AU2008201081A1 - Valvular prostheses having metal or pseudometallic construction and methods of manufacture - Google Patents

Description

P/00/011 Regulation 3.2

AUSTRALIA

Patents Act 1990

ORIGINAL

COMPLETE SPECIFICATION STANDARD PATENT Invention Title: "VALVULAR PROSTHESES HAVING METAL OR PSEUDOMETALLIC CONSTRUCTION AND METHODS OF MANUFACTURE' The following statement is a full description of this invention, including the best method of performing it known to me/us: 00 '4 -1- SVALVULAR PROSTHESES HAVING METAL OR PSEUDOMETALLIC CONSTRUCTION AND METHODS OF MANUFACTURE

O

Background of the Invention 00 5 Any discussion of the prior art throughout the specification should in no way be considered as an admission that such prior art is widely known or forms part of common 0 C general knowledge in the field.

00 0 The present invention relates generally to metal and pseudometallic films

C

suitable for implantation into mammalian subjects in need thereof More particularly, to the present invention pertains to prosthetic cardiac and venous valve implants, access ports and other implantable medical devices that employ moveable valve flaps. The implantable medical devices according to the present invention have improved valve flap members fabricated from metal and/or pseudometallic materials. It is desirable, although not essential to the present invention, that the prosthetic cardiac and venous valve implants be capable of being delivered using endovascular techniques and being implanted at an intracardiac or intravenous site without the need for anatomic valve removal. Embodiments of the prosthetic valves of the present invention are well-suited for cardiac delivery via a femoral or subclavian artery approach using a delivery catheter, and, depending upon the specific configuration selected, may be deployed within the heart to repair valve defects or disease or septal defects or disease. According to one embodiment of the invention, there is provided a chamber-to-vessel (CV) configuration that is particularly well suited as an aortic valve prosthesis to facilitate blood flow from the left ventricle to the aorta. In a second embodiment, there is provided a prosthetic valve in a chamber-to-chamber (CC) configuration that is particularly well-adapted for mitral valve replacement or repair of septal defects.

Finally, a third embodiment is provided in a vessel-to-vessel (VV) configuration, which is well suited for venous valve exclusion and replacement.

Common to each of the CV, CC and VV embodiments of the present invention are a stent support member, a graft member which covers at least a portion of either or both the luminal and abluminal surfaces of the stent and valve flap members. Both the graft member and the valve flap members are preferably fabricated from metallic and/or pseudometallic materials, the valve flaps being coupled to the stent in a manner which 00 biases the valve flaps so they close upon a zero pressure differertral across the valve region.

00 00 00 More specifically, the valve flap memnbers and the graft members of the present invention are fabricated entirely of self-supporting films made of biocompatible metals or biocompatible pseudonetas. For purposes of this application, the term "pseudometal" or "pseudometalije" is intended to mean a biocompatible material which exhibits biological 00 response and material characteristics substantially the sarne as biocompatible metals, such as for example composite materials.

As opposed to wrought materials that are made of a single metal or alloy, the 00 inventive valve flap members and graft members are made of at least two layers formed upon one another into a self-supporting laminate structure. Laminate structures are generally known to increase thc mechanical strength of sheet materials, such as wood or Paper products. Laminates are use-d in the field of thin film fabrication also to increase the mechanical properties of the thin film, specifically hardness and toughness. Laminate metal foils have not been used or dcveloped because the standard metal forming tochnologics, such as rolling and extrusion, for example, do not readily lend themselves to producing laminate structures. Vacuum depositlion technologies can be developed to yield laminate metal Is structures with improved mechanical properties. In addition, lamninate structures can be designed to provide special qualities by including layers that havc spccial ptoperties such as superelasticity, shape memiory, radio-opacity, corrosion resistance etc.

It is important for the present invention to provide orientational definitions. For purposes of the present invention, references to positional aspects of the present invention will he defined relative to the directional flow vector of blood flow through the implantable device. Thus, the termi "proximal" is intended to mean on the inflow or upstreamn flow side of the device, while "distal" is intended to mean on the outflow or downstream flow side of the device. Withi respect io the catheter delivery system described herein, the term~ -proiximal" is intended to mean toward the operator end of the catheter, while the term 2 5 "distal" is intended to meain toward the terminal end or device-carrying end of the catheter.

Con ventional mectal foils, 'Wires nd. thin-walled seamless tubes are typically produced [romn ingots it) a series of hot or cold forming steps that include some combination of rolling, pulling, exvrusion and oilher similar processes. E~ach of these processing steps is accompanied by auxiliary steps that include cleaning the surftces of the material of foreign material residues depositcd on the material by the tooling and lubricants used in the metal 00

O

Sforming processes. Additionally, chemical interaction with tooling and lubricant materials and ambient gases also introduces contaminants. Some residue will still usually remain on 0 the surface of the formed material, and there is a high probability that these contaminating residues become incorporated during subsequent processing steps into the bulk of the wrought metal product. With decreasing material product size, the significance of such 0 5 contaminating impurities increases. Specifically, a greater number of process steps, and, O therefore, a greater probability for introducing contaminants, are required to produce smaller 00 product sizes. Moreover, with decreasing product size, the relative size of non-metal or other Sforeign inclusions becomes larger. This effect is particularly important for material thicknesses that are comparable to the grain or inclusion size. For example, austenitic stainless steels have typical grain sizes on the order ofmagnitude of 10-100 micrometer.

When a wire or foil with a thickness in this range is produced, there is significant probability that some grain. boundaries or defects will extend across a large portion or even across the total thickness of the product. Such products will have locally diminished mechanical and corrosion resistance properties. While corrosion resistance is remedied by surface treatments such as electropolishing, the mechanical properties are more difficult to control.

The mechanical properties of metals depend significantly on their microstructure.

Tlhe forming and shaping processes used to fabricate metal foils, wires and thin-walled seamless tubes involves heavy deformation of a bulk material, which results in a heavily strained and deformed grain structure. Even though annealing treatments may partially alleviate the grain deformation, it is typically impossible to revert to well-rounded grain structure and a large range of grain sizes is a common result. The end result of conventional forming and shaping processes, coupled with annealing, typically results in non-uniform grain structure and less favorable mechanical properties in smaller sized wrought metal products. It is possible, therefore, to produce high quality homogeneous materials for special purposes, such as micromechanical devices and medical devices, using vacuum deposition technologies.

In vacuum deposition technologies, materials are formed directly in the desired geometry, planar, tubular, etc. The common principle of the vacuum deposition processes is to take a material in a minimally processed form, such as pellets or thick foils (the source material) and atomize them. Atomization may be carried out using heat, as is the 00 INO case in physical vapor deposition, OT using dhe effect of colisional processes, as in the case of' sputter deposition, for example. In sonie forms of deposition, a process, such as laser ablation, which creates microparticles that typically consist of one or more atoms, may 00 replace atomization; the number of atoms per particle may be in the thousands or more. The atoms or particlcs of the source material are then deposited on a substrate or mandrel to 00 5 directly fomi the desired object. In other deposition methodologies, chemical reactions between ambient gas introduced into the vacuumn chamber, the gas source, and the (71 depositod atoms and/or particles are part of the deposition process. The dcpositcd material includes compound species that are formed due to the reaction of the solid soutrce and the gas source, such as in the case of chemical vapor deposition. In most cases, the deposited to material is then either partially or completely removed from the substrate, to form the desired product.

The rate of film growth is a significant parameter of vacuum deposition processes. In order to deposit mateiials that can bc compared in functionality with wvrought mectal products, deposition rates in exces of 1. micrometersfhour are a must and indeed rates as high as 100 micrometers per hour are desirable. These are high deposition rates and it is known that at such rates the deposits always have a columnar structure, Depending on other deposition parameters, and most importantly on the substratc temperature, the columns may be amorphous or crystalline but at such high deposition rates mnicrocrystalline structure development can be expected at best. The diffcumlty is that the columns provide a mechanically weak structure in which crack propagation can occur uninhibited across the whole thickness of the deposit.

A special advantage of vacuum deposition technologies is that it is possible to deposit layered materials and thus films possessing exceptional qualities may be produced H.

Holleck, V. Schier: "Multilayer PVI) coatings for wear protection", Sw/race and Coalings Technology, Vol. 76-77 (1995) pp. 328-336). Layered materials, such as superstructures or multilaycrs, arc commonly deposited to take advantage of some chemical, electroinic, or optical property of the matcrial as a coating; a common examplc is an antirefloctivc coating on an optical lens.

It has not been recovniizcd until rulatively recently [bat multilaycr coatings may have improved mechanical propentics compared with similar coatings made of a single laycr. The 00 improved mechanical properties may be dlue to the ability of the interface between the layers INO to relieve stress. This stress relief occurs if the interface provides a slide plane, is plastic, or may delaminate locally. This property of multilayer films has been recognized in regard with their hardness but ths recolpnition has not been translated to other mechanical propertics that 00 are significant for metal products that may be used in ipplication where they replace wrought metal parts.

A technological step that interrupts the im growthi results in discontinuous columins 00 and prevents crack propagation across the entire film thickness. In this sense, it is not necessary that the struicture consist of a multiplicity of chemically disti-nct layers, as it is common in the case of thin film tehnology where multilayers are used. Such chemical 1(1 differences maybe useful and may contribute to improved properties of the materials.

As used in this application a "layer" is intended to mcan a substantially uniform material limited by interfaces between it and adjacent other substanitially homogeneous layers, substrate, or environment. The interface region between adjacent layers is an inhomogeneous region in which extensive thermodynamic parameters may change. Different layers are not necessarily charararized by differen velues of the extensive thermodynamic parameters but at the interface, there is a local change at least in somne parameters. rFor example, the interface between two steel layers that are identical in composition and microstructure may be characterized by a high local concentration of grain boundaries due to aM interruption of the film growth process. T'hus, the interface between. layers is not necessarily different in chemical composition if it is different in structure, It is necessary to provide for good adhesion between the layers and this is usually achieved by providing for a relatively broad interface region rather than for an abrupt interface. Thle width of the interface region may be defined a3 the ragc within which extensive thermodynamic parameters change. This range c-an depend on the interiee area considered and. it may mean the extent of intcrhwoe mierorougimess. In other words, adhesion may be promoted by incre-ased interfiice microroughness between adjacent layers.

By providing for a layecrcdJ Szructurc, the inventive materials consist of a controlled maximum-gize of grains and columns as extendcd defects in the direction of the film growth (perpendicular to The layers). this limit of the grain or decfect size results in materials that have increased mechanical strength and particularly increased toughness comparcd to their 00

O

ri -6- Snon-laminated counterparts, both deposited and wrought materials. In addition, limiting Sthe extent to which defects and grain boundaries reach across the laminate, corrosion resistance is also improved.

Laminated materials will have additional advantages when chemical 00 5 compositions of the layers are chosen to achieve special properties. For example, a radiopaque material such as tantalum may form one layer of a structure while other N layers are chosen to provide the material with necessary mechanical and other 0 properties.

Cl Heretofore, however, conventional implantable valves have traditionally been to fabricated of rigid metal or synthetic materials, or have been fabricated of pliant synthetic polymeric materials, each of which involved hoth hemodynamic and physiological complications.

It is an object of the present invention to overcome or ameliorate at least one of the disadvantages of the prior art, or to provide a useful alternative.

Summary of Prior Art The prior art discloses certain common device segments inherently required by a percutaneous prosthetic valve: an expandable stent segment, an anchoring segment and a flow-regulation segment.

Prior art percutaneous prosthetic valve devices include the Dobben valve, U.S.

Pat. No. 4,994,077, the Vince valve, U.S. Pat. No. 5,163,953, the Teitelbaum valve, U.S.

Pat. No. 5,332,402, the Stevens valve, U.S. Pat. No. 5,370,685, the Pavenik valve, U.S.

Pat. No. 5,397,351, the Taheri valve, U.S. Pat. No. 5,824,064, the Anderson valves, U.S.

Pat. Nos. 5,411,552 5,840,081, the Jayaraman valve, U.S. Pat. No. 5,855,597, the Besseler valve, U.S. Pat. No. 5,855,601, the Khosravi valve, U.S. Pat. No. 5,925,063, the Zadano-Azizi valve, U.S. Pat. No. 5,954,766, and the Leonhardt valve, U.S. Pat. No.

5,957,949. Each of these pre-existing stemn valve designs has certain disadvantages which are resolved by the present invention.

The Dobben valve has a disk shaped flap threaded on a wire bent like a safety pin to engage the vessel wall and anchor the valve. A second embodiment uses a stent of a cylindrical or crown shape that is made by bending wire into a zig-zag shape to anchor the device and attach the flow regulator flap. The device presents significant hemodynamic, delivery, fatigue and stability disadvantages.

00 The Vince valve has a stent comprised of atoroidal body formed of a flexible coil of %ire and a flow-regulation mechanism consistig of a flap of biologic inaterial. Numerous INDlongtudinal extensions within the stunt are provided as attachruent posts to mount the flowregulation mechanism. The device requires balloon expansion to deliver to the bud), orifice.

Ile main shortcoming of this design is delivery profile. Specifically, the device arnd miethod 00 put forth will require a 20+ French sizc catheter (approximately 9 Frencli sizes to accommodate the balloon and 14+ French sizes to accommodate the comprcsscd &~vice) 00 making the device clinically ineffctive as a minimially invasive technique. Additionally, the device does not adequately address heciodynamie, stability and anchioring coacerns.

The Teitelbaumn valve is made of shape memory nilinol and consists of two It) components. The first component is stenit-like and comprised of a meushwork braiding of nitinol wire similar to that described by Wallstcn, U.S. Pat. No. 4,655,771L, wvith trumpet like distal a proximal flares. The purpose of the stent is to maintain a scmi-ridged patent channel through the diseased cardiac valve after initial balloon dilation. Thie flared en&s are intiended to maintain the position of the stein component across the valve thereby anchoring thie device. Embodiments for the flow-regulation mechanism includc a sliding ohttirator and a caged ball both which are delivered secondary to the stent portion. The disadvantages of the device are the flow regulators reduce the cifective valve orifice and gencrate sub-optimal hemodynamic characteristics; fatigue concerns arise from the separate nature of dhe stemi and flow-regulation components; the high metal arnd exposed metal content raises thrombogenesis, valvidar stenosis and chronic anticoagulation concerns: and the separate delivery requirements (although addressing the need for small delivery profile) in addition to any initial valvuloplasty pedinrmed increases the time, costs, risks, difficulty and traumia associated with the percuttineous procedure.

The Paveik valve is a self-expanding percutaneous device comnprised of a poppet, a stent and a restraining element. The valve stent has barbed means to anchor to dhe internal passageway. The device includes a self-expanding stent of a zigzag configuration in conjunction with a cage mechanism comprised of a multiplicity of crisscrossed wires and a valve seat. The disadvantages of the device include large delivery profile, reduced cffcctivc valvular orifice, possible perival~'ular leakage, trauma-inducing turbulent flow generated by the cage occlusive apparatus and valve seat, thronibogeacsis, v'alvular stenosis, chronic 00 anticoagulationi, problematic physiological and procedural concerns duc to the barb anchors IND and complex delivery procedure that includes inflation of occlusive member after initial implantation.

Stevens discloses a percutaneous valve replacement system for the endovascular 00 removal of a malfunctioning valve followed by replacement wvith a prosthetic valve. Thle valve replacement systern- may include a prosthetic valve device comprised of a stent and 00 cusps for flow-regulation such as a fixed porcinie aortic valve, a valve introducer, an itraluminal procedure device, a procedure device capsule and a tissue cutter. The devices disclosed indicate a long and complex procedure requiring large diameter catheters. The valve device disclosed will require a large delivery catheter and does not address the key to mechanisms required of a functioning valve. Additionally, the dev'ice requires intralurnlinalsecuring moans such as suturing to anchor the device at the desired location.

The Taheri valve describes an aortic valve replacement combined with an aortic arch graft The devices and percutanous methods described require puncture of the chest cavity.

Anderson has disclosed various balloon exp~andable pci-cutaneous prosthetic valves.

The latest discloses a valve prosthesis comprised of a stent made from an expandable cylindrical. structure made of seve.TW spaced apices and an elastically collapsible valvt: mounted to the stent with the coniissural points of the valve mounted to the apices. The device is placed ait the desired location by balloon expanding the stent and valve. The main disadvantage to this design is thc 20+ French size delivery requirement. Other pn-oblemis include anchoring stability, perivalvular leakage, difficult manufacture and suspect valve performance.

The Jayaraman valve includes a star-shaped stent and a replacement valve and/or replacement graft for use in repairing a damaged cardiac valve. T'he device is comprised of a chain of intercnnected star-shaped stcat scgrents in the center of which sits a replacement valve. Tho flow-regulation. mechanism consists of three flaps cut into a flat piece of grafi material that is rolled to form. a conduit in which the three flaps may be folded inwardly in an overlapping manner. An additional flow-regulation mechanism is disclosed in which a Patch (or multiple patches) is sutured to the outside of a conduit which is then pulled inside out or inverted such ftht the patch(s) reside on the fully inverted conduit. A balloon catheter is required to assist expansion during delivery. The disadvantages of ibhis design include lack of 00 connections and sutures; lack of an adequately controlled and biased flow-regulation 00 mechanism; uncertain ctr-ectivc valve orifice, difficult manufacture; balloon dilation requirement; complex, difficult and inaccurate delivery and large deliverTy profile.

The Bcsselcr valve discloses methods and devices for the enduvascular removal of a 0 comprised of a self-expanding stent miemtber with a flexible valve disposed within. The strn.

member is of a self-expinding cylindrical shape made from a closed wire in forrmcd in a zigzag configuratinn that can be a single piece, stamped or extruded or formed by welding the free ends together. The flow-regulation mechanismu is comprised of an arcuate portion which contains a slit (or slits) to form leaflets and a cuff portion which is sutured to and encloses the stelt. The preferred flow regulator is a porcine pericardiuw with three cusps. All additional flow regulator is described in which the graft material that comprises the leaflets (no additional mechanisms. for flow-regulation) extends to form the outer cuff portion and is is attached to Ithe stcut portion. with sutures. The anchoring segment is provided by a plurality of barbs carried by die stent (and therefor penetrating the cuff-graft segment). Delivery requires endohuiinal removal of the natural valve because thie barb anchors will malfunction if they are orthotopically secured to the native leaflets instead of the more rigid tissue at tie native annulus or vessel wall- Delivery involves a catheter within which the device and a pusher rod are disposed. The disadvantages of the device are lack of at well defined and biased flowregulation mechanism, anatomnic valve removal is required thereby lengthening the procedure Lime, increasing difficulty anti rducing clinical pracicality, traumna-inducing barbs as described above and the device is unstable and -prone to migration if barbs are omitted.

Tbe Khosravi valve discloses a percutaneous prosthetic valve comprised of a coiled sheet stent similar to that described by Derbyshire, U.S. Pat. No~. 5,007,926, to which a plurality or flaps are mounted on the interior surface to form a flow-regulation mechanism that may be comprised of a biocampatible material. The disadvantages of tis design include problematic interactions between the stent and flaps in the delivery state, lack of clinical data on coiled stent performance, the lack of a detailed mechanism to ensure that the flaps vill 00 INO create a competent one-directional vzlve, lack of appropriate anchoring means, and the design requirements imposed by surrounding anatomical structures are, ignored.

The Zadno-Azizi valve discloses a device in which flow-regulation is provided by a 00 glap disposed within a frame structure capable of taking an insertion state and an expanded state. The preferred embodiment of the flow-regulation mechanism is defined by a longitudinal valve body miade of a sufficiently resilient material with a slitqs) that extends 00 longitudinally through the valve body. Increased sub-valvular pressure is said to cause the valve body to expand thereby opening the slit and allowing fluid flow there through. The valve body extends into the into the lumien of the body passage such that increased suprivalvular pressure will prevent the slit fron opcning thereby effecting onie-directional flow.

The device includes embedding the fr-ame withini the seal or graft material through injection molding, blow molding and insertion molding. The &isadvantages of the device include the flow-regulation mechanism provides a siall effective valve orifice, the turbidity caused by the multiple slit nechaniisras, the large delivery profile required by the disclosed embodiments and the lack of acute anchoring means.

Finially, the Leonhardt valve is comprised of a tubular graft havig radially compressible annular spring portions and a flow regulator, wvhich is preferably a biological valve disposed within. In addition to over-sizing the spring stent by 300/6, anchoring mneans is provided by a light-activated biocotupatible tissue adhesive is located on the outside of the tubular graft aind seals to the living tissue. The stent section is comprised of a single piece of super-elastic wire formed into a zigzag shape arnd connected together by crimping tubes, adhesives or welds. A malleable thin-walled, biocompatible, flexible, expandable, woven fabric graft material is connected to the outside of the stent that is in turn connected to the biological flow regulator. Disadvantages of this device include those profile concerns associated with biological valves and unsupportedl graft-leaflet regulators, a large diameter complex delivery system and method which requires multiple anchoring balloons and thec use of a lighit activated tissue adhesive in addition to wiy prior valvtdoplasty performed, interference with surrounding anatomny and the questionable clinical utility and feasibility of the light actuated anchoring means. As used herein the term "Graft" is intended to indicate any type of tubular member which exhibits integral columnar and circumiferential strength and which has openings which pass through the thicknesrs of thc tubular member 00 In accordance with a prefbrred embodiment of the invention, a graft member is formed as a discrete thin sheet or tubc of biocompatible metal and/or pgeudometal. A 00 plurality of openings is provided which pass transversely through the graft member. The C) ~plurality of openings may be random or may be pattarncd- ft is preferable that tile size Of 00 5 each of the plurality of openings be such as to permit cellular migration through each opening, without permitting fluid flow there through. In this manner, blood cannot flowv through the plurality of openings, but various cells or proteins may freely pass through the plurality of openings to promote graft healing Mn Ww. In accordance with another aspect of the inventive graft embodiment, it is contemplated that two graft memnbers arc employed, with an outer diameter of a first graft member being stualler than the inner diamecter of a second graft member, such that the first graft member is Concentrically engageable within a lumnen of the second graft member. Both the first and second graft members have a pattern of a plurality of openings passing there through. The first and sccond graft members are positioned concentrically with respect to one another, with the plurality of patterned openings being positioned out of phase relative to one another such as to create a tortuous cellular migration pathway through the wall of the concentrically engaged first and second graft members. In order to facilitate cellular migration through and healing of the first and second graft members in vivo. it is preferable to provide additional cellular migration pathwvays that communicate between the plurality of openings in the first and second graft members. These additional cellular migration pathways may be imparted as 1) a plurality of projections formed on either the luminal surface of the second graft or the abluminal surface of the first graft, or both, which serve as spacers and act to maintain an annular opening between the first and second graft members that permits cellular migration arid cellular communication between the plurality of openings in the first and scond graft members, or 2) a plurality of znicrogrooves, which may be random, radial, helical, or longitudinal relative to the longitudinal axis of the first and second graft members, the plurality of microgrooves being of a sufficient size to permit cellular migration and propagation along the groove without permitting fluid flow there through, the microgrooves serve as cellular migration conduits between the plurality of openings in the first and second. graft members.

00 In order to imnprove healing response, it is preferable that the materials employed have substantially homogenous surface profiles at the blood or tissue contact surfaces thereof. A substantia.Uy homogeneous surface profile is achieved by controlling htterogeneities along 00 the blood or tissue-contacting surface of the material. The heterogeneities that are controlled in. accordance with an embodiment of the present invention include: grain size, grain phase, 0 5 grain mnaterial composition, stent-material composition, and surface topography at the blood 00 flowv surfaice oftliestent. Additionally, the present invention provides methods of making amdolumninal devices having controlled ficterogeneities in the device material along the blood flow or tissue-contacting surface of the device. Material heterogeneities arm preferably controlled by using conventional methods of vacuum deposition. of materials onto a substrate.

The surface of a solid, homogencous material can be conceptualized as having unsaturated inter-atomic and intermolecular bonds fonnaing a reactive plane ready to interact.

with the environment In practice, a perfectly clean surface is unattainable because of immediate adsorption of airborne species, upon exposure to ambient air, of 0, C0) 2

SO,.

NO, hydrocarbons and. other more comple~x reactive mulecules. Reaction with oxygcn implies tie formation of oxides on a metal surface, a self-limiting process, known as passivation. An oxidized surfatce is also reactive with air-, by adsorbing simple, orgunic airborne compounds. Assumring the existence of bulk material of homnogeneous subsurface and surface composition, oxygen and hydrocarbons may adsorb homogeneously. Therefore, further exposure to another environment, such as the vascular compartment, muay be followed by a unifbrm biological response.

Current metallic vascular devices, such as stents, are madle from bulk metals made by conventional methods which employ many steps thal introduce processing aides to the metals make stent precursors, such as hypotubes. For example, olefins trapped by cold drawing and transformned into carbides or elemental carbon deposit by heat treatment, typically yield large carbon rich areas in 3 16L stainless steel tubing manufactured by cold drawing process. The conventiontal stents have marked surface and subsurface heterogeneity resulting from mianufacturing processes (friction material transfer from tooling, inclusion of lubricants, chemical segregation (rm heat treatments). This results in formation of surface and subsurface iclusions with chemicil composition and, therefore, reactivity different from the bulk material. Oxidation, organic contam-inati, water and electrolytic interaction, protein 00 INO adsorption and cellular interaction may, therefore, be altered op the surface or' such inclusion spots. Unpredictable distributions of inclusions such as those mentioned above provide unpredictable and uncontrolled heterogeneous surface available for interaction with plasma 00 proteins and cells. Specifically. those inclusions interrupt the regular distribution pattern of surface free energy and electrostatic charges on the metal surface that determine the nature i and extent. of plasma protein interaction. Plasma proteins deposit nonspecifically on. surfaces 00 accord ing to their relative affinity for polar or non-polar areas and their concentration in (71 blood. A rep lacemecnt process knowvn as the Vroman effect, V'roman L, 'Me importance of surfaces in contact phase reactions. Semfinars of Thrombosis omd Henzostasis 1987; 13(l): 79determines a Lirne-dependeat sequential replacement of predominant proteins at an artificial surflice, starting with albumin, following with lgG, fibrinogen and ending with high miolecular weight kininogen. Despite this variability it, surface adsorption specificity, some of the -adsorbcd proteins have receptors available for cell attachment and therefore constitute adhesive sites. Examples arc: fibrinogen glycoprotein rcceptor lib~la for platelets and fibronectin ROD sequence for many blood activated cells. Since the coverage of an artificial surface with cudothelial cells is a favorable L'nd-pornt in the healing process, favoring endotlielializtion in device design is desirable in implanuible vascular device mnanufacturing.

Normally, endothelial cells (BC) migrate and proliferate to cover denuded areas until confluence is achieved. Migration, quantitatively more important than proliferation, proceeds under nornal blood flow roughly at a rate of 25 pimhr or 2.5 limes the diameter of an EC, which is nominally I OpLm. BC migrate by a rolling motion of the cell membrane, coordinated by a complex system of intracellular filaments attached to clusters of cellI membrane integrin receptors, specifically focal contact points. The integrins within thc foca contact sites are cxpressed according to complex signaling mechanistrs and eventually couple to specific amino acid sequences in substrate adhesion molecules (such as RGD, mentioned above). An EC has roughly 16-22% of its cell surfae represented by integrin clusters. Davics, PPF., Robotewskyi. (Irieni M.L. Endothelial cell adhiesion in real time. J Clin.IniwsL 1993; 91:2640-2652, Davies, Robotewaski, Gricm, Quailitiative stu1dies of enidothelial cell adhesion. JCln.Ivest.l 994: 93:2031-2038. This is a dynamic process, which implies more than 50% remodeling in 30 minutes. The focal adhesion contacts vary in size and 3' disbibuiion, but 80% of themn measurc less than, 6 wvith the majority of them being about 00 I El and tend to elongate in the direction of flow and concentrate at leading edges of the IND ~cell. Although the process of recognition. and signalinig to determine specific attachment receptor response to artachment sites is incompletely understood, regular arvailability of ___attachment siteS, maore. likely than not, would favorably influence. attachment and migration.

0 various inclusions, w.ith spicing equal or smaller to one whole cell length, is likely to NI determiine alternating hostile and favorable attachment conditions along the path of a 00 mnigrating cell. These conditions may vary froin optimal attachmrent force and migration CI speed to insufficient holding strength to sustain attachment, resulting in cell slough undcr arterial flow condtions..Due to present manufacturing processes, current irmplantable vascular devices exhibit such variability in surface composition as determined by surface sensitive techiniques such as atomic force microscopy, X-ray photoelectron spectroscopy and trne-o [-flight secondary ioa mass spectroscopy.

Theire have been numerous attempts to increase endothelialization of implanted sterns, including covering the stent withi a polymeric material Patent No. 5,897,911), imparting a diamond-like carbon coating onto the stent Patent No. 5,725,573), covalently binding hydrophobic moieties to a heparin molecule Patent No. 5,955.58), coating a stent with a layer of blue to black zirconiumn oxide or zirconium nitride Patent No. 5,649,95 coating a stent with a layer of turbostratic carbon Patent No.

5,387,247), coating the tissue-ontacting surface of a sterfl with a thin layer of a Group VB metal Patent No. :5,607,463), imparting a porous coating of titanium or of a titanium alloy. such as Ti-Nb-Zr alloy, onto the surface of a stent Patent No. 5,690,670), coating the stent, under ultrasonic conditions, with a synthetic or biological, active or inactive agent, such as heparin, endothclium derived growth factor, vascular growth factors, silicone, polyurethane, or polytetrafluoroethylene, U.S. Patent No. 5,891,507), coating a stern with a silane compound with vinyl functionality, then formig a graft polymcr by polymerizationl wvith the vinyl groups of the silane compound Patent No. 5,782,908), grafting monomers, oligomers or polymers onto the surface of a stent using infrared radiatiou, microwave radiation or high voltage polymerization to impart the property of the monomer, oligomner or polymer to the stent Patent No. 5,932,299).

00 Thus, the problemis of thrombogenicity and re-cndotbelialization associated with IND stents havc been addressed by thc art in various mnanners which cover the stent with either a biologically active or an inactive covering which is less thrmbogenic than the sterit material and/or which has an increased capacity for promoting re-aidothelialization of the stent situs.

00 These solutions, however, all require the use of existiag stents as substrates for surface 5 derivatization or modification, and each of the solutions result in a biased or laminate stnicture hul; upon the stent substrate. These prior art coated stents are susceptible to 00 delaminating and/or cracking of the coating when mechanical stresses of transluminal cathaeter delivery ant/or radial expansion in vivo. Moreover, becmuse these prior art stents cnmploy coatings applied to stents fabricated in accordance with conventional stent formation techniques, cold-forming metals, dhe underlying stent substt is characterized by uncountrolled heterogeneities on the surface thereof. Thus, coatings merely are laid upon the heterogeneous scent surface, and inherently conform to the topographical heterogeneities in the stent surface and mirror these heterogeneities at the blood contact surface of the resulting coating. This is conceptually similar to adding a coat of fresh paint over an old coating of S blistered paint; the fresh coating will conform to the blistering and eventually, blister and delaminate fromn the undel7ying substrate. Thus, topographical heterogeneities are typically telegraphecd through a surface coating. Chemical heterogeneities. on the other hand, may not be telegraphed through a surface coating but may be exposed due to cracking or peeling of the adherent layer, depending upon the particular chemical heterogeneity.

The current invcntion entails creating valve flap members and other implantable septa, for example, access ports, of vacuum deposited metal and/or pseudometallic materials.

According to a preferred embodiment of the invention, the manufacture of valve flap members and other imnplantable septa fabricated of mnetallic and/or pseudometallic films is controlled to attain a regular, homogeneous aiomnic and molecular pattern of distribution along their fluid-contacting surfaces. This avoids the marked variations in surface composition, creating predictable oxidation and organic adsorption patterns and has predictable interactions wmith waler, electrolytes, proteins and cells. Particularly, EC migration is supported by a homogeneous distribution of binding domains that serve as natural or implanted cell attachment sites, in order to promote unimpeded migration and 3 0 attachment. Based on observed EC altacunent mechanisms such binding domains should 00

O

have a repeating pattern along the blood contact surface of no less than 1 Ipm radius and 2 pm border-to-border spacing between binding domains. Ideally, the inter-binding domain Sspacing is less than the nominal diameter of an endothelial cell in order to ensure that at any given time, a portion of an endothelial cell is in proximity to a binding domain.

Summary of the Invention 00 O 5 In accordance with the present invention, there is provided an improved film structure 0 for implantable moveable septa, such as valve flaps, access ports, prosthetic ventricular 00 members or similar types of anatomical prosthetic replacements.

C It is, therefore, a primary of the present invention to provide a prosthetic unidirectional valve having valve flap members fabricated of biocompatible metal and/or pseudometallic films. The valvular prosthesis of the present invention consists generally of a stent body member, a graft, and valve flaps. The stent body member may be fashioned by laser cutting a hypotube or by weaving wires into a tubular structure, and is preferably made from shape memory or super-elastic materials, such as nickel-titanium alloys known as NITINOL, but may be made of balloon expandable stainless steel or other plastically deformable stent materials as are known in the art, such as titanium or tantalum, or may be self-expanding such as by weaving stainless steel wire into a stressed-tubular configuration in order to impart elastic strain to the wire. The graft is preferably a biocompatible, fatigueresistant membrane which is capable of endothelialization, and is attached to the stent body member on at least portions of either or both the luminal and abluminal surfaces of the stent body member by suturing to or encapsulating stent struts. The valve leaflets are preferably formed by sections of the graft material attached to the stent body member.

The stent body member is shaped to include the following stent sections: proximal and distal anchors, a intermediate annular stent section, and at least one valve arm or blood flow regulator struts. The proximal and distal anchor sections are present at opposing ends of the prosthesis and subtend either an acute, right or obtuse angle with a central longitudinal axis that defines the cylindrical prosthesis. In either the CV or CC configurations, the proximal anchor is configured to assume approximately a right angle radiating outward from the central longitudinal axis of the prosthesis in a manner which provides an anchoring flange. When being delivered from a delivery catheter, the proximal anchor is deployed first 00

O

S and engages the native tissue and anatomical structures just proximal to the anatomic valve, O such as the left ventricle wall in the case ofretrograde orthotopic delivery at the aortic valve.

O Deployment of the proximal anchor permits the intermediate annular stent section to be deployed an reside within the native valve annular space and the abluminal surface of the 00 intermediate annular stent section to abut and outwardly radially compress the anatomic valve leaflets against the vascular wall. The distal anchor is then deployed and radially N expands to contact the vascular wall and retain the prosthesis in position, thereby excluding 0 the anatomic valve leaflets from the bloodflow and replacing them with the prosthetic valve C, leaflets.

Flow regulation in the inventive stent valve prosthesis is provided by the combination of the prosthetic valve leaflets and the valve arms and is biased closed in a manner similar manner to that described for a surgically implanted replacement heart valve by Boretos, U.S.

Pat. No. 4,222,126. The valve regulator-struts are preferably configured to be positioned to radiate inward from the stent body member toward the central longitudinal axis of the prosthesis. The graft-leaflet has the appearance ofa partially-everted tube where the innermost layer, on the luminal surface of the stent body member, forms the leaflets and the outer-most layer, on the abluminal surface of the stent body member, forms a sealing graft which contacts and excludes the immobilized anatomical valve leaflets. The struts of the stent are encapsulated by the outer graft-membrane. The valve regulator-struts are encapsulated by the inner leaflet-membrane and serve to bias the valve to the closed position.

The regulator-struts also prevent inversion or prolapse of the otherwise unsupported leafletmembrane during increased supra-valvular pressure. The inner leaflet-membrane may also be attached to the outer graft-membrane at points equidistant from the valve strut-arms in a manner analogous to that described for a surgically implanted replacement heart valve by Cox, U.S. Pat. No. 5,824,063. The combination of the thin walled properties of the leafletmembrane, the one-sided open lumen support of the intermediate annular stent section, the free ends of the valve leaflets, the biasing and support provided by the valve regulator-struts and the attachment points all work to provide a prosthetic valvular device capable of endoluminal delivery which simulates the hemodynamic properties of a healthy anatomical cardiac or venous valve.

00

O

-Is- In accordance with another embodiment of the invention, there is provided an implantable valvular prosthesis having a graft covering and valve flap members that are O each formed as discrete laminated films of a biocompatible metal or pseudometal. A plurality of openings is provided which pass transversely through the graft member. The 00 5 plurality of openings may be random or may be patterned. It is preferable that the size of each of the plurality of openings be such as to permit cellular migration through each N opening, without permitting fluid flow there through. In this manner, blood cannot flow 00 O through the plurality of openings, but various cells or proteins may freely pass through NC the plurality of openings to promote graft healing in vivo.

to Finally, in accordance with a further aspect of the present invention, there is provided an implantable valvular prosthesis having valve flap members and a covering graft member that are fabricated from metallic and/or pscudomctallic films that present a blood or tissue contact surface that is substantially homogeneous in material constitution.

Brief Description of Figures FIG. I is a perspective view of the inventive valve stent chamber-to-vessel embodiment in its fully deployed state.

FIG. 2 is a perspective view of the inventive valve stent chamber-to-vessel embodiment in its fully deployed state with the outermost graft layer and stent layer partially removed to show an embodiment of the valve apparatus.

FIG. 3 is a top view of the inventive valve stent chamber-to-vessel embodiment in its fully deployed state.

FIG. 4 shows the cross-section taken along line 4-4 of FIG. 1.

FIG. 5 is a bottom view of the inventive valve stent chamber-to-vessel embodiment in its fully deployed state.

FIG. 6A illustrates a cross-sectional view of a human heart during systole with the inventive valve stent chamber-to-vessel embodiment implanted in the aortic valve and illustrating a blood flow vector of an ejection fraction leaving the left ventricle and passing through the inventive vaive stent.

FIG. 6B illustrates a cross-sectional view of a human heart during diastole with the inventive valve sient chamber-to-vessel embodiment implanted in the aortic valve and 00 illustrating a blood flowv vector of blood passing- from the left atrium, through the mitral valve and into the left ventricle during and a retrograde blood flow vector blocked by tie invenitive valve stent in the aorta.

00 FIG. 7 is a perspective view of the inventive valve stent chamber-to-chiamber 5 embodiment in its fully deployed state.

FIG. 8 is a is a perspective view of the inventive valve stcnit chamnber-to-chamber 00 embodiment in its fully deployed state with the outemniost grail layer and stent layer partially removed to show an embodiment of the valve apparatus.

FIG. 9 is a top viewv of the inventive valve stent chamrber-to,-chamber enmbodimnent in its fully deployed state.

FIG. 10 shows the cross sectional view taken along line 0-10 of FIG. 7.

-FIG. I I is a bottom view of inventive valve stent chaniber-io-chumber embodiment in its fully deployed state.

IG. 12A illustrates a cn.oss-sctional view of a hiuan licar during atial systole IS with the inventive. valve stent chaniber-to-cliamher enmhoclinhnt inpliffted at. the site of the mnitral valve and illustrating a blood flow vector of a filling fraction lea ing the left itiw and entering the lefl. vcntricle.

FIG. 1213 illustrates a cross-sectional view of a human heart during atriall diastole with the inventive valve sterit charrber-to-chamber embodiment implant~ed at (lhe site of the mitral valve and illustrating a blood flow vector of an ejection fraction from the left ventricle to the aorta and the back pressure against the implanted mnitral valve prosthesis.

FIG. 13 is a perspective view of the chamiber-to-vessel coniiguratiun in the fully deployed state.

FIG. 14 is a perspective view of the same configuration in the fully deployed state with the outermost graft layer and stent layer partially removed to show an embodiment of the valve apparatus.

FIG. 15 is a top view of the saime configuration.

FIG, 16 shows the cross sectionil view of the szame con figuration for the deployed state.

3N FIG. 17 is a bottomn view of the saxuUC configuration.

00 FIG. iad I SB'show cross-sectional views of a vein and Venous valve i1llustrating die inventi ve prosthetic venous valve in the open and closed state.

FIG. 19 is a cross-sectional diagrammuatic view of a vatvuloplasty and stent valve. 00 delivery catheter in accordance with the present invention.

FIGS. 20A-201 are diagrammatic cr-oss-sectional views illustrating single catheter coo valvulloplasty, inventive stern valve delivery and stent valve operation ill situ ill accordance wvith the method of the present invention.

Detailed Description of the Preferred Emnbodiments T1he present invention consists generally of three preferred embodiments, each embodiment corresponding to a prosthetic stern valve configuration adapted for either heart chamber to blood vessel communication, chamber to chamber communication or vessel to vessel, or intravascular configuration. Certain elements are commnon to each of' the precferred embodimtents of the invention, specifically, each embodiment includes a stent body member which defines a central annula opening along the longitudinal axis of the stcrn body member, a graft member which covers at least a portion of the stcnt body member along either the iwninal or abluminal surfaces of the stein body mcmber, at least one biasing arm Is provided and projects from the 8tent body member and into the central annular opening of the stent body momber, and at least one valve flap member which is coupled to each biasing arm such that the biasing arm biases the valve flap member to occlude the central annular opening of the stein body member under conditions of a zero pressure differential across the prosthesis. The stein body member is preferably made of a shapc mernory material or superelastic maerial, such as NTlNOL, but also is fabricated from either plastically deforniablo materials or spring-elastic materials such as are well known in the art.

Additionally, the stein body member has three main operable sections, a proximal anchor section, a distal anchor section and an intermediate annular section which is intermlediate thc proximal and distal anchor sections. Depending upon the specific inventiv'e embodimen, the distal and proximal anchor sections may be either a diametrically enlarged section or may be a flanged section. The intermecdiate annular section defines a valve. exclusion region and primar-y blood flow channcl of the inventive valve stent- The intermediate annular sec'tioni defines a luminal opening through which blood flowv is established. The ti-nsverse crobs- 00 section of the lutminal opening may be circular, elliptical, ovular, triangular or quadralinear, IND depending upon the specific application for which die valve stern is being employed. Thus, for example, where a tricuspid valve is particularly stenosed, it may be prefe-rable to emiploy valve stent with a huninal opening in the initermiediate annular section Nvhich has a 0 In each of the foregoing embodiments, the graft member and the valve flap nicmbcrs N1 are fabricated of a biocompatible metal and/or a bioconipatible pseudometal arnd arc formced 00 as films of material that are preferaibly laminated to enhance their material propertics. 11c metal films may be micro or aanoporous to enhance endothelialization as described in greater detail in parent patent application U.S. Serial No. 09/853,985 filed May 11, 2001, which is bereby incorporated by ret~rence. Suitable materials to fabricated the inventive graft and valve flap members ame chosen for their biocompatihility. mechanical properties, tensile strength, yield strength, and their ewse of deposition include, without limitation, the folowing: titanium, vanadium, aluminum, nickel, tantalum, zirconium, chromiumi, silver, gold, silicon, magnesium, niobium, scandi um, platinum, cobalt, palladium, mangancsc, molybdenum and alloys thereof, such as zirconiwn-titanium-tantajum alloys, nititnol. and stainless steel. The graft memnber and the v'alve flap members are foniicd by vacuum deposition methodologies.

Chamber-ro. Vessel Configuration An imnplantable prosthesis or prosthetic valve in accordance wvith certain embodiments, of the chamber-to-vessel CV configuration of the present invention is illustrated generally in Figures t The chamber-to-vessel valve stent 10 consists of an expandable stozfl body memberl 2 and graft member 11. Th'e stent bodyv member 12 is preferably made from a shape memory and/or superelastic NVITNOL material, or therniomeebanically similar materials, but may bc made of plastically deffonnable or elastically compliant materials such as stainless steel, titanium or tantalum. The graft member I I is fabricated of biocompatiblc meta and/or pseudometallic materials, such as thin film stainless steel, nickel-titanium alloy, tantalum, titanium or carbon tibcr. ']he stent body member 12 is configured to have three fiinctional sections: a proximal anchor flange 22, an intermediate annular section 20 and a distal anchor section 16. The steintbodY menher 12.

00 IND ~as with conventional stents is formed of a plurality of stent struts 13 which dctinle interstice", 14 between adjacent stent qtruts 13. The stein body member proferably also includes a transitional section IS that interconnects thie intermiediate annular section 20 and the distal 0 10 to exclude the anatomic valve after implantation. The proximal anchor flange 22, the N" intermnediate annular section 20 and the distal. anchor section 16 arc each formed during the 00 formnation of the stein body member and are formed from the same material as the stent body mecmber and comprise stent struts 13 and intervening interstices 14 between adjacent pairs of s9tent struts 13. The anchor flange 2,2, for example, consists of a plurality of stent sixruts and a Plurality of stern interstices, which project radially outwardly away from the contra] longitudinal axis of the gtent body member. Thus, dhe different sections of the stcnt body member 12 are defined by the positional oricatation of the stent struts and intersticcs relative to the central longitudinal axis of the stent body member 12.

With reference to FIG. 2, there Is shown in greater detail the valve body 20 and Nv-e arms or flowv regulator struts 24 coupled to the stent body member L2. The valve body 26 subtends the central annular opening of the stent valve 10 and is illustrated in its closcd position In accordance with one embodiment of the present invention, the graft mecmber 11 consists of an outer or abluminal graft member I Ia and an inne or luminal graft mirnber 1 lb. The outer graft member I la encloses at least a portion of the ablumninal surface of the intermediate annular section 20 of the stent body member, while the inner graft mcmber I l b is coupled, on the lumninal surfaice of the intermediate annular section 20 of the stent body member 12, to the outer graft member I la through the interstices 14 of the steut biody member. The valve body 26 is formed by everting the inner graft member I Ib toward Che central longitudinal axis of the stein body member 12 such that free ends or valve Flap) portions 28 of the inner graft member I Ib are oriented toward the distal anchor section. 16 of the stern body membcr 12 and a pocket or envelope 27 is formed at the eversion point of the inner graft member 1 l b adjacent thc junction between the intrzmediate annular section 240 and the proximal anchor flange 22 of the stent body member 12. Alternatively, portions of the outer graft member I I a may be passed through to the luminal surface of the stent body member 12, thereby becoming the inner graft mnember 1 lb anid everted to forni the v~alve body 26.

00 Valve arms or regulator struts 24 are coupled or formed integral with the stent body member 12 and are positioned adjacent the junction point between intermediate annular section 20 and the proximial anchor flange 22 of the stein body member 12. The valve armis 24 are oriented radially inward toward the central longitudinal axis of the stent body mnbcr 00 12 when in their zero strain state. Trhe valve arms 24 are attached or coupled to the valve flap portions 28 of the inner graft member leaflets to bias the valve flap portions 28 to the closed 00 position when under zero pressure differential across the stent valve The zero strain position of Ilhe valve arms 24 is radially inward and orthogonal to the central longitudinal axis of the stent valve 10. Valve arms 24 have a length which is preferably longer than the radius of the lurninal diameter of the stent valve 10, and they exent distally into the lumen of the stent valve 1.0 such that, in conjunction with the action of the valve leaflets 28, the valve arms 24 are prevented from achieving their zero strain configuration thereby biasing the valve closed. As shown in FiG. 4, the valve arms 24 force the valve leaflets 28 to collapse into the center of the lumen of the tent. valve 10, thus biasing the valve to its closed position.

It is preferable to couple sections of the valve flaps 28, along a longitudinal scam 29, to the inner graft member lb and the outer graft member I la at points equidistant ffrm the valve arms 24 in order to impart a more cusp-like structure to the valve flaps 28. [tshould be appreciated, that the graft memiber 1.1 should cover at least a portion of the ablurninal surface of the stent body member 12 in order to exclude thc anatomic valves, but may also cover portions or all of the stent valve member 12. including the distal. anchor section 16, the intermediate annular section 20, the transition section 18 and/or thc proximal anchor flange 22, on either or both of the luminal and abluininal surfaesa of the stent body member.

In accordane with a particularly prefczrcd embodiment of the CV valve strut 10, the proximal anchor flange 22, which consists of a plurality of stent struts and stent interstices which project radially outward away from the central longitudinal axis of the valve stent is configured to have one or more stein struts eliminated from the proximal anchor flange 22 to define an open region which is positioned in such a manner as to prevent the CV valve stent 10 from interfering with or impinging upon an adjacent anatomic structure. For example, where the CV valve stent 10 is to be an aortic valve prosthesis, it is known~ that the mitral valve is immediately adjacent the aortic valve, and the mitral valve flaps deflwct 00 IND toward the lefi ventricle. Thus, placing the CV valve stent 10 such that the proximal anchor flange 22 is adjacent the mitral valve might, depending upon the particular patient anatomy, interfere with normal opening of the mitral valve flaps. By eliminating one or more of the 00 stent struts in the proximal anchor flange 22, an opening is created which permits the mitral Svalve flaps to deflect ventricularly without imipingig upon the proxiNmal anchor flange 22 of the CV valve stent 00 Similarly, the stent struts of the CV valve stent 10 may be oriented in such a manner as to create intersticos of greater or smaller area between adjacent struts, to accomrmodate a particular patice anatomy. For example, where the stern struts in the distal anchor section 16 would overly an artery branching from the aorta, such as the coronary ostreumn arteries, it may be desirable to either eliminate certain stern struts, or to configure certain stern struts to define at greater interstitial area to accommodate greater blood flow into the coronary ostreuin.

In the case of providing an orienited opening in the proximal anchor flange, or an oriented opening in the interstitial spaces of the distal anchor, it is desirable to provide radiopaque markers oa the stein body mnember 12 to penmit the CV valve srertt to be oriented orrecly relative to the anatomnic structures.

Figures 6A and 6B ilustrate the inventive CV stent valve 10 implanted in the position of the aortic valve and excluding the anatormic aortic valve AV. FIG. 6A illustrates the heart during systole in which a positive pressure is applied to. the prosthetic aortic valve by contraction of the left ventricle LV and the ejection fraction represented by the arrow. The systolic pressure overcomes the bins exerted by the valve arms 24 and causes the valve leaflets 26 to open and release the ejection fraction into the aorta. FIG. 6 B illustrates that the presence of a negative pressure head across the scent valve 10, i.e. such as that during diastole, causes the biased valve leaflets 26 which are already closed, to further close, and prevent regurgitation from the aorta into the left ventricle.

Chamnber-to- Chambcr Conf/iguration~ Figures 7-11 illustrate the inventive stein valve in the chamber-to-chamber (CC) configuration 40. The CC valve stern 40 is constructed in a manner which is virtually identical to that of ther CV valve <tent 10 described above, except that the distal1 anchor 00 section 16 of the CV valve stent 10 is not present in the CC valve stent 40, but is substituted by a distal anchor flange 42 in the CC stent valve. Thus, like the CV valve stenL described above, the CC v'alve stent 40 if' formed of a stein body member 12 and a grail 00 member 11, with the graft member having luminal I lb and abluntinal I a portions which S cover at least portions of the luntina and abiwninal surfacees of the stent body member 12 00 respectively. The CC valve stent 40 has both a proximial anchor flange 44 and a distal anchor flange 42 which are formed of sections of the stent body member 12 which project radielly outward away fronm the central long~itudinal ax is of the CC valve stein 40 at opposing ends of' the stent body member 12.

Like the CV valve stein 10, the luminal graft portion 1lb is everted inwardly toward the central longitudinal axis of the valve stent 40 and free ends 28 of the lurninal grail portion I lb to flurm valve flaps 26 which projct distally toward distal anchor flange 42. Flow regulation struts 24 are coupled to or integral with the proximal anchor flange 44 and intermediate annular section 20 and project radially inwardl toward the central longitudinal axis of the CC valve stein 40. Thie valve flaps 26 are coupled to the flow regulation struts 24 and the flow regulation struts 24 bias the valve flaps 26 to a closed position under a zero strain load.

Like with the CV stent. valve 10, it is preferable to couple sections of the valve flaps 28, along a longitudinal seam 29, to the inner graft member 1 lb and the outer graft member I a at points equidistant from the valve arms 24 in order to impart a more cusp-like structure to the valve flaps 28.

Turning to Figures 12A and B (here is illustrated the inventive CC stent valve implanted in the position of the mitral valve and excluding the anatomic Mitral valve MV.

FIG. 12A illustrates the heart during atri systole in which a positive pressure is applied to the prosthetic mitral valve by contraction of the left atrium LA and the pressure exerted by the blood flow represented by the arrow. The atrial systolic pressure overcomes the bias exerted by the valve arms 24 onto the valve leaflets 26, and causes the valve leaflets 26 1o open and release the atrial ejection fraction into the left ventricle, FIG. 12 B illustrates that the presence of a negative pressure head across the stein valve 40, L e- such as that during atria) diastole, causes the biased valv-e leaflets 26 which are alredY closed, to further close, and prevent bacifflow from the leti ventricle into thc lell atrium.

00 In accordance with another preferred embodiment of the invention, the CC IND configuration may be adapted for use in repairing septal defects. By simply substituting a membrane for the valve leaflets 26, the lumen of the stent body' memiber 12 is occluded. The CC scent valve 40 may be delivered endohaninally and placed into a position to subtend a 0 S septa] defect and deployed to occlude the septal defect.

CK1 Vessel-ro- Vcssel Con~figuration 00 Turning nowv to Figures 13-17, there is illustrated the inventive stent valve in its v'essel-to-vessel (VV) valve stein configuration 50. The V'V valve stein 50 is constructed in a manner which is virtually identical to that of the CV valve stent 10 described above, except that the proximal anchor flange 22 of the CV valve stcnt 10 is not present in the VV valve steal. S0, but is substituted by a proximal anchor section 52 in the VV stent valve. '1'us, like the CV valve stent 10, described abovc, the V V valve stein 50 is formed of a. stent body member 12 and a graft rmmber 11, %Nith the graft member having luminal I lb and abhuminal IS I a portions which cover at least portions of the lumninal and abluminal surfaccs of the stein body member 12, respectively. T1he VV valve stcnt 50 has both a proximal anchor section 52 and a distal anchor section 54 which are formed of sections of the stent body member 12 which are diametrically greater than the intermediate annular section 20 of the VV valve stent 50. Transition sections 56 and 58 taper outwardly away from the central longitudinal axis of the VV valve stent 50 and interconnect the intermuediate annular section 20 to eachi of the distal anchor section 54 and the proximal anchor section 52, respectively.

Like the CV valve stern 10. in the VV valve stint 50, the graft. member 1 1.

particularly the lurninal graft portion I lb or the ablumiaal graft portion I I a, or both, is everted inwardly toward the central longitudinal axis of the valve slant 40 and free ends 28 of the lumninal graft. portion 1 l b to form valve flaps 26 which project distally toward distal anichor flange 42. Flow regulation struts 24 are coupled to or integral with the stein body member at thec proximal transition section 58 and project radially inward toward the centrul longitudinal axis of the VIV valve stent 50. The valve fflps 26 are coupled to the flow rcgulationstruts 24 and the flow regulation struts 24 bias the valve flaps 26 to a closed position under a zero strain load. Like with the CV stent valve 10 and the CC stent valve it is preferable to couple sections of the valve flaps 28, along a longitudinal seamn 29, to the 00 inner graft member I Ilb and the outer graft member I Ila at points equidistant from the valve arms 24 in order to impart a more cusp-like structure to the valve flaps 28.

00 Turning to Figurcs 18A and 13 there is illustrated the inventive VV stent valve implanted in the position of a venous; valve and excluding the anatomnic venous valve flaps VE. FIG. I 8A illustrates the vein under systolic blood pressre in wvhich a positive pressure 00 is applied to thie prosthetic venous valve and tile pressure exerted by tile blood flow represented by the arrowv. The systolic pressure overcomes the bias exerted by the valve arms 24 onto the valve leaflets 26, and causes Whe valve leaflets 26 to open and permit blood flow tlu'ough the prosthesis. FIG. 18 B illustrates that the presence of a negative pressure head across the VV stent valve 50, i.e. such as wvhich~ exists at physiological diastolic pressures, causes the biased valve leaflets 26 which ae already closed, to futrther close, and prevent baclcflow from the left. ventricle into thc left atrium.

Thec purpose of the proximal 54 and distal 52 anchor sections of the stent body member 12 is to anchor the prosthesis at the anatomic vessel-vessel junction, such as a venous valve, while causing minimal interference with adjacent tissue. The intermediate annular section 20 of the VV steal valve 50 excludes diseaed anatomic leaflets and surrouinding tisme fromn the flow field. The flare angle of the transition sections 56, 58 bet-ween the intermediate annular section 20 and each of the proximal and distal anchor sections 54, 52, respectively, may be an Hcute angle, a right angle or an obtuse angle, depending upon the anatomical physiological requirements of the implantation site.

Alternatively, the tranisition. sections 56, 58 may be coplanar with the proximal and distal anchor section 52, 54, respectively, thereby, eliminating any transition flare angle, depending uipon the anatomical and physiological requirements of the delivery site.

Single Cathzeter Valvailoplasty Slent Valve Del he~y System and MetAod a/Delivery In accordwice with the present invention, there is also provide a single catheter valvialoplasty and valve stern delivery system 200 illustrated in FIG. 19. The objective of the single catheter delivery system 200 is to permit the surgeon or interventionalist to percutaneously deliver and deploy the inventive valve stent 10, 40 or 50 at the desired ,0J anazomcal site and to perform valvuloplasty -Mth a single catheter. in accordance w-ith thc preferred embodiment of the single catheter delivery system 200 of the present invention, 00 there is provided a catheter body2l0 having dual iurnens212, 216. A first lumen.212 is provided as a guidewire lumen and is defined by a guidewvire shaft 222 that traverses the length of the catheter body 210. A second lumen is an. inflation lumen 216 for comnrunicatine an inflation fluid, such as saline, fromn art external source, through an 00 5 inflation port 240 at the operator end of the catheter 210, to an inflatable balloon 214 located at or near the distal cnd of the catheter body 210. The inflation lumen 216 is defined by an annular .space between the luirinal surface of the catheter body 2-10 and the abluminal. surface 00 of the guidewire shall 222. A capture sheath 217 is provided at the distal end 215 of the catheter body 210 and is positioned adjacent and distal the balloon 214. The capture sheajth 21i7 defines an anniular space about the guidewirc lumen 212 and the capture sheath 217 into which tile sterit valve 10, 40 or 50 is positioned and retained during delivery. An annular plug mnember 220 is within the inflation lumen 216 distal the baloon 214 and terminates the inflation lunien 216 in a fluid tight manner. Annular plug member 220 has a central annular opening 221 through which the guidewvire shaft 222 passes. The annular plug member 220 is coupled to the guidewire shaft 222 and is moveable axially along the central longitudinal axis of the ctheiter 200 by moving the gttidewire shaft 222. The annular plug member 220 also serves to abut ih-c stent valve. 10, 40 and 50 when the stent valve 10, 40 and 50 is positioned wvithin the capture sheathi 217. The guidewire shaft 222L passes through the capture sheath 217 and termninatesw'itli an atrmtaurac tip 218'which facilitates endolurninal delivery without injuring the native tissue encountered during delivery. With this configuration, the stent valve is exposed by proxinmally withdrawing the catheter body 210, while the guidewire shaft 222 is maintained in a fixed position, such that the annular plug member 220 retains the position of the stent valve as it is uncovered by capture sheath 217 as the capture sheath 217 is being proximally withdrawn with the catheter body 210.

In many cases the anatomic valve will be significantly stenosed, and the valve flaps of the anatomic valve will be significantly non-compliant. The stenosed valves may be incapable of complete closure permitting blood regurgitation across the anatomic valve.

*rhus. it may be desirable to configure the inflatable balloon 21.4 to assume an inflation profile which is modeled to maximally engage and dilatate the anatomic valves. For examplc, a tricuspid valve, such as the aofic valve may stenose to an opening which has a Scuerally triangular configurarior. In order to maximally dilatatc this triangular opening, it 00 May be desirable to employ a balloon profile which assumes a triangular inflation profile.

Alternatively, it may be advantageous to configure the balloon such that it does not fully 00 occlude the anatomic lumen when inflated, but permits a quantum of blood flowv to pass around the balloon in its inflated state. This may be accomplished by providing channels or ridges on the abluminal surfaice of the balloon. Additionally, irrcgular inflation profliles of 00 the balloon may facilitate continuous blood flow about the inflated balloon. Firthermiore, ii may be desirable to configure the balloon to have an hour-glass inflation profile to preveni migrtionor sippae of the balloon in the aaomic valve durn valvuloplasty.

In accordance with the present inv'ention, it is preferable that the capture sheath 217 be made of a material which is sufficicntly strong so as prevent the stent valve 10. 40, from impinging upon and scaling into the capture sheath 217 due to the expansive pressure exerted by the stern valve 10, 40, 50 against the capture sheathi. Alternatively, the capture sheath 217 may be lined with a lubricious material, such as polytetrafluoroethylene, which will prevent the capture sheath 217 from exerting drag or frictional farces against the stern valve during deployment of the stent valve.

In accordanc with thec present invention, it is also contemplated that the position of the balloon 2114 find the capture sheath 217 may be reversed, such that the balloon 214 is distal the capture sheath 'A.17. In this configuration, the anatomic valve may be radially enlarged by dilatating, the balloon 214, then the catheter moved distally to position the capture sheath 217 at the anatomnic valve and deployed in the manner described above- This would also allow for post-deployment halloon expansion of the deployed stent valve without the need to traverse t-he prosthetic valve in a retrograde fashiion. Alternatively, the catheter 200 of the present invention may be provided without a balloon 214 in those cases wvhere val)vuloplasty is not reqluired. where a stenotic valve does not need to be opened such as %with a regurgitating valve, and the ciatheter 200 is terminated at its distal end with only a capture sheath 217, and deployment occurs as described above.

Turning now to Figures 20A-201 there is illustrated the sequence of steps i deliveryv of the stent valve of the preseti invention, valvuloplasty of the aortic valve and deployment of the stent, valve at the position of the aortic valve. The single catheter delivery system 501 having a distal ballooni 502 and a capture sheath 503 covering the valve steit. 10 (riot shown in Figs 20A-B), is delivered percutaneously either through a femnoral or subclav'ian artery 00 approach, and traverses the aortanind is passed thlrough the aortic valve 510 such that the balloon 503 on the distal end of catheter 501 is adjacent the aortic valve 510 and the capture sheath 503 is within the lenl ventricle 504. A valvuloplasty step 520 is performed by 00 t inflating balloon 503 to dilate the aortic valve and deform the aortic valve flaps against (lie aoria wall adjacent ffie aortic valve. After the valvuloplasty step 520, delivery of the valve 00 stecit 505 is initiated by stabilizing the guidewire shaft (not shown) while the catheter body is withdrawn. antegr-ade relative to the blood flow until the proximal anchor flange section of the valve stent 505 is exposed by the withdrawal of the capture sheath 503. Thle distal anchor flange of the valve stern 505 is then positioned at the Junction between the aortic valve and the lefl ventricle at step 540, such that the distal anchor flange engages the ventricular surface of the aortic valve. The valve !-tent is fully deployed at step 550 by retrgrade withdrawal of thec catheter body 50 1 which contuiues to uncover the interm-ediate annular section of the valve stent and. release the aortic valve stent 505. at the aortic valve site 510. In step 560, the valve stent 505 is completely deployed froma the catheter 501 and the capture sheath 503.

The distal anchor section of the valve stent 505 expands and contacts the luminal wvall of the aorta, inmmediately distal. the aortic valve, thereby excluding the aortic valve flaps from the lumen of the prosthetic aortic valve stent 505. lIntstep 570, the atr-aumnatic cip and. guidewirre are retrated by retrograde movement of the guidewire shaft of the catheter, and the catheter 501 is withdrawn from the patient. Figures 2011 and 201 depict the implanted valve stent. 505; during diastole and systole, respectively. Dtuig ventricular diastole 580, the left ventricle expands to draw blood flow 506 from the left atrium into the left ventricle. A resuiltant negative pressure gradient is exerted across the valve stent 505, and the valve arms and. valve flaps 506 of the valve st Cnt 505 are biased to the closed position to prevent a regurgitation flow 507 from passing tlrough the valve stent 505 and into the left ventricle 504. During ventricular systole 590, the left ventricle contracts and exerts a positive pressure across the valve stent 505, which overcomes the bias of the valve armis and valve flaps. which open 508 agaiinst the luminal -wall of the intermnediate annular section of the valve stent and permit the ejection fraction 509 to be ejected fromi the left ventricle and into the aorta.

The method for delivery of the CC valve stent 40 or the NN valvec stent 50 is identical to that of the CV steit 10 depicted in Figures 2OA-201, except that the anatomical location m.herc delivery and deploymnrt of the valve stent: occurs is, of course, different.

00 Thus, white the present invention, icluding the different embodiments of the valve stent, the delivery and deployment miethod and the single catheter valvuloplasty and delivery system, have been described with reference to their preferred embodiments, those of ordinary 00 sk"Il in the art will understand and appreciate that the present irnvention is limited in scope 5 only by the claims appended hereto.

00

Claims (7)

1. An implantable valvular prosthesis having a stent body at least partially covered by a graft member, at least one biasing art projecting from the stent O 5 body into a central lumen of the stent body member and at least one valve flap O member coupled to the biasing art, the improvement comprising: the at least one valve flap member being comprised of a biocompatible material selected from the 00 group consisting of metals and pseudometals.

2. The implantable valvular prosthesis according to Claim 1, wherein the biocompatible material further comprises a plurality of layers.

3. The implantable valvular prosthesis according to Claim 1, wherein the biocompatible material is selected from the group consisting of titanium, vanadium, aluminum, nickel, tantalum, zirconium, chromium, silver, gold, silicon, magnesium, niobium, scandium, platinum, cobalt, palladium, manganese, molybdenum and alloys thereof, such as zirconium-titanium-tnntalum alloys, nitinol, and stainless steel.

4. The implantable valvular prosthesis according to Claim 1, wherein the !0 graft member further comprises a biocompatible metal film.

The implantable valvular prosthesis according to Claim 2, wherein the graft member further comprises a biocompatible metal film.

6. The implantable valvular prosthesis according to Claim 4, wherein biocompatible metal film of the graft member is selected from the group consisting of titanium, vanadium, aluminum, nickel, tantalum, zirconium, chromium, silver, gold, silicon, magnesium, niobium, scandium, platinum, cobalt, palladium, manganese, molybdenum and alloys thereof, such as zirconium-titanium-tantalum alloys, nitinol, and stainless steel. 00

7. An implantable valvular prosthesis having a stent body at least partially covered by a grait member, at least one biasing arm projecting from the stent IND body into a central lumnen of the stent body member and at least one valve flap member coupled to the biasing ar 1 the improvement comprising: the at least one valve flap member being comprised of a biocoinpatibie fiirn fabricated of a material 00 selected from metals and pseudometals. 0 biocompatiblc pseudometallic film further comprises a plurality of film layvers at least one layer being a pseudometailic material.