# Patent

## Title
Percutaneous methods for creating native tissue venous valves

## Abstract

Percutaneous methods of forming a venous valve from autologous tissue are disclosed. The methods include percutaneously creating one or two subintimal dissections for forming one or two flaps of intimal tissue. In one method, a puncture element is delivered by a catheter based delivery system to a treatment site where a new venous valve is to be created. The puncture element is deployed to gain access to a subintimal layer of the vein wall. A dilation balloon is than positioned and inflated within the subintimal layer to create a flap and corresponding pocket/sinus in the vein, which than acts as a one-way monocuspid valve in the manner of a native venous valve. In a similar manner, methods of forming new bicuspid venous valves by subintimal dissections are also disclosed.

## Background
FIELD OF THE INVENTION
The invention relates to apparatus and methods for percutaneously creating a one-way venous valve in vivo from autologous tissue.
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 that 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 tissue that assists in generating flow due to muscle contraction during normal walking or exercising. Veins in the lower leg have a static pressure while standing of approximately 80-90 mm Hg that may reduce during exercise to 60-70 mm Hg. 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. 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 possible limb amputation.
Chronic Venous Insufficiency (CVI) occurs in patients that have deep and superficial venous valves of their lower extremities (below their pelvis) that have failed or become incompetent due to congenital valvular abnormalities and/or pathophysiologic disease of their vasculature. As a result, these 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 such that the fluid velocity decreases within the incompetent vein segment, 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 problem 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 leading to thrombus and/or valve failure due to leaflet thickening/stiffening, non-physiologic flow conditions, non-biocompatible materials and/or excessive dilation of the vessels with a subsequent decrease in blood flow rates.
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 addition, venous valve formation from autologous tissue has been disclosed in U.S. Pat. No. 6,902,576 to Drasler et al. Drasler et al. suggests use of autologous tissue with blood contact of an endothelial layer to eliminate biocompatibility issues and also alleviate thrombus formation due to low flow. However, methods of in situ venous valve formation according to Drasler et al. are surgical in nature and involve re-shaping a distended, diseased vein, which carries with it the risk of rupture or tearing of the thin-walled structure.
In view of the foregoing, there is still a need for methods and apparatus to restore normal venous circulation to patients suffering from venous valve insufficiency, wherein the methods and apparatus may be used in percutaneous, minimally invasive procedures. Further, such percutaneous methods and apparatus should attend to biocompatibility and thrombosis issues that current approaches do not adequately address.
BRIEF SUMMARY OF THE INVENTION
Embodiments hereof are directed to percutaneous methods for creating monocuspid, bicuspid, and tricuspid venous valves from autologous tissue. One method disclosed herein includes obtaining percutaneous access to a lumen of a vein and tracking a guidewire to a target location within the vein lumen where a venous valve is to be created. A catheter having a deployable puncture element is advanced over the guidewire to the target location. The puncture element is deployed to penetrate into a wall of the vein without passing therethrough to create a subintimal pathway in the vein wall. A subsequent guidewire is advanced into the subintimal pathway so that intimal and/or medial tissue of the vein wall is separated or dissected from the remaining tissue of the vein wall to create a dissection plane. A balloon catheter is then advanced over the in-dwelling guidewire and into the dissection plane, wherein inflation of the balloon within the dissection plane further dissects the intimal and/or medial tissue from the remaining tissue to thereby simultaneously form a flap of intimal and/or medial tissue and a pocket between the flap and the remaining tissue layer of the vein wall. The flap of intimal and/or medial tissue and the pocket constitute a new monocuspid venous valve of autologous tissue according to an embodiment hereof. The aforementioned dissection steps may be repeated to form a second flap and second pocket at a position in the vein opposed to the original flap and pocket in order to create a new bicuspid venous valve of autologous tissue.
Other embodiments hereof include methods of intimal dissection wherein first and second flaps or leaflets and their corresponding pockets or sinuses are formed simultaneously in order to more efficiently create a new bicuspid venous valve.



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 sectional view of the anatomy of a healthy vein and valve thereof.
FIGS. 4-6 are schematic representations of a method of forming a venous valve from autologous tissue.
FIG. 7A is a schematic representation of a monocuspid venous valve formed in accordance with embodiments hereof.
FIG. 7B is a cross-sectional view of FIG. 7A taken along line B-B.
FIG. 7C is a schematic representation of a bicuspid venous valve formed in accordance with embodiments hereof.
FIG. 7D is a cross-sectional view of FIG. 7C taken along line D-D.
FIG. 8 is a side view of a catheter in accordance with an embodiment hereof.
FIG. 8A is a cross-sectional view of the catheter of FIG. 8 taken along line A-A.
FIG. 8B is a cross-sectional view of the catheter of FIG. 8 taken along line B-B.
FIG. 8C depicts sectional views of alternate embodiments of the catheter of FIG. 8 within area C.
FIG. 9 is a side view of a catheter in accordance with another embodiment hereof.
FIGS. 10-13 are schematic representations of a method of forming a venous valve from autologous tissue in accordance with another embodiment hereof.
FIG. 14 is a schematic representation of a bicuspid venous valve formed in accordance with embodiments hereof.
FIG. 14A is a schematic representation of a tapered stent for use in venous valves formed in accordance with embodiments hereof.
FIG. 14B is a schematic representation of a biasing element for use in venous valves formed in accordance with embodiments hereof.
FIG. 15 is a sectional view of a tri-lumen catheter in accordance with another embodiment hereof.
FIGS. 16-21 are schematic representations of a method of forming a venous valve from autologous tissue in accordance with another embodiment hereof.



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 deep and superficial veins of the leg, 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.
FIG. 3 depicts a sectional view of the anatomy of a vein wall, which for purposes of this description is shown to consist essentially of an outside layer 301, a middle layer 303 and an inside layer 305. Outside layer 301, called the adventitia, is made of collagen, vasa vasorum and nerve cells. Middle layer 303, or media, is made of smooth muscle cells, where as inside layer 305, or intima, is made up of endothelial cells. The endothelium provide a nonthrombogenic surface for flowing blood. Venous valve 304 having two leaflets is formed from folds of the inner or intimal layer such that both upstream and downstream blood contacting surfaces of valve 304 are covered with endothelium.
FIGS. 4-6 are schematic representations of a method of forming a venous valve from autologous tissue in accordance with an embodiment hereof, wherein the method includes creating at least one flap in a vein which than acts as a one-way valve in the manner of a native venous valve. Initially luminal access to a desired peripheral vein 400, such as the greater or lesser saphenous, femoral, or popliteal veins, is obtained using standard percutaneous techniques. It should be understood by one of skill in the art that methods as described herein may be used to form an autologous valve in any vein of sufficient thickness to enable a dissection to occur as described in greater detail below. A guidewire 416 is then maneuvered through the vasculature to rest across a target location within lumen 415 of vein 400 where a new vein valve is to be created. A catheter 418 having a deployable puncture element 420 is than advanced over guidewire 416 to the target location. As shown in FIGS. 4 and 5, catheter 418 includes a side exit port 422 for directing puncture element 420 toward a wall of vein 400. Catheters having side exit ports for accommodating a deployable puncture element as well as other catheter designs suitable for use in embodiments hereof, such as passageway-forming catheter device (100) with tissue penetrating element (102) and variations thereof, are shown and described in U.S. Pat. No. 6,190,353 to Makower et al., which is hereby incorporated by reference in its entirety. Additionally, a catheter manufactured by Medtronic, Inc. of Minneapolis, Minn. and sold as a product called the PIONEER Catheter may also be used in performing methods hereof.
Puncture element 420 is distally advanced out of side exit port 422 to puncture or pierce an intimal layer 405 of the wall of vein 400. As shown in FIG. 5, once puncture element 420 is distally advanced, a distal tip 424 thereof is pushed into and through the intimal layer 405 to create a subintimal pathway into the vein wall that substantially parallels a longitudinal axis of vein 400. The subintimal pathway may longitudinally extend between intimal layer 405 and medial layer 403, between medial layer 403 and adventitial layer 401, or within medial layer 403; with care being taken that puncture element 420 does not pass entirely through the wall of vein 400. (Each of layers 401, 403, and 405 of the wall of vein 400 are shown in FIG. 4, but it should be noted that this detail has been removed in subsequent figures for clarity.)
Puncture element 420 may be a hollow needle-like instrument, as shown in FIGS. 4 and 5, having a lumen that permits a second guidewire 526 to be distally advanced into the subintimal pathway. Second guidewire 526 is then distally advanced further within the wall of vein 400 so that tissue of the vein wall is separated to thereby create a dissection plane. In order for guidewire 526 to perform the dissection, a distal end thereof may be sharpened to have a pencil-like point that will more readily slice through the tissue. In an alternate embodiment, puncture element 420 may be a solid puncture wire, such as a sharpened mandrel or small, solid mini Trocar, that not only makes the initial subintimal pathway into the vein wall but also may be distally advanced to create a dissection plane within the vein wall eliminating the need for a second guidewire.
Fluoroscopic guidance of the advancing second guidewire 526 may be utilized to assure a length of the dissection plane created within the vein wall, as a length of the dissection plane will determine a length of the resulting flap. In order to make a monocuspid flap, the flap must have a free edge length of greater than half of the circumference of the vessel lumen with the depth of the dissection plane being sufficient to allow the resulting flap to touch the opposite side of the vessel wall. In order to make a bicuspid flap, each flap must have a free edge length of roughly half of the circumference of the vessel lumen with the depth of each dissection plane being sufficient enough to allow the resulting flaps to touch one another in the centerline of the vessel lumen. In order to determine an accurate depth/length of the dissection plane, an accurate measurement of the diameter of the vessel may be obtained by using fluoroscopy and quantitative coronary angiography (QCA). In such a procedure, the clinician uses a tool to “mark” the monitor with the fluoroscopic image. It has a calibrated measurement system so the clinician can accurately measure the diameter of the vein.
After the dissection plane is created, catheter 418 and puncture element 420 are proximally retracted and removed while a position of a distal end of second guidewire 526 is maintained within the dissection plane. It should be understood that a remainder of second guidewire 526 proximally extends within the vasculature such that a proximal end thereof (not shown) is available to a clinician outside the patient.
To complete the formation of the new venous valve, a balloon catheter 628 is backloaded onto the proximal end of second guidewire 526 to be tracked thereover until a balloon 630 is positioned within the dissection plane, as shown in FIG. 6. Balloon 630 of balloon catheter 628 is subsequently inflated within the dissection plane to further dissect the intimal and/or medial tissue from the remaining wall tissue and thereby simultaneously form a flap 732 of tissue and a pocket or sinus 734 between flap 732 and the remaining tissue of the vein wall, which are best shown in FIGS. 7A and 7B where balloon catheter 628 is removed. A flap by definition is a moveable piece of tissue partly connected to the body, and accordingly, it should be understood by the preceding description that a distal end of flap 732 remains connected to the remaining tissue of vein 400 while a proximal end or edge of the flap 732 is dissected away from the remaining tissue of the vein wall. Balloon 630 has a tapered shape with a distal inflated diameter that is smaller than a proximal inflated diameter in order to create a conically shaped recess between the dissected flap 732 and the remaining tissue of the vein wall. The conically shaped recess or space defines pocket or sinus 734 and the shape, which mimics a native valve sinus, aids in permitting blood to fill pocket 734 and close flap 732.
In the embodiment of FIGS. 7A and 7B, flap 732 includes a free edge 736 of a sufficient length to make contact with an opposing wall 738 of lumen 415, such that in the absence of antegrade blood flow, represented by arrow AF, free edge 736 seals against opposing wall 738 while retrograde or gravitational blood flow, represented by arrow RF, fills pocket 734. When antegrade blood flow AF is once again present in vein 400, flap 732 is pushed away from opposing wall 738, as shown in FIG. 7B, to allow blood flow through venous valve 714 on its way back to the heart. In such an embodiment, flap 732 and pocket 734 constitute a one-way monocuspid or one-leaflet venous valve 714 of autologous tissue.
In another embodiment hereof, the method of creating a flap and pocket as described above may be repeated at an opposed location within the vein, or approximately 180 degrees away from where first flap 732 and pocket 734 have been made, in order to form a second flap 732′ and a second pocket 734′ as shown in FIGS. 7C and 7D. Such an embodiment forms a bicuspid or two-leaflet venous valve 714′ where free edges 736, 736′ meet to close lumen 415 in the absence of antegrade blood flow AF when retrograde blood flow RF fills pockets 734, 734′. In another embodiment (not shown), the method of creating a flap and pocket may be performed three times to form a tricuspid or three-leaflet valve.
In each of the aforementioned embodiment, the dissected flaps 732, 732′ provide the same internal, i.e., facing the blood flow, tissue structure as a native valve thus providing a distinct advantage over prosthetic valve approaches. If the newly created flaps or leaflets 732, 732′ do not exhibit enough structural integrity to take the shape of a cusp or leaflet or if the flaps remain adhered to the remaining tissue of the vein wall the performance of those structures may be supplemented via biasing elements placed into pockets 734, 734′. The biasing elements are designed to hold a shape of the pockets and do not offer much resistance to antegrade blood flow but instead collapse and allow the valve to open in the presences of antegrade flow as will be discussed in more detail below with reference to FIGS. 14, 14A and 14B.
Other embodiments hereof include multilumen catheter systems for simultaneously creating directly opposing flaps and corresponding pockets/sinuses in the venous wall by utilizing subintimal dissection techniques. Since many venous valves have two cusps, flaps or leaflets that come together to prevent the back flow of blood through the vein, multilumen catheters allowing both flaps to be created at the same time are an improvement over the previously described methods that require making the flaps one at a time.
FIG. 8 depicts a multilumen catheter 840 according to an embodiment hereof, with FIGS. 8A, 8B, and 8C showing various sectional views thereof. Multilumen catheter 840 includes an elongate catheter shaft 842 with a proximal end 841 and a distal end 843. Catheter shaft 842 defines an inflation lumen 845 and proximal portions of first and second delivery lumens 847, 849. A balloon 844, shown inflated in FIG. 8, distally extends from and is fluidly coupled to distal end 843 of catheter shaft 842, such that an interior of balloon 844 is in fluid communication with inflation lumen 845. Similarly, first and second delivery shafts 846, 848, which respectively define distal portions of first and second delivery lumens 847, 849, extend from and are attached to distal end 843 of catheter shaft 842, such that the proximal and distal portions of first and second delivery lumens 847, 849 form continuous lumens. Catheters according to embodiments hereof may be made from any suitable material known to one of skill in the art of catheter construction, including by example, polyethylene, Polyimide, PEBAX, nylon, co-polyester elastomer, and PEEK.
As shown in FIGS. 8 and 8A, first delivery shaft 846 has a first distal port 852 that is positioned on one side of balloon 844 and second delivery shaft 848 has a second distal port 854 that is positioned on the other side of balloon 844 approximately 180° from first distal port 852. First and second delivery shafts 846, 848 are detached from balloon 844 except at bonds 851, 853, which are made proximate first and second distal ports 852, 854. In such a configuration, semi-detached first and second delivery shafts 846, 848 do not interfere with the inflation of balloon 844. In an alternate embodiment, first and second delivery shafts 846, 848 may be attached along their length to the balloon working length.
FIG. 8C depicts alternate sectional views of area C in FIG. 8, wherein each sectional view represents an embodiment of multilumen catheter 840. Each of the sectional views shows the distal end of first delivery shaft 846 being attached by bond 851 to balloon 844. However, in one sectional view first distal port 852 opens in an end surface of first delivery shaft 846, whereas in the other sectional view first distal port 852′ opens in a side surface of first delivery shaft 846 and includes a ramp 855 for directing instruments delivered through first delivery lumen 847 toward a vein wall in vivo.
In the embodiment of FIG. 8B, catheter shaft 842 is a polymeric extrusion with inflation lumen 845 and first and second delivery lumens 847, 849 formed therein during the extrusion process. A guidewire shaft 850 defining a guidewire lumen extends within inflation lumen 845 of catheter shaft 842 through an interior of balloon 844 to a distal tip 856. It would be understood by one skilled in the art of catheter design that there are numerous ways to produce catheter shaft 842 having an inflation lumen, two delivery lumens and a guidewire lumen without departing from the scope of the present invention.
FIG. 9 depicts a multilumen catheter 940 according to another embodiment hereof. Multilumen catheter 940 is of similar construction to multilumen catheter 840 and for convenience where the structure is the same as that previously described with reference to multilumen catheter 840 in FIG. 8 it bears the same reference numbers in FIG. 9 and will not be further described here. Similar to the embodiment of FIG. 8, first and second delivery shafts 946, 948, which respectively define distal portions of first and second delivery lumens 847, 849, extend from and are attached to distal end 843 of catheter shaft 842, such that the proximal and distal portions of first and second delivery lumens 847, 849 form continuous lumens. However, in the embodiment of FIG. 9, first and second delivery shafts 946, 948 extend from a proximal end 960 of balloon 844 to a distal end 962 of balloon 844. A first distal port 952 is disposed in a sidewall of first delivery shaft 946 and is radially positioned on one side of balloon 844 and a second distal port 954 is disposed in a sidewall of second delivery shaft 948 and is radially positioned on the other side of balloon 844 approximately 180° from first distal port 952. In an embodiment, first and second distal ports 952, 954 are longitudinally positioned at approximately the midpoint of the working length of balloon 844. Each of first and second distal ports 952, 954 open so that when multilumen catheter 940 is placed within a vessel lumen each port faces an opposed surface of the vessel wall. In another embodiment, a ramp, such as ramp 855 of FIG. 8C, may be made within first and second delivery lumens 847, 849 proximate first and second distal ports 952, 954 for directing instruments delivered through first and second delivery lumens 847, 849 toward the vein wall in vivo.
First and second delivery shafts 946, 948 are detached from balloon 844 except at first bonds 951, 953 at the balloon proximal end 960 and second bonds 961, 963 at the balloon distal end 962. In various embodiments, the first and second bonds may be made by an adhesive or by creating a thermal bond between the materials of the components with, by e.g., heat shrink tubing. In such a configuration, semi-detached first and second delivery shafts 946, 948 do not interfere with the inflation of balloon 844. Shown in outline in FIG. 9 is an optional stretchable sheath 966 that holds the detached portions of first and second delivery shafts 946, 948 in apposition with balloon 844 during tracking of multilumen catheter 940 through the vasculature but that also allows for inflation of balloon 844 at the treatment site without being removed. Sheath 966 has first and second side openings 952′, 954′ that correspond with first and second distal ports 952, 954 to allow egress of medical instruments from first and second delivery lumens 847, 849 via the ports. In an embodiment, sheath 966 may be polyurethane or another elastomeric material and may be attached to the balloon by either a friction fit, with an adhesive, or thermal bonding the ends. Multilumen catheter 940 is used to create a new bicuspid venous valve of autologous tissue in a vein in a manner to be described below with reference to FIGS. 10-14 and the multilumen catheter of FIG. 8.
With reference to FIGS. 10-14, a method of creating a bicuspid venous valve of autologous tissue utilizing multilumen catheter 840 will now be described. Lumenal access to the venous vasculature is obtained using standard percutaneous techniques. A guidewire 1016 is maneuvered to a treatment site within vein 1000 where a new bicuspid valve is to be created. Multilumen catheter 840 with balloon 844 in a deflated, low-profile configuration (not shown) is tracked over guidewire 1016 through the vasculature to the treatment site.
Next, first and second puncture wires 1120, 1120′ are simultaneously or contemporaneously backloaded into respective proximal ends (not shown) of first and second delivery lumens 847, 849. In various embodiments, puncture wires 1120, 1120′ may be formed from needles or guidewire proximal portions of approximately 0.014′′ in diameter that have sharpened distal ends. Puncture wires 1120, 1120′ are advanced through first and second delivery lumens 847, 849 until distal ends thereof are positioned within the lumens just proximate of first and second distal ports 852, 854, respectively. In another embodiment, puncture wires 1120, 1120′ may be preloaded within first and second delivery lumens 847, 849 prior to tracking catheter 840 to the treatment site. Balloon 844 is than inflated via inflation fluid supplied through the inflation lumen of multilumen catheter 840. It would be understood by one skilled in the art of making catheters that a hub or other adapter would be attached to proximal end 841 of multilumen catheter 840 to connect a supply of inflation fluid for use in expanding balloon 844. The inflation of balloon 844 presses first and second delivery shafts 846, 848 into apposition with the interior surface of the vein wall.
Puncture wires 1120, 1120′ are than pushed further distally to exit first and second distal ports 852, 854, respectively, to penetrate into the vein wall and thereby creating opposing subintimal pathways. Puncture wires 1120, 1120′ are subsequently distally advanced further into the subintimal space an appropriate length to create opposing dissection planes in the vein wall, as shown in FIG. 11. The distance puncture wires 1120, 1120′ extend within the dissection plane may be observed fluoroscopically and should be at least as long as half the vessel diameter to achieve a mid-line meeting or coaptation of the created valves. With puncture wires 1120, 1120′ maintained in place within the subintimal space, balloon 844 may be deflated and multilumen catheter 840 removed from the patient's body, as shown in FIG. 12.
Next, a dual balloon catheter 1328 having a first balloon 1330 and a second balloon 1330′ is advanced over puncture wires 1120, 1120′ until the respective balloons 1330, 1330′ are properly positioned within the respective dissection planes made in the wall of vein 1000. Balloons 1330, 1330′ are simultaneously inflated within their respective dissection planes to create first and second flaps 1332, 1332′ and first and second pockets/sinuses 1434, 1434′, as shown in FIGS. 13-14. Balloons 1330, 1330′ are than deflated and dual balloon catheter 1328 is removed from the vessel. In another embodiment hereof, first and second balloon catheters may be used in performing this step of the intimal dissection instead of dual balloon catheter 1320.
In an embodiment, first and second balloons 1330, 1330′ have tapered shapes with a distal inflated diameter that is smaller than a proximal inflated diameter. The tapered shape of balloons 1330, 1330′ create conically shaped recesses between the dissected first and second flaps 1332, 1332′ and the respective remaining medial tissue. The conically shaped recesses or spaces define first and second pockets or sinuses 1434, 1434′ and their shape, which mimics native valve sinuses, aids in permitting blood to fill first and second pockets 1434, 1434′ and close first and second flaps 1332, 1332′. An expanded proximal diameter of balloons 1330, 1330′ may be selected such that the resulting flaps 1332, 1332′, and particularly a length of free edges 1436, 1436′, are able to contact each other within the lumen in the absence of antegrade blood flow AF thus forming a new one-way valve 1414 in the vessel.
Accordingly, new venous valve 1414 formed in accordance with this embodiment operates as a bicuspid or two-leaflet venous valve where first and second free edges 1436, 1436′ meet to close lumen 1015 in the absence of antegrade blood flow AF when retrograde blood flow RF fills first and second pockets 1434, 1434′. The dissected first and second flaps 1432, 1432′ provide the same internal, i.e., facing the blood flow, tissue structure as a native valve thus providing a distinct advantage over prosthetic valve approaches.
In order to increase the structural integrity of first and second flaps 1332, 1332′, optional biasing elements, such as spring clip devices 1458, 1458′ shown in FIG. 14, may be placed into first and second pockets 1434, 1434′ to aid in completely closing lumen 1015 in the absence of antegrade blood flow AF by biasing first and second flaps 1332, 1332′ against one and other. In this manner, retrograde blood flow RF is impeded from seeping through free edges 1436, 1436′ and causing reflux to instead fill first and second pockets 1434, 1434′. When antegrade blood flow AF once again pushes upon first and second flaps 1332, 1332′, spring clip devices 1458, 1458′ are compliant enough to compress to allow first and second flaps 1332, 1332′ to part such that antegrade blood flows through bicuspid valve 1414. Spring clip devices 1458, 1458′ would be percutaneously delivered. In an embodiment the spring clips may be manufactured from a superelastic material such as nitinol. The clips may be shaped into a FIG. 8, as shown in FIG. 14B, and then folded at the mid-point to an appropriate angle, as shown in FIG. 14. In an embodiment, a suitable range for this angle is between 20 to 60 degrees. The spring-clip may be shape-set into this configuration using an oven set to an appropriate temperature for the material, by e.g., 525° C. for nitinol. The spring clip would then be loaded into a catheter assembly at the distal tip and advanced to the tissue pockets (sinus). A pusher rod may or other delivery mechanism may then be used to push the spring-clip out of the distal tip of the catheter and into the tissue pocket. Because of the materials superelasticity, the spring clip will self-expand to its original folded FIG. 8 configuration. Thus the material would contact the inner edge of the vessel wall and the inner edge of the created tissue pocket. In another embodiment, a tapered compliant stent 1458A as shown in FIG. 14A may be placed in each of first and second pockets 1434, 1434′ to function in the same manner as previously described for spring clip devices 1458, 1458′. Compliant stent 1458A may be made of nitinol with a very thin wall, such as having a wall thickness of between 0.001 to 0.005 inches.
FIG. 15 depicts a multilumen delivery catheter 1540 according to another embodiment hereof for use in a method of simultaneously creating directly opposing flaps and corresponding pockets/sinuses in the venous wall by utilizing subintimal dissection techniques as described in previous embodiments. Delivery catheter 1540 includes an elongate catheter shaft 1542 with a proximal end 1541 and a distal end 1543. Catheter shaft 1542 defines a central delivery lumen 1564 and first and second outer delivery lumens 1563, 1565. In an embodiment, central delivery lumen 1564 may have a greater inner diameter than each of first and second outer delivery lumens 1563, 1565 in order to accommodate delivery of medical devices having larger profiles. In various embodiments, catheter shaft 1542 may be an extruded shaft having an oval, circular or asymmetrically shaped cross-sectional profile. Catheters according to embodiments hereof may be made from any suitable material known to one of skill in the art of catheter construction, including by example, polyethylene, PEBAX, nylon, Polyimide, and PEEK.
With reference to FIGS. 16-21, a method of creating a bicuspid venous valve of autologous tissue utilizing delivery catheter 1540 will now be described. FIG. 16 depicts delivery catheter 1540 preloaded in a delivery configuration with a balloon catheter 1670 loaded within central delivery lumen 1564, first tapered balloon catheter 1672 loaded within first outer delivery lumen 1563 and second tapered balloon catheter 1674 loaded within second outer delivery lumen 1565. Centering balloon 1671 of balloon catheter 1670 distally extends from distal end 1543 of delivery catheter shaft 1542, whereas first and second tapered balloons 1673, 1675 of first and second tapered balloon catheters 1672, 1674 extend for the full-lengths of first and second outer delivery lumens 1563, 1565, respectively, such that distal ends 1677, 1679 of each is positioned proximal of and within the distal end 1543 of catheter shaft 1542. Guidewire 1616 is than preloaded within balloon catheter 1670 such that a distal end of guidewire 1616 extends beyond a distal tip 1656 of balloon catheter 1670. In a similar manner, first and second puncture wires 1820, 1820′ are preloaded within first and second tapered balloon catheters 1672, 1674, respectively, such that a distal end of each puncture wire does not extend beyond a respective distal end 1677, 1679 of first and second tapered balloons 1673, 1675.
As in the methods described above, lumenal access to the venous vasculature is obtained using standard percutaneous techniques. Guidewire 1616 is distally advanced from balloon catheter 1670 to be maneuvered to a treatment site within vein 1700 where a new bicuspid valve is to be created. Delivery catheter 1540 with centering balloon 1671 in a deflated, low-profile configuration is tracked over guidewire 1616 through the vasculature to the treatment site. At the treatment site, first and second tapered balloons 1673, 1675 are distally advanced out of first and second outer delivery lumens 1563, 1565 until each is positioned on an opposite side of centering balloon 1671 along a working length thereof, as best shown in FIG. 17.
Centering balloon 1671 is than inflated via inflation fluid supplied through an inflation lumen of balloon catheter 1670. The inflation of centering balloon 1671 presses first and second tapered balloons 1673, 1675 into apposition with the interior surface of the vein wall and provides a proper angle of approach for directing puncture wires 1820, 1820′ into the vessel wall. In another embodiment centering balloon 1671 may be tapered proximally along its working length such that a distal diameter is bigger than a proximal diameter to provide an appropriate angle of approach for the tapered balloons.
As shown in FIG. 18, first puncture wire 1820 is distally advanced from distal end 1677 of first tapered balloon 1673 to penetrate into the vein wall and thereby creating a first subintimal pathway and second puncture wire 1820′ is distally advanced from distal end 1679 of second tapered balloon 1675 to penetrate into the vein wall and thereby creating a second subintimal pathway. Puncture wires 1820, 1820′ are subsequently distally advanced further into the subintimal space an appropriate length to create first and second dissection planes in the vein wall, as shown in FIG. 19. In an embodiment, puncture wires 1820, 1820′ are distally pushed or advanced simultaneously in order to concurrently form the subintimal pathways and/or the dissection planes. With first and second puncture wires 1820, 1820′ maintained in place within the subintimal space, centering balloon 1671 may be slightly deflated to allow first and second tapered balloons 1673, 1675 to be advanced within the first and second dissection planes, respectively, as shown in FIG. 20. Centering balloon 1671 may be slightly deflated again to allow first and second tapered balloons 1673, 1675 to be fully inflated within the first and second dissection planes, respectively, as shown in FIG. 21, to create first and second flaps 2132, 2132′ and first and second pockets/sinuses 2134, 2134′. In an embodiment, first and second tapered balloons 1673, 1675 are simultaneously inflated in order to concurrently form the first and second flaps 2132, 2132′ and corresponding first and second pockets/sinuses 2134, 2134′, as simultaneous inflation may result in more uniform creation of the tissue flaps to assure alignment from one another. Centering balloon 1671 and first and second tapered balloons 1673, 1675 are than fully deflated so that delivery catheter 1540 may be removed from the vessel.
Accordingly, a new venous valve is formed in accordance with the apparatus and method depicted in FIGS. 15-21 that operates as a bicuspid or two-leaflet venous valve where first and second free edges 2136, 2136′ meet to close lumen 1715 in the absence of antegrade blood flow AF when retrograde flow RF fills first and second pockets 2134, 2134′. As in previous embodiments, the dissected first and second flaps 2132, 2132′ provide the same internal, i.e., facing the blood flow, tissue structure as a native valve.
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 hereof 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.

## Claims

1. A percutaneous method for creating a venous valve from autologous tissue, the method comprising the steps of:
deploying a puncture element to penetrate into a wall of a vein to form a subintimal pathway in the vein wall;
advancing the puncture element into the subintimal pathway to form a dissection plane where intima and/or media tissue of the vein wall is separated from remaining tissue of the vein wall;
advancing a balloon catheter into the dissection plane; and
inflating the balloon catheter within the dissection plane to further dissect the intimal and/or medial tissue from the remaining tissue of the vein wall and thereby simultaneously form a flap of tissue and a sinus between the flap and the remaining tissue of the vein wall, wherein the flap and the sinus constitute at least a portion of the venous valve.

2. The method of claim 1, wherein a free edge of the flap is of a length that is greater than half the circumference of the vein lumen to form a monocuspid leaflet of the venous valve.

3. The method of claim 2, wherein a depth of the sinus is of sufficient length to allow the free edge to make contact with the opposite side of the vessel wall.

4. The method of claim 1, wherein a free edge of the flap is of a length that permits the free edge of the flap to touch against the opposing wall of the vein to close a lumen of the vein in the absence of antegrade flow.

5. The method of claim 1, wherein the puncture element is a hollow needle-like instrument.

6. The method of claim 1, wherein the puncture element is a guidewire with a sharpened distal end.

7. The method of claim 1, wherein the balloon has a proximal diameter that is larger than a distal diameter to have a tapered shape when inflated.

8. The method of claim 7, wherein inflating the balloon forms a conically shaped sinus between the dissected intima and media tissue and the remaining tissue of the vein wall.

9. The method of claim 1, wherein the vein is selected from one of the saphenous, popliteal and femoral veins.

10. The method of claim 1, wherein fluoroscopic guidance is used while advancing the puncture element into the subintimal pathway to determine a length of the dissection plane created.

11. The method of claim 1, further comprising:
positioning a biasing element within the sinus to aid in holding the sinus open in the absence of antegrade blood flow to allow the sinus to fill with retrograde blood flow.

12. The method of claim 1 further comprising:
deploying the puncture element a second time to penetrate into the wall of the vein to create a second subintimal pathway in the vein wall at a position that is approximately 180° from the first subintimal pathway;
advancing the puncture element into the second subintimal pathway to create a second dissection plane where intimal and medial tissue of the vein wall is separated from remaining tissue of the vein wall;
advancing the balloon catheter into the second dissection plane; and
inflating the balloon catheter within the second dissection plane to further dissect the intimal and medial tissue from the remaining tissue of the vein wall to thereby form a second flap and a second sinus between the second flap and the remaining tissue of the vein wall, wherein the first and second flaps and first and second sinuses constitute a venous valve having bicuspid leaflets.

13. The method of claim 12, wherein a free edge of the first flap and a free edge of the second flap each have a length that permits the free edges of the first and second flaps to touch against each other to close a lumen of the vein in the absence of antegrade flow.

14. A percutaneous method for creating a bicuspid venous valve from autologous tissue, the method comprising the steps of:
advancing a balloon catheter to a target location within a lumen of the vein where a venous valve is to be created, wherein the balloon catheter includes at least first and second delivery shafts defining first and second delivery lumens, the first delivery shaft having a first distal port that is positioned on one side of the balloon and the second delivery shaft having a second distal port that is positioned on the other side of the balloon approximately 180° from the first distal port;
expanding the balloon catheter to bias the first and second distal ports of the balloon catheter against a wall of the vein;
deploying a first puncture element through the first delivery lumen and deploying a second puncture element through the second delivery lumen such that the first and second puncture elements penetrate into the vein wall to create respective first and second subintimal pathways in the vein wall; and
advancing each puncture element into the respective subintimal pathway so that intimal and/or medial tissue of the vein wall is separated from remaining tissue of the vein wall such that each puncture element creates a dissection plane.

15. The method of claim 14, further comprising:
removing the balloon catheter with the puncture elements remaining in place;
advancing a dual balloon catheter over the puncture elements such that a first balloon tracks over the first puncture element into one dissection plane and a second balloon tracks over the second puncture element into the other dissection plane; and
inflating the first and second balloons within the respective dissection planes to further dissect the intimal and/or medial tissue from the remaining tissue of the vein wall,
wherein inflation of the first balloon forms a first flap and a first sinus between the first flap and the remaining tissue of the vein wall and inflation of the second balloon forms a second flap and a second sinus between the second flap and the remaining tissue of the vein wall, wherein the first and second flaps and the respective first and second sinuses constitute a bicuspid venous valve.

16. The method of claim 14, further comprising:
removing the balloon catheter with the puncture elements remaining in place;
advancing a second balloon catheter over the first puncture element and into the respective dissection plane;
advancing a third balloon catheter over the second puncture element and into the respective dissection plane; and
inflating the second and third balloon catheters within the respective dissection planes to further dissect the intimal and/or medial tissue from the remaining tissue of the vein wall,
wherein inflation of the second balloon catheter forms a first flap and a first sinus between the first flap and the remaining tissue of the vein wall and inflation of the third balloon catheter forms a second flap and a second sinus between the second flap and the remaining tissue of the vein wall, wherein the first and second flaps and the respective first and second sinuses constitute a bicuspid venous valve.

17. A percutaneous method for creating a bicuspid venous valve from autologous tissue, the method comprising the steps of:
advancing a delivery catheter to a target location within a lumen of the vein where a venous valve is to be created, wherein the delivery catheter has a catheter shaft defining a center lumen and first and second outer delivery lumens that extend from a proximal end to a distal end thereof, whereby the center lumen has a balloon catheter preloaded therein, the first outer delivery lumen has a first tapered balloon catheter preloaded therein and the second outer delivery lumen has a second tapered balloon catheter preloaded therein;
inflating a centering balloon of the balloon catheter to bias first and second tapered balloons of the first and second tapered balloon catheters against a wall of the vessel;
deploying a first puncture element via the first tapered balloon catheter and deploying a second puncture element via the second tapered balloon catheter such that each puncture element penetrates into the vein wall to create a respective subintimal pathway in the vein wall;
distally advancing each puncture element into the respective subintimal pathway so that intimal and/or medial tissue of the vein wall is separated from remaining tissue of the vein wall such that each puncture element creates a dissection plane;
distally advancing the first tapered balloon into one dissection plane and distally advancing the second tapered balloon into the other dissection plane; and
inflating the first and second tapered balloons within the respective dissection planes to further dissect the intimal and/or medial tissue from the remaining tissue of the vein wall,
wherein inflation of the first tapered balloon forms a first flap and a first sinus between the first flap and the remaining tissue of the vein wall and inflation of the second tapered balloon forms a second flap and a second sinus between the second flap and the remaining tissue of the vein wall, wherein the first and second flaps and the respective first and second sinuses constitute a bicuspid venous valve.

18. The method of claim 17, wherein the first and second puncture elements are preloaded within the first and second tapered balloon catheters respectively.

19. The method of claim 17, further comprising:
positioning the centering balloon of the balloon catheter distal of the distal end of the delivery catheter shaft prior to advancing the preloaded delivery catheter to the target location; and
distally advancing the first and second tapered balloons to be adjacent to a working length of the centering balloon prior to inflating the centering balloon.

20. The method of claim 19, wherein the subintimal pathways are made in the vessel wall at a first and second location that are 180 degrees opposed from one and other.