tab includes a first portion that extends along the circumferential direction of the frame and contacts a coupling member, and a second portion that extends along the radial direction of the frame and contacts a corresponding second portion of the other tab of the pair, and connects the first portion to the central portion of the valve leaflet, of any example herein, particularly any one of Examples 36 - 47 of an artificial heart valve.

[0250] Example 49 An artificial heart valve according to any example herein, particularly Example 48, wherein the coupling member comprises a flexible cloth or fabric.

[0251] Example 50 An artificial heart valve according to any example herein, particularly any one of Examples 48 - 49, wherein the coupling member comprises a third sealing layer of a hydrophobic polymer material, and the third sealing layer is substantially non - porous or has pores sized to prevent intracellular colonization.

[0252] Example 51 An artificial heart valve comprising a frame, a valve structure coupled to the frame and including multiple valve leaflets, and means for preventing cell proliferation from the patient's original tissue on the valve leaflets of the valve structure.

[0253] Example 52 Any embodiment of this specification, in particular the artificial heart valve according to Example 51, includes one or more sealing layers arranged between the valve structure and the surrounding intrinsic tissue, for preventing cell inoculum when the artificial heart valve is implanted in a patient.

[0254] Example 53 Any embodiment of this specification, in particular the artificial heart valve described in Example 52, wherein each sealing layer comprises a hydrophobic polymer material and is substantially non-porous or has pores therein that are sized to inhibit intracellular proliferation.

[0255] Example 54 The hydrophobic polymer material includes polytetrafluoroethylene (PTFE), expanded PTFE (ePTFE), urethane, polyurethane (PU), thermoplastic PU (TPU), silicone, or combinations or copolymers thereof, as described in any example herein, particularly the artificial heart valve described in Example 53.

[0256] Example 55 An artificial heart valve according to any embodiment of this specification, particularly any one of Examples 1 to 54, wherein the valve structure is a bicuspid structure having two leaflets and two commissure assemblies, and the valve structure is coupled to the frame via commissure assemblies located on opposite sides of the frame.

[0257] Example 56 An artificial heart valve according to any embodiment of this specification, particularly any one of Examples 1 to 54, wherein the valve structure is a tricuspid structure having three leaflets and three commissure assemblies, and the valve structure is coupled to the frame via the three commissure assemblies which are arranged at equal intervals along the circumferential direction of the frame.

[0258] Example 57 An artificial heart valve according to any embodiment of this specification, particularly any one of Examples 1 to 56, wherein the frame is formed of a plastically expandable material or a self-expanding material.

[0259] Example 58 An artificial heart valve configured for implantation into an existing heart valve in a patient, as described in any embodiment of this specification, in particular, the artificial heart valve according to any one of Examples 1 to 57.

[0260] Example 59 An artificial heart valve constructed for implantation at an aortic or mitral valve location, as described in any embodiment of this specification, particularly any one of Examples 1 to 58.

[0261] Example 60 An assembly comprising a delivery device including an elongated shaft, and one of the artificial heart valves from Examples 1 to 59 mounted on the elongated shaft in a radially compressed configuration for delivery into the patient's body.

[0262] Example 61 A method for implanting an artificial heart valve in a patient's body includes inserting the distal end of a delivery device into the patient's vascular structure such that the delivery device includes an elongated shaft and the artificial heart valve according to any one of claims 1 to 59 is removably mounted on the elongated shaft of the delivery device in a radially compressed configuration; advancing the artificial heart valve to a desired implantation site; and expanding the artificial heart valve to a radially expanded configuration using the delivery device, thereby implanting the artificial heart valve at the desired implantation site.

[0263] Example 62 A method for implanting an artificial heart valve in a patient's body includes inserting the distal end of a delivery device into the patient's vascular structure such that the delivery device includes an elongated shaft and an artificial heart valve described in any one of Examples 1 to 59 is removably mounted on the elongated shaft of the delivery device in a radially compressed configuration; advancing the artificial heart valve to a desired implantation site; and unfolding the artificial heart valve from the delivery device such that the artificial heart valve self-expands into a radially expanded configuration, thereby implanting the artificial heart valve at the desired implantation site.

[0264] Example 63 The method according to any embodiment of this specification, in particular any one of Examples 61 to 62, further comprising placing a valve dock at a desired implantation site, wherein an artificial heart valve having a radially extended configuration is mounted within the valve dock.

[0265] Example 64 Any embodiment of this specification, particularly the method of any one of Examples 61-63, wherein advancement to the desired transplant site is by a transfemoral, transventricular, transapical, or transseptal approach.

[0266] Example 65 A method for assembling an artificial heart valve having multiple leaflets is to provide an inner skirt on the radially inner surface of an annular frame, wherein the annular frame is radially foldable and expandable between a radially compressed configuration and a radially expanded configuration, the annular frame having an inlet end and an outlet end spaced apart from the inlet end along the axial direction of the frame, the inner skirt including a sealing layer, the sealing layer including a layer formed directly on the radially inner surface of the annular frame, and to form a plurality of commissure assemblies having a plurality of leaflets, wherein each leaflet has a pointed edge and tabs on both sides with respect to the leaflet's centerline, the pointed edge being on the leaflet's centerline The invention includes forming each commissure assembly such that it is curved along at least a portion thereof to form a apex, and each commissure assembly is formed by a pair of tabs of adjacent leaflets, and connecting each commissure assembly to an annular frame, wherein an inner skirt is positioned along the radial direction of the annular frame between the annular frame and the pointed edge of each leaflet, and the inner skirt extends along the axial direction of the frame at least from the apex of the pointed edge of the leaflet to at least a number of commissure assemblies, and the sealing layer is constructed such that when the artificial heart valve is implanted in the patient, inward proliferation of cells from the patient's original tissue into the sealing layer is prevented.

[0267] Example 66 Any embodiment of this specification, particularly the method of Example 65, wherein providing an inner skirt includes electro-spinning, dip-coating, or spray-coating a sealing layer onto the radially inner surface of the annular frame.

[0268] Example 67 The method according to any embodiment of this specification, in particular any one of Examples 65-66, wherein a sealing layer is formed on an annular frame so as to be joined therewithout sutures.

[0269] Example 68 The method according to any embodiment of this specification, in particular any one of Examples 65 to 67, further comprising providing an outer skirt on a portion of the radially outer surface of an annular frame, wherein the outer skirt comprises a second sealing layer of a hydrophobic polymer material, the second sealing layer being substantially non-porous or having pores therein sized to inhibit intracellular proliferation.

[0270] Example 69 Any embodiment of this specification, particularly the method of Example 68, wherein providing an outer skirt includes electro-spinning, dip-coating, or spray-coating a second sealing layer onto the radially outer surface of the annular frame.

[0271] Example 70 The method according to any embodiment of this specification, wherein providing an outer skirt includes tying the outer skirt to the radially outer surface portion of the annular frame using one or more sutures.

[0272] Example 71 Any embodiment of this specification, particularly the method of Example 70, wherein the second sealing layer of the outer skirt is formed by extrusion or casting.

[0273] Example 72 A method for assembling an artificial heart valve having multiple leaflets is to bond an inner skirt to the radially inner surface of an annular frame, wherein the annular frame is radially foldable and expandable between a radially compressed configuration and a radially expanded configuration, wherein the annular frame has an inlet end and an outlet end spaced apart from the inlet end along the axial direction of the frame, and the inner skirt includes a sealing layer, and to form a plurality of commissure assemblies having a plurality of leaflets, wherein each leaflet has a pointed edge and tabs on both sides with respect to the leaflet's centerline, and the pointed edge has a small portion of its length to form a apex on the leaflet's centerline. The invention includes forming each commissure assembly such that it is curved along at least part of the valve leaflet, and that each commissure assembly is formed by a pair of tabs of adjacent leaflets, and connecting each commissure assembly to an annular frame, wherein the inner skirt is positioned along the radial direction of the annular frame between the annular frame and the pointed edge of each leaflet, and the inner skirt extends along the axial direction of the frame at least from the apex of the pointed edge of the leaflet to at least a number of commissure assemblies, and the sealing layer is constructed such that, once the artificial heart valve is implanted in the patient, inward proliferation of cells from the patient's original tissue into the sealing layer is prevented.

[0274] Example 73 Any embodiment of this specification, particularly the method of Example 72, wherein the sealing layer of the inner skirt is formed by extrusion or casting before the inner skirt is joined to the annular frame.

[0275] Example 74 Any embodiment of this specification, particularly the method of Example 73, wherein the inner skirt is joined to the annular frame by one or more sutures.

[0276] Example 75 The method according to any embodiment of this specification, particularly any one of Examples 72-74, further comprising providing an outer skirt on a portion of the radially outer surface of an annular frame, wherein the outer skirt comprises a second sealing layer of a hydrophobic polymer material, the second sealing layer being substantially non-porous or having pores therein sized to inhibit intracellular proliferation.

[0277] Example 76 Any embodiment of this specification, particularly the method of Example 75, wherein providing an outer skirt includes electro-spinning, dip-coating, or spray-coating a second sealing layer onto the radially outer surface of the annular frame.

[0278] Example 77 Any embodiment of this specification, particularly the method of Example 75, wherein providing an outer skirt includes tying the outer skirt to the radially outer surface portion of the annular frame using one or more sutures.

[0279] Example 78 Any embodiment of this specification, particularly the method of Example 77, wherein the second sealing layer of the outer skirt is formed by extrusion or casting.

[0280] Example 79 The method according to any embodiment of this specification, in particular any one of Examples 72 to 78, wherein the sealing layer is an extruded layer or a cast layer.

[0281] Example 80 The method according to any embodiment of this specification, particularly any one of Examples 72 to 79, wherein joining the inner skirt to the annular frame includes attaching the sealing layer to the supports of the annular frame using one or more sutures.

[0282] Example 81 Any embodiment of this specification, particularly the method of any one of Examples 65 to 79, further comprising using one or more sutures to connect the pointed edges of each valve leaflet to the inner skirt.

[0283] Example 82 The method according to any embodiment of this specification, particularly embodiment 81, wherein the inner skirt is bonded to the radially inner surface of the annular frame such that the scrim layer of the inner skirt is positioned in a region along the axial direction, with the pointed edges attached to the inner skirt being positioned in that region.

[0284] Example 83 The method according to any embodiment of this specification, in particular any one of Examples 65 to 82, wherein the inner skirt substantially covers the entire radial inner surface of the annular frame between the inlet and outlet ends.

[0285] Example 84 The method according to any embodiment of this specification, particularly any one of Examples 65 to 83, wherein the sealing layer is substantially non-porous or has pores therein that are sized to inhibit intracellular proliferation, and / or the sealing layer is formed from a hydrophobic polymer material.

[0286] Example 85 The method according to any embodiment of this specification, particularly any one of embodiments 65 to 84, further comprising: forming an opening in the inner skirt at a position corresponding to the commissure window of the annular frame, thereby joining each commissure assembly to the annular frame, including inserting the tab of the commissure assembly through one of the openings and one of the commissure windows in the inner skirt such that the first portion of the tab is positioned radially outward of the annular frame; separating and folding the first portion of the tab so that the first portions extend away from each other along the circumferential direction of the annular frame; and attaching the first portion of the tab to each commissure window, a portion of the valve leaflet radially inward of the commissure window, or any combination thereof, using one or more sutures.

[0287] Example 86 The method according to any embodiment of this specification, particularly Example 85, further comprising attaching one or more protective covers to a first portion of the radially outer tab of an annular frame, each protective cover comprising a third sealing layer of a hydrophobic polymer material, the third sealing layer being substantially non-porous or having pores therein sized to inhibit intracellular proliferation.

[0288] Example 87 Any embodiment of this specification, particularly the method of Example 86, wherein one or more protective covers are a single annular cover wrapped around a radially outer surface portion of an annular frame.

[0289] Example 88 The method according to any embodiment of this specification, in particular any one of Examples 65 to 84, wherein connecting each joint assembly to the annular frame includes connecting each joint assembly to the inner skirt.

[0290] Example 89 A method for assembling an artificial heart valve having multiple leaflets includes: enclosing an annular frame with a sealing layer, wherein the annular frame is radially collapsible and expandable between a radially compressed configuration and a radially expanded configuration, the annular frame having an inlet end and an outlet end spaced apart from the inlet end along the axial direction of the frame, and the sealing layer being constructed such that when the artificial heart valve is implanted in the patient, inward proliferation of cells from the patient's natural tissue into the sealing layer is prevented; forming a plurality of commissure assemblies having a plurality of leaflets, wherein each leaflet has a pointed rim and tabs on both sides with respect to the leaflet's centerline, the pointed rim being curved along at least a portion thereof to form a apex on the leaflet's centerline, and each commissure assembly being formed by the paired tabs of adjacent leaflets; and connecting each commissure assembly to the annular frame.

[0291] Example 90 The method according to any embodiment herein, particularly embodiment 89, further comprising bonding the outer skirt to a portion of the radially outer surface of the annular frame, wherein the outer skirt extends axially from the inlet end of the frame.

[0292] Example 91 Any embodiment of this specification, particularly the method of Example 90, wherein the outer skirt comprises polyethylene terephthalate (PET).

[0293] Example 92 The method according to any embodiment of this specification, in particular any one of Examples 90-91, wherein the annular frame of the outer skirt is joined via one or more sutures.

[0294] Example 93 The method according to any embodiment of this specification, in particular any one of Examples 90 to 92, wherein the outer skirt substantially covers the entire radial outer surface of the annular frame between the inlet and outlet ends.

[0295] Example 94 Any embodiment of this specification, particularly the method of any one of Examples 89 to 93, may further include bonding the pointed edges of each valve leaflet to a sealing layer.

[0296] Example 95 Any embodiment of this specification, particularly the method of Example 94, wherein the pointed edge of each valve leaflet is attached to the sealing layer by one or more sutures.

[0297] Example 96 The method according to any embodiment of this specification, in particular any one of Examples 89 to 95, wherein the scrim layer is positioned in a region along the axial direction in which its pointed edge is attached to the sealing layer.

[0298] Example 97 The method according to any embodiment of this specification, particularly any one of Examples 89 to 96, further comprising: forming an opening in the sealing layer at a position corresponding to the commissure window of the annular frame, thereby joining each commissure assembly to the annular frame, including inserting the tab of the commissure assembly through one of the openings in the sealing layer and one of the commissure windows such that the first portion of the tab is positioned radially outward of the annular frame; separating and folding the first portion of the tab so that the first portion extends away from each other along the circumferential direction of the annular frame; and attaching the first portion of the tab to the respective commissure window, the portion of the valve leaflet radially inward of the commissure window, the sealing layer, or any combination thereof, using one or more sutures.

[0299] Example 98 The method according to any embodiment of this specification, particularly the method of Example 97, may further include attaching one or more protective covers to a first portion of the radially outer tab of the annular frame, each protective cover comprising a second sealing layer of a hydrophobic polymer material, the second sealing layer being substantially non-porous or having fewer pores therein, sized to inhibit cell inbreeding.

[0300] Example 99 Any embodiment of this specification, particularly the method of Example 98, wherein one or more protective covers are a single annular cover wrapped around a radially outer surface portion of an encapsulated annular frame.

[0301] Example 100 The method according to any embodiment of this specification, in particular any one of Examples 89 to 99, wherein bonding each joint assembly to an annular frame includes bonding each joint assembly to a sealing layer.

[0302] Example 101 Any embodiment of this specification, particularly the method of any one of Examples 65 to 100, wherein each sealing layer, a portion of the sealing layers, or one of the sealing layers includes lamination of a sublayer.

[0303] Example 102 Each sealing layer, part of a sealing layer, or all of a sealing layer is substantially non-porous or has pores therein that are sized to inhibit intracellular proliferation, and / or each sealing layer, part of a sealing layer, or all of a sealing layer is formed from a hydrophobic polymer material, according to any embodiment of this specification, particularly any one of Examples 65 to 101.

[0304] Example 103 Any example of this specification, particularly any one of Examples 65 to 102, wherein each sealing layer, part of a sealing layer, or one of the sealing layers comprises polytetrafluoroethylene (PTFE), expanded PTFE (ePTFE), urethane, polyurethane (PU), thermoplastic PU (TPU), silicone, or a combination or copolymer thereof.

[0305] Example 104 A valve leaflet for the valve structure of an artificial heart valve includes a first portion, first and second tabs located on either side of the first portion with respect to the centerline of the first portion, each tab having a base edge and an outer edge, the outer edges of the first and second tabs being substantially parallel to each other, and a second portion having a semi-elliptical or semi-elliptical shape defining a pointed edge, the pointed edge extending from the base edge of the first tab to the base edge of the second tab, the pointed edge curving along its entire length between the base edge of the first tab and the base edge of the second tab.

[0306] Example 105 Any embodiment of this specification, in particular the valve leaflet described in Embodiment 104, wherein the pointed edge of the second portion has a tangent to the outer edge of the first tab at the base edge of the first tab, and the pointed edge of the second portion has a tangent to the outer edge of the second tab at the base edge of the second tab.

[0307] Example 106 A valve leaflet according to any embodiment of this specification, in particular any one of Examples 104 to 105, wherein the first portion defines a first edge extending between the first tab and the second tab, and the second portion is located on the side of the first portion opposite the first edge.

[0308] Example 107 The valve leaflets according to any embodiment of this specification, in particular, according to any one of Examples 104 to 106, wherein the outer edges of the first and second tabs are parallel to the centerline of the first portion.

[0309] Example 108 The apex of the pointed edge of the second part is aligned with the centerline of the first part, the valve leaflet as described in any embodiment of this specification, in particular any one of Examples 104 to 107.

[0310] Example 109 A valve leaflet according to any embodiment of this specification, in particular, one of any of Examples 104 to 108, wherein the major axis of the semi-elliptical or semi-elliptical shape is perpendicular to the center line of the first part.

[0311] Example 110 A valve leaflet according to any embodiment of this specification, in particular any one of Examples 104 to 109, wherein the major axis of the semi-elliptical or semi-elliptical shape substantially coincides with the base edges of the first and second tabs.

[0312] Example 111 A valve leaflet according to any embodiment of this specification, in particular any one of Examples 104 to 110, wherein the thickness of one or more of the first portion of the valve leaflet, the second portion of the valve leaflet, and the tab is 0.012 inches (305 μm) or less.

[0313] Example 112 An artificial heart valve comprising: an annular frame that is radially foldable and expandable between a radially compressed configuration and a radially expanded configuration, the annular frame having an inlet end and an outlet end away from the inlet end along the axial direction of the frame; a valve structure supported within the annular frame and comprising a plurality of leaflets, each leaflet being as described in any one of Examples 104 to 111, the valve structure being coupled to the frame via a plurality of commissure assemblies formed by pairs of tabs from adjacent leaflets; and an inner skirt disposed and coupled to the radially inner surface of the annular frame, wherein the leaflet edges of the second portion of each leaflet are coupled to the inner skirt at their respective leaflets, one or more sutures coupling the leaflets of each leaflet to the inner skirt, the suture line formed by one or more sutures following the curvature of the leaflet, and the suture line formed by one or more sutures continuing substantially from the apex of the leaflet to the commissure assembly.

[0314] Example 113 Any embodiment of this specification, in particular the artificial heart valve described in Example 112, wherein the suture line extends to the base edges of the first and second tabs of each leaflet, or to their respective positions substantially adjacent to the base edges of the first and second tabs of the leaflet.

[0315] Example 114 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 112 to 113, wherein the outer edge of the leaflet tab is substantially parallel to the axial direction of the frame.

[0316] Example 115 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 112 to 114, in an open configuration of the valve structure, wherein the centerlines of the first portions of each valve leaflet are substantially parallel to the axial direction of the frame.

[0317] Example 116 An artificial heart valve according to any embodiment of this specification, in particular any one of embodiments 112 to 115, wherein each commissure assembly has a tab that has a first part extending along the circumferential direction of the frame and in contact with a connecting member, and a second part that extends along the radial direction of the frame and in contact with a corresponding second part of the other tab of the pair, connecting the first part to a first portion of the valve leaflet, such that the tabs are separated and folded to form a T-shape.

[0318] Example 117 Any embodiment of this specification, in particular the artificial heart valve according to Example 116, wherein the connecting member includes a flexible cloth or fabric.

[0319] Example 118 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 112 to 117, wherein the second portions of adjacent valve leaflets are connected to each other only indirectly via coupling to an inner skirt.

[0320] Example 119 The artificial heart valve includes an annular frame having an inlet end and an outlet end separated from the inlet end along the axial direction of the frame, and a valve means that regulates blood flow through the artificial heart valve in hemodynamic conditions at the implanted site in the patient where the pressure gradient across the artificial heart valve is 30 mmHg or less.

[0321] Example 120 Any embodiment of this specification, particularly the artificial heart valve described in Example 119, wherein the valve means comprises a valve structure including a plurality of valve leaflets, which is supported within an annular frame, and the valve structure is coupled to the frame via a plurality of commissure assemblies formed by pairs of tabs of adjacent valve leaflets.

[0322] Example 121 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 119 to 120, wherein the valve means further includes one or more sutures connecting the pointed edges of each leaflet of the valve structure to an inner skirt attached to an annular frame, the suture line being formed by one or more sutures following the curvature of the pointed edge, and the suture line being substantially continuous from the apex of the pointed edge to the commissure assembly.

[0323] Example 122 In the open configuration of the valve structure, the centerlines of each valve leaflet are substantially parallel to the axial direction of the frame, as described in any embodiment of this specification, in particular any one of Examples 119 to 121.

[0324] Example 123 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 112 to 122, further comprising an outer skirt positioned on the radially outer surface portion of an annular frame, wherein the outer skirt extends axially from the inlet end of the frame.

[0325] Example 124 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 112 to 123, wherein the valve structure is a bicuspid structure having two leaflets and two commissure assemblies, and the valve structure is coupled to the frame via commissure assemblies located on opposite sides of the frame.

[0326] Example 125 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 112 to 123, wherein the valve structure is a tricuspid structure having three leaflets and three commissure assemblies, and the valve structure is coupled to the frame via the three commissure assemblies which are arranged at equal intervals along the circumferential direction of the frame.

[0327] Example 126 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 112 to 125, wherein the frame is formed of a plastically expandable material or a self-expanding material.

[0328] Example 127 An artificial heart valve constructed for implantation into an existing heart valve or vascular structure in a patient experiencing a pressure gradient of 30 mmHg or less, as described in any embodiment of this specification, particularly any one of Examples 112 to 126.

[0329] Example 128 An artificial heart valve constructed for implantation at the mitral valve position or the tricuspid position, as described in any embodiment of this specification, in particular any one of Examples 112 to 127.

[0330] Example 129 The assembly includes a delivery device comprising an elongated shaft and one of the artificial heart valves from Examples 112 to 128, mounted on the elongated shaft in a radially compressed configuration for delivery into the patient's body.

[0331] Example 130 A method for implanting an artificial heart valve in a patient's body includes inserting the distal end of a delivery device into the patient's vascular structure such that the delivery device includes an elongated shaft and an artificial heart valve described in any one of Examples 112 to 128 is removably mounted on the elongated shaft of the delivery device in a radially compressed configuration; advancing the artificial heart valve to a desired implantation site; and using the delivery device to expand the artificial heart valve to a radially expanded configuration, thereby implanting the artificial heart valve at the desired implantation site.

[0332] Example 131 A method for implanting an artificial heart valve in a patient's body includes inserting the distal end of a delivery device into the patient's vascular structure such that the delivery device comprises an elongated shaft and an artificial heart valve according to any one of claims 112 to 128, which is removably mounted on the elongated shaft of the delivery device in a radially compressed configuration; advancing the artificial heart valve to a desired implantation site; and unfolding the artificial heart valve from the delivery device so that the artificial heart valve self-expands into a radially expanded configuration, thereby implanting the artificial heart valve at the desired implantation site.

[0333] Example 132 The method according to any embodiment of this specification, in particular any one of Examples 130 to 131, which may further include placing a valve dock at a desired implantation site, and having an artificial heart valve having a radially extended configuration mounted within the valve dock.

[0334] Example 133 Any embodiment of this specification, particularly the method of any one of Examples 130-132, wherein advancement to the desired transplant site is by a transfemoral, transventricular, transapical, or transseptal approach.

[0335] Example 134 A method for assembling an artificial heart valve having multiple leaflets is to provide an inner skirt on the radially inner surface of an annular frame, wherein the annular frame is radially foldable and expandable between a radially compressed configuration and a radially expanded configuration, wherein the annular frame has an inlet end and an outlet end separated from the inlet end along the axial direction of the frame, and to form a plurality of leaflets and a plurality of commissure assemblies, wherein each leaflet has a first portion, a first tab and a second tab, and a second portion, wherein the first tab and the second tab are on either side of the first portion with respect to the centerline of the first portion, and each tab has a base edge and an outer edge, the outer edges of the tabs are substantially parallel to each other, and the second portion of each leaflet has a tip The invention includes forming each commissure assembly such that it has a semi-elliptical or semi-elliptical shape defining a commissure, the pointed edge of each leaflet extends from the base edge of a first tab to the base edge of a second tab, the pointed edge of each leaflet curves along its entire length between the base edge of the first tab and the base edge of the second tab, and each commissure assembly is formed by a pair of tabs of adjacent leaflets; connecting each commissure assembly to an annular frame; and connecting the pointed portion of the second part of each leaflet to the inner skirt via one or more sutures at each pointed edge, such that the suture line is formed by one or more sutures following the curvature of the pointed edge, and the suture line is continuous substantially from the apex of the pointed edge to the commissure assembly.

[0336] Example 135 Any embodiment of this specification, particularly the method of Example 134, wherein providing an inner skirt includes bonding the inner skirt to the radially inner surface via one or more sutures.

[0337] Example 136 Any embodiment of this specification, particularly the method of any one of Examples 134-135, further comprising joining an outer skirt to the radially outer surface portion of an annular frame via one or more sutures.

[0338] Example 137 The method according to any embodiment of this specification, in particular any one of Examples 134 to 136, wherein the second portion of an adjacent valve leaflet is not directly joined together before the pointed edge of each valve leaflet is joined to the inner skirt.

[0339] Example 138 An artificial heart valve comprises a radially foldable and expandable annular frame having an inlet end and an inlet end separated from an outlet end along the axial direction of the frame, and a valve structure supported within the annular frame and comprising a plurality of leaflets. Each leaflet comprises a first portion, first and second tabs on either side of the first portion with respect to the centerline of the first portion, each tab having a base edge and an outer edge, the outer edges of the first and second tabs being substantially parallel to each other, and a second portion having a semi-elliptical or semi-elliptical shape defining a pointed edge extending from the base edge of the first tab to the base edge of the second tab, the pointed edge curving along the entire length between the base edge of the first tab and the base edge of the second tab. The artificial heart valve further includes an inner skirt positioned on the radially inner surface of an annular frame and coupled thereto, the inner skirt including a sealing layer configured such that when the artificial heart valve is implanted in the patient, cell proliferation from the patient's natural tissue into the sealing layer is prevented; and an outer skirt positioned on the radially outer surface of the annular frame, the outer skirt covering substantially the entire radially outer surface of the annular frame between the inlet and outlet ends. The valve structure is connected to the frame via a plurality of commissure assemblies formed by pairs of tabs from adjacent leaflets, and an inner skirt is positioned between the annular frame and the second portion of each leaflet along the radial direction of the annular frame, the inner skirt extending along the axial direction of the frame from at least the apex of the leaflet's pointed edge to at least a plurality of commissure assemblies, the pointed edge portion of the second portion of each leaflet at each pointed edge is connected to the inner skirt by one or more sutures, the suture line is formed by one or more sutures following the curvature of the pointed edge, and the suture line is continuous substantially from the apex of the pointed edge to the commissure assembly.

[0340] Example 139 Any embodiment of this specification, particularly the artificial heart valve described in Example 138, wherein the sealing layer is substantially non-porous or has pores therein that are sized to inhibit intracellular proliferation.

[0341] Example 140 An artificial heart valve according to any embodiment of this specification, particularly any one of Examples 138 to 139, wherein the sealing layer is formed from a hydrophobic polymer material comprising polytetrafluoroethylene (PTFE), expanded PTFE (ePTFE), urethane, polyurethane (PU), thermoplastic PU (TPU), silicone, or a combination or copolymer thereof.

[0342] Example 141 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 138-140, wherein the inner skirt further comprises a scrim layer whose pointed edge is positioned in a region along the axial direction to which the inner skirt is attached.

[0343] Example 142 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 138 to 141, wherein the inner skirt substantially covers the entire radial inner surface of the annular frame between the inlet and outlet ends.

[0344] Example 143 Any embodiment of this specification, in particular the artificial heart valve described in Embodiment 142, wherein the commissure assembly extends radially through each opening in the inner skirt and through each commissure window in the annular frame.

[0345] Example 144 An artificial heart valve according to any embodiment of this specification, particularly the embodiment 143, further comprising one or more protective covers, each protective cover comprising a second sealing layer of a hydrophobic polymer material, the second sealing layer being substantially non-porous or having pores therein sized to prevent intracellular growth, and one or more protective covers being positioned on each radially outer surface portion of an annular frame through which the commissure assembly extends.

[0346] Example 145 An artificial heart valve according to any embodiment of this specification, particularly the embodiment 144, wherein one or more protective covers are a single annular cover wrapped around the radially outer surface of the annular frame.

[0347] Example 146 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 138 to 145, wherein the sealing layer includes lamination of sublayers.

[0348] Example 147 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 138 to 146, wherein the sealing layer includes a layer formed directly on the radially inner circumferential surface of the annular frame.

[0349] Example 148 An artificial heart valve according to any embodiment of this specification, particularly any one of Examples 138 to 147, wherein the sealing layer comprises an electrospin layer, a dip coating layer, or a spray coating layer on the radially inner surface of the annular frame.

[0350] Example 149 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 138 to 148, wherein a sealing layer is formed on the frame so as to be joined therewithout sutures.

[0351] Example 150 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 138 to 148, wherein the sealing layer includes a layer that is formed separately from the frame and subsequently attached to the frame.

[0352] Example 151 An artificial heart valve according to any embodiment of this specification, particularly the embodiment 150, wherein the sealing layer is an extruded or cast layer attached to the annular frame by one or more sutures.

[0353] Example 152 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 138 to 151, wherein the outer skirt is connected to an annular frame or an inner skirt by one or more sutures.

[0354] Example 153 An artificial heart valve according to any embodiment of this specification, particularly any one of Examples 138 to 152, wherein the outer skirt comprises a third sealing layer of a hydrophobic polymer material, the third sealing layer being substantially non-porous or having pores sized to inhibit intracellular proliferation.

[0355] Example 154 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 138 to 153, wherein a portion of the outer skirt faces or overlaps with a portion of the inner skirt at the inlet end of the annular frame and is coupled to the portion of the inner skirt.

[0356] Example 155 Any embodiment of this specification, in particular Example 153, of the artificial heart valve, wherein the inner and outer skirts are part of the same single-skirt structure wound around the inlet end of the annular frame, and the sealing layer and the third sealing layer are the same sealing layer.

[0357] Example 156 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 153 to 155, wherein the third sealing layer includes lamination of sublayers.

[0358] Example 157 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 153 to 156, wherein the third sealing layer includes a layer formed directly on the radial outer surface of the annular frame.

[0359] Example 158 An artificial heart valve according to any embodiment of this specification, particularly any one of Examples 153 to 157, wherein the third sealing layer comprises an electrospin layer, a dip coating layer, or a spray coating layer on the radial outer surface of the annular frame.

[0360] Example 159 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 153 to 158, wherein a third sealing layer is formed on the frame so as to be joined thereto without sutures.

[0361] Example 160 Any embodiment of this specification, particularly Example 153, includes a third sealing layer which is formed separately from the frame and subsequently attached to the frame. An artificial heart valve listed in any one of the 159 items.

[0362] Example 161 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 153 to 160, wherein the third sealing layer is an extruded or cast layer attached to the annular frame by one or more sutures.

[0363] Example 162 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 138 to 152, wherein the outer skirt comprises polyethylene terephthalate (PET).

[0364] Example 163 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 138 to 162, wherein the suture line extends to the base edges of the first and second tabs of each leaflet, or to their respective positions substantially adjacent to the base edges of the first and second tabs of the leaflet.

[0365] Example 164 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 138 to 163, wherein, for each valve leaflet, the pointed edge of the second portion has a tangent substantially parallel to the outer edge of the first tab at the base edge of the first tab, and the pointed edge of the second portion has a tangent substantially parallel to the outer edge of the second tab at the base edge of the second tab.

[0366] Example 165 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 138 to 164, wherein the outer edge of the leaflet tab is substantially parallel to the axial direction of the frame.

[0367] Example 166 In an open configuration of the valve structure, the centerline of the first portion of each valve leaflet is substantially parallel to the axial direction of the frame, as described in any embodiment of this specification, in particular any one of Examples 138 to 165.

[0368] Example 167 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 138 to 166, wherein the second portions of adjacent valve leaflets are indirectly coupled to each other only via coupling to an inner skirt.

[0369] Example 168 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 138 to 167, wherein the semi-elliptical or semi-elliptical long axis of each valve leaflet substantially coincides with the base edges of the corresponding first and second tabs.

[0370] Example 169 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 138 to 168, wherein for each valve leaflet, the thickness of one or more of the first portion, second portion, first tab, and second tab is 0.012 inches (305 μm) or less.

[0371] Example 170 An artificial heart valve according to any embodiment of this specification, in particular any one of embodiments 138 to 169, wherein each tab of each commissure assembly includes a first part extending radially outward from each commissure window along the circumferential direction of the frame and in contact with a coupling member; a second part extending radially through each commissure window and connecting the first part to a first portion of the valve leaflet; a third part extending radially inward from each commissure window along the circumferential direction of the frame and in contact with a first portion of the valve leaflet.

[0372] Example 171 The artificial heart valve according to claim 170, wherein the connecting member includes a flexible cloth or fabric.

[0373] Example 172 The artificial heart valve according to any one of claims 170 to 171, wherein the bonding member comprises a fourth sealing layer of a hydrophobic polymer material, the fourth sealing layer being substantially non-porous or having pores therein that are sized to prevent intracellular proliferation.

[0374] Example 173 An artificial heart valve comprises a radially foldable and expandable annular frame between a radially compressed configuration and a radially expanded configuration, the annular frame having an inlet end and an inlet end separated from an outlet end along the axial direction of the frame, and a valve structure supported within the annular frame and comprising a plurality of leaflets. Each leaflet comprises a first portion, first and second tabs on either side of the first portion with respect to the centerline of the first portion, each tab having a base edge and an outer edge, the outer edges of the first and second tabs being substantially parallel to each other, and a second portion having a semi-elliptical or semi-elliptical shape defining a pointed edge extending from the base edge of the first tab to the base edge of the second tab, the pointed edge curving along the entire length between the base edge of the first tab and the base edge of the second tab. The annular frame is enclosed by a sealing layer that is constructed to prevent cell proliferation from the patient's natural tissue into the sealing layer when the artificial heart valve is implanted in the patient, and the valve structure is connected to the frame via a plurality of commissure assemblies formed by pairs of tabs from adjacent leaflets, and the pointed edges of the second portion of each leaflet at each pointed edge are connected to the sealing layer by one or more sutures, and a suture line is formed by one or more sutures following the curvature of the pointed edge, and the suture line is continuous substantially from the apex of the pointed edge to the commissure assembly.

[0375] Example 174 Any embodiment of this specification, in particular the artificial heart valve described in Example 173, wherein the sealing layer is substantially non-porous or has pores therein that are sized to inhibit intracellular proliferation.

[0376] Example 175 An artificial heart valve according to any embodiment of this specification, particularly any one of Examples 173 to 174, wherein the sealing layer is formed from a hydrophobic polymer material comprising polytetrafluoroethylene (PTFE), expanded PTFE (ePTFE), urethane, polyurethane (PU), thermoplastic PU (TPU), silicone, or a combination or copolymer thereof.

[0377] Example 176 Any embodiment of this specification, particularly Example 173, includes a scrim layer positioned between an annular frame and a sealing layer, wherein the scrim layer has a pointed edge in a region along the axial direction to which it is attached to the sealing layer. An artificial heart valve listed in any one of the 175 items.

[0378] Example 177 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 173 to 176, wherein the sealing layer includes lamination of sublayers.

[0379] Example 178 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 173 to 177, wherein the sealing layer comprises an electrospin layer, a dip coating layer, or a spray coating layer.

[0380] Example 179 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 173 to 178, wherein the suture line extends to the base edges of the first and second tabs of each leaflet, or to their respective positions substantially adjacent to the base edges of the first and second tabs of the leaflet.

[0381] Example 180 In any embodiment of this specification, particularly Embodiment 173, the outer edge of the leaflet tab is substantially parallel to the axial direction of the frame. An artificial heart valve listed in any one of the 179 items.

[0382] Example 181 In an open configuration of the valve structure, the centerline of the first portion of each valve leaflet is substantially parallel to the axial direction of the frame, as described in any embodiment of this specification, in particular any one of Examples 173 to 180.

[0383] Example 182 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 173 to 181, further comprising an outer skirt positioned on the radially outer surface of an encapsulated annular frame, wherein the outer skirt covers substantially the entire radially outer surface between the inlet and outlet ends.

[0384] Example 183 An artificial heart valve according to any embodiment of this specification, particularly the one described in Example 182, wherein the outer skirt is bonded to an annular frame or a sealing layer.

[0385] Example 184 Any embodiment of this specification, particularly Example 182, in which the outer skirt comprises polyethylene terephthalate (PET). An artificial heart valve as described in any one of the 183 items.

[0386] Example 185 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 173 to 184, wherein the commissure assembly extends radially through each opening in the sealing layer and through each commissure window of the annular frame, and the commissure assembly is coupled to the commissure window.

[0387] Example 186 The artificial heart valve according to claim 185, further comprising one or more protective covers, each protective cover comprising a second sealing layer of a hydrophobic polymer material, the second sealing layer being substantially non-porous or having pores therein sized to prevent intracellular growth, and one or more protective covers being positioned on each radially outer surface portion of an annular frame through which a commissure assembly extends.

[0388] Example 187 The artificial heart valve according to claim 186, wherein one or more protective covers are a single annular cover wrapped around a portion of the radially outer surface of an annular frame.

[0389] Example 188 An artificial heart valve according to any embodiment of this specification, in particular any one of embodiments 173 to 187, wherein each tab of each commissure assembly includes a first part extending circumferentially along the frame on the radially outer side of each commissure window and in contact with a coupling member; a second part extending radially through each commissure window and connecting the first part to a first portion of the valve leaflet; a third part extending circumferentially along the frame on the radially inner side of each commissure window; and a fourth part projecting radially inward from the third part and in contact with a first portion of the valve leaflet.

[0390] Example 189 Any embodiment of this specification, in particular the artificial heart valve described in Example 188, wherein the connecting member includes a flexible cloth or fabric.

[0391] Example 190 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 188 to 189, wherein the binding member comprises a third sealing layer of a hydrophobic polymer material, the third sealing layer being substantially non-porous or having pores therein that are sized to inhibit intracellular proliferation.

[0392] Example 191 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 173 to 190, wherein, for each valve leaflet, the pointed edge of the second portion has a tangent substantially parallel to the outer edge of the first tab at the base edge of the first tab, and the pointed edge of the second portion has a tangent substantially parallel to the outer edge of the second tab at the base edge of the second tab.

[0393] Example 192 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 173 to 191, wherein the outer edge of the leaflet tab is substantially parallel to the axial direction of the frame.

[0394] Example 193 In the open configuration of the valve structure, the centerline of the first portion of each valve leaflet is substantially parallel to the axial direction of the frame, as described in any embodiment of this specification, in particular any one of Examples 173 to 192.

[0395] Example 194 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 173 to 193, wherein the second portions of adjacent valve leaflets are indirectly coupled to each other only through coupling to a sealing layer.

[0396] Example 195 For each valve leaflet, the semi-elliptical or semi-elliptical long axis substantially coincides with the base edges of the corresponding first and second tabs, as described in any embodiment of this specification, in particular any one of Examples 173 to 194.

[0397] Example 196 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 173 to 195, wherein for each valve leaflet, the thickness of one or more of the first portion, second portion, first tab, and second tab is 0.012 inches (305 μm) or less.

[0398] Example 197 The artificial heart valve comprises an annular frame that is radially foldable and expandable between a radially compressed configuration and a radially expanded configuration, having an inlet end and an outlet end separated from the inlet end along the axial direction of the frame; a valve means for regulating blood flow through the artificial heart valve in hemodynamic conditions at the patient's implanted site where the pressure gradient across the artificial heart valve is 30 mmHg or less; and means for preventing cell proliferation from the patient's surrounding innate tissue on the leaflets of the valve means.

[0399] Example 198 Any embodiment of this specification, in particular the artificial heart valve according to Example 197, includes one or more sealing layers arranged so as to be positioned between the valve leaflets of the valve means and the surrounding original tissue when the artificial heart valve is implanted in a patient, for preventing cell endoplasty.

[0400] Example 199 Any embodiment of this specification, particularly the artificial heart valve described in Example 198, wherein each sealing layer comprises a hydrophobic polymer material and / or each sealing layer is substantially non-porous or has pores therein that are sized to inhibit intracellular proliferation.

[0401] Example 200 Any embodiment of this specification, particularly the artificial heart valve described in Example 199, wherein each sealing layer comprises polytetrafluoroethylene (PTFE), expanded PTFE (ePTFE), urethane, polyurethane (PU), thermoplastic PU (TPU), silicone, or a combination or copolymer thereof.

[0402] Example 201 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 197 to 200, wherein the valve means comprises a valve structure including a plurality of valve leaflets, the valve structure being coupled to the frame via a plurality of commissure assemblies formed by pairs of tabs of adjacent valve leaflets.

[0403] Example 202 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 197 to 201, wherein the valve means further includes one or more sutures coupled to the pointed edge of each leaflet of the valve structure to an inner skirt attached to an annular frame, the suture line being formed by one or more sutures following the curvature of the pointed edge, and the suture line being substantially continuous from the apex of the pointed edge assembly to the commissure assembly.

[0404] Example 203 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 197 to 202, having an open configuration of the valve structure in which the centerlines of each valve leaflet are substantially parallel to the axial direction of the frame.

[0405] Example 204 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 138 to 203, wherein the valve structure is a bicuspid structure having two leaflets and two commissure assemblies, and the valve structure is coupled to the frame via the commissure assemblies located on opposite sides of the frame.

[0406] Example 205 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 138 to 203, wherein the valve structure is a tricuspid structure having three leaflets and three commissure assemblies, and the valve structure is coupled to the frame via the three commissure assemblies which are arranged at equal intervals along the circumferential direction of the frame.

[0407] Example 206 An artificial heart valve according to any embodiment of this specification, in particular any one of Examples 138 to 205, wherein the frame is formed of a plastically expandable or self-expanding material.

[0408] Example 207 An artificial heart valve is constructed to be implanted in the mitral valve position in a patient in place of an existing heart valve, as described in any embodiment of this specification, in particular, the artificial heart valve according to any one of Examples 138 to 206.

[0409] Example 208 The assembly includes a delivery device comprising an elongated shaft and one of the artificial heart valves from Examples 138 to 207, mounted on the elongated shaft in a radially compressed configuration for delivery into the patient's body.

[0410] Example 209 A method for implanting an artificial heart valve in a patient's body includes inserting the distal end of a delivery device into the patient's vascular structure such that the delivery device includes an elongated shaft and that an artificial heart valve described in any one of Examples 138 to 207 is removably mounted on the elongated shaft of the delivery device in a radially compressed configuration; advancing the artificial heart valve at the mitral valve position in the patient's heart into the original valve or a previously implanted artificial valve; and using the delivery device to expand the artificial heart valve into a radially expanded configuration, thereby implanting the artificial heart valve at the mitral valve position.

[0411] Example 210 A method for implanting an artificial heart valve in a patient's body includes inserting the distal end of a delivery device into the patient's vascular structure such that the delivery device includes an elongated shaft and that an artificial heart valve described in any one of Examples 138 to 207 is removably mounted on the elongated shaft of the delivery device in a radially compressed configuration; advancing the artificial heart valve at the mitral valve position in the patient's heart into the original valve or a previously implanted artificial valve; and unfolding the artificial heart valve from the delivery device such that the artificial heart valve self-expands into a radially expanded configuration, thereby implanting the artificial heart valve at the mitral valve position.

[0412] Example 211 The method according to any embodiment of this specification, particularly any one of Examples 209-210, which may further include setting the valve dock at the mitral valve position, and having an artificial heart valve having a radially extended configuration mounted within the valve dock.

[0413] Example 212 Advancement to the mitral valve position is performed using a transfemoral approach, a transventricular approach, a transapical approach, a transseptal approach, or any combination thereof, as described in any embodiment of this specification, particularly the method of any one of Examples 209 to 211.

[0414] Example 213 A method for assembling an artificial heart valve having multiple leaflets is to provide an inner skirt on the radially inner surface of an annular frame, wherein the annular frame is radially foldable and expandable between a radially compressed configuration and a radially expanded configuration, the annular frame having an inlet end and an outlet end spaced apart from the inlet end along the axial direction of the frame, and the inner skirt includes a sealing layer configured to prevent inward proliferation of cells from the patient's natural tissue into the sealing layer when the artificial heart valve is implanted in the patient, wherein the sealing layer includes a layer formed directly on the radially inner surface of the annular frame, and to form a plurality of commissure assemblies having multiple leaflets, each leaflet having a first portion, first and second tabs, and a second portion, wherein the first and sec...

Claims

1. It is an artificial heart valve, A radially foldable and expandable annular frame having an inlet end and an outlet end separated from the inlet end along the axial direction of the annular frame, between a radially compressed configuration and a radially expanded configuration, A valve structure supported within the annular frame and coupled to the annular frame, comprising a valve structure including a plurality of valve leaflets, A sealing layer having at least a portion disposed on the radially inner circumferential surface of the annular frame, configured to prevent cell proliferation from the patient's original tissue into the sealing layer when the artificial heart valve is implanted in the patient, Each of the aforementioned valve leaflets is The first part, First and second tabs on both sides of the first portion with respect to the center line of the first portion, each of the tabs having a base edge and an outer edge, and the outer edges of the first and second tabs being substantially parallel to each other, An artificial heart valve comprising: a second portion having a semi-elliptical or semi-elliptical shape defining a pointed edge, wherein the pointed edge extends from the base edge of the first tab to the base edge of the second tab, and the pointed edge curves along the entire length between the base edge of the first tab and the base edge of the second tab.

2. The artificial heart valve according to claim 1, wherein the sealing layer is substantially non-porous or has pores therein that are sized to prevent intracellular proliferation.

3. The artificial heart valve according to any one of claims 1 to 2, wherein the sealing layer is formed from a hydrophobic polymer material including polytetrafluoroethylene (PTFE), expanded PTFE (ePTFE), urethane, polyurethane (PU), thermoplastic PU (TPU), silicone, or a combination or copolymer thereof.

4. The artificial heart valve according to any one of claims 1 to 3, wherein the sealing layer includes lamination of a sublayer.

5. The annular frame further includes an inner skirt disposed on the radially inner surface, The inner skirt includes the sealing layer, Each valve leaflet has tabs on both sides and pointed edges that curve along at least a portion thereof, forming an apex at the centerline of the valve leaflet. The valve structure is connected to the annular frame by a plurality of commissure assemblies formed by pairs of tabs of adjacent valve leaflets. The inner skirt is positioned radially between the annular frame and the pointed edges of each valve leaflet, and extends along the axial direction of the annular frame, at least from the apex of the pointed edges to at least the plurality of connecting assembly parts. The artificial heart valve according to any one of claims 1 to 4, wherein the pointed edges of each valve leaflet are attached to the inner skirt.

6. The artificial heart valve according to claim 5, wherein the inner skirt further includes a scrim layer disposed in a region along the axial direction to which the pointed edge is attached.

7. An artificial heart valve according to any one of claims 5 to 6, further comprising one or more protective covers, each protective cover comprising a sealing layer of a hydrophobic polymer material, wherein the sealing layer of the hydrophobic polymer material is substantially non-porous or has pores therein that are sized to prevent intracellular growth, and the one or more protective covers are positioned on each radially outer surface portion of the annular frame on which the commissure assembly is formed.

8. An artificial heart valve according to any one of claims 1 to 7, further comprising an outer skirt disposed on at least a portion of the radial outer surface of the annular frame, the outer skirt extending along the axial direction of the annular frame.

9. The artificial heart valve according to claim 8, wherein the outer skirt comprises a sealing layer of a hydrophobic polymer material, the sealing layer of the hydrophobic polymer material being substantially non-porous or having pores therein that are sized to prevent intracellular proliferation.

10. The artificial heart valve according to any one of claims 1 to 4, wherein the sealing layer encloses the annular frame.

11. A method for assembling an artificial heart valve according to any one of claims 1 to 10, A valve structure containing multiple valve leaflets is arranged within an annular frame configured for expansion between a radially compressed configuration and a radially expanded configuration, The valve structure is connected to the annular frame via a plurality of commissure assemblies formed by the plurality of valve leaflets, A method comprising arranging at least a portion of a sealing layer on the radially inner surface of the annular frame, wherein the sealing layer is configured to prevent cell proliferation from the patient's original tissue into the sealing layer when the artificial heart valve is implanted in the patient.

12. An artificial heart valve, A radially foldable and expandable annular frame having an inlet end and an outlet end separated from the inlet end along the axial direction of the annular frame, between a radially compressed configuration and a radially expanded configuration, A valve structure supported within the annular frame and coupled to the annular frame, comprising a valve structure including a plurality of valve leaflets, A sealing layer having at least a portion disposed on the radially inner circumferential surface of the annular frame, configured to prevent cell proliferation from the patient's original tissue into the sealing layer when the artificial heart valve is implanted in the patient; The annular frame includes an inner skirt disposed on the radially inner surface of the annular frame, The inner skirt includes the sealing layer, Each valve leaflet has tabs on both sides and pointed edges that curve along at least a portion thereof, forming an apex at the centerline of the valve leaflet. The valve structure is connected to the annular frame by a plurality of commissure assemblies formed by pairs of tabs of adjacent valve leaflets. The inner skirt is positioned radially between the annular frame and the pointed edges of each valve leaflet, and extends along the axial direction of the annular frame, at least from the apex of the pointed edges to at least the plurality of connecting assembly parts. An artificial heart valve in which the pointed edges of each valve leaflet are attached to the inner skirt.

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