Patent Publication Number: US-2010131049-A1

Title: One-Way valve Prosthesis for Percutaneous Placement Within the Venous System

Description:
FIELD OF THE INVENTION 
     The invention relates to valve prostheses for percutaneous placement within a vein. 
     BACKGROUND OF THE INVENTION 
     Venous valves are found within native venous vessels and are used to assist in returning blood back to the heart in an antegrade direction from all parts of the body. The venous system of the leg for example includes the deep venous system and the superficial venous system, both of which are provided with venous valves which are intended to direct blood toward the heart and prevent backflow or retrograde flow which can lead to blood pooling or stasis in the leg. Incompetent valves can also lead to reflux of blood from the deep venous system to the superficial venous system and the formation of varicose veins. Superficial veins which include the greater and lesser saphenous veins have perforating branches in the femoral and popliteal regions of the leg that direct blood flow toward the deep venous system and generally have a venous valve located near the junction with the deep system. Deep veins of the leg include the anterior and posterior tibial veins, popliteal veins, and femoral veins. Deep veins are surrounded in part by musculature tissues that assist in generating flow due to muscle contraction during normal walking or exercising. Veins in the lower leg of a healthy person may range from 0 mm Hg to over 200 mm Hg, depending on factors such as the activity of the body (i.e., stationary or exercising), the position of the body (i.e., supine or standing), and the location of the vein (i.e., ankle or thigh). For example, venous pressure may be approximately 80-90 mm Hg while standing and may be reduced to 60-70 mm Hg during exercise. Despite exposure to such pressures, the valves of the leg are very flexible and can close with a pressure drop of less than one mm Hg. 
       FIGS. 1A-1B  are schematic representations of blood flow through a healthy native valve  104  within a vein  100 . Valves within the venous system are configured in a variety of shapes that depend on anatomical location, vessel size, and function. For example, the shape of the venous valve may include leaflets or leaflets with sinuses. The natural venous valve leaflet configuration referenced herein is for clarity of function and is not limiting in the application of the referenced embodiments. Venous valve  104  controls blood flow through lumen  102  of vein  100  via leaflets  106 ,  108 . More particularly, venous valve  104  opens to allow antegrade flow  112  through leaflets  106 ,  108  as shown in  FIG. 1A . Venous valve  104  closes to prevent backflow or retrograde flow  114  through leaflets  106 ,  108  as shown in  FIG. 1B . 
     Veins typically in the leg can become distended from prolonged exposure to excessive pressure and due to weaknesses found in the vessel wall causing the natural venous valves to become incompetent leading to retrograde blood flow in the veins. Such veins no longer function to help pump or direct the blood back to the heart during normal walking or use of the leg muscles. As a result, blood tends to pool in the lower leg and can lead to leg swelling and the formation of deep venous thrombosis and phlebitis. The formation of thrombus in the veins can further impair venous valvular function by causing valvular adherence to the venous wall with possible irreversible loss of venous function. Continued exposure of the venous system to blood pooling and swelling of the surrounding tissue can lead to post phlebitic syndrome with a propensity for open sores, infection, and may lead to limb amputation. 
     Chronic Venous Insufficiency (CVI) occurs in patients that have deep and superficial venous valves of their lower extremities (distal to their pelvis) that have failed or become incompetent due to congenital valvular abnormalities and/or pathophysiologic disease of the vasculature. As a result, such patients suffer from varicose veins, swelling and pain of the lower extremities, edema, hyper pigmentation, lipodermatosclerosis, and deep vein thrombosis (DVT). Such patients are at increased risk for development of soft tissue necrosis, ulcerations, pulmonary embolism, stroke, heart attack, and amputations. 
       FIG. 2  is a schematic representation of blood flow through an incompetent venous valve. Backflow or antegrade flow  114  leaks through venous valve  104  creating blood build-up that eventually may destroy the venous valve and cause a venous wall bulge  110 . More specifically, the vessel wall of vein  100  expands into a pouch or bulge, such that the vessel has a knotted appearance when the pouch is filled with blood. The distended vessel wall area may occur on the outflow side of the valve above leaflets  106 ,  108  as shown in  FIG. 2 , and/or on the inflow side of the valve below leaflets  106 ,  108 . After a vein segment becomes incompetent, the vessel wall dilates and fluid velocity there through decreases, which may lead to flow stasis and thrombus formation in the proximity of the venous valve. Repair and replacement of venous valves presents a formidable challenge due to the low blood flow rate found in native veins, the very thin wall structure of the venous wall and the venous valve, and the ease and frequency of which venous blood flow can be impeded or totally blocked for a period of time. Surgical reconstruction techniques used to address venous valve incompetence include venous valve bypass using a segment of vein with a competent valve, venous transposition to bypass venous blood flow through a neighboring competent valve, and valvuloplasty to repair the valve cusps. These surgical approaches may involve placement of synthetic, allograft and/or xenograft prostheses inside of or around the vein. However, such prostheses have not been devoid of problems, such as thrombus formation and valve failure due to the implanted prostheses causing non-physiologic flow conditions and/or excessive dilation of the vessels with a subsequent decrease in blood flow rates. In addition, many venous valve prostheses include leaflets and/or hinged flaps and are similar to valves placed into the heart, which are complex and designed for high blood pressures associated with the heart instead of lower venous blood pressures associated with veins in the lower extremities. 
     Percutaneous methods for treatment of venous insufficiency are being studied some of which include placement of synthetic, allograft and/or xenograft prosthesis that suffer from similar problems as the surgically implanted ones discussed above. 
     In light of these limitations, there is a need for an improved device to restore normal venous circulation to patients suffering from venous valve insufficiency. The present disclosure is directed to a simple, one-way valve prosthesis that may be percutaneously placed within a vein to replace an existing insufficient venous valve. After placement, the valve prosthesis re-establishes proper flow through the vein segment and protects any damaged area(s) of the native valve for healing. 
     BRIEF SUMMARY OF THE INVENTION 
     Embodiments hereof are directed to a one-way venous valve prosthesis for percutaneous placement within a vein, the valve including a valve body having an inlet and an outlet with a lumen that extends there between. The valve body is operable to alternate between a closed configuration wherein the valve body has a double cone shape and an open configuration wherein the valve body has a double frustoconical shape. When the valve body is in the double cone shape, conical apexes are located at a midsection of the valve body and define a valve seat within the lumen of the valve body. The valve seat is constricted to prevent flow there through when the valve body is in the double cone shape of the closed configuration and the valve seat is open to allow flow there through when the valve body assumes the double frustoconcial shape in the open configuration. The valve seat expands to the open configuration in response to an actuation pressure and returns to the closed configuration in the absence of the actuation pressure. 
    
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
       The foregoing and other features and advantages of the invention will be apparent from the following description of the invention as illustrated in the accompanying drawings. The accompanying drawings, which are incorporated herein and form a part of the specification, further serve to explain the principles of the invention and to enable a person skilled in the pertinent art to make and use the invention. The drawings are not to scale. 
         FIGS. 1A-1B  are schematic representations of blood flow through a healthy valve within a vein. 
         FIG. 2  is a schematic representation of blood flow through an incompetent valve within a vein. 
         FIG. 3  is a perspective view of a double cone valve prosthesis according to an embodiment hereof, wherein the valve prosthesis is in a closed configuration. 
         FIG. 4  is a side view of the double cone valve prosthesis shown in  FIG. 3 , wherein the valve prosthesis is in an open configuration. 
         FIG. 5  is an end view of the double cone valve prosthesis shown in  FIG. 4 . 
         FIG. 6  is a schematic sectional view of an incompetent valve within a vein. 
         FIG. 7  is a schematic view of the double cone valve prosthesis shown in  FIG. 3  placed within the incompetent valve of  FIG. 6 , wherein the double cone prosthesis is in the closed configuration to prevent blood flow there through. 
         FIG. 8  is a schematic view of the double cone valve prosthesis shown in  FIG. 3  placed within the incompetent valve of  FIG. 6 , wherein the double cone prosthesis is in the open configuration to allow blood flow there through. 
         FIG. 9  is a side view of a double cone valve prosthesis according to an embodiment hereof. 
         FIG. 10  is a side view of a double cone valve prosthesis according to another embodiment hereof. 
         FIG. 11  is a side view of a double cone valve prosthesis according to yet another embodiment hereof. 
         FIGS. 12-13  are a side view and a perspective view, respectively, of a double cone valve prosthesis according to yet another embodiment hereof. 
         FIG. 14  is a perspective view of a double cone valve prosthesis having self-expanding anchors according to yet another embodiment hereof. 
         FIG. 15  is an example of a delivery system for delivering a double cone valve prosthesis. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Specific embodiments hereof are now described with reference to the figures, wherein like reference numbers indicate identical or functionally similar elements. The terms “distal” and “proximal” are used in the following description with respect to a position or direction relative to the treating clinician. “Distal” or “distally” are a position distant from or in a direction away from the clinician. “Proximal” and “proximally” are a position near or in a direction toward the clinician. 
     The following detailed description is merely exemplary in nature and is not intended to limit the invention or the application and uses of the invention. Although the description of the invention is in the context of treatment of blood vessels such as the veins, the invention may also be used in any other body passageways where it is deemed useful. Furthermore, there is no intention to be bound by any expressed or implied theory presented in the preceding technical field, background, brief summary or the following detailed description. 
     Referring to  FIGS. 3-5 , a venous valve  116  according to an embodiment hereof is shown. Valve  116  has a continuous body portion  117  that defines a lumen  128  extending between an inlet  124  and an outlet  126 . Valve  116  is operable to alternate between a closed configuration, shown in  FIG. 3 , in which a midsection  121  of valve body  117  is constricted to prevent flow there through and an open configuration, shown in  FIG. 4 , in which midsection  121  is open or expanded enough to allow flow there through.  FIG. 3  illustrates venous valve  116  in a relaxed state, which is the valve closed configuration, and  FIGS. 4-5  illustrate venous valve  116  in a working or flow state, which is the valve open configuration. 
     More particularly, in the closed configuration illustrated in  FIG. 3 , body portion  117  of venous valve  116  has a continuous double cone shape having a first conical section  118   a  and a second conical section  118   b  that are oriented apex to apex. In an embodiment, a length of first conical section  118   a  is equal to a length of second conical section  118   b . However, conical sections  118   a ,  118   b  may be of unequal lengths. From a downstream end, first conical section  118   a  has a cone shape that extends from a first circular base  122   a , which defines inlet  124  of valve  116 , to a first apex  120   a , and second conical section  118   b  has a cone shape that extends from a second apex  120   b  to a second circular base  122   b , which defines outlet  126  of valve  116 . It should be understood that first apex  120   a  and second apex  120   b  are so defined at midsection  121  of valve body portion  117  only in the closed, relaxed configuration when venous valve  116  has the double cone shape. At a corresponding location of apexes  120   a ,  120   b  within lumen  128  of valve body portion  117 , a valve seat  129  is defined. When valve  116  is in the closed configuration, valve seat  129  is constricted or closed in such a manner as to prevent flow there through. 
     Referring now to  FIGS. 4-5 , when venous valve  116  is in the open configuration, valve body portion  117  has a continuous double frustoconical shape. From a downstream end, first conical section  118   a  assumes a frustoconical shape that extends from first circular base  122   a  to radially expanded apex  120   a , and second conical section  118   b  assumes a frustoconical shape that extends from radially expanded apex  120   b  to second circular base  122   b . As in the closed configuration, the radially expanded apexes  120   a ,  120   b  of conical sections  118   a ,  118   b  are defined/located at midsection  121  of valve body portion  117 , such that venous valve  116  has the double frustoconical shape in the open configuration. In the open configuration, valve seat  129 , which as previously described is defined within lumen  128  of valve body portion  117  at midsection  121 , is radially expanded to allow flow there through, as best shown in the end view of  FIG. 5 . 
     Referring now to  FIGS. 6-8 , the operation of valve  116  transitioning between the closed configuration and the open configuration for regulating flow there through is described.  FIG. 6  is an illustration of an incompetent valve  604  of a vein  600 . Valve  604  includes two leaflets  606 ,  608 , for controlling blood flow through lumen  602  of vein  600  in an antegrade direction indicated by directional arrow  612 . However, valve leaflets  606 ,  608  do not completely close and thus allow some venous blood to flow in a retrograde direction. The backflow causes a distended area or bulge  610 , which is a localized area of blood pooling that creates a bulging of the venous wall. As the bulging progresses, vein  600  becomes further enlarged and valve leaflets  606 ,  608  move farther apart, allowing even more blood to backflow. Thus, once valve  604  becomes incompetent, the venous insufficiency/incompetency progressively worsens. 
       FIG. 7  is a schematic view of venous valve  116  placed within incompetent valve  604  of vein  600 . Valve  116  is delivered to and deployed within vein  600  in a percutaneous manner, as will be described in more detail below, and is positioned to span across valve leaflets  606 ,  608  of incompetent valve  604 . Although not shown in  FIGS. 6-8 , valve body portion  117  may include one or more radiopaque or echogenic markers attached thereto to assist in positioning valve  116  across incompetent valve  614 . Thus, prosthetic valve  116  may be implanted without requiring removal of native valve  604  from vein  600 . In addition, since valve body  117  of venous valve  116  spans across insufficient valve  604 , valve  116  will arrest the progressive damage to vein  600  caused by the marginal function of native valve  604 . Blood flow will then be directed through lumen  128  of valve  116  and thus bypass distended or bulged area  610 . The damaged venous wall will thus be protected and allowed to scar and/or heal. 
       FIG. 7  illustrates valve  116  in the closed configuration described above with respect to  FIG. 3 , in which valve  116  has a double cone shape such that midsection  121  of valve body  117  is constricted or closed to prevent flow there through. As shown in  FIG. 7 , valve  116  is secured to the wall of vein  600  by one or more anchors  125 . In one embodiment, an anchor  125  is attached to each end of valve  116  such that inlet  124  of valve  116  is secured to the vessel wall and outlet  126  of valve  116  is secured to the vessel wall. Anchors  125  are annular, self-expanding structures that are attached to valve  116  in order to prevent migration thereof. For example, anchors  125  may be self-expanding spring members that are deployed upon release from a restraining mechanism such as a retractable sheath to bias valve  116  into conforming fixed engagement with an interior surface of vein  600 . Anchors  125  may be constructed of a superelastic material such as nickel-titanium (nitinol) and have any suitable configuration. For example, anchors  125  may be annular bands as shown in  FIGS. 7-8  biased in a radially outward direction. Alternatively, anchors  125  may be sinusoidal patterned wire rings or scaffolds  1425  biased in a radially outward direction as shown in  FIG. 14 . Examples of suitable annular support members that may be used as anchors  125  are described, for example, in U.S. Pat. No. 5,713,917 to Leonhardt et al. and U.S. Pat. No. 5,824,041 to Lenker et al., which are incorporated by reference herein in their entirety. When used with valve  116 , anchors  125  have sufficient radial spring force and flexibility to conformingly engage the prosthesis with the body lumen inner wall, to avoid excessive leakage, and prevent pressurization of the native valve, i.e., to provide a leak-resistant seal. 
     Once implanted in vein  600 , venous valve  116  operates as a one-way valve that allows fluid to flow in only an antegrade direction in order to control blood flow through lumen  602  of vein  600 . Once the pressure on the inflow area of valve  116  reaches and/or exceeds an actuation pressure PA, valve  116  expands to the open configuration. The actuation pressure PA is related to the pressure differential that occurs during normal blood circulation between the pumped blood on the valve inflow area and the gravity fed blood on the valve outflow area to allow valve  116  to operate in a manner similar to a natural venous valve. More particularly, when the pumped blood causes the inflow pressure to reach a value equal to or greater than the combination of the gravity fed blood pressure and the valve&#39;s resistance to opening, i.e., the actuation pressure PA, valve  116  opens in response thereto. The valve&#39;s resistance to opening may depend on several factors, including the stiffness of the valve material, the thickness of the valve material, and/or the geometry of the valve inflow and outflow areas. By manipulating these factors, valve  116  may be designed to open under inflow pressure conditions that depend on the particular implantation site of the prosthetic valve within the vasculature. As will be described in more detail below, valve  116  is constructed such that midsection  121  of valve body  117  expands to the open configuration in which valve seat  129  of lumen  128  is sufficiently open to accommodate flow there through in response to actuation pressure PA. In the absence of actuation pressure PA, such as during normal pauses of blood circulation through the body, valve seat  129  resumes the closed configuration. The relatively simple construction of venous valve  116  does not include leaflets or hinged flaps that may thicken, tear or fail, avoids tissue ingrowth of such leaflets, and also avoids pooling of blood within such leaflets that may result in clots. 
     More specifically, when pumped blood is advanced through vein  600  during normal circulation, blood enters valve  116  through inlet  124  and subjects the interior surface of the inflow side of valve body portion  117  to an inlet fluid pressure PI. With venous applications including valves in the lower extremities, PI ranges from 200 mm Hg to 5 mm Hg. When in the closed configuration having the constricted midsection  121 , pressure PI acts only on the inflow side of valve  116  from inlet  124  to apex  120   a . When inlet pressure PI equals or exceeds actuation pressure PA, midsection  121  of valve body  117  radially expands to at least partially open valve seat  129  and allow flow there through as shown in  FIG. 8 . Stated another way, the inlet pressure PI radially expands apexes  120   a ,  120   b  to open valve seat  129 , such that the conical portions  118   a ,  118   b  of valve body  117  assume frustoconical shapes. Under certain inlet pressures, valve  116  may approach a tubular or cylindrical shape in the open configuration. However, midsection  121  need radially expand only to a point sufficient to allow flow through valve seat  129  and thus valve  116  may have a shape resembling an hourglass in the open configuration. Generally, venous valve  116  will expand to permit the flow of blood at a rate of about 0.25 L/min to about 5 L/min when in the open configuration. 
     Accordingly, when an actuation pressure PA is reached the venous blood is pumped through the at least partially open valve seat  129  of lumen  128  and exits valve  116  through outlet  126 . During natural pauses of blood flow, inlet pressure PI ceases and thus the fluid pressure acting on the interior surface of the inflow side of the valve body decreases. When inlet pressure PI is less than actuation pressure PA, valve  116  returns to its closed configuration of  FIG. 7  in which midsection  121  is constricted and valve seat  129  closes to prevent venous blood from backflowing through valve  116 . When in the closed configuration having the constricted midsection  121 , an outlet pressure PO acts on the interior surface of the outflow side of valve  116  from second apex  120   b  to outlet  126 . The fluid outlet pressure PO generally results from gravity which causes blood to backflow into the outflow side of valve  116  through outlet  126 . With venous applications including valves in the lower extremities, PO typically ranges from 200 mm Hg to 5 mm Hg. In one embodiment, valve  116  will remain in the closed configuration when subjected to backflow pressures of less than about 10 mmHg. 
     Valve  116  is constructed from a durable biocompatible material such as silicone that is designed to provide enough resistance to remain in the closed configuration and prevent antegrade blood flow there through, yet flexible enough to allow the pumped blood to transform the valve to the open configuration and allow pumped venous blood to flow there through. Other suitable materials include polymeric materials such as polyurethanes, PEBAX, ePTFE, etc. 
     There are several ways to construct the valve prosthesis such that the midsection of the venous valve body portion expands to the open configuration in response to actuation pressure PA. For example,  FIG. 9  illustrates one embodiment hereof in which the wall thickness of valve  916  is optimally varied such that midsection  921  will expand to the open configuration in response to actuation pressure PA. First conical section  918   a  has a tapered wall thickness that continually decreases from a first wall thickness T 1  at first circular base  922   a  to a second wall thickness T 2  at apex  920   a  such that the wall thickness becomes thinner as midsection  921  approaches. Similarly, second conical section  918   b  has a tapered wall thickness that continually increases from a third wall thickness T 3  at apex  920   b  to a fourth wall thickness T 4  at second circular base  922   b  such that the wall thickness becomes thicker as outlet  926  approaches. Tapering both first conical section  918   a  and second conical section  918   b  as shown in  FIG. 9  results in the wall thickness surrounding midsection  921  being relatively thinner, and accordingly less stiff, than the remaining valve body. Stiffness refers to the resistance of an elastic body to deflection or deformation by an applied force. Due to the wall thickness variation, the ends of valve body  917  have a greater stiffness (or more resistance to bending) than relatively thinner midsection  921 . Thus, when inlet pressure PI equals or exceeds actuation pressure PA, the relatively thinner and less stiff midsection  921  of valve body  917  will radially expand to at least partially open valve seat  929  and allow flow there through. In one embodiment, wall thicknesses T 1 , T 2 , T 3 , and T 4  may each range between 0.001 inch to 0.012 inch. 
     In one embodiment, shown in  FIG. 9 , it may be desirable to form second conical section  918   b  with a more gradual taper such that the wall thickness of second conical section  918   b , when considered as a whole, is generally thinner than first conical section  918   a . Particularly, first wall thickness T 1  at first circular base  922   a  is greater than fourth wall thickness T 4  at second circular base  922   b  and second wall thickness T 2  at apex  920   a  is greater than third wall thickness T 3  at apex  920   b . Such a construction allows the wall of outlet  926  to be relatively thinner than the wall of inlet  924  to ensure than second conical section  918   b  will expand in response to the actuation pressure PA and valve seat  929  of valve  916  will be sufficiently open to allow flow there through. 
       FIG. 10  illustrates another embodiment for constructing the valve prosthesis such that the midsection assumes the open configuration in response to an actuation pressure. Valve  1016  includes an expandable annular band  1050  attached to an outside surface  1052  of valve body portion  1017 . In its relaxed or formed configuration, annular band  1050  surrounds valve  1016  to constrain or close the valve seat (not shown) at midsection  1021 . However, annular band  1050  is formed from an expandable material that will assume the open configuration in response to an actuation pressure. For example, the expandable annular band  1050  may be formed from nickel-titanium (nitinol) or another superelastic material. Annular band  1050  may have any suitable configuration such as annular bands or sinusoidal patterned wire rings. 
       FIG. 11  illustrates yet another embodiment for constructing the valve prosthesis such that the valve seat assumes or expands to the open configuration in response to an actuation pressure. Valve  1116  includes first conical section  1118   a  and second conical section  1118   b , similar to the embodiments described above. However, portions of valve  1116  may be constructed to have different stiffness values such that the midsection  1121  is relatively more flexible than the remaining valve body. As previously mentioned, stiffness refers to the resistance of an elastic body to deflection or deformation by an applied force. More particularly, a first end portion  1160  of valve  1116  and a second end portion  1164  of valve  116  are formed with a first stiffness. An intermediate portion  1162  of valve  1116  extends between first end portion  1160  and second end portion  1164 , and includes midsection  1121  of valve body portion  1117 . Intermediate portion  1162  is formed with a second stiffness that is different than the first stiffness. The first stiffness is greater than the second stiffness to result in a more flexible area surrounding midsection  1121  than the remaining valve body such that the midsection  1121  opens to the open configuration in response to an actuation pressure, such as described above with respect to the embodiment of  FIG. 9 . 
     In one embodiment, a first end portion  1160  and a second end portion  1164  are formed with a first material having the first stiffness while intermediate portion  1162  is formed with a second, different material having the second stiffness. End portions  1160 ,  1164  and intermediate portion  1162  are sealingly coupled and/or joined in order to form the continuous valve body of valve  1116 . Any suitable coupling mechanisms or methods may be employed for connecting end portions  1160 ,  1664  to intermediate portion  1162 . For example, the ends of intermediate section  1162  may be bonded to first and second end portions  1160 ,  1162 . Any one of numerous types of bonding may be employed, such as, for example, ultra-violet cure, instant cure, epoxy type, or cyanoacrylate type. Suitable materials for the first, stiffer material include PEBAX or Polyurethane, and suitable materials for the second, more flexible material include silicone or ePTFE. 
     In another embodiment, cross-linking of the material may be employed in order to alter the modulus of elasticity at end portions  1160 ,  1164 . More particularly, intermediate portion  1162  and end portions  1160 ,  1164  are integrally formed and/or machined from the same material having the first stiffness. End portions  1160 ,  1164  are heat treated or irradiated in order to change the modulus thereof and obtain the second stiffness. Suitable materials for this integral, seamless embodiment include, but are not limited to, thermoplastics such as polyethylene or PEBAX. 
       FIGS. 12 and 13  illustrate yet another embodiment for constructing the valve prosthesis such that the midsection assumes the open configuration in response to an actuation pressure.  FIG. 12  is a side view of valve  1216  in a closed valve configuration, and  FIG. 13  is a perspective view of valve  1216  is a closed valve configuration. Valve  1216  has a valve body  1217  including first conical section  1218   a  and second conical section  1218   b , similar to the embodiments described above. However, valve  1216  includes folds  1266  of the valve body material that open or unfold in response to an actuation pressure. When valve  1216  is expanded, folds  1266  allow valve body  1217  to approach a generally tubular or cylindrical shape to accommodate a large volume of flow through valve seat  1229 . 
     In this embodiment, valve  1216  is integrally formed and/or machined from the same material and folds  1266  are formed within the material at an intermediate portion  1262  positioned between inlet  1224  and outlet  1226  of the valve. In a closed configuration (shown), folds  1266  form a constricted midsection  1221  that prevents flow there through. The intermediate portion  1262  of valve  1216  having folds  1266  has a wall thickness less than the wall thickness of the remainder of the valve body, as may be achieved e.g., by making two different extrusions of the same material or by necking/thinning the valve body at intermediate portion  1262 . As such, similar to above embodiments, intermediate portion  1262  is relatively more flexible and less stiff than the remainder of the valve body such that valve seat  1229  may assume or expand to the open configuration in response to an actuation pressure. When pumped blood is advanced during normal circulation, blood enters valve  1216  through inlet  1224  and subjects the interior surface of the inflow side of valve  1216  to inlet fluid pressure PI. When inlet pressure PI equals or exceeds actuation pressure PA, folds  1266  open such that midsection  1221  radially expands to allow flow there through. 
     The valve prostheses described herein are preferably delivered in a percutaneous, minimally invasive manner and may be delivered by any suitable delivery system. In general, a venous valve prosthesis having one or more self-expanding anchors is loaded into a sheathed delivery system, compressing the self-expanding anchors. As previously described, the self-expanding anchors may have an annular bands configuration as shown in  FIGS. 7-8  or may have a sinusoidal patterned configuration as shown in  FIG. 14 . Optionally, the valve prosthesis may include one or more radiopaque or echogenic markers thereon in order to aid in positioning the valve prosthesis to span across the incompetent native valve. The delivery system is percutaneously introduced into the patient&#39;s vasculature. Access to the vasculature may be achieved through a branch of the femoral vein, or alternatively, may be achieved through a branch of the subclavian vein. The delivery system is then threaded or tracked through the vascular system of the patient until venous valve  116  is located within a predetermined target site, an incompetent native valve within a vein. Once properly positioned, the sheath of the delivery system is removed to allow the anchors to self-expand, appose the venous wall, and secure the valve prosthesis inside of the native valve within the vein, thus deactivating the incompetent native valve and surrounding area. Once the venous valve prosthesis is properly positioned at the target site, the delivery system may be retracted and removed from the patient. 
     For example,  FIG. 15  illustrates a schematic side view of an exemplary delivery system for delivering and deploying a valve prosthesis having one or more self-expanding anchors attached thereto as described above. Self-expanding anchors  125 ,  1425  effectively make the valve prosthesis a self-expanding conduit. The delivery system includes a retractable outer shaft  1530  having a proximal end  1532  and a distal end  1536 , and an inner shaft  1538  having a proximal end  1540  and a distal end  1542 . Outer shaft  1530  defines a lumen extending there through (not shown), and inner shaft  1538  slidably extends through the lumen of outer shaft  1530  to a distal tip  1544  of the delivery system. Distal tip  1544  is coupled to distal end  1542  of inner shaft  1538 , and may be tapered and flexible to provide trackability in tight and tortuous vessels. In an embodiment, inner shaft  1538  may define a guidewire lumen (not shown) for receiving a guidewire there through or may instead be a solid rod without a lumen extending there through. 
     The valve prosthesis (not shown in  FIG. 15 ) is mounted on distal end  1542  of inner shaft  1538 . The valve prosthesis may be mounted on distal end  1542  of inner shaft  1538  by any suitable manner known in the art, such as self-expanding attachment bands, a cap coupled to the distal end of the inner shaft to retain the valve prosthesis in a radially compressed configuration, and/or the inclusion of slots, ridges, pockets, or other prosthesis retaining features (not shown) formed into the exterior surface of the inner shaft to secure the valve prosthesis in frictional engagement with the delivery system. Outer shaft  1530  covers and constrains the valve prosthesis while the delivery system is tracked through a body lumen to the deployment site. Outer shaft  1530  is movable in an axial direction along and relative to inner shaft  1538  and extends to a proximal portion of the delivery system where it may be controlled via an actuator, such as a handle  1534 , to selectively expand the valve prosthesis. When the actuator is operated, outer shaft  1530  is retracted over inner shaft  1538  in a proximal direction as indicated by directional arrow  1546 . When outer shaft  1530  is proximally retracted with respect to the hub of the delivery system, the self-expanding valve prosthesis is released and allowed to assume its expanded configuration. An exemplary suitable delivery system is described in U.S. Pat. No. 7,264,632 to Wright et al., which is hereby incorporated by reference in its entirety. 
     Although the valve prosthesis is described herein as self-expanding for percutaneous placement, it should be understood that the valve prosthesis may alternatively be surgically implanted within a vein in a non-percutaneous manner and may be anchored to the vein in any suitable manner, such as via sutures, clips, or other attachment mechanisms. 
     While various embodiments hereof have been described above, it should be understood that they have been presented by way of illustration and example only, and not limitation. It will be apparent to persons skilled in the relevant art that various changes in form and detail can be made therein without departing from the spirit and scope of the invention. Thus, the breadth and scope of the present invention should not be limited by any of the above-described exemplary embodiments, but should be defined only in accordance with the appended claims and their equivalents. It will also be understood that each feature of each embodiment discussed herein, and of each reference cited herein, can be used in combination with the features of any other embodiment. All patents and publications discussed herein are incorporated by reference herein in their entirety.