MEDICAL DEVICE THAT INCLUDES A REFRACTORY METAL ALLOY

Abstract

A medical device that is at least partially formed of a refractory metal alloy, and a method for inserting the medical device in a patient.

Claims

1. A medical device for implantation into a body passageway; said medical device includes an expandable metal frame that is configured to expand in the body passageway when said medical device is positioned in a treatment site in the body passageway; said expandable metal frame expandable to an outer diameter of at least 25 mm; at least 50 wt. % of said expandable metal frame formed of a refractory metal alloy; said refractory metal alloy is not a self-expanding metal alloy; said expandable metal frame of said medical device includes a plurality of struts and strut joints; said expandable metal frame has a) a plurality of strut joints that is less than 0.7 mm, b) a plurality of struts having an average width along a longitudinal of said strut that is no more than 0.3 mm, c) a recoil percentage of less than 5% when said expandable metal frame is crimped to a crimped state, d) a recoil of less than 5% when said expandable metal frame is expanded from said crimped state, and/or e) a foreshortening percentage of less than 20% when said expandable metal frame is expanded from said crimped state.

2. The medical device as defined in claim 1, wherein said expandable metal frame i) has a recoil percentage of no more than 2% when said expandable metal frame is crimped to a crimped state, ii) a recoil of no more than 2% when said expandable metal frame is expanded from said crimped state, and/or iii) a foreshortening percentage of no more than 15% when said expandable metal frame is expanded from said crimped state.

3. The medical device as defined in claim 1, wherein, said refractory metal alloy is selected from the group consisting of MoRe alloy, ReW alloy, MoReCr alloy, MoReTa alloy, MoReTi alloy, WCu alloy, ReCr alloy, Mo alloy, Re alloy, W alloy, Ta alloy, and Nb alloy, said refractory metal alloy includes at least 20 wt. % of one or more of Mo, Re, Nb, Ta or W.

4. The medical device as defined in claim 1, wherein, said refractory metal alloy includes 30-60 wt. % Re and 40-70 wt. % one or more metal additives selected from the group consisting of Mo, Bi, Nb, Ni, Ta, Ti, V, W, Mn, Zr, Ir, Tc, Ru, Rh, Hf, Os, Cu, and Y.

5. The medical device as defined in claim 1, wherein, said refractory metal alloy includes 30-60 wt. % Re and 40-70 wt. % Mo.

6. The medical device as defined in claim 1, wherein said expandable metal frame that includes said refractory metal alloy I) has a hydrophilicity wherein a contact angle of a water droplet on a surface of said refractory metal alloy on said expandable metal frame is 25-45°, and/or II) said refractory metal alloy on said expandable metal frame has a maximum ion release of a primary component of said refractory metal alloy when inserted or implanted on or in the body of the patient of no more than 0.5 μg/cm.sup.2 per day, wherein said primary component constitutes at least 2 wt. % of said refractory metal alloy.

7. The medical device as defined in claim 1, wherein said medical device is an expandable stent, and expandable valve, expandable graph, or expandable sheath.

8. The medical device as defined in claim 1, wherein said medical device is a prosthetic heart valve; said prosthetic heart valve includes said expandable metal frame, a leaflet structure supported by said expandable metal frame, and an inner skirt secured to said expandable metal frame; said expandable metal frame A) having at least 10% less material as compared to a similar shaped frame formed of CoCr alloy and/or TiNi alloy that can be expanded outer diameter of at least 25 mm, and wherein said expandable metal frame has the same or greater ultimate tensile strength, greater yield strength, greater elastic deformation latitude, greater stress to plastic deformation and failure, greater stiffness, greater strength, greater durability, and/or greater fatigue ductility as compared to a said similar shaped frame formed of CoCr alloy and/or TiNi alloy, B) having at least 10% greater conformity to a treatment area when expanded as comparted to a similar shaped frame formed of CoCr alloy and/or TiNi alloy that can be expanded outer diameter of at least 25 mm, C) having at least a 10% greater hydrophilicity as compared to Tin a similar shaped frame formed of CoCr alloy and/or TiNi alloy that can be expanded outer diameter of at least 25 mm, D) having at least 20% less corrosion and/or metal ion release when exposed to fluid in a blood vessel as compared to a similar shaped frame formed of CoCr alloy and/or TiNi alloy that can be expanded outer diameter of at least 25 mm.

9. The prosthetic heart valve as defined in claim 8, wherein said expandable metal frame is a radially collapsible and expandable annular frame, said expandable metal frame includes a plurality of rows and wherein each row is formed of a plurality of struts; said leaflet structure comprising a plurality of leaflets, each of said leaflets has an upper edge portion, a lower edge portion and two side flaps, wherein each side flap is connected to an adjacent side flap of another leaflet, at least a portion of said leaflet structure connected to said expandable metal frame.

10. The prosthetic heart valve as defined in claim 8, wherein said leaflet structure is attached to said expandable metal frame using a plurality of sutures, staples or adhesive.

11. A method for crimping an expandable medical device on a medical device delivery system, said method comprising: a. providing said expandable medical device that includes an expandable metal frame; at least 50 wt. % of said expandable metal frame is formed of a refractory metal alloy; said refractory metal alloy is not a self-expanding metal alloy; b. positioning said expandable metal frame of said medical device about a portion of said medical device delivery system; and, c. crimping said expandable metal frame of said expandable medical device on to at least a portion of said medical device delivery system by applying radial forces on an outer perimeter of at least a portion of said expandable medical device; and, d. removing said radial forces on said outer perimeter of at least a portion of said expandable medical device after said expandable frame has been crimped to said crimped state; said expandable frame having no more than 5% recoil after said radial forces have been removed on said outer perimeter of at least a portion of said expandable medical device.

12. The method as defined in claim 11, wherein said expandable metal frame has a recoil percentage of no more than 2% when said expandable metal frame is crimped to a crimped state.

13. The method as defined in claim 11, wherein, said refractory metal alloy is selected from the group consisting of MoRe alloy, ReW alloy, MoReCr alloy, MoReTa alloy, MoReTi alloy, WCu alloy, ReCr alloy, Mo alloy, Re alloy, W alloy, Ta alloy, and Nb alloy, said refractory metal alloy includes at least 20 wt. % of one or more of Mo, Re, Nb, Ta or W.

14. The method as defined in claim 11, wherein, said refractory metal alloy includes 30-60 wt. % Re and 40-70 wt. % one or more metal additives selected from the group consisting of Mo, Bi, Nb, Ni, Ta, Ti, V, W, Mn, Zr, Ir, Tc, Ru, Rh, Hf, Os, Cu, and Y.

15. The method as defined in claim 11, wherein, said refractory metal alloy includes 30-60 wt. % Re and 40-70 wt. % Mo.

16. The method as defined in claim 11, wherein said expandable metal frame that includes said refractory metal alloy I) has a hydrophilicity wherein a contact angle of a water droplet on a surface of said refractory metal alloy on said expandable metal frame is 25-45°, and/or II) said refractory metal alloy on said expandable metal frame has a maximum ion release of a primary component of said refractory metal alloy when inserted or implanted on or in the body of the patient of no more than 0.5 μg/cm.sup.2 per day, wherein said primary component constitutes at least 2 wt. % of said refractory metal alloy.

17. The method as defined in claim 11, wherein said medical device is an expandable stent, and expandable valve, expandable graph, or expandable sheath.

18. The method as defined in claim 11, wherein said medical device is a prosthetic heart valve; said prosthetic heart valve includes said expandable metal frame, a leaflet structure supported by said expandable metal frame, and an inner skirt secured to said expandable metal frame; said expandable metal frame A) having at least 10% less material as compared to a similar shaped frame formed of CoCr alloy and/or TiNi alloy that can be expanded outer diameter of at least 25 mm, and wherein said expandable metal frame has the same or greater ultimate tensile strength, greater yield strength, greater elastic deformation latitude, greater stress to plastic deformation and failure, greater stiffness, greater strength, greater durability, and/or greater fatigue ductility as compared to a said similar shaped frame formed of CoCr alloy and/or TiNi alloy, B) having at least 10% greater conformity to a treatment area when expanded as comparted to a similar shaped frame formed of CoCr alloy and/or TiNi alloy that can be expanded outer diameter of at least 25 mm, C) having at least a 10% greater hydrophilicity as compared to re a similar shaped frame formed of CoCr alloy and/or TiNi alloy that can be expanded outer diameter of at least 25 mm, D) having at least 20% less corrosion and/or metal ion release when exposed to fluid in a blood vessel as compared to a similar shaped frame formed of CoCr alloy and/or TiNi alloy that can be expanded outer diameter of at least 25 mm.

19. The method as defined in claim 11, wherein said step of crimping causing a cross-sectional area of said expandable frame prior to said step of crimping to be reduced in cross-sectional area by at least 50%.

20. A method for delivering an expandable medical device to a treatment area in a body passageway, said method comprising: a. providing said expandable medical device that has been crimped on medical device delivery system; said expandable medical device includes an expandable metal frame that is in a crimped state; at least 50 wt. % of said expandable metal frame is formed of a refractory metal alloy; said refractory metal alloy is not a self-expanding metal alloy; said expandable metal frame of said medical device includes a plurality of struts and strut joints; b. inserting said expandable medical device and at least a portion of said medical device delivery system into said body passageway; c. moving said expandable medical device and at least a portion of said medical device delivery system to a treatment area in said body passageway; d. expanding said expandable metal frame of said expandable medical device at said treatment area; and wherein said expandable metal frame having less than 5% recoil after being expanded from said crimped stated in said treatment area, and wherein said expandable metal frame having less than 20% foreshortening after being expanded from said crimped stated in said treatment area.

21. The method as defined in claim 20, wherein said expandable metal frame is configured to expand to an outer diameter of at least 25 mm; said expandable frame includes a) a plurality of strut joints that is less than 0.7 mm, and b) a plurality of struts having an average width along a longitudinal of said strut that is no more than 0.3 mm.

22. The method as defined in claim 20, wherein said expandable metal frame i) a recoil of no more than 2% when said expandable metal frame is expanded from said crimped state, and/or ii) a foreshortening percentage of no more than 15% when said expandable metal frame is expanded from said crimped state.

23. The method as defined in claim 20, wherein, said refractory metal alloy is selected from the group consisting of MoRe alloy, ReW alloy, MoReCr alloy, MoReTa alloy, MoReTi alloy, WCu alloy, ReCr alloy, Mo alloy, Re alloy, W alloy, Ta alloy, and Nb alloy, said refractory metal alloy includes at least 20 wt. % of one or more of Mo, Re, Nb, Ta or W.

24. The method as defined in claim 20, wherein, said refractory metal alloy includes 30-60 wt. % Re and 40-70 wt. % one or more metal additives selected from the group consisting of Mo, Bi, Nb, Ni, Ta, Ti, V, W, Mn, Zr, Ir, Tc, Ru, Rh, Hf, Os, Cu, and Y.

25. The method as defined in claim 20, wherein, said refractory metal alloy includes 30-60 wt. % Re and 40-70 wt. % Mo.

26. The method as defined in claim 20, wherein said expandable metal frame that includes said refractory metal alloy I) has a hydrophilicity wherein a contact angle of a water droplet on a surface of said refractory metal alloy on said expandable metal frame is 25-45°, and/or II) said refractory metal alloy on said expandable metal frame has a maximum ion release of a primary component of said refractory metal alloy when inserted or implanted on or in the body of the patient of no more than 0.5 μg/cm.sup.2 per day, wherein said primary component constitutes at least 2 wt. % of said refractory metal alloy.

27. The method as defined in claim 20, wherein said medical device is an expandable stent, and expandable valve, expandable graph, or expandable sheath.

28. The method as defined in claim 20, wherein said medical device is a prosthetic heart valve; said prosthetic heart valve includes said expandable metal frame, a leaflet structure supported by said expandable metal frame, and an inner skirt secured to said expandable metal frame; said expandable metal frame A) having at least 10% less material as compared to a similar shaped frame formed of CoCr alloy and/or TiNi alloy that can be expanded outer diameter of at least 25 mm, and wherein said expandable metal frame has the same or greater ultimate tensile strength, greater yield strength, greater elastic deformation latitude, greater stress to plastic deformation and failure, greater stiffness, greater strength, greater durability, and/or greater fatigue ductility as compared to a said similar shaped frame formed of CoCr alloy and/or TiNi alloy, B) having at least 10% greater conformity to a treatment area when expanded as comparted to a similar shaped frame formed of CoCr alloy and/or TiNi alloy that can be expanded outer diameter of at least 25 mm, C) having at least a 10% greater hydrophilicity as compared to re a similar shaped frame formed of CoCr alloy and/or TiNi alloy that can be expanded outer diameter of at least 25 mm, D) having at least 20% less corrosion and/or metal ion release when exposed to fluid in a blood vessel as compared to a similar shaped frame formed of CoCr alloy and/or TiNi alloy that can be expanded outer diameter of at least 25 mm.

29. The method as defined in claim 20, wherein said step of expanding is at least partially by use of an inflatable balloon that can be inflated, and partially and fully deflated; said inflatable balloon configured to create outward radial force on at least a portion of an interior of said expandable metal frame to at least partially cause said expansion of said expandable metal frame.

30. An expandable medical device that is configured to be inserted or implanted on or in the body of a patient; said expandable medical device includes an expandable metal frame at least partially formed of a refractory metal alloy; said expandable metal frame including a plurality of struts, said expandable metal frame configured to be crimped to a crimped state such that a maximum outer diameter of said expandable metal frame when in said crimped state is at least 50% less than a maximum outer diameter of said expandable metal frame when expanded to an expanded state; said refractory metal alloy is not a self-expanding metal alloy; said refractory metal alloy selected from the group of alloys consisting of MoRe alloy, ReW alloy, MoReCr alloy, MoReTa alloy, MoReTi alloy, WCu alloy, ReCr alloy, molybdenum alloy, rhenium alloy, tungsten alloy, tantalum alloy, and niobium alloy; said refractory metal alloy including at least 20 wt. % of one or more metals selected from the group consisting of molybdenum, rhenium, tungsten, tantalum, and niobium; said refractory metal including less than 0.05 wt. % impurities; said expandable metal frame having two or more properties selected form the group consisting of a) a recoil of less than 5% after being subjected to a first crimping process, b) a recoil of less than 5% after being expanded from said crimped state to said expanded state, c) a foreshortening percentage of less than 20% when said expandable metal frame is expanded from said crimped state, d) a hydrophilicity wherein a contact angle of a water droplet on a surface of said refractory metal alloy of said expandable metal frame is 25-45°, e) a maximum ion release of a primary component of said refractory metal alloy form said expandable metal frame when inserted or implanted on or in the body of the patient of no more than 0.5 μg/cm.sup.2 per day, wherein said primary component constitutes at least 2 wt. % of said refractory metal alloy, and f) an absolute increase in ion release per dose of refractory metal alloy in tissue about said expandable metal frame medical device after said expandable metal frame is inserted or implanted on or in the body of a patient for at least 90 days of no more than 50.

31. The expandable medical device as defined in claim 30, wherein said expandable metal frame is expandable to an outer diameter of at least 25 mm; at least 50 wt. % of said expandable metal frame formed of a refractory metal alloy; said expandable metal frame of said medical device includes a plurality of struts and strut joints; said expandable metal frame has a) a plurality of strut joints that is less than 0.7 mm, b) a plurality of struts having an average width along a longitudinal of said strut that is no more than 0.3 mm.

32. The expandable medical device as defined in claim 30, wherein said expandable metal frame i) has a recoil percentage of no more than 2% when said expandable metal frame is crimped to a crimped state, ii) a recoil of no more than 2% when said expandable metal frame is expanded from said crimped state, and/or iii) a foreshortening percentage of no more than 15% when said expandable metal frame is expanded from said crimped state.

33. The expandable medical device as defined in claim 30, wherein, said refractory metal alloy is selected from the group consisting of MoRe alloy, ReW alloy, MoReCr alloy, MoReTa alloy, MoReTi alloy, WCu alloy, ReCr alloy, Mo alloy, Re alloy, W alloy, Ta alloy, and Nb alloy, said refractory metal alloy includes at least 20 wt. % of one or more of Mo, Re, Nb, Ta or W.

34. The expandable medical device as defined in claim 30, wherein, said refractory metal alloy includes 30-60 wt. % Re and 40-70 wt. % one or more metal additives selected from the group consisting of Mo, Bi, Nb, Ni, Ta, Ti, V, W, Mn, Zr, Ir, Tc, Ru, Rh, Hf, Os, Cu, and Y.

35. The expandable medical device as defined in claim 30, wherein, said refractory metal alloy includes 30-60 wt. % Re and 40-70 wt. % Mo.

36. The expandable medical device as defined in claim 30, wherein said expandable metal frame that includes said refractory metal alloy I) has a hydrophilicity wherein a contact angle of a water droplet on a surface of said refractory metal alloy on said expandable metal frame is 25-45°, and/or II) said refractory metal alloy on said expandable metal frame has a maximum ion release of a primary component of said refractory metal alloy when inserted or implanted on or in the body of the patient of no more than 0.5 μg/cm.sup.2 per day, wherein said primary component constitutes at least 2 wt. % of said refractory metal alloy.

37. The expandable medical device as defined in claim 30, wherein said medical device is an expandable stent, and expandable valve, expandable graph, or expandable sheath.

38. The expandable medical device as defined in claim 30, wherein said medical device is a prosthetic heart valve; said prosthetic heart valve includes said expandable metal frame, a leaflet structure supported by said expandable metal frame, and an inner skirt secured to said expandable metal frame; said expandable metal frame A) having at least 10% less material as compared to a similar shaped frame formed of CoCr alloy and/or TiNi alloy that can be expanded outer diameter of at least 25 mm, and wherein said expandable metal frame has the same or greater ultimate tensile strength, greater yield strength, greater elastic deformation latitude, greater stress to plastic deformation and failure, greater stiffness, greater strength, greater durability, and/or greater fatigue ductility as compared to a said similar shaped frame formed of CoCr alloy and/or TiNi alloy, B) having at least 10% greater conformity to a treatment area when expanded as comparted to a similar shaped frame formed of CoCr alloy and/or TiNi alloy that can be expanded outer diameter of at least 25 mm, C) having at least a 10% greater hydrophilicity as compared to a similar shaped frame formed of CoCr alloy and/or TiNi alloy that can be expanded outer diameter of at least 25 mm, D) having at least 20% less corrosion and/or metal ion release when exposed to fluid in a blood vessel as compared to a similar shaped frame formed of CoCr alloy and/or TiNi alloy that can be expanded outer diameter of at least 25 mm.

39. A medical device that is configured to be inserted or implanted on or in the body of a patient; said medical device includes a refractory metal alloy; said refractory metal alloy is not a self-expanding metal alloy; said refractory metal alloy selected from the group of alloys consisting of MoRe alloy, ReW alloy, MoReCr alloy, MoReTa alloy, MoReTi alloy, WCu alloy, ReCr alloy, molybdenum alloy, rhenium alloy, tungsten alloy, tantalum alloy, and niobium alloy; said refractory metal alloy including at least 20 wt. % of one or more metals selected from the group consisting of molybdenum, rhenium, tungsten, tantalum, and niobium; said refractory metal including less than 0.05 wt. % impurities; said medical device having two or more properties selected form the group consisting of a) a recoil of less than 5% after being subjected to a first crimping process, b) a recoil of less than 5% after being expanded from said crimped state to said expanded state, c) a foreshortening percentage of less than 20% when said expandable metal frame is expanded from said crimped state, d) a hydrophilicity wherein a contact angle of a water droplet on a surface of said refractory metal alloy of said expandable metal frame is 25-45°, e) a maximum ion release of a primary component of said refractory metal alloy form said expandable metal frame when inserted or implanted on or in the body of the patient of no more than 0.5 μg/cm.sup.2 per day, wherein said primary component constitutes at least 2 wt. % of said refractory metal alloy, and f) an absolute increase in ion release per dose of refractory metal alloy in tissue about said expandable metal frame medical device after said expandable metal frame is inserted or implanted on or in the body of a patient for at least 90 days of no more than 50.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0149] Non-limiting and non-exhaustive embodiments are described with reference to the following drawings, wherein like labels refer to like parts throughout the various views unless otherwise specified. The sizes and relative positions of elements in the drawings are not necessarily drawn to scale. For example, the shapes of various elements are selected, enlarged, and positioned to improve drawing legibility. The particular shapes of the elements as drawn have been selected for ease of recognition in the drawings. Reference may now be made to the drawings, which illustrate various embodiments that the disclosure may take in physical form and in certain parts and arrangement of parts wherein:

[0150] FIGS. 1A-1E are illustrations of a TAV, a portion of a catheter and a typical TAVR procedure for inserting the TAV into a valve of a heart.

[0151] FIG. 2A is an illustration of a TAV that includes an inner skirt and leaflet structure.

[0152] FIG. 2B is an illustration of a TAV frame.

[0153] FIGS. 3 and 4 are illustrations of a prior art TAV frame formed of CoCr alloy and a TAV frame in accordance with the present disclosure formed of refractory metal alloy of MoRe alloy and having a similar shape and configuration to the TAV frame formed of CoCr alloy, and which illustrates that the frame of the TAV formed of CoCr alloy requires multiple crimping cycles to fully crimp the TAV which can result increased incidence of leaflet damage, and the frame of the TAV formed of MoRe alloy only requires a single crimping cycle to fully crimp the TAV, thereby resulting in reduced incidence of leaflet damage during crimping, and also which results in a decrease crimped outer diameter as compared to a TAV formed of CoCr alloy, and which also illustrates that after each crimping procedure, the frame formed of CoCr alloy has a recoil of greater than 9% after each crimping cycle whereas the recoil of the frame of the refractory metal alloy has a recoil of less than 2% after each crimping cycle, and wherein the final crimped diameter of the frame formed of CoCr alloy after multiple crimping cycles is 24-27Fr and the final crimped diameter of the frame formed of refractory metal alloy after a single crimping cycle is 18-21 Fr.

[0154] FIG. 5 is a graph that illustrates the amount of recoil of several different metal alloys.

[0155] FIG. 6 is an illustration of a prior art TAV frame formed of CoCr alloy and a TAV frame in accordance with the present disclosure formed of refractory metal alloy, and which illustrates that the recoil after balloon expansion of the TAV frame formed of CoCr is greater than the recoil of the TAV frame formed of refractory metal alloy after balloon expansion, thus the effective orifice area after expansion of the TAV frame formed of refractory metal alloy is greater than the effective orifice area after expansion of the TAV frame formed of CoCr alloy.

[0156] FIG. 7 is an illustration that compares the conformability of a metal strip or wire formed of refractory metal to the shape of a die surface as compared to the conformity of a metal strip or wire of CoCr alloy on the same die surface.

[0157] FIG. 8 is an illustration that compares the conformability of a TAV frame formed of refractory metal alloy that is expanded in a non-circular aortic valve that includes calcium deposits to a similar shaped and configured TAV frame formed of CoCr alloy that is expanded in the same non-circular aortic valve, and which illustrates that the paravalvular leak (PVL) about a TAV having a frame formed of CoCr alloy is greater than the PVL about a TAV having a frame formed of refractory metal alloy due the increase conformability of the frame formed of refractory metal alloy as compared to the conformability of the frame formed of CoCr alloy.

[0158] FIGS. 9A-9C illustrate stress vs. reduction in percent area graphs of TiAlV alloy, CoCr alloy and MoRe alloy.

[0159] FIG. 10 is a graph that illustrates the differences of stiffness and yield strength of a MoRe alloy, CoCr alloy and TiAlV alloy.

[0160] FIGS. 11-13 are graphs that illustrate the strength and fatigue ductility of a TiAlV alloy, CoCr alloy and MoRe alloy.

[0161] FIG. 14 illustrates the durability of a MoRe alloy compared to CoCr alloy and a TiAlV alloy.

[0162] FIG. 15 illustrates the purity of a MoRe alloy to a CoCr alloy and a TiAlV alloy.

[0163] FIG. 16 illustrates the hydrophilicity of a MoRe alloy, a CoCr alloy, and a TiAlV alloy.

[0164] FIGS. 17-18 illustrate the ion release rates of a refractory metal alloy such as MoRe.

[0165] FIG. 19 illustrates the ion release rates in tissue from a MoRe alloy, a CoCr alloy, and a TiAlV alloy.

DESCRIPTION OF NON-LIMITING EMBODIMENTS OF THE DISCLOSURE

[0166] A more complete understanding of the articles/devices, processes and components disclosed herein can be obtained by reference to the accompanying drawings. These figures are merely schematic representations based on convenience and the ease of demonstrating the present disclosure, and are, therefore, not intended to indicate relative size and dimensions of the devices or components thereof and/or to define or limit the scope of the exemplary embodiments.

[0167] Although specific terms are used in the following description for the sake of clarity, these terms are intended to refer only to the particular structure of the embodiments selected for illustration in the drawings and are not intended to define or limit the scope of the disclosure. In the drawings and the following description below, it is to be understood that like numeric designations refer to components of like function.

[0168] The singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise.

[0169] As used in the specification and in the claims, the term “comprising” may include the embodiments “consisting of” and “consisting essentially of.” The terms “comprise(s),” “include(s),” “having,” “has,” “can,” “contain(s),” and variants thereof, as used herein, are intended to be open-ended transitional phrases, terms, or words that require the presence of the named ingredients/steps and permit the presence of other ingredients/steps. However, such description should be construed as also describing compositions or processes as “consisting of” and “consisting essentially of” the enumerated ingredients/steps, which allows the presence of only the named ingredients/steps, along with any unavoidable impurities that might result therefrom, and excludes other ingredients/steps.

[0170] Numerical values in the specification and claims of this application should be understood to include numerical values which are the same when reduced to the same number of significant figures and numerical values which differ from the stated value by less than the experimental error of conventional measurement technique of the type described in the present application to determine the value.

[0171] All ranges disclosed herein are inclusive of the recited endpoint and independently combinable (for example, the range of “from 2 grams to 10 grams” is inclusive of the endpoints, 2 grams and 10 grams, and all the intermediate values).

[0172] The terms “about” and “approximately” can be used to include any numerical value that can vary without changing the basic function of that value. When used with a range, “about” and “approximately” also disclose the range defined by the absolute values of the two endpoints, e.g., “about 2 to about 4” also discloses the range “from 2 to 4.” Generally, the terms “about” and “approximately” may refer to plus or minus 10% of the indicated number.

[0173] Percentages of elements should be assumed to be percent by weight of the stated element, unless expressly stated otherwise.

[0174] Although the operations of exemplary embodiments of the disclosed method may be described in a particular, sequential order for convenient presentation, it should be understood that disclosed embodiments can encompass an order of operations other than the particular, sequential order disclosed. For example, operations described sequentially may in some cases be rearranged or performed concurrently. Further, descriptions and disclosures provided in association with one particular embodiment are not limited to that embodiment, and may be applied to any embodiment disclosed.

[0175] For the sake of simplicity, the attached figures may not show the various ways (readily discernable, based on this disclosure, by one of ordinary skill in the art) in which the disclosed system, method and apparatus can be used in combination with other systems, methods and apparatuses. Additionally, the description sometimes uses terms such as “produce” and “provide” to describe the disclosed method. These terms are abstractions of the actual operations that can be performed. The actual operations that correspond to these terms can vary depending on the particular implementation and are, based on this disclosure, readily discernible by one of ordinary skill in the art.

[0176] Referring now to FIGS. 1A-1E, these figures are illustrations of implantable prosthetic heart valve 100 (e.g., TAV) and a method for inserting the prosthetic heart valve 100 in a valve region A (e.g., aortic valve, etc.) of a heart H. The prosthetic heart valve 100 can be implanted in the annulus of the native aortic valve A; however, the prosthetic heart valve 100 also can be configured to be implanted in other valves of the heart. Although the medical device illustrated is a TAV, the present disclosure is not limited to TAVs or any other heart valve replacement. The medical device in accordance with the present disclosure can be any medical device that can be inserted or otherwise applied to a patient. Non-limiting medical devices in accordance with the present disclosure include orthopedic devices, PFO devices, stents, valves (e.g., heart valve, etc.), spinal implants, devices for treating aneurysms, occlusive devices for use in blood vessels and other body passageways, flow adjusting and/or diversion devices for blood vessels, devices for de-endothelializing a wall of an aneurysm, frame and other structures for use with a spinal implants, vascular implant, graft, dental implant, wire for used in medical procedures, bone implant; artificial disk, artificial spinal disk, prosthetic implant or device to repair, replace and/or support a bone and/or cartilage, bone plate, nail; rod, screw, post; cage, plate, pedicle screw, joint system, anchor, bone spacer, or disk that is used in a body to support a structure, mount a structure, and/or repair a structure in a body such as, but not limited to, a human body, animal body, etc.

[0177] Referring now to FIG. 1A, the prosthetic heart valve 100 generally comprises a frame 110 or stent formed of a plurality of posts and/or struts 112, 114 strut joints 113, leaflet structure 200 supported by the frame 110, and an inner skirt 300 secured to the outer surface of the frame 110 and/or leaflet structure 200. The prosthetic heart valve 100 has a “lower” end 120 and an “upper” end 130, wherein the lower end 120 of the prosthetic heart valve 100 is the inflow end and the upper end 130 of the prosthetic heart valve 100 is the outflow end.

[0178] The configuration of the frame 110 of the prosthetic heart valve 100 is non-limiting. Many different frame configurations can be used for the frame 110 of the prosthetic heart valve 100. The frame 110 includes a plurality of spaced, vertically extending struts or posts 112, or non-vertically extending struts 114 that are connected together at strut joints 113. As can be appreciated, the frame 110 can be fully formed of non-vertically extending struts 114 that are connected together at strut joints 113.

[0179] As illustrated in FIG. 1A, the frame 110 has a 12-post configuration wherein twelve vertically extending struts or post 112 are position about the upper portion of the frame 110. The vertically extending struts or posts 112 are interconnected via a lower row of circumferentially non-vertically extending struts 114 at strut joints 113 and an upper row of circumferentially non-vertically extending struts 114. The non-vertically extending struts 114 can be arrangement in a variety of patterns (e.g., zig-zag pattern, saw-tooth pattern, triangular pattern, polygonal pattern, oval pattern, S-shaped, Y-shaped, H-shaped, E-shaped, V-shaped, Z-shaped, L-shaped, J-sped, W-shaped, U-shaped, N-shaped, M-shaped, C-shaped, X-shaped, F-shaped, etc.). One or more of the posts and/or struts 112, 114 can have the same or different a) thicknesses, b) cross-sectional shape, and/or c) cross-sectional area along a portion or all of the longitudinal length.

[0180] As illustrated in FIG. 1A, the upper portion of the frame 110, when expanded, forms twelve hexagonal shaped structures on the upper portion of the frame 110, and three rings of quadrangle shaped structures that form the lower portion of the frame 110. The twelve hexagonal shaped structures are formed of a combination of vertically extending struts or post 112 and non-vertically extending struts 114, and the three rings of quadrangle shaped structures are formed only of non-vertically extending struts 114. As can be appreciated, many of the frame configurations can be used to form frame 110 for the prosthetic heart valve 100.

[0181] The frame 110 is partially or fully formed of a refractory metal alloy in accordance with the present disclosure. Non-limiting refractory metal alloys include a Re alloy (30-60 wt. % Re, 40-70 wt. % one or more metal additives [e.g., Mo, Bi, Nb, Ni, Ta, Ti, V, W, Mn, Zr, Ir, Tc, Ru, Rh, Hf, Os, Cu, Y); MoRe alloy, ReW alloy, MoReCr alloy, MoReTa alloy, MoReTi alloy, WCu alloy, ReCr alloy, Mo alloy, W alloy, Ta alloy, Nb alloy, etc. In one non-limiting embodiment, 90-100% of the frame 110 of the prosthetic heart valve 100 is formed of a refractory metal alloy. In one non-limiting example, 90-100% of the frame 110 of the prosthetic heart valve 100 is formed of MoRe alloy (e.g., 40-60 wt. % Mo, 40-60 wt. % Re and 0-10 wt. % of one or more other metal additives).

[0182] The frame 110 can be optionally be coated with a polymer material (e.g., silicone, PTFE, ePTFE, polyurethane, polyolefins, hydrogels, biological materials [e.g., pericardium or biological polymers such as collagen, gelatin, or hyaluronic acid derivatives], etc.). The coating can be used to partially or fully encapsulate one or more of the vertically extending struts or posts 112 and/or non-vertically extending struts 114 on the frame 110 and/or to partially of fully fill-in one or more of the openings between the non-vertically extending struts 114 and/or vertically extending struts or posts 112.

[0183] The inner skirt 300 can be formed of a variety of flexible materials (e.g., polymer (e.g., polyethylene terephthalate (PET), polyester, nylon, Kevlar, silicon, etc.), composite material, metal, fabric material, etc. In one non-limiting embodiment, the material used to partially or fully form the inner skirt 300 can be substantially non-elastic (i.e., substantially non-stretchable and non-compressible). In another non-limiting embodiment, the material used to partially or fully form the inner skirt 300 can be a stretchable and/or compressible material (e.g., silicone, PTFE, ePTFE, polyurethane, polyolefins, hydrogels, biological materials [e.g., pericardium or biological polymers such as collagen, gelatin, or hyaluronic acid derivatives], etc.). The inner skirt 300 can optionally be formed from a combination of a cloth or fabric material that is coated with a flexible material or with a stretchable and/or compressible material so as to provide additional structural integrity to the inner skirt 300. The size, configuration and thickness of the inner skirt 300 is non-limiting (e.g., thickness of 0.1-20 mils and all values and ranges therebetween). The inner skirt 300 can be secured to the inside and/or outside of the frame 110 using various means (e.g., sutures, clips, clamp arrangement, etc.).

[0184] The inner skirt 300 can be used to 1) at least partially seal and/or prevent perivalvular leakage, 2) at least partially secure the leaflet structure 200 to the frame 110, 3) at least partially protect one or more of the leaflets of the leaflet structure 200 from damage during the crimping process of the prosthetic heat valve 100, 4) at least partially protect one or more of the leaflets of the leaflet structure 200 form damage during the operation of the prosthetic heart valve 100 in the heart H.

[0185] The prosthetic heart valve 100 can optionally include an outer skirt or sleeve (not shown) that is positioned at least partially about the exterior region of the frame 110. The outer skirt or sleeve, when used, generally is positioned completely around a portion of the outside of the frame 110. Generally, the outer skirt is positioned about the lower portion of the frame 110 and does not fully cover the upper portion of the frame 110; however, this is not required. The outer skirt can be connected to the frame 110 by a variety of arrangements (e.g., sutures, adhesive, melted connection, clamping arrangement, etc.). At least a portion of the outer skirt can optionally be located on the interior surface of the frame 110; however, this is not required. Generally, the outer skirt is formed of a more flexible and/or compressible material than the inner skirt 300; however, this is not required. The outer skirt can be formed of a variety of a stretchable and/or compressible material (e.g., silicone, PTFE, ePTFE, polyurethane, polyolefins, hydrogels, biological materials [e.g., pericardium or biological polymers such as collagen, gelatin, or hyaluronic acid derivatives], etc.). The outer skirt can optionally be formed from a combination of a cloth or fabric material that is coated with the stretchable and/or compressible material so as to provide additional structural integrity to the outer skirt. The size, configuration and thickness of the outer skirt is non-limiting. The thickness of the outer skirt is generally 0.1-20 mils (and all values and ranges therebetween).

[0186] The leaflet structure 200 can be can be attached to the frame 110 and/or inner skirt 300. The connection arrangement used to secure the leaflet structure 200 to the frame 110 and/or inner skirt 300 is non-limiting (e.g., sutures, melted bold, adhesive, clamp arrangement, etc.). The material used to form the one or more leaflets of the leaflet structure 200 include, but are not limited to, bovine pericardial tissue, biocompatible synthetic materials, or various other suitable natural or synthetic materials.

[0187] The leaflet structure 200 can be comprised of two or more leaflets (e.g., 2, 3, 4, 5, 6, etc.). In one non-limiting arrangement, the leaflet structure 200 includes three leaflets that are arranged to collapse in a tricuspid arrangement. The size, shape and configuration of the one or more leaflets of the leaflet structure 200 are non-limiting. In one non-limiting arrangement, the leaflets have generally the same shape, size, configuration and thickness.

[0188] Two of more of the leaflets of the leaflet structure 200 can optionally be secured to one another at their adjacent sides to form commissures of the leaflet structure 200 (the edges where the leaflets come together). The leaflet structure 200 can be secured to the frame 110 and/or inner skirt 300 by a variety of connection arrangement (e.g., sutures, adhesive, melted bond, clamping arrangement, etc.).

[0189] One or more leaflets of the leaflet structure 200 can optionally include reinforcing structures or strips to 1) facilitate in securing the leaflets together, 2) facilitate in securing the leaflets to the inner skirt 300 and/or frame 110, and/or 3) inhibit or prevent tearing or other types of damage to the leaflets.

[0190] The prosthetic heart valve 100 is configured to be radially collapsible to a collapsed or crimped state for introduction into the body on a delivery catheter (FIG. 1B) and radially expandable to an expanded state for implanting the prosthetic heart valve 100 at a desired location in the heart H (e.g., the aortic valve A, etc.) (FIG. 1E). The frame 110 of the prosthetic heart valve 100 is made of a plastically-expandable material (e.g., refractory metal alloy) that permits crimping of the frame 110 to a smaller profile for delivery and expansion of the prosthetic heart valve 100 using an expansion device such as the balloon B of a balloon catheter C.

[0191] Referring now to FIG. 1B, the prosthetic heart valve 100 is crimped into a portion of balloon B of the balloon catheter C. Various type of crimping apparatus and techniques can be used to crimp the prosthetic heart valve on the balloon delivery catheter. The process of crimping a prosthetic heart valve 100 using a crimping device is known in the art and will not be described herein. During a crimping procedure, damage to the leaflets of leaflet structure 200 should be avoided.

[0192] As illustrated in FIGS. 1C-1E, once the prosthetic heart valve 100 is crimped on the balloon B of a balloon delivery catheter C, the balloon delivery catheter C is inserted through a blood vessel and to the location in the heart H wherein the prosthetic heart valve 100 is to be deployed (See FIG. 1C). At the treatment location, the balloon B on the balloon delivery catheter C is expanded to thereby cause the prosthetic heart valve 100 to be expanded and secured in a valve region A of the heart H (See FIG. 1D). Thereafter, the balloon B is deflated and the balloon delivery catheter C is removed from the patient (See FIG. 1E).

[0193] The frame 110 of the prosthetic heart valve 100 can be configured such that it can be crimped onto a delivery catheter C so that the crimped prosthetic heart valve 100 can be inserted in heart valves that are less than 22 Fr. Commercially available prior art prosthetic heart values can only be crimped to a diameter of about 24-27 FR (8-9 mm) due to the materials used to form the frame of such prosthetic heart valves. As such, the prosthetic heart valve 100 in accordance with the present disclosure can be inserted into smaller sized heart valves that could not previously be treated with prior art prosthetic heart valves. As can be appreciated, the prosthetic heart valve 100 in accordance with the present disclosure can be sized and configured to be inserted in heart valves that are greater than 22 Fr.

[0194] The refractory metal alloy frame 110 of the prosthetic heart valve 100 and other types of expandable medical devices (e.g., stents, etc.) can be crimped to have a crimped outer diameter that is at least 5% and up to a 33% smaller (e.g., 5-33% smaller and all value and ranges therebetween) than a crimped outer diameter of a frame of the same size, configuration and shape that is formed of Co—Cr alloy (e.g., L605; MP35N; Phynox; Eligory; 35Co-35Ni-20Cr-10Mo; 40Co-20Cr-16Fe-15Ni7Mo; Co-20Cr-15W-10Ni; 15-30 wt. % Cr, 10-20 wt. % W, 5-35 wt. % Ni, 0-3 wt. % Fe, 0-2 wt. % Mn, 0-10 wt. % Mo, 0-1 wt. % Ti, 0.0.5 wt. % Si).

[0195] The refractory metal alloy frame 110 of the prosthetic heart valve 100 and other types of expandable medical devices (e.g., stents, etc.) can be crimped to have a crimped outer diameter that is at least 5% and up to a 50% smaller (e.g., 5-50% smaller and all value and ranges therebetween) than a crimped outer diameter of a frame of the same size, configuration and shape that is formed of stainless steel (e.g., 316, 316L). In the medical industry, expandable frames for prosthetic heart valves are only formed of certain cobalt-chromium alloys and NiTi alloys. Stainless steel and other alloys such as TiAlV alloys, that can be used in other types of expandable medical devices (e.g., stents, etc.), are not used for prosthetic heart valves for various reasons. Although the present disclosure illustrates the many advantages for using a refractory metal alloy in accordance with the present disclosure in expandable medical devices, comparisons of the refractory metal alloy of the present disclosure to cobalt-chromium alloys and NiTi alloys will only be made in this disclosure when referring to expandable prosthetic heart valves such as, but not limited to TAVR devices.

[0196] The refractory metal alloy frame 110 of the prosthetic heart valve 100 and other types of expandable medical devices (e.g., stents, etc.) can be crimped to have a crimped outer diameter that is at least 5% and up to a 40% smaller (e.g., 5-40% smaller and all value and ranges therebetween) than a crimped outer diameter of a frame of the same size, configuration and shape that is formed of nitinol (self-expanding nickel titanium alloy— 49-60% wt. % Ni and 40-51 wt. % Ti).

[0197] The refractory metal alloy frame 110 of the prosthetic heart valve 100 and other types of expandable medical devices (e.g., stents, etc.) can be crimped to have a crimped outer diameter that is at least 5% and up to a 40% smaller (e.g., 5-40% smaller and all value and ranges therebetween) than a crimped outer diameter of a frame of the same size, configuration and shape that is formed of TiAlV alloys (e.g., Ti-6A1-4V; 5.5-6.5 wt. % Al, 3.5-4.5 wt. % V and balance Ti; 3.5-4.5 wt. % vanadium, 5.5-6.75 wt. % aluminum, 0.3 wt. % max iron, 0.2 wt. % max oxygen, 0.08 wt. % max carbon, 0.05 wt. % max nitrogen, 0.015 wt. % max hydrogen H, 0.05 wt. % max yttrium, balance titanium).

[0198] As such, outer crimp diameters of the prosthetic heart valve 100 of 6-7 mm (18-21 FR) for a TAVR that was designed to be expanded to have an effective orifice area (EOA) of at least 585 mm.sup.2, which were previously unachievable using stainless steel, CoCr alloy, nitinol, and can now be obtained by using a frame 110 formed of a refractory metal in accordance with the present disclosure.

[0199] Most commercially available expandable frames used for prosthetic heart valves are formed of cobalt-chromium alloy (e.g., MP35N, etc.) or NiTi alloy (e.g., Nitinol, etc.). Frames formed of stainless steel for prosthetic heart valves have fallen out of favor due to the problems associated with the corrosion of the stainless steel and the required larger strut thicknesses required to form a frame strong enough for use in a heart valve. Frames for expandable medical devices such as stents are still sometimes formed of stainless steel and other alloys such as TiAlV alloys.

[0200] As illustrated in Table 1, a frame for a prosthetic heart device (e.g., TAVR, etc.) that is formed of a refractory metal alloy in accordance with the present disclosure has improved properties as compared to frames for prosthetic heart valves that are formed of MP35N or NiTi alloy. As illustrated below, for a frame of a prosthetic heart valve that is designed to expand to 25 mm, the frame of the prosthetic heart valve that is formed of a refractory metal alloy (e.g., MoRe, etc.) has several advantages over frames for prosthetic heart valves that are formed of MP35N or NiTi alloy, namely 1) the outer diameter (OD) of the crimped prosthetic valve having a frame formed of refractory metal alloy is smaller than the OD crimped diameter of the crimped prosthetic valve having a frame formed of MP35N (e.g., cobalt-chromium alloy) or NiTi alloy, 2) the strut joint width on the frame (e.g., the location that the end of a strut is connected to another portion of the frame) that is formed of a refractory metal alloy can be less than the strut joint width on the frame formed of MP35N or NiTi alloy, 3) the strut width on the frame that is formed of a refractory metal alloy is less than the strut width on the frame formed of MP35N or NiTi alloy, 4) the amount of recoil of a frame that is formed of a refractory metal alloy after the frame has been crimped or after the frame has been expanded is less than the amount of recoil of a frame that is formed of a MP35N or NiTi alloy after such frame has been crimped or after the frame has been expanded, and 5) the amount of foreshortening of a frame that is formed of a refractory metal alloy after the frame has been expanded is less than the amount of foreshortening of a frame that is formed of a MP35N or NiTi alloy after such frame has been expanded.

[0201] The strength of the refractory metal alloy is greater than a cobalt-chromium alloy, stainless steel, nickel-titanium alloy or a TiAlV alloy, thus the strut width and strut joints of expandable frames can be made smaller than frames formed of such other alloys, thereby a frame for a medical formed of a refractory metal alloy can be made smaller without sacrificing the strength of the frame. The amount of recoil of a frame formed of refractory metal alloy when the frame is crimped or expanded from the crimped state is less than the amount of recoil of a frame formed of cobalt-chromium alloy, stainless steel, nickel-titanium alloy or a TiAlV alloy. As such, a reduced number of crimping cycles (typically only one crimping cycle is required) is needed to obtain the desired crimped profile of the frame as compared to multiple crimped cycles are required to obtain the desired crimped profile of the frame that are formed of cobalt-chromium alloy, stainless steel, nickel-titanium alloy or a TiAlV alloy. The amount of recoil of a frame formed of a refractory metal alloy when the frame is crimped or when the frame is expanded from a crimped stated is generally no more than 8% (e.g., 0-8% and all values and ranges therebetween), typically no more than 5%, more typically no more than 3%, still more typically no more than 2%, and even more typically less than 2%. The amount of foreshortening of a frame formed of refractory metal alloy when the frame is expanded from a crimped state is less than the amount of foreshortening of a frame formed of cobalt-chromium alloy, stainless steel, nickel-titanium alloy or a TiAlV alloy. Generally the amount of foreshortening of a frame formed of a refractory metal alloy from a crimped state to an expanded state is 0-20% (and all values and ranges therebetween), typically 0-15%, more typically 0-10%, and still more typically 0-5%. As such, a reduced amount of foreshortening facilitates in ensuring the medical device when the frame is expanded from the crimped state maintains its proper position in the treatment area. Frames of medical devices that foreshorten reduce in longitudinal length when the frame is expanded. Such reduction in longitudinal length during expansion of the frame can result in the mis-location of the expanded device in a treatment area, which mis-location can result in a) improper operation of the implanted medical device, b) damage to the implanted medical device, c) potential damage to the tissue about the implanted medical device, d) reduced life of the medical device, e) causing plaque and/or calcium deposits to form about the medical device, etc.

TABLE-US-00002 TABLE 1 TABLE 1 Expanded OD (for 25 mm valve, this is size Radial specific and Strength Strut Crimped OD material after Joint Strut of the Valve independent) Maximum Expansion Width Width % % Frame alloy (average mm) (mm) EOA (N) (mm) (mm) Recoil Foreshortening MoRe <7 23-27 2.8 35 0.3-0.7 0.3 <2 0 (52.5% Mo- 47.5% Re) MP35N 7.7 26 2.45 35 0.7 0.3 >5 30 NiTi 7.7 25 at 3 35 0.85 0.33 >5 20 (Nitinol - sufficient 49-60% outward wt. % Ni force to and 40-51 maintain wt. % Ti) position

[0202] Table 1 illustrates that for a frame formed of a non-self-expanding metal alloy for use in a prosthetic heat valve, the frame formed of a refractory metal alloy in accordance with the present invention has superior properties to frame formed of cobalt chromium alloy with regard to crimped OD, maximum EOA, strut joint width, % recoil, and % foreshortening. It is noted that even for self-expanding frames that are formed of Nitinol, frame formed of refractory metal alloy in accordance with the present invention has superior properties to frame formed of Nitinol with regard to crimped OD, strut joint width, % recoil, and % foreshortening. Due to the self-expanding nature of Nitinol, the Nitinol frame has improved EOA as compared to the frame formed of refractory metal alloy.

[0203] Referring now to FIGS. 2A-2B, the post width PW and/or the strut joint width SJW of a frame 110 that is formed of a refractory metal alloy in accordance with the present disclosure can be smaller than the post width PW and/or the strut joint width SJW of a frame formed of stainless steel, nitinol, Co—Cr alloy or TiAlV alloy, and still have the same or greater radial strength when the frame is expanded as compared to a frame formed of stainless steel, nitinol, Co—Cr alloy or TiAlV alloy.

[0204] Generally, refractory metal alloys (e.g., 30-60 wt. % Re, 40-70 wt. % one or more metal additives [e.g., Mo, Bi, Nb, Ni, Ta, Ti, V, W, Mn, Zr, Ir, Tc, Ru, Rh, Hf, Os, Cu, Y]; MoRe alloy, ReW alloy, MoReCr alloy, MoReTa alloy, MoReTi alloy, WCu alloy, ReCr alloy, Mo alloy, Re alloy, W alloy, Ta alloy, Nb alloy, etc.) used to form struts and posts and strut joint on expandable frames of TAV frames have an average cross-sectional area that is 5-40% (and all values and ranges therebetween) less than the cross-sectional area of the struts and posts and strut joints on TAV frames formed of CoCr alloy (e.g., L605; MP35N), and wherein such refractory metal alloy struts, posts and strut joints have the same or greater strength than such struts, posts and strut joints formed of CoCr alloy.

[0205] Generally, refractory metal alloys (e.g., 30-60 wt. % Re, 40-70 wt. % one or more metal additives [e.g., Mo, Bi, Nb, Ni, Ta, Ti, V, W, Mn, Zr, Ir, Tc, Ru, Rh, Hf, Os, Cu, Y]; MoRe alloy, ReW alloy, MoReCr alloy, MoReTa alloy, MoReTi alloy, WCu alloy, ReCr alloy, Mo alloy, Re alloy, W alloy, Ta alloy, Nb alloy, etc.) used to form struts and posts and strut joint on expandable frames of TAV frames have an average cross-sectional area that is 5-50% (and all values and ranges therebetween) less than the cross-sectional area of less than the cross-sectional area of the struts and posts and strut joints on TAV frames formed of stainless steel (e.g., 316, 316L), and wherein such refractory metal alloy struts, posts and strut joints have the same or greater strength than such struts, posts and strut joints formed of stainless steel.

[0206] Generally, refractory metal alloys (e.g., 30-60 wt. % Re, 40-70 wt. % one or more metal additives [e.g., Mo, Bi, Nb, Ni, Ta, Ti, V, W, Mn, Zr, Ir, Tc, Ru, Rh, Hf, Os, Cu, Y]; MoRe alloy, ReW alloy, MoReCr alloy, MoReTa alloy, MoReTi alloy, WCu alloy, ReCr alloy, Mo alloy, Re alloy, W alloy, Ta alloy, Nb alloy, etc.) used to form struts and posts and strut joint on expandable frames of TAV frames have an average cross-sectional area that is 5-40% (and all values and ranges therebetween) less than the cross-sectional area of the struts and posts and strut joints on TAV frames formed of TiAlV alloy (e.g., Ti-6A1-4V), and wherein such refractory metal alloy struts, posts and strut joints have the same or greater strength than such struts, posts and strut joints formed of TiAlV alloy.

[0207] Generally, refractory metal alloys (e.g., 30-60 wt. % Re, 40-70 wt. % one or more metal additives [e.g., Mo, Bi, Nb, Ni, Ta, Ti, V, W, Mn, Zr, Ir, Tc, Ru, Rh, Hf, Os, Cu, Y]; MoRe alloy, ReW alloy, MoReCr alloy, MoReTa alloy, MoReTi alloy, WCu alloy, ReCr alloy, Mo alloy, Re alloy, W alloy, Ta alloy, Nb alloy, etc.) used to form struts and posts and strut joint on expandable frames of TAV frames have an average cross-sectional area that is 5-40% (and all values and ranges therebetween) less than the cross-sectional area of the struts and posts and strut joints on TAV frames formed of Nitinol (e.g., 50-60 wt. % Ni and 40-60 wt. % Ti), and wherein such refractory metal alloy struts, posts and strut joints have the same or greater strength than such struts, posts and strut joints formed of Nitinol.

[0208] The use of the refractory metal alloy to form the frame of TAV frames allows for smaller expandable TAVs to be manufactured. Such smaller expandable TAVs can be inserted into smaller blood vessels or other body passageways that previously could not be accessed using TAVs formed of other types of metal alloys.

Example 1

[0209] There is provided one frame for a prosthetic heart valve formed of a refractory alloy such a MoRe (e.g., 40-60 wt. % Mo, 40-60 wt. % Re, 0-10 wt. % one or more metal additives) and another frame for a prosthetic heart valve formed of CoCr alloy (35Co-35Ni-20Cr-10Mo)— [wherein a) both frames have the same number of posts and struts, b) both frames have the same post and strut configuration and shape, c) both frames can be expanded to create an effective orifice area (EOA) of at least 585 mm.sup.2, d) both frames have the same frame shape and configuration, and e) the frame formed of MoRe has the same or greater radial strength in an expanded stated as the frame formed of CoCr in an expanded state]-, the frame that is formed of MoRe can have both thinner SJWs (0.5 mm) and PWs (0.2 mm) than the SJWs (0.7 mm) and PWs (0.3 mm) of the frame formed of CoCr alloy. Because the SJWs and PWs for the frame formed of MoRe alloy are smaller than the SJWs and PWs of the frame formed of CoCr alloy, I) the amount of material required to form the frame of MoRe alloy is less than the amount of material required to form of the frame of CoCr alloy, and II) the frame formed of MoRe can be crimped to have an outer crimped diameter (6-7 mm or 18-21 Fr) that is less (up to 33+% less) than the outer crimped diameter of the frame formed of CoCr (8-9 mm or 24-27 Fr), which frame is used to form a EOA of at least 585 mm.sup.2.

[0210] Due to the properties of the refractory metal alloy, a TAV frame formed of refractory metal alloy as compared to a TAV frame formed of CoCr alloy [wherein both frames have a) the same number of posts and struts, b) the same post and strut configuration and shape, c) the frame formed of refractory metal alloy can be expanded to the same or greater effective orifice area (EOA) as the expanded frame formed of CoCr, and d) the frame formed of MoRe has the same or greater radial strength in an expanded state as the frame formed of CoCr in an expanded state] can 1) be formed of at least 5% less material (e.g., 5-35% less material and all values and ranges therebetween), 2) have SJWs that are at least 5% thinner (e.g., 5-35% thinner and all values and ranges therebetween), c) have PWs that are at least 5% thinner (e.g., 5-35% thinner and all values and ranges therebetween), and 3) have a crimped outer diameter that is at least 5% smaller (e.g., 5-22.2% smaller and all values and ranges therebetween).

[0211] The post width and strut joint width using a refractory metal alloy can thus be reduced as compared to post widths and strut joint widths on frames formed of CoCr alloy without a reduction in the strength of the frame in the expanded state. Due to the smaller crimped outer diameter of the frame that is achievable using a refractory metal alloy, the outer crimped diameter of the prosthetic heart valve using a frame formed of refractory metal alloy is less than a prosthetic heart valve using a frame formed of CoCr alloy.

Example 2

[0212] There is provided one frame for a prosthetic heart valve formed of a refractory alloy such a MoRe (e.g., 40-60 wt. % Mo, 40-60 wt. % Re, 0-10 wt. % one or more metal additives) and another frame for a prosthetic heart valve formed of stainless steel (e.g., 316 [16-19 wt. % Cr, 10-14 wt. % Ni, 2-3 wt. % Mo, less than 2 wt. % Mn, less than 1 wt. % Si, up to 0.08 wt. % C, and balance Fe], 316L [16-19 wt. % Cr, 10-14 wt. % Ni, 2-3 wt. % Mo, less than 2 wt. % Mn, less than 1 wt. % Si, up to 0.05 wt. % C, and balance Fe])— [wherein a) both frames have the same number of posts and struts, b) both frames have the same post and strut configuration and shape, c) both frames can be expanded to create an effective orifice area (EOA) of at least 585 mm.sup.2, d) both frames have the same frame shape and configuration, and e) the frame formed of MoRe has the same or greater radial strength in an expanded stated as the frame formed of stainless steel in an expanded state]-, the frame that is formed of MoRe can have both thinner SJWs (0.5 mm) and PWs (0.2 mm) than the SJWs (0.8 mm) and PWs (0.4 mm) of the frame formed of stainless steel. Because the SJWs and PWs for the frame formed of MoRe alloy are smaller than the SJWs and PWs of the frame formed of stainless steel, I) the amount of material required to form the frame of MoRe alloy is less than the amount of material required to form of the frame of stainless steel, and II) the frame formed of MoRe can be crimped to have an outer crimped diameter (6-7 mm or 18-21 Fr) that is less (up to 50+% less) than the outer crimped diameter of the frame formed of stainless steel (9-10 mm or 27-30 Fr), which frame is used to form a EOA of at least 585 mm.sup.2.

[0213] Due to the properties of the refractory metal alloy, a TAV frame formed of refractory metal alloy as compared to a TAV frame formed of stainless steel [wherein both frames have a) the same number of posts and struts, b) the same post and strut configuration and shape, c) the frame formed of refractory metal alloy can be expanded to the same or greater effective orifice area (EOA) as the expanded frame formed of stainless steel, and d) the frame formed of MoRe has the same or greater radial strength in an expanded state as the frame formed of stainless steel in an expanded state] can 1) be formed of at least 5% less material (e.g., 5-50% less material and all values and ranges therebetween), 2) have SJWs that are at least 5% thinner (e.g., 5-50% thinner and all values and ranges therebetween), c) have PWs that are at least 5% thinner (e.g., 5-50% thinner and all values and ranges therebetween), and 3) have a crimped outer diameter that is at least 5% smaller (e.g., 5-40% smaller and all values and ranges therebetween).

[0214] The post width and strut joint width using a refractory metal alloy can thus be reduced as compared to post widths and strut joint widths on frames formed of stainless steel without a reduction in the strength of the frame in the expanded state. Due to the smaller crimped outer diameter of the frame that is achievable using a refractory metal alloy, the outer crimped diameter of the prosthetic heart valve using a frame formed of refractory metal alloy is less than a prosthetic heart valve using a frame formed of stainless steel.

Example 3

[0215] There is provided one frame for a prosthetic heart valve formed of a refractory alloy such a MoRe (e.g., 40-60 wt. % Mo, 40-60 wt. % Re, 0-10 wt. % one or more metal additives) and another frame for a prosthetic heart valve formed of Nitinol (e.g., 50-60 wt. % Ni and 40-60 wt. % Ti)— [wherein a) both frames have the same number of posts and struts, b) both frames have the same post and strut configuration and shape, c) both frames can be expanded to create an effective orifice area (EOA) of at least 585 mm.sup.2, d) both frames have the same frame shape and configuration, and e) the frame formed of MoRe has the same or greater radial strength in an expanded stated as the frame formed of Nitinol in an expanded state]-, the frame that is formed of MoRe can have both thinner SJWs (0.5 mm) and PWs (0.2 mm) than the SJWs (0.7 mm) and PWs (0.3 mm) of the frame formed of Nitinol. Because the SJWs and PWs for the frame formed of MoRe alloy are smaller than the SJWs and PWs of the frame formed of Nitinol, I) the amount of material required to form the frame of MoRe alloy is less than the amount of material required to form of the frame of Nitinol, and II) the frame formed of MoRe can be crimped to have an outer crimped diameter (6-7 mm or 18-21 Fr) that is less (up to 50+% less) than the outer crimped diameter of the frame formed of Nitinol (8-9 mm or 24-27 Fr), which frame is used to form a EOA of at least 585 mm.sup.2.

[0216] Due to the properties of the refractory metal alloy, a TAV frame formed of refractory metal alloy as compared to a TAV frame formed of Nitinol [wherein both frames have a) the same number of posts and struts, b) the same post and strut configuration and shape, c) the frame formed of refractory metal alloy can be expanded to the same or greater effective orifice area (EOA) as the expanded frame formed of Nitinol, and d) the frame formed of MoRe has the same or greater radial strength in an expanded state as the frame formed of Nitinol in an expanded state] can 1) be formed of at least 5% less material (e.g., 5-50% less material and all values and ranges therebetween), 2) have SJWs that are at least 5% thinner (e.g., 5-50% thinner and all values and ranges therebetween), c) have PWs that are at least 5% thinner (e.g., 5-50% thinner and all values and ranges therebetween), and 3) have a crimped outer diameter that is at least 5% smaller (e.g., 5-40% smaller and all values and ranges therebetween).

[0217] The post width and strut joint width using a refractory metal alloy can thus be reduced as compared to post widths and strut joint widths on frames formed of Nitinol without a reduction in the strength of the frame in the expanded state. Due to the smaller crimped outer diameter of the frame that is achievable using a refractory metal alloy, the outer crimped diameter of the prosthetic heart valve using a frame formed of refractory metal alloy is less than a prosthetic heart valve using a frame formed of Nitinol.

Example 4

[0218] There is provided one frame for a prosthetic heart valve formed of a refractory alloy such a MoRe (e.g., 40-60 wt. % Mo, 40-60 wt. % Re, 0-10 wt. % one or more metal additives) and another frame for a prosthetic heart valve formed of TiAlV alloy (e.g., Ti-6A1-4V)— [wherein a) both frames have the same number of posts and struts, b) both frames have the same post and strut configuration and shape, c) both frames can be expanded to create an effective orifice area (EOA) of at least 585 mm.sup.2, d) both frames have the same frame shape and configuration, and e) the frame formed of MoRe has the same or greater radial strength in an expanded stated as the frame formed of TiAlV alloy in an expanded state]-, the frame that is formed of MoRe can have both thinner SJWs (0.5 mm) and PWs (0.2 mm) than the SJWs (0.7 mm) and PWs (0.3 mm) of the frame formed of TiAlV alloy. Because the SJWs and PWs for the frame formed of MoRe alloy are smaller than the SJWs and PWs of the frame formed of TiAlV alloy, I) the amount of material required to form the frame of MoRe alloy is less than the amount of material required to form of the frame of TiAlV alloy, and II) the frame formed of MoRe can be crimped to have an outer crimped diameter (6-7 mm or 18-21 Fr) that is less (up to 50+% less) than the outer crimped diameter of the frame formed of TiAlV alloy (8-9 mm or 24-27 Fr), which frame is used to form a EOA of at least 585 mm.sup.2.

[0219] Due to the properties of the refractory metal alloy, a TAV frame formed of refractory metal alloy as compared to a TAV frame formed of TiAlV alloy [wherein both frames have a) the same number of posts and struts, b) the same post and strut configuration and shape, c) the frame formed of refractory metal alloy can be expanded to the same or greater effective orifice area (EOA) as the expanded frame formed of TiAlV alloy, and d) the frame formed of MoRe has the same or greater radial strength in an expanded state as the frame formed of TiAlV alloy in an expanded state] can 1) be formed of at least 5% less material (e.g., 5-50% less material and all values and ranges therebetween), 2) have SJWs that are at least 5% thinner (e.g., 5-50% thinner and all values and ranges therebetween), c) have PWs that are at least 5% thinner (e.g., 5-50% thinner and all values and ranges therebetween), and 3) have a crimped outer diameter that is at least 5% smaller (e.g., 5-40% smaller and all values and ranges therebetween).

[0220] The post width and strut joint width using a refractory metal alloy can thus be reduced as compared to post widths and strut joint widths on frames formed of TiAlV alloy without a reduction in the strength of the frame in the expanded state. Due to the smaller crimped outer diameter of the frame that is achievable using a refractory metal alloy, the outer crimped diameter of the prosthetic heart valve using a frame formed of refractory metal alloy is less than a prosthetic heart valve using a frame formed of TiAlV alloy.

[0221] Referring now to FIGS. 3-4, one of the advantages of forming a frame of a prosthetic heart valve using a refractory metal alloy such as Mo—Re alloy is that refractory metal alloy exhibits less recoil when both crimped and expanded.

[0222] During the crimping of a TAV frame, the metal alloy used to form the TAV frame will recoil after the radial crimping forces are removed from the TAV frame. Likewise, when the crimped TAV frame is expanded, the expanded TAV frame will recoil to a smaller outer diameter after the expansion forces (e.g., expansion force from the inflation of a balloon on a catheter, etc.) on the TAV frame are removed.

[0223] As illustrated in FIG. 4, the crimping of a TAV frame formed of a refractory metal alloy such as (e.g., 40-60 wt. % Mo, 40-60 wt. % Re, 0-10 wt. % one or more metal additives) will recoil and expand by less than 2% (e.g., 0.1-2% and all values and ranges therebetween) after the radial crimping forces are removed from the frame. Generally, TAV frames formed of refractory metal alloys will recoil 0.1-5% (and all values and ranges therebetween) when subjected to a single crimping cycle, typically TAV frames formed of refractory metal alloys will recoil less than 2% when subjected to a single crimping cycle, and more typically TAV frames formed of refractory metal alloys will recoil about 0.1-1.95% when subjected to a single crimping cycle. Due to the low amount of recoil, the TAV frame only needs to be subjected to a single crimping cycle to obtain the smallest crimping outer diameter of the crimped frame. Also, such TAV frames can be crimped to smaller outer diameters than TAV frames formed of CoCr alloy.

[0224] As illustrated in FIGS. 3 and 5, the crimping of a TAV frame that is formed of CoCr alloy (e.g., 35Co-35Ni-20Cr-10Mo) will recoil by 9% or more (e.g., 9-15% and all values and ranges therebetween) after the radial crimping forces are removed from the frame.

[0225] As illustrated in FIG. 5, TAV frames formed of refractory metals also have less recoil when crimped and expanded as compared to frames formed of TiAlV alloy. TAV frames formed of Ti alloy (e.g., e.g., Ti-6A1-4V) will recoil by 6% or more (e.g., 6-10% and all values and ranges therebetween) after the radial crimping forces are removed from the frame.

[0226] TAV frames formed of refractory metals also have less recoil when crimped expanded as compared to frames formed of stainless steel. TAV frames formed of stainless steel (e.g., 316, 316L) will recoil by 7% or more (e.g., 6-15% and all values and ranges therebetween) after the radial crimping forces are removed from the frame.

[0227] Due to the recoil of TAV frames formed of CoCr alloy, stainless steel or TiAlV alloy, the number of crimping cycles required to crimp a TAV frame formed of refractory metal alloy is significantly less than the number of crimping cycles needed to crimp a TAV frame formed of stainless steel, CoCr or TiAlV. Typically, a TAV frame formed of refractory metal alloy requires only one crimping cycles to obtain the desired crimped profile of the TAV frame. Typically, a TAV frame formed of stainless steel, CoCr or TiAlV requires at least two and generally three of more crimping cycles to obtain the desired crimped profile of the TAV frame. Due to such recoil of frames formed of stainless steel, CoCr alloy or TiAlV alloy, the frame of the TAV must be repeatedly subjected to a crimping force to attempt to obtain the smallest crimping outer diameter of the crimped frame. The need to subject the TAV frame to multiple crimping cycles or procedures can potentially result in damage to the frame, damage the leaflets of the TAV, damage the inner and/or outer skirt on the TAV, and/or damage to other components of the medical device (e.g., damage to balloon on the catheter, damage to one or more components on the catheter, etc.).

[0228] For example, due to the recoil of CoCr alloy, the TAV frame made of CoCr alloy after one crimping cycle is no more than 91% of the smallest crimping profile, thus requiring at least three crimping cycles to obtain a crimping profile that is 98% or more of the smallest crimping profile of the TAV frame. Also, due to the recoil of TiAlV alloy, the TAV frame made of TiAlV alloy after one crimping cycle is no more than 94% of the smallest crimping profile, thus requiring at least two crimping cycles to obtain a crimping profile that is 98% or more of the smallest crimping profile of the TAV frame. Due to the very small recoil of a refractory metal alloy such as Mo—Re alloy, the TAV frame made of a refractory metal alloy only requires a single crimping cycle to obtain 98-99.9% of the smallest crimping profile of the TAV frame.

[0229] A frame formed of a refractory metal alloy such as MoRe alloy was found to have less recoil after being expanded than a frame formed of CoCr alloy. Specifically, it was found that a frame formed of MoRe alloy had a recoil of less than 2% after expansion has compared to a frame formed of CoCr alloy that had 9% or more recoil after expansion. Generally, frames formed of a refractory metal alloy have a recoil that is 1.5-8 times less (and all values and ranges therebetween) than a frame formed of a CoCr alloy, stainless steel, or a TiAlV alloy. As such, a frame formed of a refractory metal alloy will better conform to the shape of the heart passageway wherein the frame is expanded, thus reducing the amount of paravalvular or paraprosthetic leak (PVL) about the prosthetic heart valve after expansion. Furthermore, a frame formed of a refractory metal alloy will expand to its desired expanded state from a single inflation of the balloon of the balloon delivery catheter. Due to the significant recoil of a frame formed of CoCr alloy, stainless steel, and TiAlV alloy after expansion, the balloon of the balloon delivery catheter typically needs to be inflated multiple times to cause the frame to conform to the shape of the heart passageway wherein the frame is expanded. Such multiple inflations of the balloon can result in increased incidence of damage to the prosthetic heart valve and/or to the heart passageway wherein the frame is expanded.

[0230] FIG. 6 illustrates two frames for a TAV that are configured to be expanded in a 30 mm annulus of a heart. The maximum cross-sectional area of a 30 mm is 706.86 mm.sup.2. TAV frame F1 on the left is formed of a CoCr alloy (e.g., MP35N, etc.) and TAV frame F2 on the right is formed of a refractory metal alloy (e.g., 40-60 wt. % Mo, 40-60 wt. % Re, 0-10 wt. % one or more metal additives). When TAV frame F1 formed of CoCr alloy is expanded to a 30 mm diameter by an inflatable balloon, the TAV frame recoils by more than 9% to a diameter of less than 27.3 mm. As such, the maximum cross-sectional area of the expanded TAV frame F1 or the effective orifice area (EOA) after being initially expanded is less than 585.35 mm.sup.2. When TAV frame F2 formed of refractory metal alloy is expanded to a 30 mm diameter by an inflatable balloon, the TAV frame recoils by less than 2% to a diameter of greater than 29.4 mm. As such, the maximum cross-sectional area of the expanded TAV frame F2 or the effective orifice area (EOA) after being initially expanded is greater than 678.87 mm.sup.2. The reduction in recoil after the expansion of the TAV frame formed of refractory metal alloy results in the TAV frame of the better conforming to the size of the orifice in the body passageway or organ (e.g., heart, etc.). As such, the increased EOA results in a reduction of perivalvular leak (i.e., a leak caused by a space between the patient's natural heart tissue and the valve replacement). The larger recoil of the TAV frame formed of CoCr alloy results in reduced EOA and increase amount of perivalvular leak about the prosthetic heart valve. Similar issues exist for the large recoil values of stainless frames (7+% recoil) and TiAlV alloy frames (6+% recoil).

[0231] As illustrated in FIGS. 3-6, the amount of recoil of a TAV frame formed of refractory metal alloy after being crimped is significantly less than the amount of recoil of a TAV frame formed of CoCr alloy, and TiAlV alloy after being crimped. Also, the amount of recoil of a TAV frame formed of refractory metal alloy after being expanded is significantly less than the amount of recoil of a frame formed of stainless steel, CoCr, and TiAlV alloy after being expanded. Such reduction in the amount of recoil of the TAV frame form of refractory metals as compared to TAV frames formed from stainless steel, CoCr and TiAlV alloys represents a significant advancement in the manufacture and properties of TAVs.

[0232] FIG. 7 illustrates two different wires formed of CoCr and a refractory metal such as MoRe to illustrate the conformability to bending of the two types of wires. When the TAV frame is expanded, the struts and posts of the TAV frame plastically deform (e.g., generally deform outwardly) due to the expansion of the inflatable balloon or from some other expansion device. Generally, the treatment location where the TAV device is expanded is not perfectly cylindrical nor has a perfectly shaped circular cross-sectional shape. Generally, the treatment area is damaged and/or includes plaque, calcium deposits and/or other materials (e.g., prior implanted medical devices, etc.) that cause the shape of the treatment area to be non-cylindrical-shaped or have a non-circular cross-sectional shape. As such, TAV frames that can better conform to the irregular shapes in a treatment location result in a TAV that better fits the treatment area and can result in a reduction of perivalvular leak or other types of leakage about the outer perimeter of the expanded TAV. It has been found that refractory metal alloys (e.g., MoRe alloys, etc.) better conform to bending that metal alloys such as stainless steel, CoCr, Nitinol, and TiAlV alloys.

[0233] FIG. 7 illustrates that when a MoRe rod and a CoCr rod are subjected to the same bending force, the MoRe wire better conforms to the ideal bending shape IBS than the CoCr wire. The bent rods represented by the top portion of FIG. 7 illustrate that when the two wires were bent, the CoCr wire had a greater deviation from the ideal bent shape region than the wire formed of refractory metal alloy such a MoRe. The two wire bending tests illustrate that the rod formed of refractory metal alloy such a MoRe had 23% and 31% better conformity to the ideal bending shape than the wire formed of CoCr. The ability to conform to a specific shape is largely dependent upon the recoil associated with the material.

[0234] It has been found that wires formed of the refractory metal alloy (e.g., MoRe alloy, ReW alloy, MoReCr alloy, MoReTa alloy, MoReTi alloy, WCu alloy, ReCr alloy, Mo alloy, Re alloy, W alloy, Ta alloy, Nb alloy) have about 15-45% (and all values and ranges therebetween) better conformity to bending to an idea bending shape formed by a die than the same sized wire formed of stainless steel, CoCr alloy, and TiAlV alloy. Such better shape conformity exhibited by the refractory metal alloy is believed to be due in part to the reduced recoil of the refractory metal alloy and one or more other properties of the refractory metal alloy (e.g., strength of alloy, etc.). Such improved shape conformity of refractory metal alloys results in improved conformity of an expanded TAV frame formed of refractory metal alloy to the treatment area shape compared to frames formed of traditional metal alloys as illustrated in FIGS. 8A and 8B.

[0235] FIG. 8A illustrates the conformability of an expanded TAV frame 500 formed of CoCr alloy in an irregularly shaped annulus 400 of a heart wherein the treatment area includes calcium deposits CD and leakage regions PVL about the outer perimeter of the expanded TAV frame. The expanded TAV frame forms an EOA of about 585 mm.sup.2. Due to the inability of the CoCr alloy to readily conform to irregular shapes in the annulus, an open area of about 46 mm.sup.2 is located about the outer perimeter of the expanded frame of the TAV to allow for PVL about the expanded TAV.

[0236] FIG. 8B illustrates the conformability of an expanded TAV frame 600 formed of a refractory metal alloy such as MoRe in an irregularly shaped annulus 400 of a heart. The expanded TAV frame forms an EOA of about 679 mm.sup.2 due to the improved ability of the refractory metal alloy to conform to irregular shapes in the annulus. As such, only an area of about 14 mm.sup.2 is located about the outer perimeter of the expanded frame of the TAV. The expanded TAV frame formed of refractory metal alloy is illustrated as being more than 30% (e.g., 30-40% and all values and ranges therebetween) more conformable to the irregularly shaped annulus 400 of a heart as compared to an expanded frame of the TAV formed of CoCr alloy. Such improved conformity also results in nearly 70% less open area about the expanded frame of the TAV that is formed of a refractory metal alloy as compared to an expanded frame of a TAV formed of CoCr alloy. In general, expandable TAV frames form of refractory metal alloy are about 10-50% (and all values and ranges therebetween) more conformable to irregularly shaped body passageways as compared to an expanded TAV frame formed of stainless steel, CoCr alloy, or NiTi alloys.

[0237] Because the expandable TAV frame formed of a refractory metal alloy such as MoRe alloy betters conform to the shape of a body passageway wherein the TAV frame is expanded, there is a reduction in the amount of paravalvular or paraprosthetic leak (PVL) or other type of leakage about the TAV after expansion. Furthermore, an expandable TAV frame formed of a refractory metal alloy such as MoRe alloy will expand to its desired expanded state from a single inflation of the balloon of a balloon delivery catheter. Due to the significant recoil of an expandable TAV frame formed of stainless steel, CoCr alloy, or TiAlV alloy after expansion, the balloon of the balloon delivery catheter typically needs to be inflated multiple times to cause the expandable frame to conform as close as possible to the shape of the body passageway wherein the expandable frame is expanded. Such multiple inflations of the balloon can result in increased incidence of damage to the medical device and/or to the body passageway wherein the expandable frame is expanded.

[0238] The reduced amount of recoil, improved bending conformity and greater radial strength of expanded TAV frames that are at least partially formed of refractory metal alloy as compared to expandable TAV frames formed of stainless steel, CoCr alloy, and TiAlV alloy results in the following non-limiting advantages: 1) formation of a frame for a medical device having thinner posts, struts, and/or strut joints which results in i) safer vascular access when inserting the medical device through a body passageway and to the treatment area, and/or ii) decreased the risk of bleeding and/or damage to the body passageway and/or the treatment area when the medical device is delivered to the treatment area and/or expanded at the treatment area; 2) easier deliverability of the medical device to the treatment area which can result in i) decreased trauma to the body passageway (e.g., blood vessel, aortic arch trauma, etc.) during the insertion and/or expansion of the medical device at the treatment area, and/or ii) decreased risk of neuro complications-stroke; 3) less recoil which results in i) reduced crimping profile size, ii) increased conformability of the expanded medical device at the treatment area after expansion in the treatment area, iii) increased radial strength of the frame of the medical device after expansion at the treatment area, iv) only require a single crimping cycle to crimp the medical device on a balloon catheter or other type of delivery device, v) reduced incidence of damage to components of the medical device (e.g., struts, posts, strut joints, and/or other components of the expandable frame, leaflets, skirts, coatings, etc.) during the crimping, expansion, and operation of the medical device, vi) greater effective orifice area (EOA) of the medical device after expansion of the medical device, vi) decreased pulmonary valve regurgitation (PVR) after expansion of the medical device in the treatment area, and/or vii) require only a single expansion cycle of the balloon on the balloon catheter or other expansion mechanism to fully expand the medical device; and/or 4) creating a medical device having superior material biologic properties to I) improved tissue adhesion and/or growth on or about medical device, II) reduced adverse tissue reactions with the medical device, III) reduced toxicity of medical device, IV) potentially decreased in-valve thrombosis during the life of the medical device, and/or V) reduced incidence of infection during the life of the medical device.

[0239] FIGS. 9A-9C illustrate stress vs. reduction in percent area graphs of a TiAlV alloy, a CoCr alloy, and a MoRe alloy. These graphs illustrate that a TAV frame formed of a refractory metal alloy such as MoRe as illustrated in FIG. 9C has improved properties such as strength, yield strength, ultimate tensile strength, fatigue ductility, greater deformation latitude, material integrity between plastic deformation and failure, and durability as compared to materials such a CoCr alloys (FIG. 9B) and TiAlV alloys (FIG. 9A). A refractory metal alloy such as MoRe can have a strength of 1.5-5 times (and all values and ranges therebetween) greater than that of CoCr alloys and TiAlV alloys. Although not illustrated, the refractory metal alloys such as MoRe alloy have improved properties such as strength, yield strength, ultimate tensile strength, fatigue ductility, greater deformation latitude, material integrity between plastic deformation and failure, and durability as compared to stainless steel.

[0240] As illustrated in FIG. 10, refractory metal alloys such as MoRe alloy have a greater stiffness and yield strength compared to CoCr alloys and TiAlV alloys. The top curve of FIG. 10 is a MoRe alloy that includes 47.5 wt. % Re and the balance Mo. The middle curve of FIG. 10 is a CoCr alloy that includes 28 wt. % Cr, 6 wt. % Mo and the balance Co. The bottom curve of FIG. 10 is a TiAlV alloy that includes 6 wt. % Al, 4 wt. % V and the balance Ti. Although not illustrated, refractory metal alloys such as MoRe alloy have a greater stiffness and yield strength compared to stainless steel.

[0241] FIGS. 11-13 are graphs that illustrate the yield strength, ultimate strength, and fatigue ductility of a TiAlV alloy, CoCr alloy, and MoRe alloy after such alloys are cold worked to reduce the cross-sectional area of the alloy. After being cold worked, a refractory metal alloy such as MoRe alloy has greater fatigue ductility, yield strength, and ultimate strength than CoCr alloys and TiAlV alloys. Also, the cold working of the MoRe alloy results in the increased ductility of the alloy, wherein CoCr alloys and TiAlV alloys have a reduction in ductility as additional cold working is applied to the alloy. Although not illustrated, the same is true for a refractory metal alloy as compared to stainless steel.

[0242] FIG. 14 illustrates that a refractory metal alloy such as MoRe alloy has a greater durability than CoCr alloys and TiAlV alloys. As such, the longevity of a TAV frame formed of a refractory metal that is subjected to bending stresses when inserted into a patient is greater than the longevity of a TAV frame formed of CoCr and TiAlV alloys. Although not illustrated, the same is true for a refractory metal alloy as compared to stainless steel.

[0243] FIG. 15 compares the purity level of a refractory metal alloy such as MoRe alloy to alloys such as CoCr alloys and TiAlV alloys. The purity level of a refractory metal such as MoRe is significantly greater than CoCr alloys and TiAlV alloys. The MoRe alloy is illustrated as including 47.4995 wt. % molybdenum and 52.4995 wt. % rhenium. The CoCr alloy includes 62 wt. % cobalt, 28 wt. % chromium, 6 wt. % molybdenum, and impurities such as 1 wt. % nickel, 1 wt. % silicon, 1 wt. % manganese, 0.25 wt. % iron, and 0.75 wt. % other elements. The TiAlV alloy includes 89 wt. % titanium, 6 wt. % aluminum, 4 wt. % vanadium, and impurities such as 0.25 wt. % iron, and 0.75 wt. % other elements. It is believed that impurities in an alloy can result in reduced fatigue life of the alloy, adverse tissue reactions when exposed to the alloy, undesirable metal ion release from the alloy, and/or allergic reactions when tissue and/or fluids are exposed to the alloy. The use of refractory metals for the metal device overcomes these potential issues that other alloys have with regard to impurity content of the alloy.

[0244] FIG. 16 illustrates the hydrophilicity of a refractory metal alloy such as a MoRe alloy compared to a CoCr alloy or TiAlV alloy. Hydrophilicity of a material implanted in a patient is an important property of the material with regard to the cell adhesion, cell migration, and cell multiplication of tissue on the material. As illustrated in FIG. 16, CoCr alloys are hydrophobic materials resulting in a large contact angle (93°±1°) of a water droplet (e.g., distilled water) positioned on the surface of the CoCr alloy. TiAlV alloys are a little more hydrophilic than CoCr alloys and exhibit a contact angle of 58°±8° when a water droplet is positioned on the surface of the Ti alloy. Refractory metal alloys such as a MoRe alloy have a much greater hydrophilicity than CoCr alloys and TiAlV alloys. The MoRe alloy has a contact angle of 37°±3° when a water droplet is positioned on the surface of the MoRe alloy. The refractory metal alloys generally have a hydrophilicity wherein the contact angle of a water droplet on the surface of the refractory metal alloy is 25°-45° (and all values and ranges therebetween), and typically 30-42°.

[0245] FIGS. 17-19 illustrate the ion release of a refractory metal alloy such as MoRe alloy. As illustrated in FIG. 17, during the first day of implanting the medical device in a patient, the ion release of molybdenum is about 0.244 μg/cm.sup.2 per day and the ion release of rhenium is about 0.115 μg/cm.sup.2 per day. From days 1-3, the ion release of molybdenum is about 0.019 μg/cm.sup.2 per day and the ion release of rhenium is about 0.013 μg/cm.sup.2 per day. From days 3-7, the ion release of molybdenum is less than 0.001 μg/cm.sup.2 per day and the ion release of rhenium is about 0.002 μg/cm.sup.2 per day. From days 7-15, the ion release of molybdenum is about 0.002 μg/cm.sup.2 per day and the ion release of rhenium is less than 0.001 μg/cm.sup.2 per day. From days 15-30, the ion release of Mo is about 0.003 μg/cm.sup.2 per day and the ion release of rhenium is less than 0.001 μg/cm.sup.2 per day. The graph illustrates that after the seventh day of implantation in tissue, the ion release of molybdenum and rhenium from the MoRe alloy is effectively nonexistent.

[0246] FIG. 18 illustrates that the ion release of molybdenum from the MoRe alloy is less than 1.5% of the allowed daily exposure to molybdenum during the first day of insertion of the MoRe alloy in a patient, and such daily ion exposure of molybdenum drops to 0.04% of the allowed daily exposure after 15 days. FIG. 18 also illustrates that the ion release of rhenium from the MoRe alloy is less than 0.31% of the allowed daily exposure to rhenium during the first day of insertion of the MoRe alloy in a patient, and such daily ion exposure of rhenium drops to less than 0.01% of the allowed daily exposure after 15 days.

[0247] FIG. 19 is a table that illustrates the amount of the primary metals in the alloys of TiAlV, CoCr, stainless steel, and MoRe released into a patient after the medical device including such alloys is inserted into a patient for 90 days. As illustrated in the table, the amount of molybdenum and rhenium contained in the tissue surrounding the MoRe alloy after 90 days is significantly lower than any of the primary metals of the other alloys. The amount of molybdenum metal ion in a gram of tissue from a 0.028 cm.sup.2/g dose of MoRe in the tissue after 90 days is 0.023 μg/g. As such, the absolute increase in molybdenum metal ion relative to the dose size of the MoRe alloy in the tissue was 0.82. The amount of rhenium metal ion in a gram of tissue from a 0.028 cm.sup.2/g dose of MoRe in the tissue after 90 days is 0.014 μg/g. As such, the absolute increase in Re metal ion relative to the dose size of the MoRe alloy in the tissue was 0.5. Based on absolute increase in metal ions in the tissue relative to the dose of the metal alloy in the tissue, both the molybdenum and rhenium content in the tissue form the MoRe alloy after the MoRe alloy was implanted in the tissue for 90 days was over 120 times less than the molybdenum from the CoCr alloy, and many more times less than the other primary metals of the tested alloys. Generally, the absolute ion release of the primary elements of the refractory metal alloys (e.g., primary is an element in an alloy that is at least 2 wt. % of the alloy) relative to the dose of the refractory metal alloy in the tissue after 90 days is at least 120 times less than any of the primary components of the alloys of TiAlV, CoCr, stainless steel. As such, less potentially irritating metal ions are released from the refractory metal alloy compared to CoCr alloys, TiAlV alloys, and stainless steel. In general, the refractory metal alloy has a maximum ion release of a primary component of said refractory metal alloy when inserted or implanted on or in the body of the patient of no more than 0.5 μg/cm.sup.2 per day (e.g., 0-0.5 μg/cm.sup.2 per day and all values and ranges therebetween). The primary component of the refractory metal alloy is a metal that constitutes at least 2 wt. % of the refractory metal alloy. Also, the refractory metal alloy, when implanted into tissue for at least 90 days, has an absolute increase in ion release per dose of refractory metal alloy in the tissue about said medical device no more than 50 (e.g., 0.01-50 and all values and ranges therebetween).

[0248] Medical devices, such as expandable heart valves that are at least partially formed of the refractory metal in accordance with the present disclosure, overcome several unmet needs that exist in expandable medical device formed of CoCr alloys, TiAlV alloys, and stainless steel. Such unmet needs addressed by the medical devices in accordance with the present disclosure include 1) not having to form a large hole in large arterial vessels or other blood vessels for initial insertion of the crimped medical device into the atrial vessel or other blood vessel, thereby reducing the incidence of lethal bleeding during a treatment; 2) enabling the medical device to be delivered and implanted in abnormally shaped heart valves or through an abnormally shaped arterial vessel due to calcination in the prosthetic heart valve and/or calcination and/or plaque in the arterial vessel by creating a medical device (e.g., stent, prosthetic heart valve, etc.) having a reduced crimped profile that is smaller than medical devices formed of CoCr alloys, TiAlV alloys, and stainless steel; 3) reducing the incidence of a perivalvular leak and/or other types of leakage about the implanted medical device when the medical device is expanded in the treatment region by using a frame formed of the refractory metal alloy that better conforms to the shape of the abnormally shaped heart valve orifice upon expansion of the prosthetic heart valve comparted to prior art prosthetic heart valves formed of CoCr alloys, TiAlV alloys, and stainless steel, thereby reducing the incidence of stroke and/or by increasing the incidence of success of the implanted medical device; 4) improving the radial strength of the expanded struts, posts, and/or strut joints in the expandable frame and the strength of the expandable frame itself after expansion the medical device; 5) reducing the amount of recoil of the expandable frame during the crimping and/or expansion of the expandable frame of the medical device; 6) enabling the medical device to be used in a heart that has a permanent pacemaker; 7) reducing the incidence of minor stroke during the insertion and operation of the medical device at the treatment area; 8) reducing the incidence of coronary ostium compromise; 9) improving foreshortening; 10) reducing further aortic valve calcification and/or calcification in a blood vessel after implantation of the medical device; 11) reducing the need for multiple crimping cycles when inserting the medical device on a catheter or other type of delivery system; 12) reducing the incidence of frame/stent fracture during the crimping and/or expansion of the medical device; 13) reducing the incidence of biofilm-endocarditis after implantation of the medical device; 14) reducing allergic reactions to the medical device after implantation of the medical device; 15) improving the hydrophilicity of the medical device to improve tissue growth on and/or about the implanted medical device, 16) reduce the magnetic susceptibility of the medical device, 17) reduce the toxicity of the medical device, 18) reduce the amount of metal ion release from the medical device, and/or 19) increasing the longevity of leaflets and/or stent/frame and/or other components of the medical device after insertion of the medical device.

[0249] It will thus be seen that the objects set forth above, among those made apparent from the preceding description, are efficiently attained, and since certain changes may be made in the constructions set forth without departing from the spirit and scope of the disclosure, it is intended that all matter contained in the above description and shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense. The disclosure has been described with reference to preferred and alternate embodiments. Modifications and alterations will become apparent to those skilled in the art upon reading and understanding the detailed discussion of the disclosure provided herein. This disclosure is intended to include all such modifications and alterations insofar as they come within the scope of the present disclosure. It is also to be understood that the following claims are intended to cover all of the generic and specific features of the disclosure herein described and all statements of the scope of the disclosure, which, as a matter of language, might be said to fall therebetween.

[0250] To aid the Patent Office and any readers of this application and any resulting patent in interpreting the claims appended hereto, applicants do not intend any of the appended claims or claim elements to invoke 35 U.S.C. 112(f) unless the words “means for” or “step for” are explicitly used in the particular claim.