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`United States Patent Application
`Kind Code
`Nguyen; Than ; et al.
`
`( 1 of 1 )
`
`20110172765
`A1
`July 14, 2011
`
`Heart Valve Prosthesis and Methods of Manufacture and Use
`
`Abstract
`
`A heart valve prosthesis is provided having a self-expanding multi-level frame that supports a valve body
`comprising a skirt and plurality of coapting leaflets. The frame transitions between a contracted delivery
`configuration that enables percutaneous transluminal delivery, and an expanded deployed configuration
`having an asymmetric hourglass shape. The valve body skirt and leaflets are constructed so that the center of
`coaptation may be selected to reduce horizontal forces applied to the commissures of the valve, and to
`efficiently distribute and transmit forces along the leaflets and to the frame. Alternatively, the valve body
`may be used as a surgically implantable replacement valve prosthesis.
`
`Inventors: Nguyen; Than; (Placentia, CA) ; Nguyen; Hung; (Garden Grove, CA) ; Nguyen; Mykim;
`(Santa Ana, CA) ; Komatsu; Stanley; (Laguna Hills, CA) ; Michiels; Robrecht; (Laguna Hills,
`CA)
`Assignee: Medtronic CoreValve LLC
`Mounds View
`MN
`
`Family ID: 37420182
`Appl. No.: 13/072194
`March 25, 2011
`Filed:
`
`Related U.S. Patent Documents
`
`Application Number
`11128826
`13072194
`
`Filing Date
`May 13, 2005
`
`Patent Number
`7914569
`
`

`

`Current U.S. Class:
`Current CPC Class:
`
`Class at Publication:
`International Class:
`
`623/2.18 ; 623/2.17
`A61F 2/2412 20130101; A61F 2/2415 20130101; A61F 2/2418
`20130101
`623/2.18 ; 623/2.17
`A61F 2/24 20060101 A61F002/24
`
`Claims
`
`1. A valve prosthesis comprising: a valve body comprising a plurality of leaflets affixed to a skirt, adjoining
`leaflets affixed together to form commissures; and a frame supporting the valve body, the frame having a
`longitudinal axis, wherein the commissures are affixed to the frame along a region of the frame that increases
`in diameter along the longitudinal axis, wherein the commissures are longitudinally offset from the center of
`coaptation, and each leaflet has a free edge that is suspended from the leaflet's respective commissures to
`define coaptation edges and a center of coaptation, and wherein the length of each free edge forms a
`substantially continuous curve extending downwardly between the respective commissures so that the free
`edges of the leaflets generally define the shape of catenaries to substantially uniformly distribute loads over
`the leaflets.
`
`2. The valve prosthesis of claim 1, wherein the catenaries are configured to reduce horizontal loads applied to
`the commissures.
`
`3. The valve prosthesis of claim 1, wherein each leaflet is individually formed and comprises an enlarged
`lateral end having a plurality of flaps that are folded over to increase the durability of the commissures.
`
`4. The valve prosthesis of claim 1, wherein the skirt further comprises a plurality of longitudinally-oriented
`reinforcing tabs.
`
`5. The valve prosthesis of claim 1, wherein the leaflets comprise porcine, bovine, equine or other mammalian
`pericardial tissue, synthetic material, or polymeric material.
`
`6. The valve prosthesis of claim 1, wherein the frame is self expanding, and wherein the leaflets are affixed to
`the skirt at joints, and the joints are affixed to the frame to evenly distribute forces through the valve body to
`the frame.
`
`7. The valve prosthesis of claim 6, wherein the frame further comprises a cell pattern that defines a contour
`configured to support the joints.
`
`8. The valve prosthesis of claim 4, wherein the frame is self expanding, and wherein and the reinforcing tabs
`are affixed to the frame.
`
`9. The valve prosthesis of claim 1, wherein the frame is self expanding, and wherein the frame has a
`contracted delivery configuration and an expanded deployed configuration.
`
`10. The valve prosthesis of claim 9, wherein the frame comprises a cell pattern defined by unequal length zig-
`zags.
`
`11. The valve prosthesis of claim 9, wherein the commissures are affixed to the frame at a location proximal
`
`

`

`of the center of coaptation.
`
`12. The valve prosthesis of claim 9, wherein the frame comprises a cell pattern and the commissures include
`flaps that span an entire area of at least one cell of the cell pattern.
`
`13. The valve prosthesis of claim 9, wherein the skirt further comprises a plurality of end tabs adapted to be
`affixed to a proximal-most row of cells of the frame.
`
`14. The valve prosthesis of claim 9, wherein the valve body is deployed superannularly of a patient's aortic
`annulus when the valve prosthesis is delivered within a patient's aortic valve and the frame is in the expanded
`deployed configuration.
`
`15. The valve prosthesis of claim 9, wherein the frame is configured to hold a patient's native valve
`permanently open in the expanded deployed configuration.
`
`16. The valve prosthesis of claim 9, wherein the frame is configured to permit access to a patient's coronary
`arteries in the expanded deployed configuration.
`
`17. The valve prosthesis of claim 9, wherein the frame has proximal and distal ends and a plurality of cell
`patterns that vary in size between the proximal and distal ends.
`
`18. The valve prosthesis of claim 9, wherein the frame has, in the expanded deployed configuration, an
`enlarged outflow section with a first nominal diameter, a conical inflow section having a second nominal
`diameter and a constriction region having a third fixed diameter smaller than the first and second nominal
`diameters.
`
`19. The valve prosthesis of claim 18, wherein the conical section has a proximal end and the conical section
`flares outward towards the proximal end.
`
`20. The valve prosthesis of claim 18, wherein the constriction region comprises a plurality of cell patterns
`configured to provide a pre-determined radius of curvature for a transition from the constricted region to the
`outflow section.
`
`21. The valve prosthesis of claim 18, wherein the third fixed diameter is a predetermined diameter.
`
`22. The valve prosthesis of claim 1, wherein, when the valve is in the closed position, the length of each free
`edge forms a substantially continuous curve extending downwardly between the respective commissures so
`that the free edges of the leaflets generally define the shape of catenaries to substantially uniformly distribute
`loads over the leaflets.
`
`23. A valve prosthesis comprising: a valve body comprising three leaflets, wherein adjoining leaflets are
`sewn together to form commissures; and a self-expanding frame, the frame having an inflow section having a
`first row of cells, an outflow section having a second row of cells and including an eyelet, and a middle
`region between the inflow section and the outflow section, wherein the middle region is configured to avoid
`blocking blood flow to the coronary arteries when the frame is implanted in a body, wherein the area of
`individual cells in the first row of cells is less than the area of individual cells in the second row of cells,
`wherein the frame supports the valve body, wherein the frame has a longitudinal axis, wherein the frame has
`a contracted delivery configuration and an expanded deployed configuration, wherein, when the frame is in
`the expanded deployed configuration, the outflow section has a larger diameter than the inflow section,
`wherein a plurality of cells of the frame are positioned between the cells spanned by commissures, wherein
`
`

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`each leaflet has a free edge that is suspended from the leaflet's commissures to define coaptation edges and a
`center of coaptation, and wherein the length of each free edge forms a substantially continuous curve
`extending downwardly between the respective commissures so that the free edges of the leaflets generally
`define the shape of catenaries to substantially uniformly distribute loads over the leaflets.
`
`24. The valve prosthesis of claim 23, wherein the leaflets comprise porcine, bovine, equine or other
`mammalian pericardial tissue, synthetic material, or polymeric material.
`
`25. The valve prosthesis of claim 23, wherein the leaflets are sewn to a skirt at joints, wherein the skirt is
`sewn to the inflow section of the frame, and wherein the joints are affixed to the frame to evenly distribute
`forces through the valve body to the frame.
`
`26. The valve prosthesis of claim 25, wherein the frame further comprises a cell pattern that defines a contour
`configured to support the joints.
`
`27. The valve prosthesis of claim 23, wherein the frame comprises a cell pattern defined by unequal length
`zig-zags.
`
`28. The valve prosthesis of claim 23, wherein the commissures are affixed to the frame at a location proximal
`of the center of coaptation.
`
`29. The valve prosthesis of claim 23, wherein the commissures include flaps that span an entire area a cell.
`
`30. The valve prosthesis of claim 23, wherein the frame is configured to permit access to a patients coronary
`arteries in the expanded deployed configuration.
`
`31. The valve prosthesis of claim 23, wherein at least one cell in the outflow section is larger than at least one
`cell in the inflow section.
`
`32. The valve prosthesis of claim 23, wherein a cell in the outflow section has a first area, wherein a cell in
`the inflow section has a second area, and wherein the first area is larger than the second area.
`
`33. The valve prosthesis of claim 23, wherein the inflow section includes a first row of cells, wherein the
`outflow section includes a second row of cells, and wherein the number of cells in the first row of cells is
`equal to the number of cells in the second row of cells.
`
`34. The valve prosthesis of claim 23, wherein the middle region and the outflow section comprise a cell
`pattern that provides a pre-determined radius of curvature for a transition from the middle region to the
`outflow section when the frame is in the expanded deployed configuration.
`
`35. The valve prosthesis of claim 23, wherein the diameter of the constriction region is less than the diameter
`of the inflow section.
`
`36. The valve prosthesis of claim 23, wherein the outflow section includes exactly three eyelets.
`
`37. The valve prosthesis of claim 23, wherein the frame includes four rows of cells.
`
`38. A valve prosthesis comprising: a valve body comprising three leaflets, wherein adjoining leaflets are
`sewn together to form commissures; and a self-expanding frame comprising a plurality of cells, the frame
`having an inflow section, an outflow section, and a middle region between the inflow section and the outflow
`
`

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`section, wherein the middle region is configured to avoid blocking blood flow to the coronary arteries when
`the frame is implanted in a body, wherein the frame supports the valve body, wherein the frame has a
`longitudinal axis, wherein the frame has a contracted delivery configuration and an expanded deployed
`configuration, wherein, when the frame is in the expanded deployed configuration, the outflow section has a
`larger diameter than the inflow section, wherein each commissure is configured to span a cell of the frame to
`distribute force within the commissures and to the frame, and wherein a plurality of cells of the frame are
`positioned between the cells spanned by commissures, wherein each leaflet has a free edge that is suspended
`from the leaflet's commissures to define coaptation edges and a center of coaptation, and wherein the length
`of each free edge forms a substantially continuous curve extending downwardly between the respective
`commissures so that the free edges of the leaflets generally define the shape of catenaries to substantially
`uniformly distribute loads over the leaflets.
`
`Description
`
`BACKGROUND OF THE INVENTION
`
`[0001] 1. Field of the Invention
`
`[0002] The present invention relates to replacement valves for improving the cardiac function of a patient
`suffering from cardiac valve dysfunction, such as aortic valve regurgitation or aortic stenosis. More
`particularly, the present invention relates to heart valve prostheses that provide improved durability and are
`particularly well-suited for percutaneous delivery.
`
`[0003] 2. Background of the Invention
`
`[0004] Heart valve replacement has become a routine surgical procedure for patients suffering from valve
`regurgitation or stenotic calcification of the leaflets. While certain procedures may be performed using
`minimally-invasive techniques (so-called "keyhole" techniques), the vast majority of valve replacements
`entail full sternotomy and placing the patient on cardiopulmonary bypass. Traditional open surgery inflicts
`significant patient trauma and discomfort, requires extensive recuperation times and may result in life-
`threatening complications.
`
`[0005] To address these concerns, within the last decade efforts have been made to perform cardiac valve
`replacements using minimally-invasive techniques. In these methods, laparascopic instruments are employed
`to make small openings through the patient's ribs to provide access to the heart. While considerable effort has
`been devoted to such techniques, widespread acceptance has been limited by the clinician's ability to access
`only certain regions of the heart using laparoscopic instruments.
`
`[0006] Still other efforts have been focused on percutaneous transluminal delivery of replacement cardiac
`valves to solve the problems presented by traditional open surgery and minimally-invasive surgical methods.
`In such methods; a valve prosthesis is compacted for delivery in a catheter and then advanced, for example,
`through an opening in the femoral artery and through the descending aorta to the heart, where the prosthesis
`then is deployed in the aortic valve annulus. Although transluminal techniques have attained widespread
`acceptance with respect to delivery of stents to restore vessel patency, only mixed results have been obtained
`with respect to percutaneous delivery of relatively more complicated valve prostheses.
`
`[0007] One such example of a previously-known device heart valve prosthesis is described in U.S. Pat. No.
`6,454,799 to Schreck. The prosthesis described in that patent comprises a fabric-based heart valve disposed
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`

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`within a plastically deformable wire-mesh base, and is delivered via expansion of a balloon catheter. One
`drawback with balloon catheter delivery of the prosthetic valve is that the valve leaflets may be damaged
`when compressed between the balloon and the base during deployment. In addition, because balloon
`expandable structures tend to experience some recoil following balloon deflation, perivalvular leaks may
`develop around the circumference of the valve prosthesis.
`
`[0008] Accordingly it would be desirable to provide a percutaneously-deliverable valve prosthesis that
`reduces the risk of leaflet damage during deployment of the prosthesis. It further would be. desirable to
`provide a valve prosthesis that reduces the risk of perivalvular leaks resulting from recoil of the prosthesis
`following deployment.
`
`[0009] U.S. Pat. No. 6,027,525 to Suh, et al. describes a valve prosthesis comprising a series of self-
`expanding units affixed to a polymeric cover and having a valve disposed therein. Such devices are not
`suitable for cardiac valve replacement because of the limited ability to compact the valve disposed within the
`prosthesis. Moreover, such valve prostheses would be particularly undesirable for treating aortic valve
`defects, because the polymeric cover would obscure the ostia of the coronary arteries, both disrupting blood
`flow to the coronary arteries and preventing subsequent catheterization of those arteries. Accordingly, it
`would be desirable to provide a valve prosthesis that is self-expanding, yet permits the valve to be compacted
`to a greater degree than previously-known designs.
`
`[0010] U.S. Pat. No. 6,682,559 to Myers, et al. also describes a valve prosthesis having an essentially tubular
`design. One drawback of such configurations is that relatively large horizontal forces arise along the
`coaptation edges of the leaflets and are transmitted to the commissural points. These forces may adversely
`affect the durability of the leaflets and lead to valve failure. In view of this, it would be desirable to provide a
`valve wherein the center of coaptation of the leaflets may be selected so as to reduce horizontal forces applied
`to coaptation edges of the leaflets and commissural points, thereby improving durability of the valve. In
`addition, it would be desirable to provide a valve design that more uniformly distributes horizontal forces
`over the coaptation edges of the leaflets, rather than concentrating those forces at the commissural points.
`
`[0011] In an effort to more nearly recreate the force distribution along the leaflets of natural tissue valves,
`some previously-known valve designs include circular base portions having longitudinal projections that
`function as anchors for the commissural points, such as described in U.S. Pat. No. 5,855,601 to Bessler, et al.
`and U.S. Pat. No. 6,582,462 to Andersen, et al.
`
`[0012] While the valve prostheses of Bessler and Andersen may be readily collapsed for delivery, those
`designs are susceptible to problems once deployed. For example, the longitudinal projections of such
`prostheses may not provide sufficient rigidity to withstand compressive forces applied during normal
`movements of the heart. Deformation of the commissural anchors may result in varied forces being imposed
`on the commissures and leaflets, in turn adversely impact functioning of the leaflets. In addition, because the
`exteriors of the foregoing valve prostheses are substantially cylindrical, the prostheses are less likely to
`adequately conform to, and become anchored within the valve annulus anatomy during deployment. As a
`result, cyclic loading of the valve may result in some slippage or migration of the anchor relative to the
`patient's anatomy.
`
`[0013] In view of the foregoing, it would be desirable to provide a valve that is capable of conforming to a
`patient's anatomy while providing a uniform degree of rigidity and protection for critical valve components.
`It therefore would be desirable to provide a valve prosthesis having portions that are capable of deforming
`circumferentially to adapt to the shape of the pre-existing valve annulus, but which is not susceptible to
`deformation or migration due to normal movement of the heart. Still further, it would be desirable to provide
`a valve prosthesis having a multi-level component that is anatomically shaped when deployed, thereby
`
`

`

`enhancing anchoring of the valve and reducing the risk of migration and perivalvular leaks.
`
`BRIEF SUMMARY OF THE INVENTION
`
`[0014] In view of the foregoing, it is an object of the present invention to provide a valve prosthesis that
`overcomes the drawbacks of previously-known designs, and which may be implanted using open surgical,
`minimally invasive or percutaneous implantation techniques.
`
`[0015] It is also an object of the present invention to provide a percutaneously-deliverable valve prosthesis
`that reduces the risk of leaflet damage during deployment of the prosthesis.
`
`[0016] It is a further object of this invention to provide a valve prosthesis that reduces the risk of perivalvular
`leaks resulting from elastic recoil of the prosthesis following deployment.
`
`[0017] It is another object of the present invention to provide a valve prosthesis that is self-expanding, yet
`permits the valve to be compacted to a greater degree than previously-known designs and permits ready
`access to adjoining anatomical structures, such as the coronary arteries.
`
`[0018] It is a still further object of the present invention to provide a valve in which the center of coaptation
`of the leaflets may be selected so as to reduce horizontal forces applied to coaptation edges of the leaflets and
`commissural points, thereby improving durability of the valve.
`
`[0019] In addition, it is an object of this invention to provide a valve design that more uniformly distributes
`forces over the coaptation edges of the leaflets, rather than concentrating those forces at the commissural
`points.
`
`[0020] It is yet another object of this invention to provide a valve that is anatomically shaped, provides a
`uniform high degree of rigidity and protection for critical valve components, and which is less susceptible to
`deformation arising from normal movement of the heart.
`
`[0021] It is an object of the present invention to provide a valve prosthesis having portions that are capable of
`deforming circumferentially to adapt to the shape of the pre-existing valve annulus, but which is not
`susceptible to deformation or migration due to normal movement of the heart.
`
`[0022] It is also an object of this invention to provide a valve prosthesis having a multi-level component that
`is anatomically shaped when deployed, thereby enhancing anchoring of the valve and reducing the risk of
`migration and perivalvular leaks.
`
`[0023] It is a further object of the present invention to provide a valve prosthesis wherein a valve is disposed
`within a rigid portion of a multilevel frame, so that valve area and function are not impaired, but inflow
`and/or outflow portions of the multilevel frame are capable of conforming to patient anatomy anomalies.
`
`[0024] It is a further object of the present invention to provide a valve prosthesis that facilitates alignment of
`the heart valve prosthesis with the direction of blood flow.
`
`[0025] These and other objects of the present invention are accomplished by providing a heart valve
`prosthesis wherein a self-expanding multi-level frame supports a valve body comprising a skirt and plurality
`of coapting leaflets. The frame has a contracted delivery configuration, in which the prosthesis may be stored
`within a catheter for percutaneous delivery, and an expanded deployed configuration having an asymmetric
`hourglass shape. The valve body skirt and leaflets preferably are constructed of porcine, bovine, equine or
`
`

`

`other mammalian tissue, such as pericardial tissue, and are sewn, welded, molded or glued together so as to
`efficiently distribute forces along the leaflets and to the frame. Alternatively, the valve body may comprise a
`synthetic or polymeric material.
`
`[0026] In accordance with the principles of the present invention, the frame comprises multiple levels,
`including a proximal conical inflow section, a constriction region and a flared distal outflow section. Each of
`the inflow and outflow sections is capable of deforming to a non-circular cross-section to conform to the
`patient's anatomy, while the constriction region is configured to retain a circular cross-section that preserves
`proper functioning of the valve body.
`
`[0027] The frame comprises a plurality of cells having a pattern that varies along the length of the frame to
`provide a high degree of anchoring and alignment of the valve prosthesis. The cell pattern further is selected
`to provide a uniform diameter where the commissural joints of the leaflets are attached to the frame, while
`permitting the inflow and outflow regions to expand to conform to the patient's anatomy. In this manner,
`optimal functioning of the valve body may be obtained even though the frame may be deployed in anatomies
`having a range of sizes. In addition, the frame resists deformation caused by movement of the heart and
`enables a functional portion of the valve body to be disposed supra-annularly to the native valve, with a
`portion of the valve prosthesis extending into the native valve annulus.
`
`[0028] In one embodiment suitable for aortic valve replacement, the valve body comprises a skirt coupled to
`three leaflets. Each of the components preferably is formed of animal pericardial tissue or synthetic material,
`and then sewn, glued, welded or molded together. The lateral ends of the leaflets include enlarged regions
`that are folded to both form the commissural joints and fasten the commissural joints to the frame. The skirt
`and leaflets further are configured so that the joints align with contours of the cell pattern of the frame.
`
`[0029] In a preferred embodiment, the commissural joints are affixed to the frame at locations above the area
`of coaptation, to provide a selectable center of coaptation of the leaflets. This design provides a more
`efficient delivery configuration because the commissures are not compressed against the leaflets when the
`valve prosthesis is reduced to the contracted delivery configuration. Additionally, by lengthening the distance
`to the commissures, the design mimics the functioning of natural tissue valves by distributing forces along
`the coaptation edges and reducing horizontal forces transmitted to the commissural joints.
`
`[0030] In alternative embodiments, the valve body of the present invention may include a sewing ring in lieu
`of the frame to facilitate surgical implantation, and may employ as few as two and as many as four leaflets.
`
`[0031] Methods of making and using the valve prostheses of the present invention are also provided.
`
`BRIEF DESCRIPTION OF THE DRAWINGS/FIGURES
`
`[0032] The above and other objects and advantages of the present invention will be apparent upon
`consideration of the following detailed description, taken in conjunction with the accompanying drawings, in
`which like reference numerals refer to like parts throughout, and in which:
`
`[0033] FIGS. 1A, 1B and 1C are, respectively, side and top end views of an exemplary valve prosthesis of the
`present invention in the expanded deployed configuration and an enlarged region of the frame of the valve
`prosthesis;
`
`[0034] FIG. 2 is a side view of the frame of the valve prosthesis of FIG. 1 in a contracted delivery
`configuration;
`
`

`

`[0035] FIGS. 3A and 3B are, respectively, plan views of a leaflet and the skirt employed in the valve body of
`the present invention;
`
`[0036] FIGS. 4A and 4B are, respectively, a perspective view of a leaflet with its enlarged regions folded,
`and a plan view of the valve body of the present invention, wherein the leaflets are fastened to the skirt;
`
`[0037] FIG. 5 is a side view of the valve body of FIG. 4B fully assembled; and
`
`[0038] FIG. 6 is a side view depicting the valve prosthesis of the present invention deployed atop a patient's
`aortic valve.
`
`DETAILED DESCRIPTION OF THE INVENTION
`
`[0039] The present invention is directed to a heart valve prosthesis having a self-expanding frame that
`supports a valve body. In a preferred embodiment, the frame has a tri-level asymmetric hourglass shape with
`a conical proximal section, an enlarged distal section and a constriction region having a predefined curvature
`when the frame is deployed. In the context of the present application, the proximal section constitutes the
`"inflow" portion of the valve prosthesis and is disposed in the aortic annulus of the patient's left ventricle,
`while the distal section constitutes the "outflow" portion of the valve prosthesis and is positioned in the
`patient's ascending aorta.
`
`[0040] In a preferred embodiment the valve body comprises three leaflets that are fastened together at
`enlarged lateral end regions to form commissural joints, with the unattached edges forming the coaptation
`edges of the valve. The leaflets are fastened to a skirt, which is in turn affixed to the frame. The enlarged
`lateral end regions of the leaflets permit the material to be folded over to enhance durability of the valve and
`reduce stress concentration points that could lead to fatigue or tearing of the leaflets. The commissural joints
`are mounted above the plane of the coaptation edges of the valve body to minimize the contracted delivery
`profile of the valve prosthesis, while the configuration of the edges permits uniform stress distribution along
`the coaptation edges.
`
`[0041] Referring to FIG. 1, an exemplary embodiment of a valve prosthesis constructed in accordance with
`the principles of the present invention is described. Valve prosthesis 10 comprises expandable frame 12
`having valve body 14 affixed to its interior surface, e.g., by sutures. Frame 12 preferably comprises a self-
`expanding structure formed by laser cutting or etching a metal alloy tube comprising, for example, stainless
`steel or a shape memory material such as nickel titanium. The frame has an expanded deployed configuration
`which is impressed upon the metal alloy tube using techniques that are per se known in the art. Valve body
`14 preferably comprises individual leaflets assembled to a skirt, where all of the components are formed from
`a natural or man-made material. Preferred materials for valve body 14 include mammalian tissue, such as
`porcine, equine or bovine pericardium, or a synthetic or polymeric material.
`
`[0042] Frame 12 preferable includes multiple levels, including outflow section 15, inflow section 16 and
`constriction region 17. As depicted in the enlarged view of FIG. 1B, the frame comprises a plurality of cells
`having sizes that vary along the length of the prosthesis. As indicated by dotted lines a, b and c, each cell
`comprises two zig-zag structures having unequal-length struts, wherein the vertices of the zig-zags are
`coupled together. For example, zig-zag 18 has length z.sub.1 whereas zig-zag 19 has greater length Z.sub.2.
`This cell design permits each level of cells between the proximal and distal ends of the frame to be tailored to
`meet specific design requirements, such as, compressibility, expansion characteristics, radial strength and so
`as to define a suitable contour for attachment of the valve body.
`
`[0043] The cell pattern of frame 12 also enables the frame to expand to the tri-level asymmetric hourglass
`
`

`

`shape depicted in FIG. 1A, having conical inflow section, enlarged outflow section and fixed diameter
`constricted region. Each section of frame 12 has a substantially circular cross-section in the expanded
`deployed configuration, but in addition the cell patterns of the inflow and outflow sections permit those
`sections to adapt to the specific anatomy of the patient, thereby reducing the risk of migration and reducing
`the risk of perivalvular leaks. The cell patterns employed in the constriction region are selected to provide a
`uniform circular cross-section area for the constriction region when deployed, and a pre-determined radius of
`curvature for the transition between the constriction region and outflow section of the frame. In particular, the
`convex-concave shape of frame 12 within the constriction region ensures that the frame is held away from the
`opposing sinus wall in the ascending aorta, thus ensuring adequate blood flow to the coronary arteries and
`facilitating catheter access to the coronary arteries.
`
`[0044] Enlarged outflow section has nominal deployed diameter D.sub.o, inflow section has nominal
`deployed diameter D.sub.I, and constriction region has deployed substantially fixed diameter D.sub.c. The
`conical shape of the inflow region and smooth transitions between adjacent sections of frame 12 are expected
`to be particularly advantageous in directing blood flow through the valve body with little or no turbulence, as
`compared to step changes in diameter observed for surgically implanted replacement valves.
`
`[0045] The above-described cell pattern permits each of the inflow and outflow sections of frame 12 to
`expand to a diameter within a range of deployed diameters, while retaining constriction region 17 at a
`substantially constant diameter. Thus, for example, outflow diameter D.sub.o may range from 30 to 55 mm,
`while inflow diameter D.sub.I may vary from 19 to 34 mm. Illustratively, frame 12 may be manufactured in
`four sizes having a range of diameters D.sub.o, D.sub.I and D.sub.o as set forth in Table 1 below:
`
`TABLE-US-00001 TABLE 1 Size A Size B Size C Size D D.sub.o 40 mm 50 mm 40 mm 50 mm D.sub.c 22
`mm 22 mm 24 mm 24 mm D.sub.I 26 mm 26 mm 29 mm 29 mm
`
`[0046] Advantageously, these four frame sizes are expected to cover a wide range of patient anatomies, while
`requiring construction of only two sizes of valve bodies (22 and 24 mm). Compared to previously-known
`commercially available surgical valves, which vary from approximately 17 mm to 31 mm in one millimeter
`increments, it is expected that the above four sizes of valve prosthesis of the present invention could be used
`for more than 75% of the patient population, thus greatly 20 reducing the costs associated with manufacturing
`and inventorying large numbers of parts.
`
`[0047] When configured as a replacement for an aortic valve, inflow section 16 extends into and anchors
`within the aortic annulus of a patient's left ventricle and 25 outflow section 15 is positioned in the patient's
`ascending aorta. Importantly, the configuration of outflow section 15 is expected to provide optimal
`al