Patent Description:
The venous system includes a series of valves that function to assist the flow of blood returning to the heart. These natural valves are particularly important in the lower extremities to prevent blood from pooling in the lower legs and feet during situations, such as standing or sitting, when the weight of the column of blood in the vein can act to prevent positive blood flow toward the heart. This condition, commonly known as 'chronic venous insufficiency', is primarily found in individuals in which gradual dilation of the veins, thrombotic events, or other conditions prevent the leaflets of the native valves from closing properly. This leads to significant leakage of retrograde flow such that the valve is considered 'incompetent'. Chronic venous insufficiency is a potentially serious condition in which the symptoms can progress from painful edema and unsightly spider or varicose veins to skin ulcerations. Elevation of the feet and compression stocking can relieve symptoms, but do not treat the underlying disease. Untreated, the disease can impact the ability of individuals to perform in the workplace or maintain their normal lifestyle.

To treat venous valve insufficiency, a number of surgical procedures have been employed to improve or replace the native valve, including placement of artificial valve prosthesis. These efforts have met with limited success and have not been widely adopted as a method of treating chronic venous insufficiency. More recently, the search has been to find a suitable self-expanding or radially-expandable artificial valve that can be placed using minimally invasive techniques rather than requiring open surgery and its obvious disadvantages. Thus far, use of prosthetic venous valves has remained experimental only.

Reference is directed to <CIT>, which discloses a kit that comprises a prosthetic valve, which is to be implanted, and a stent. The document teaches that the valve and the stent are made in such a way that when the stent is expanded, the valve is situated outside the zone(s) of the stent which are to be expanded.

Reference is also directed to <CIT>, which discloses a device and method for facilitating the positive fixation of implanted prosthetic members in a living body. The device comprises a tubular sleeve of deformable material to which the prosthetic member is secured and which is capable of being expanded radially into intimate engagement with surrounding tissue. The fixation device and prosthetic member, such as heart valve, vessel graft, etc., are prepared by assembly prior to surgery. The assembly may be introduced into the transplant situs during surgery and secured in place by expansion of the deformable sleeve by use of an expansion tool.

In one embodiment, the fixation device includes a plurality of longitudinal wire struts separating two expandable and relatively narrow metal mesh ring sections.

Reference is additionally directed to <CIT>, which discloses an artificial valve stent for maintaining patent one way flow within a biological passage. The artificial valve includes a tubular graft having radially compressible annular spring portions for biasing proximal and distal ends of the graft into conforming fixed engagement with the interior surface of a generally tubular passage. The preferred embodiment of the valve stent is comprised of three elements: a stent, a biological valve, and graft material. In this preferred embodiment, the stent is formed of a single piece of super elastic wire with two crimping tubes. Specifically, the wire is crimped so that the stent forms two cylinders that are spaced a predetermined distance from each other by a connecting bar. This connecting bar is the central part of the continuous wire from which the stent is formed.

Reference is further directed to <CIT>, which discloses a prosthetic valve that includes a rigid frame. The rigid frame is a tube from which sections have been removed in order to provide three equally spaced longitudinal ribs that connect together two ring-shaped portions at either longitudinal end of the frame.

Furthermore, reference is further directed to <CIT>, which discloses a support comprising a structure adapted to be radially contracted to enable the insertion of the support/valve assembly into the patient's body, and to be unfolded to enable said structure to be supported against the wall of the site to be equipped with the cusp. The support structure comprises: an axial portion supporting the cusp, having a thread or thread network structure adapted to be supported against the cardiac ring remaining after removal of the deficient native cusp: at least an axial wedging portion, having a thread or thread network structure separate from the structure of said axial portion of the cusp support, and with a diameter greater than the diameter of said axial portion enabling it to be supported against the wall bordering said remaining cardiac ring; at least a thread linking point-to-point said portions.

While attempts have been made to mimic the function of the natural valve, there is no expandable valve for venous transcatheter placement that includes a combination of the native structural features that individually or collectively, may prove highly advantageous or critical for a successful valve. One common problem evident from early experiences with prosthetic valves is the formation of thrombus around the base of the leaflets, probably due at least in part to blood pooling in that region. In a natural valve, the leaflets are typically located within a sinus or enlargement in the vein. There is some evidence that the pockets formed between the leaflets and the walls of the sinus create vortices of flowing blood that help flush the pocket and prevent blood from stagnating and causing thrombosis around the valve leaflets, which can interfere with the function of the valve. It is thought that the stagnating blood prevents oxygen from reaching the endothelium covering the valve cusps, leading to hypoxia of the tissues which may explain increased thrombus formation typical in that location. Expandable-frame valve prostheses typically are of a generally cylindrical in shape and lack an artificial sinus or pocket space that is sufficient for simulating these natural blood flow patterns. What is needed is an intravenously placed artificial valve that is configured to create more effective flow patterns around the valve structure to circulate the blood or bodily fluids and reduce the likelihood of stagnation and the potential clinical problems that may result.

The following disclosure describes a valve prosthesis, such as an artificial venous valve, having a valve structure and a self-expanding or otherwise expandable support structure that upon deployment within the vein, helps create an artificial sinus or larger pocket in the vessel surrounding the valve structure of sufficient size and shape to stimulate flow patterns or vortices which facilitate clearing of the blood or other bodily fluid that would otherwise pool therein. The structural adaptations result in more turbulent flow, increased velocity of flow, larger and/or more numerous vortices, other factors, or a combination of the above that prevent stagnant, hypoxic areas from occurring around the valve structure. Furthermore, the modified flow may also contribute to helping close the leaflets to form a seal and prevent leakage of fluid back through the valve. The artificial sinus or enlarged pockets simulate the function of the natural sinus that exists at the site of most natural valves in the deep veins of the lower legs and which may explain why the problem of thrombus forming around the valve structure has been observed to be a common problem in prosthetic venous valve designs lacking such a sinus area.

In one aspect, the collapsible support structure of the valve prosthesis is expandable to a particular diameter upon deployment, with the valve prosthesis being configured such that the prosthesis includes an intermediate, substantially 'open' section such that the artificial sinus is created by a portion of the duct or vessel that is substantially unsupported by the support structure. The unsupported portion of the vessel can advantageously assume a diameter that is larger than the deployment diameter of the vessel-anchoring or 'closed' sections or portions of the collapsible support structure, thereby creating an artificial sinus as blood (or bodily fluid) exerts pressure on the unsupported portion of the vessel wall. In one exemplary embodiment, the expandable support structure comprises a first, proximal portion and a second, distal portion that are interconnected by one or more thin members or struts, such that the largely unsupported region between the first and second (proximal and distal) sections of the support structure forms an artificial sinus (proximal being defined herein as have the same positional orientation as the orifice or opening of the valve structure, which is typically toward the heart in a venous valve). The valve structure is attached about the support structure such that it is largely situated within the unsupported region forming the artificial sinus. For example, the valve structure (defined herein as one or more cooperating leaflets, tubular members, or any flexible structure adapted to seal a passageway in response to changing fluid pressure differentials thereacross) may be attached to the interconnecting members, which can comprise oppositely placed struts having attachment points, (e.g., suture or any suitable structure or method) to facilitate attachment of the valve material.

In another aspect, the expandable support structure of the valve prosthesis comprises a framework or anchoring portion having an intermediate region that includes an enlarged diameter configured to create an artificial sinus about the valve structure, which is attached inside the intermediate region. In one embodiment, the support structure is made of a superelastic material, such as nitinol, and the intermediate region comprises an expanded or bulging portion that is formed by heat setting the nitinol tubular frame around a mandril or other fixture of the desired configuration using a method well known in the medical arts. The intermediate portion expands to a diameter larger than the proximal and distal portions when the prosthesis is deployed from the delivery system, thereby producing larger pockets around the valve structure which create more effective flow patterns to reduce pooling. In another embodiment, the proximal, distal, and intermediate sections are separate, interconnected sections, such as zig-zag frame or other expandable or self-expanding support or anchoring frames. The intermediate section comprising the artificial sinus includes a first and a second radially expandable or self-expanding portions in which the adjoining ends of each are larger in diameter than the ends which adjoin the proximal and distal sections, respectively. The frustoconical shape of the respective intermediate sections can be accomplished by either forming the section into that shape (i.e., plastic deformation of a tubular prosthesis, heat setting nitinol, laser cutting a frustoconical section of tubing, etc.) or a constraining means, such as a suture or thin wire, can be used to manipulate the relative diameters by feeding the constraining means through the apices of the bend or apertures therein and applying the appropriate amount of tension to create the desired shape. Optionally, a tubular or band-like section can be positioned between opposing frustoconical sections to create a longer artificial sinus.

In yet another aspect, the proximal end of the collapsible support at which the valve structure is located is expanded (e. g flared outward) such that the expanded end or a combination of the expanded end and adjacent area of the vein forms the artificial sinus.

In still yet another aspect, the proximal and distal sections are configured to include a substantially open area between them with the valve structure being attached to the distal section such that it is positioned just below the artificial sinus. Optionally, a sleeve of a biomaterial (e. g a bioremodelable material such as small intestinal submucosa (SIS) or another collagenous extracellular matrix) or fabric can be attached over the proximal and distal sections such that it forms a seal between the prosthesis and the vessel wall, including the artificial sinus.

In still yet another aspect, the support structure of the prosthesis is configured such that the attachment pathway (defined herein as the interface between the lateral, outer edges of the leaflets and the struts and/or vessel walls to which they are attached to establish and define the shape and configuration of the plurality of leaflets comprising the valve structure as deployed) has a first, proximal portion in which the one or more longitudinal attachment struts extending from the proximal bends or commissures that carry and support the proximal outer edges of the leaflets (and span the orifice) have a strongly longitudinal orientation with respect to the longitudinal axis of the prosthesis and valve structure, and a distal portion of the attachment pathway that extends circumferentially (laterally) and distally from the longitudinal axis to form the bottom or distal edge of the outer leaflet edge or perimeter. When viewed from the side, the support frame and attached leaflet is configured such that the angle (angle α) formed between the opposing leaflets, as carried along the proximal attachment pathway, is substantially less than the angle (angle β) formed between distal attachment pathways and the vessel walls. This configuration results in leaflets having large coaptable area relative to the overall surface area, which improves sealing (including reducing the effects of retraction by the valve material) and allows for larger pockets surrounding the leaflets which, like the sinus, facilitate the creation of larger, stronger vortices of retrograde flow that help close the leaflets and clear away blood or fluid that could otherwise stagnate under conditions where the surrounding pockets are smaller in size. As used herein, the term 'retrograde flow' is defined as bodily fluid traveling in a distal direction (toward the feet), whether due to gravitational forces, redirection due to contact with the prosthesis or bodily lumen walls, or by some other means.

A first embodiment of this aspect includes a frame comprising a pair of longitudinal attachment struts originating from each commissure bend. The struts extend in generally longitudinal direction, diverging relatively or not at all toward the distal end of the prosthesis before more acutely diverging as they curve laterally and circumferentially away from the proximal strut portions such that the transition between the proximal and distal portions of attachment pathway comprises a bend having a radius that is distinctly smaller than that of the adjacent strut portions (the proximal portions being straight some embodiments). The distal attachment pathways converge to define the bottom outer edge of each leaflet. In a second embodiment of this aspect, the support frame of the prosthesis includes a pair of substantially parallel longitudinal attachment struts to which the leaflets are attached to form the proximal portion of the attachment pathway, and distal attachment struts extending circumferentially and laterally outward from the substantially parallel struts to form the distal portion of the attachment pathway. The support frame carrying the valve structure may be advantageously comprised of radial sections (e.g., quadrants in a bicuspid valve) that are of an identical pattern but with alternating orientation such as to provide for radial stability and better expandability characteristics. The radial section not carrying the leaflet proximal outer edges serves as lateral support structure for adding longitudinal stability and help protecting the leaflets from adhering to the vessel walls. The parallel struts provide for advantageous bending and torsional characteristics such that the frame has utility as a stent. In an alternate embodiment of the support structure, the lateral outer edges of the opposing leaflets can be attached to single longitudinal attachment strut having a pair of distal struts extending laterally outward and circumferentially to carry the bottom half of the leaflet and define the overall shape thereof. The strut may be thicker than adjacent struts and include aperture therealong for facilitating attachment of the valve structure.

In still yet another aspect, the proximal section of the valve is wider in diameter at its proximal end, which anchors the prosthesis in the vessel, and narrower at the interface between the proximal and intermediate sections. This, in combination with a leaflet structure that maximizes pocket size, results in retrograde flow being subject to a Venturi effect which increases flow and the strength of the vortices to close the valve and clear the pockets of potentially stagnating fluids.

The configuration of the basic units of the support structure and valve structure is not particularly critical for an understanding of the invention. Numerous examples are well known in the prior art and may be found in the disclosure of Applicant's provisional application Ser.

Embodiments of the present invention will now be described by way of example with reference to the accompanying drawings, in which:.

<FIG>, <FIG> illustrates a collapsible, self expanding or otherwise expandable artificial valve prosthesis <NUM> that is deployed within a bodily passageway <NUM>, such as a vessel or duct, of a patient typically delivered and implanted using well-known transcatheter techniques for self-expanding prostheses, the valve prosthesis having a first or proximal end <NUM> and a second or distal end <NUM>, with the normal, antegrade fluid flow typically traveling from the distal end to proximal end of the prosthesis, the latter being located closest to the heart in a venous valve when placed within the lower extremities of a patent. The valve prosthesis <NUM> comprises a support structure <NUM> and a valve structure <NUM>, such as the illustrative valve structure, attached about the support structure and configured to selectively restrict fluid flowing therethrough by closing with changes in the fluid pressure differential, such as in the presence of retrograde flow. The present invention includes structural features that modify the flow dynamics within the prosthesis such that fluid collecting in pockets <NUM> near the base of the leaflets <NUM> is more likely to be flushed away or effectively mixed with fresher incoming bodily fluid on a continual basis.

It should be understood that the materials used to comprise the support structure <NUM> can be selected from a well-known list of suitable metals and polymeric materials appropriate for the particular application, depending on necessary characteristics that are required (self-expansion, high radial force, collapsibility, etc.). The materials used for the valve structure <NUM> can comprise a synthetic material or biologically-derived material appropriate for the clinical application; however, investigational studies have demonstrated that a bioremodelable material (such as an collagenous extracellular matrix (e.g., small intestinal submucosa), pericardial, or a growth factor-enhanced material may have superior anti-thrombogenic properties within the body as the native cells and tissues gradually replace the original leaflet material. The number of leaflets possible for embodiments of the present invention can be two, three, four, or any practical number, but bi-leaflet valves may prove advantageous in low-flow venous situation as compared to tri-leaflet embodiments, such the type used as heart valves which are subject to high-flow situations where thrombus formation is far less of a problem.

In the artificial valve prostheses of <FIG>, the support structure <NUM> is configured such that when the device is deployed within the bodily passage <NUM>, such as a vein of the lower legs or feet, an artificial sinus <NUM> is formed adjacent to and surrounding the valve structure <NUM> such that the blood or other bodily fluids collecting within the pockets <NUM> formed around the bases of the valve leaflets <NUM> is more likely to be flushed out on a continual basis due to the advantageous geometry created by the artificial sinus <NUM>. The principle is illustrated in the example of <FIG> which shows a natural venous valve <NUM> in which retrograde blood <NUM> flowing or falling back down and closing the valve is thought to create a series of vortices <NUM> as it contacts the leaflets. It is believed that the rounded shape of the enlarged natural sinus <NUM> surrounding the valve <NUM> facilitates creation of these vortices, thereby preventing blood from pooling or stagnating within the pockets <NUM> at the base of the valve <NUM>, which may lead to thrombus formation or other problems. The present invention, by virtue of the configuration of the support structure <NUM>, creates an artificial sinus <NUM> that attempts to reproduce the function served by the natural sinus <NUM> in the vein.

<FIG> depicts a side view of an illustrative embodiment of the present invention in which the prosthesis <NUM> includes a first or proximal section <NUM> and a second or distal section17 that are spaced apart from one another, defining an intermediate, substantially open section <NUM> for creating the artificial sinus <NUM> in the vessel <NUM>. The term 'substantially open' is used herein to define a largely unsupported portion of the bodily passage in which at least some minimal interconnecting structure (e.g., thin or flexible elements aligned with the leaflet commissures) is present that traverses the unsupported portion of the bodily passage, but it comprises very limited surface area and typically supplies minimal, if any, force against the walls of the passageway lateral to the valve structure <NUM>. The proximal and distal sections <NUM>,<NUM>, comprise a pair of radially expandable anchoring portions <NUM>, are joined by a pair of connection struts <NUM>,<NUM> that allows the intermediate section <NUM> to be otherwise open and free of scaffolding so that the vein walls <NUM> along that section of the vessel <NUM> are able to expand due to pressure exerted by the blood flowing within the vein.

In the embodiments of the present invention, the anchoring portions <NUM> may function as stents to help the bodily passage remain patent, but their primary function is limited to engaging the bodily passage to anchor the prosthesis thereagainst. The support structure <NUM> and anchoring portions <NUM> also may be configured to be readily collapsible as with a normal vein. Since the diameters of the proximal and distal sections <NUM>,<NUM> generally assume a fixed diameter after deployment, the intermediate section, which is mostly unsupported or covered by structure, expands to form a bulging region of the vessel that functions as an artificial sinus <NUM>. Although the interconnecting means <NUM> advantageously permit the proximal and distal sections <NUM>,<NUM> to be deployed together at a fixed distance from one another, it is within the scope of the invention to have the valve prosthesis <NUM> comprise separate unconnected sections that are deployed sequentially at an effective distance from one another to create an artificial sinus 34therebetween. Additionally, the interconnecting means <NUM> can comprise suture, fabric, or some other non-rigid material to join the proximal and distal sections <NUM>,<NUM> and define the optimal length of the intermediate section <NUM>, without interfering with the creation of the artificial sinus <NUM>. To deploy a prosthesis <NUM> having a flexible interconnecting means <NUM>, one of either the proximal or the distal sections <NUM>,<NUM> can be deployed first with the delivery system then being slowly withdrawn until the interconnecting means <NUM> becomes taut, whereby the opposite section is then deployed.

According to the present invention, the valve structure <NUM> comprises a pair of leaflets <NUM> that are situated in the intermediate section and attached to the proximal section <NUM> at two commissural points <NUM>,<NUM>, each located at the proximal ends of the interconnecting struts <NUM>,<NUM>, using an appropriate attachment means <NUM>, such as suture, adhesive, fasteners, tissue welding using heat and/or pressure, etc. The leaflets <NUM> are attached about their distal ends <NUM> to the distal section <NUM> of the support structure <NUM> using the same or an other suitable attachment means <NUM>. The valve structure <NUM> is configured so that it advantageously expands with the deployment of the proximal and distal sections <NUM>,<NUM> such that the outer edges <NUM> thereof contact the vessel wall sufficiently to at least substantially prevent leakage of bodily fluid around the valve structure <NUM>. Optionally, the wall-engaging outer edges of the leaflets <NUM> can be reinforced with a separate frame <NUM> that is attached to or incorporated into the outer edges <NUM> to improve sealing with the vessel wall <NUM>. An example of such a frame <NUM> is depicted in embodiment shown in <FIG> in which the frame <NUM> also serves as the interconnecting means <NUM> between the proximal and distal section <NUM>,<NUM> of the support structure <NUM>, with the struts <NUM>, <NUM> being laser cut from the same tube used to form the remainder of the support structure <NUM>. The valve frame <NUM> (that portion of the support structure <NUM> that reinforces the valve structure <NUM>) can either be configured to exert relatively little radial force beyond what might be required to ensure adequate contact with the vessel wall <NUM>, or it may be configured such that the frame <NUM> exerts sufficient radial force such that it assists in creating an artificial sinus <NUM> in the portion of the vein along the intermediate section <NUM> of the valve prosthesis <NUM>.

Another method of creating the artificial sinus <NUM> is depicted in <FIG>, which are examples that are useful for the understanding of the present invention in which the support structure <NUM> includes an expanded portion <NUM>, larger in diameter than the remainder of the support structure <NUM>, that upon deployment, creates an artificial sinus <NUM> surrounding the valve structure <NUM>. The diameter of the artificial sinus <NUM> caused extending the vessel wall <NUM> is, at its widest point, preferably about <NUM>-<NUM>% larger than the diameters of the proximal and distal sections <NUM>,<NUM> when fully deployed (unrestrained from within the delivery sheath), with a more preferred differential of about <NUM>-<NUM>% and a most preferred difference of <NUM>-<NUM>% larger, depending on the diameter of the vein, the valve structure geometry, fluid column pressures at that location, and other factors. In the examples illustrated, the transition between the proximal and distal section <NUM>,<NUM> and the expanded intermediate section <NUM> is curvilinear, creating a bulge-like or flared configuration (<FIG>, respectively). In the examples depicted, the support structure comprises a single tubular anchoring portion <NUM> that is plastically, resiliently, or otherwise deformed into a second configuration that includes the expanded portion <NUM>. For example, the anchoring portion <NUM> can be laser cut from a tube of nitinol, placed around a mandril having the desired shape, and heat set to produce the final desired shape. In the artificial valve prosthesis of <FIG>, the expanded portion <NUM> comprises the intermediate section <NUM> of the prosthesis <NUM>, such that the artificial sinus <NUM> is created between the proximal and distal sections <NUM>,<NUM> and the valve structure <NUM> is located therein. In <FIG>, the expanded portion <NUM>, which comprises the proximal section <NUM> of the support structure <NUM>, includes a flared configuration that extends outward from the distal section <NUM> (no separately functional intermediate section <NUM> is present). The valve structure <NUM> is attached about the proximal end <NUM>, while the flared, expanded portion <NUM> thereabout ca uses the vessel <NUM> to bulge outward, thus creating an artificial sinus <NUM> about the proximal end of the prosthesis <NUM>. The artificial sinus <NUM> comprises a combination of a supported and an unsupported portion in the embodiment of <FIG>. In both the illustrated examples the valve structure <NUM> is sewn to the struts <NUM> of the support structure within the passageway of the anchoring portion <NUM>. Other alternative methods of attachment include adhesives, staples or other fasteners, wire, engagement barbs on the frame, tissue welding, etc..

<FIG> depict examples of artificial valve prostheses similar to that of <FIG>, except that the proximal, intermediate, and distal sections <NUM>,<NUM>,<NUM> comprise separate anchoring portions <NUM> (having a serpentine or 'zig-zag' configuration in the example illustrated) that are attached to one another in well-known manner, such as by feeding the illustrative thread material <NUM> or suture through the apices <NUM> of adjoining bends and securing it therearound. In the example of an artificial valve prosthesis of <FIG>, the intermediate section <NUM> comprises a first and a second intermediate subsection <NUM>,<NUM> of opposing frustoconical-shaped anchoring portion <NUM> that are coupled to form the artificial sinus <NUM>. The first and second subsections <NUM>,<NUM> can be manipulated into a frustoconical shape by plastically deforming the anchoring portion <NUM> into that shape, or by increasing constraint of the frame about the distal end of a cylindrical-shaped proximal portion <NUM> and the proximal end of a cylindrical-shaped distal portion <NUM> with a constraining means <NUM>, such as thread, suture, wire, band, covering, etc., so that the respective sections <NUM>,<NUM> assume a frustoconical shape. Additional constraining means <NUM> may be included at the first and second ends <NUM>,<NUM>, as depicted, to maintain the cylindrical shape of the proximal and distal <NUM>,<NUM> sections. The thread or suture <NUM> (constraining means) at the interface <NUM> interconnecting the first and second intermediate subsections <NUM>,<NUM> may or may not function to tension the apices <NUM> of those respective subsections. The example of artificial valve prosthesis of <FIG> is similar to that of <FIG> except that the intermediate section <NUM> also comprises a third intermediate subsection <NUM>, located between intermediate subsection <NUM> and <NUM>, that extends the length of the artificial sinus. The illustrative third intermediate section <NUM> comprises a short cylindrical or band-shaped portion whose width can be adjusted to create the desired geometry of the artificial sinus <NUM>. Additional subsections can be added as well, if so desired.

<FIG> depicts an example of an artificial valve prosthesis in which the support structure <NUM> comprises a proximal portion <NUM> joined to a distal portion <NUM> by a interconnecting strut <NUM>, the entire support structure being cut from a single piece of cannula, such as stainless steel or nitinol. The valve structure <NUM>, comprising a plurality of leaflets <NUM>, is attached to the distal portion <NUM> such that the artificial sinus <NUM> is formed in the largely open, unsupported region between the proximal and distal sections <NUM>,<NUM> by virtue of the vessel <NUM> bulging outward, as in the embodiment of <FIG>. The valve prosthesis <NUM> further includes an optional covering <NUM>, such as an outer sleeve of SIS (or other suitable biological or synthetic material), that is attached to both the proximal and distal sections <NUM>,<NUM> of the support structure <NUM>, which helps seal the prosthesis to prevent leakage of retrograde fluid therearound. The covering <NUM> is preferably of a constitution and configuration such that it does not interfere with the creation of the artificial sinus <NUM>.

<FIG>, and <FIG> comprise examples of an artificial valve prosthesis <NUM> in which support structure <NUM> carrying the leaflets <NUM> is configured to increase the leaflet contact (coaptable) area <NUM> about the proximal portion of the valve structure <NUM> without relying on built-in slack within the material to bring the leaflets in closer proximity and provide for a extensive sealing area, longitudinally. As defined in this application, the leaflet contact area <NUM> comprises a longitudinal portion along the valve structure <NUM> in which the facing surfaces of opposing leaflets <NUM> (two or more) coapt or lie in close proximity to one other while in a dry or resting, neutral state (i.e., the pressure differentials across the valve orifice are essentially equalized such that the leaflets are not being forced together or apart due to external forces, such as fluid flow), when the prosthesis is an expanded or deployed configuration. The support frame <NUM> may be configured for maximizing the extent of the leaflet contact area <NUM> by including one or more longitudinal attachment struts <NUM>,<NUM> that define at least the proximal portion <NUM> of the attachment pathway <NUM> of each leaflet lateral outer edge <NUM>,<NUM> (the terms outer edge <NUM> and lateral outer edges <NUM>,<NUM> being defined herein as the area or zone along the leaflet that comprises the sealing interface). The longitudinal attachment struts <NUM>,<NUM>/proximal attachment pathways <NUM> have a substantially longitudinal orientation (e.g., substantially parallel) with respect to the longitudinal axis <NUM> of the prosthesis (and valve structure <NUM>). At a point generally proximate the distal end <NUM> of the leaflet contact area <NUM> (the proximal portion <NUM> of the leaflet), the distal portions <NUM> of the adjacent attachment pathways <NUM> (which are joined proximally about a commissural point) diverge from one another (forming a generally Y-shaped pathway configuration) and assume a much more circumferential orientation than that of the proximal portion <NUM> of the pathway such that the outer leaflet lateral edges <NUM>,<NUM> of each leaflet converge at a point lateral to the free inner edge <NUM> thereof to seal the passageway and form the distal portion <NUM> of the leaflet that defines the bottom <NUM> or 'floor' of the pocket <NUM> or intravascular space adjacent the outer surfaces of each of the leaflets, which generally assumes a strongly cupped or curved shape such that the leaflet assumes a generally 'folded' appearance due to the acutely angled attachment pathway <NUM> with the proximal portion of the leaflet having a strong longitudinal orientation with respect to the prosthesis and vessel and the bottom portion <NUM> having a strongly perpendicular orientation relative to the longitudinal axis of the vessel and prosthesis. It should be noted that the commissures <NUM>,<NUM>, while located about the proximal end <NUM> of the illustrative prosthesis <NUM>, may be located proximal thereto such that additional support structure <NUM> extends proximally, such as in the artificial valve prostheses of <FIG>, <FIG>.

By extending or maximizing the leaflet contact area and decreasing the radius of the curvature of the leaflet (increasing curvature) about the distal portion thereof, the basal or distal portion of the pocket <NUM> adjacent each leaflet is enlarged to facilitate and maximize the size and/or velocity of the flow vortices <NUM>,<NUM> formed therein during retrograde flow. During pre-clinical investigations, these broader pockets have been shown to be especially advantageous in bi-leaflet artificial valve designs implanted in the venous system, these valves exhibiting a marked reduction in thrombus formation as compared to earlier designs. The improvement in flow dynamics for the purpose of clearing the pocket <NUM> of stagnant blood that can thrombose and compromise valve function or lead to other complications is depicted in a comparison of <FIG>. Laboratory analysis of the patterns of retrograde flow within a valve has shown that multiple vortices are typically created. In the example of an artificial valve prosthesis of <FIG>, which has a generally (inverted) V-shaped attachment pathway <NUM>, a first vortex <NUM> is created below which a second, smaller vortex <NUM> is usually present, usually having opposite flow, which may be at least partially inadequate for clearing away blood pooling about the base of the leaflets <NUM>,<NUM> in a venous valve. In the example of an artificial valve prosthesis depicted in <FIG>, which has a generally (inverted) Y-shaped attachment pathway <NUM>, the larger pocket (at least at the basal portion) allows for a larger and stronger second vortex <NUM> of fluid created by retrograde flow that is more optimal for clearing away any pooling blood that would otherwise collect there and potentially provide for greater downforce on the leaflets <NUM>,<NUM> to improve closure of the valve.

<FIG> depict an artificial venous valve prosthesis <NUM> in which the frame <NUM> of the support structure <NUM> is configured such that the pair of longitudinal attachment struts <NUM>,<NUM> extending from each of the commissures <NUM>,<NUM> that represent the proximal attachment points for the valve structure (not shown) form a first angle <NUM> (α) with respect to one another that is less than the second angle <NUM> (β) that is formed between the distal attachment struts <NUM>,<NUM>, which comprise continuations of the longitudinal attachment struts <NUM>,<NUM> (together comprising the legs <NUM> of the frame <NUM>), and the inside <NUM> of the vessel wall <NUM>. The first angle <NUM> is preferably between -<NUM> and <NUM>° (a negative angle being possible with a sufficiently large-radius bend about the commissure) with a more preferred angle being <NUM>-<NUM>° and a most preferred angle of <NUM>-<NUM>°. The longitudinal attachment struts <NUM>,<NUM> may both diverge and converge at various points therealong (i.e., bow inward or outward), which in case, the first angle may be relevant for only the proximal portion <NUM> or is measurable between vectors representing the best straight line longitudinally traversing each strut <NUM>,<NUM>. The example illustrated also includes a pair of optional stabilizing arms <NUM>,<NUM> that extend laterally from the legs <NUM>,<NUM> to help center the prosthesis <NUM> within the vessel <NUM>. Ideally, the angles depicted in the frame <NUM> configuration of <FIG> results in the opposing leaflets <NUM>,<NUM> being much more in alignment (e.g., parallel) with one another than in a prosthesis where the angles <NUM>,<NUM> are relatively the same, such as the prior art valve shown in <FIG>, particularly over the proximal half of the leaflets <NUM>,<NUM>. The result is the creation of a larger pocket around the base of the leaflets <NUM>,<NUM> that helps create larger and/or stronger vortices of retrograde blood flow. A second clinical benefit is that there is a larger area of coaptation between the leaflets <NUM>,<NUM>, which helps provide a better seal against possible reflux through the valve orifice.

<FIG> depict another group of examples of an artificial valve prosthesis configured for maximizing the coaptation distance or region between the leaflets in which the attachment pathway <NUM> comprises a proximal portion <NUM> that generally extends along one or more longitudinal attachment struts <NUM>,<NUM> that are generally aligned with the longitudinal axis <NUM> of the prosthesis and a distal portion <NUM> that is angled laterally from the longitudinal attachment struts and generally follows the distal attachment struts <NUM>,<NUM> which unlike the artificial valve prosthesis of <FIG>, extend laterally outward from the longitudinal struts <NUM>,<NUM> as separate struts. As with the embodiment of <FIG>, the distal attachment struts/portions converge at a point oppositely facing each leaflet <NUM>,<NUM> where they attach to the lateral support structure <NUM>,<NUM>, which helps center the prosthesis in the vessel and protects the leaflets from adhering to the vessel wall. In the artificial valve prostheses of <FIG>, the support frame <NUM> further includes proximal support arms <NUM>,<NUM> that attach to and extend from the longitudinal attachment struts <NUM>,<NUM> about the commissure points <NUM>,<NUM> and provide an interconnection with the lateral support structure <NUM>,<NUM> (also shown in <FIG>).

The example of an artificial valve prosthesis depicted in <FIG> comprises a pair of longitudinal attachment struts <NUM>,<NUM>, generally parallel to one another, which are adapted for attaching the respective leaflets <NUM> therealong, thus creating a large leaflet contact or coaptable area <NUM> that extends over half of the length of the prosthesis. As depicted in <FIG>, The lateral support structure <NUM>,<NUM> shares or mirrors the configuration of the longitudinal attachment strut regions which they interconnect, except that they are located <NUM>° therefrom and oriented oppositely thereto, such that the support structure <NUM> generally forms a serpentine configuration adapted to be readily collapsible and expandable. In the example illustrated, the support structure <NUM> or frame can be divided into four sections or quadrants <NUM>,<NUM>,<NUM>,<NUM> that are identical except for their orientation, sections <NUM> and <NUM> being oriented with the commissures <NUM>,<NUM> and longitudinal attachment struts <NUM>,<NUM> carrying the valve structure <NUM> being oriented proximally toward the first end <NUM> of the prosthesis <NUM>. The repeating, uniform design of the support structure <NUM> of the example depicted advantageously provides better structural stability, compressibility/expandability, and overall integrity than a support structure that does that comprise a non-uniform, non-repeating frame pattern.

The lateral arms <NUM>,<NUM> of the lateral support structure <NUM>,<NUM>, that connect to the longitudinal attachment struts <NUM>,<NUM> each include a strut <NUM> that carries a proximal radiopaque marker <NUM> used to facilitate orientation of the device <NUM> and provide additional support. An identical distal strut <NUM> and an optional radiopaque marker <NUM> is located distal to the longitudinal attachment struts <NUM>,<NUM> and attached to the distal attachment struts <NUM>,<NUM> to serve a similar orientation and stabilization function. An integral barb <NUM> is located about the commissural bends <NUM>,<NUM> that interconnect the longitudinal attachment struts <NUM>,<NUM>. The parallel longitudinal attachment struts <NUM>,<NUM> are also interconnected about their distal ends by a short interconnecting strut <NUM> such that an elongate closed cell <NUM> is formed. The width of cell <NUM> is not critical, although it may be made sufficiently narrow such that it serves to further pin or anchor the leaflets <NUM>,<NUM> to the struts <NUM>,<NUM>, which could be especially advantageous in fixation if the leaflet material retracts during the remodeling process. A preferred width between the two struts <NUM>,<NUM> would be between <NUM>-<NUM>, with <NUM>-<NUM> being more preferred and <NUM>-<NUM> being most preferred. If the spacing is too wide, gaps may be created between the opposing leaflets which could allow for an unacceptable amount of reflux through the valve.

A similar frame design is shown in <FIG> which includes a single longitudinal attachment strut <NUM> to which both leaflets <NUM>,<NUM> are sewn or otherwise attached allowing for similar extended coaptation between leaflets. The leaflets <NUM>,<NUM> can be attached such that each abuts the strut <NUM> (and sewn or attached without being wrapped over the strut) or the first lateral leaflet edge (not shown) is wrapped around the strut <NUM> while the second leaflet lateral edge of the opposite leaflet is sewn over the first lateral leaflet edge and strut <NUM>. The single attachment strut can be of a width that is generally uniform with respect to the other support structure or it may be made substantially thicker, such as shown in <FIG>. Furthermore, a thicker strut <NUM> could include apertures <NUM> or slots of any shape or length distributed therealong for receiving sutures or other attachment elements <NUM>, such as clips, rings, etc., for affixing or anchoring the leaf outer edges thereto. <FIG> depicts an example of an artificial valve prosthesis having a pair of longitudinal attachment struts <NUM>,<NUM> with anchoring structure <NUM>, such as the illustrative scalloped edge that is strategically configured therealong to help prevent or limit the attachment element <NUM> and the valve structure itself, from sliding down the longitudinal attachment struts <NUM>,<NUM>, especially during any retraction that may occur with a bioremodelable material. The anchoring structure can comprise any projections or other structure that provides a shoulder or irregularities along the edges of the struts that helps limit sliding of the leaflets along the longitudinal attachment struts <NUM>,<NUM>. Further examples of adaptations for limiting movement or migration of attachment elements (e.g., sutures) and covering material are disclosed in an application to<CIT>.

<FIG> depicts an example of an artificial valve prosthesis having generally, but not absolutely parallel longitudinal attachment struts <NUM>,<NUM> which slightly converge toward the distal end <NUM> of the prosthesis <NUM> (and are spaced more distant from each other than the artificial valve prosthesis of <FIG>. The commissural bends <NUM>,<NUM> and distal bends <NUM> interconnect the longitudinal attachment struts and form a closed cell <NUM> as in the artificial valve prosthesis of <FIG>. The distal attachment struts <NUM>,<NUM> provide the interconnection between the opposite closed cells <NUM> as well as the distal portion <NUM> of the attachment pathway <NUM>. They also carry a lateral arm <NUM> and together comprise the lateral support structure <NUM>,<NUM> that provide longitudinal support/stabilization and leaflet protection. The artificial valve prosthesis of <FIG> lacks proximal support arms <NUM>,<NUM> of the artificial valve prosthesis of <FIG>.

The illustrative support structure <NUM> in <FIG>, <FIG> is not critical to achieve the optimal leaflet angles in the valve structure <NUM> for creating larger pockets, as depicted. For example, the attachment pathway <NUM> of the valve structure <NUM> can comprise an attachment to an outside support frame to form the illustrative configuration with the frame <NUM> that is not necessarily extending along the outer edges <NUM> of the leaflets <NUM>,<NUM>, but rather attached to selected strut that cross the attachment pathway <NUM>, especially along the distal portion <NUM> of the pathway. Furthermore, at least a portion of the outer edges <NUM> can be directly affixed to the vessel wall (such as being sutured, heat welded, or anchored with barbs, adhesives, etc.) with the frame <NUM> being absent or reinforcing or shaping only a limited portion of the leaflet outer edges <NUM>, thus allowing for the vein to naturally collapse (at least partially) when not filled with blood. For example, the frame <NUM> might comprise a partial support of a hair-pin configuration that includes a proximal bend about each commissure <NUM>,<NUM> with free-ended longitudinal attachment struts <NUM>,<NUM> extending therefrom which help form the leaflet angle <NUM>, while the distal portion <NUM> of the attachment pathway <NUM> comprises an alternative attachment that does not result in the leaflet material being urged thereagainst by a radially expandable frame. Methods include surgical attachment, tissue welding, adhesives, barbs and other well-known methods, teachings of which is included in a co-pending U. Patent Application entitled, 'Percutaneously Deployed Vascular Valves with Wall-Adherent Adaptations (Case et al. ) filed April <NUM>, <NUM> The angle of the leaflets <NUM>,<NUM> relative to the longitudinal axis <NUM> of the prosthesis and vessel (half of the first angle <NUM> or a/<NUM>) is preferably -<NUM>-<NUM>° with a more preferred angle of <NUM>-<NUM>° and a most preferred angle of <NUM>-<NUM>°. The relatively small or shallow angles of the longitudinal attachment struts <NUM>,<NUM> about the commissures <NUM>,<NUM> allows for a larger space adjacent the leaflets <NUM>,<NUM> and broader pockets <NUM> at the base of the leaflets. The longitudinal attachment struts <NUM>,<NUM> of the support structure can be formed generally parallel to one another along the proximal portions of the longitudinal attachment struts <NUM>,<NUM> to create the maximum pocket size and greater coaptation of the leaflets. For example, the pocket <NUM> areas would be maximized in an attachment pathway <NUM> where angle <NUM> is zero (or a negative angle) and angle <NUM> is at least <NUM>°, such that the attachment pathway along each leaflet lateral outer edge <NUM> ,<NUM> is generally L-shaped such that the distal portion <NUM> of the attachment pathway angles abruptly from the proximal portion rather than assuming a dog-leg configuration as shown in the examples illustrated.

The amount of contactable or coaptable area <NUM> can be expressed in different ways. In the present invention, the length of the leaflet contact area <NUM> (or proximal portion <NUM> of the attachment pathway) in a typical venous valve prosthesis is preferably at least <NUM> and as much as <NUM> (depending on the configuration of the valve prosthesis), with a more preferred length of <NUM>-<NUM> and a most referred range of <NUM>-<NUM>. In an average sized venous valve having a length of <NUM>, the preferred range of the leaflet contact area <NUM> or proximal attachment pathway <NUM> would be <NUM>-<NUM>% of the prosthesis length (<NUM>-<NUM>), assuming the valve structure <NUM> is generally as long as the support frame <NUM>. A more preferred leaflet contact area <NUM> would comprise <NUM>-<NUM>% with <NUM>-<NUM>% being most preferred in a prosthesis of the same general type as depicted. The relationship between leaf contact area and the diameter of the vessel may be a factor in optimizing the functionality of the valve prosthesis <NUM>. Preferably, the length of the longitudinal attachment struts <NUM>,<NUM> and/or leaflet contact area <NUM> is <NUM> to <NUM>% of the nominal vessel diameter with a more preferred range of <NUM>-<NUM>%.

The amount of slack in the leaflet material also helps determine how well the leaflets coapt during retrograde flow and how large of an opening they permit during antegrade flow. Preferably, but not essentially, the prosthesis is configured such that the distance formed between the leaflets in their fully open position and the vessel diameter remains preferably between <NUM>-<NUM>% of the vessel diameter, with a more preferred range of <NUM>-<NUM>% of the vessel diameter and a most preferred range of <NUM>-<NUM>%. By substantially orienting the longitudinal attachment struts <NUM>,<NUM> with the longitudinal axis <NUM> of the prosthesis, less slack is necessary for optimal or extended coaptation. Not having the leaflets regularly contact the outer walls of the vessel can be especially important when using a bioremodelable material, such as an ECM, which can partially or completely adhere to the wall over time as tissue grows into the leaflets, thus compromising the functionality of the valve.

Claim 1:
An artificial valve prosthesis (<NUM>) for implantation in a vessel having a vessel wall, the artificial valve prosthesis comprising:
a support structure (<NUM>) comprising:
a proximal section (<NUM>) comprising a first radially expandable anchoring portion that includes first and second commissures;
a distal section (<NUM>) comprising a second radially expandable anchoring portion;
the proximal (<NUM>) and distal (<NUM>) sections spaced apart from one another to define an intermediate section (<NUM>), the intermediate section comprising a substantially open section of the support structure;
a first strut (<NUM>) joining the proximal and distal sections, the first strut extending from the first commissure (<NUM>); and
a second strut (<NUM>) joining the proximal and distal sections, the second strut extending from the second commissure (<NUM>);
a valve structure (<NUM>) comprising two leaflets (<NUM>) situated in the intermediate section (<NUM>), the leaflets attached to the proximal section (<NUM>) at two commissural points (<NUM>, <NUM>) located at the proximal ends of the first and second struts of the support structure, and wherein the leaflets (<NUM>) are attached about their distal ends to the distal section (<NUM>) and the valve structure (<NUM>) is configured to restrict fluid flow therethrough.