Patent Description:
Prosthetic cardiac valves have been used for many years to treat cardiac valvular disorders. The native heart valves (such as the aortic, pulmonary and mitral valves) serve critical functions in assuring the forward flow of an adequate supply of blood through the cardiovascular system. These heart valves can be rendered less effective by congenital, inflammatory, or infectious conditions. Such damage to the valves can result in serious cardiovascular compromise or death. For many years the definitive treatment for such disorders was the surgical repair or replacement of the valve during open-heart surgery, but such surgeries are prone to many complications. More recently, a transvascular technique has been developed for introducing and implanting a prosthetic heart valve using a flexible catheter in a manner that is less invasive than open heart surgery.

In this technique, a prosthetic valve is mounted in a crimped state on the end portion of a flexible catheter and advanced through a blood vessel of the patient until the prosthetic valve reaches the implantation site. The prosthetic valve at the catheter tip is then expanded to its functional size at the site of the defective native valve, such as by inflating a balloon on which the prosthetic valve is mounted. Alternatively, the prosthetic valve can have a resilient, self-expanding stent or frame that expands the prosthetic valve to its functional size when it is advanced from a delivery sheath at the distal end of the catheter.

The native valve annulus in which an expandable prosthetic valve is deployed typically has an irregular shape mainly due to calcification. As a result, small gaps may exist between the expanded frame of the prosthetic valve and the surrounding tissue. The gaps can allow for regurgitation (leaking) of blood flowing in a direction opposite the normal flow of blood through the valve. To minimize regurgitation, various sealing devices have been developed that seal the interface between the prosthetic valve and the surrounding tissue.

<CIT> discloses prosthetic heart valves having sealing devices configured to seal the interface between the prosthetic valve and the surrounding tissue of the native annulus in which the prosthetic valve is implanted.

The invention is a prosthetic heart valve as defined by claim <NUM>.

The present disclosure is directed to embodiments of catheter-based prosthetic heart valves, and in particular, prosthetic heart valves having sealing members configured to seal the interface between the prosthetic valve and the surrounding tissue of the native annulus in which the prosthetic valve is implanted. The present disclosure also discloses new methods of making an introducer sheath with an inner liner for percutaneous insertion of a medical device into a patient.

In one representative embodiment, a prosthetic heart valve comprises a collapsible and expandable annular frame that is configured to be collapsed to a radially collapsed state for mounting on a delivery apparatus and expanded to a radially expanded state inside the body. The frame has an inflow end, an outflow end, and a longitudinal axis extending from the inflow end to the outflow end, and comprises a plurality of struts defining a plurality of rows of a plurality of cells. The prosthetic heart valve also comprises a collapsible and expandable valve member mounted within the annular frame, and a collapsible and expandable skirt assembly mounted within the annular frame. The skirt assembly comprises an upper skirt, a lower skirt, and a sealing skirt. The upper and lower skirts prevent the sealing skirt from contacting the valve member and can also couple the valve member to the annular frame. When the annular frame is expanded to its radially expanded state, portions of the sealing skirt protrude outwardly through cells of the frame.

In particular embodiments, the sealing skirt is made of loop yarn. In further embodiments, the sealing skirt is mounted within the annular frame of the prosthetic heart valve by sutures that secure the sealing skirt and the lower skirt to the frame of the prosthetic heart valve. In additional embodiments, from the longitudinal axis of the prosthetic heart valve, the valve member is positioned radially outward from the lower skirt, the upper skirt is positioned radially outward from the valve member; and the sealing skirt is positioned radially outward from the upper skirt. In more embodiments, an outflow portion of the lower skirt is sutured to an inflow portion of the valve member; and the inflow portion of the valve member is sutured to an inflow portion of the upper skirt.

In another representative embodiment, a method of making an introducer sheath with an inner liner for percutaneous insertion of a medical device into a patient is provided. The method comprises inserting a metal sleeve into a mold, inserting a polymer tube comprising a closed end and an open end into the metal sleeve, and pressurizing and heating the polymer tube to cause the polymer tube to expand against an inner surface of the metal sleeve so as to form the inner liner of the sheath.

In particular embodiments of the method, the preform cylindrical polymer tube is made of nylon-<NUM>, polyethylene, or fluorinated ethylene propylene (FEP). In further embodiments, the inner liner formed from the polymer tube has a radial wall thickness of from about <NUM> (about <NUM> inch) to about <NUM> (about <NUM> inch). In still more embodiments, the metal sleeve has a radial wall thickness of from about <NUM> (about <NUM> inch) to about <NUM> (about <NUM> inch). Pressurizing and heating the polymer tube can comprise injecting heated compressed gas into the polymer tube. Alternatively, pressurizing the polymer tube can comprise injecting compressed gas into the polymer tube and heating the polymer tube can comprise heating with a heat source separate from the pressurized gas. In several embodiments, the introducer sheath is configured for percutaneous insertion of a prosthetic heart valve through the femoral artery of the patient.

In several embodiments, the method can include forming an introducer sheath with an inner liner and an outer liner for percutaneous insertion of the medical device into the patient. In some embodiments of the method, a preform cylindrical polymer tube is used to form the outer liner. In particular embodiments, the preform cylindrical polymer tube used to form the outer liner can be made of nylon-<NUM>, polyether block amides, or polyethylene. In further embodiments, the outer liner has a radial wall thickness of from about <NUM> (about <NUM> inch) to about <NUM> (about <NUM> inch).

The foregoing and other objects, features, and advantages of the invention will become more apparent from the following detailed description, which proceeds with reference to the accompanying drawings.

For purposes of this description, certain aspects, advantages, and novel features of the embodiments of this disclosure are described herein. The described methods, systems, and apparatus should not be construed as limiting in any way. Instead, the present disclosure is directed toward all novel and nonobvious features and aspects of the various disclosed embodiments, alone and in various combinations and subcombinations with one another. The disclosed methods, systems, and apparatus are not limited to any specific aspect, feature, or combination thereof, nor do the disclosed methods, systems, and apparatus require that any one or more specific advantages be present or problems be solved.

Although the operations of some of the disclosed methods are described in a particular, sequential order for convenient presentation, it should be understood that this manner of description encompasses rearrangement, unless a particular ordering is required by specific language set forth below. Moreover, for the sake of simplicity, the attached drawings may not show the various ways in which the disclosed methods, systems, and apparatus can be used in conjunction with other systems, methods, and apparatus.

As used herein, the terms "a", "an", and "at least one" encompass one or more of the specified element. That is, if two of a particular element are present, one of these elements is also present and thus "an" element is present. The terms "a plurality of" and "plural" mean two or more of the specified element.

As used herein, the term "and/or" used between the last two of a list of elements means any one or more of the listed elements. For example, the phrase "A, B, and/or C" means "A", "B", "C", "A and B", "A and C", "B and C", or "A, B, and C".

As used herein, the term "coupled" generally means physically coupled or linked and does not exclude the presence of intermediate elements between the coupled items absent specific contrary language.

Referring first to <FIG>, there is shown a prosthetic aortic heart valve <NUM>, according to one embodiment. The prosthetic valve <NUM> includes an expandable frame member, or stent, <NUM> that supports an expandable valve member, which in the illustrated embodiment comprises a flexible leaflet section <NUM>. The prosthetic valve <NUM> is radially compressible to a compressed state for delivery through the body to a deployment site and expandable to its functional size shown in <FIG> at the deployment site. In certain embodiments, the prosthetic valve <NUM> is self-expanding; that is, the prosthetic valve can radially expand to its functional size when advanced from the distal end of a delivery sheath. Apparatuses particularly suited for percutaneous delivery and implantation of a self-expanding prosthetic valve are described in detail below. In other embodiments, the prosthetic valve can be a balloon-expandable prosthetic valve that can be adapted to be mounted in a compressed state on the balloon of a delivery catheter. The prosthetic valve can be expanded to its functional size at a deployment site by inflating the balloon, as known in the art.

The illustrated prosthetic valve <NUM> is adapted to be deployed in the native aortic annulus, although it also can be used to replace the other native valves of the heart (the mitral, tricuspid, and pulmonary valves). Moreover, the prosthetic valve <NUM> can be adapted to replace other valves within the body, such venous valves.

<FIG> show the stent <NUM> without the leaflet section <NUM> for purposes of illustration. As shown, the stent <NUM> can be formed from a plurality of longitudinally extending, generally sinusoidal-shaped frame members, or struts, <NUM>. The struts <NUM> are formed with alternating bends and are welded or otherwise secured to each other at nodes <NUM> formed from the vertices of adjacent bends so as to form a mesh structure. The struts <NUM> can be made of a suitable shape memory material, such as the nickel titanium alloy known as Nitinol, that allows the prosthetic valve to be compressed to a reduced diameter for delivery in a delivery apparatus (such as described below) and then causes the prosthetic valve to expand to its functional size inside the patient's body when deployed from the delivery apparatus. If the prosthetic valve is a balloon-expandable prosthetic valve that is adapted to be crimped onto an inflatable balloon of a delivery apparatus and expanded to its functional size by inflation of the balloon, the stent <NUM> can be made of a suitable ductile material, such as stainless steel.

The stent <NUM> has an inflow end <NUM> and an outflow end <NUM>. The mesh structure formed by struts <NUM> comprises a generally cylindrical "upper" or outflow end portion <NUM>, an outwardly bowed or distended intermediate section <NUM>, and an inwardly bowed "lower" or inflow end portion <NUM>. The intermediate section <NUM> desirably is sized and shaped to extend into the sinuses of Valsalva in the aortic root to assist in anchoring the prosthetic valve in place once implanted. As shown, the mesh structure desirably has a curved shape along its entire length that gradually increases in diameter from the outflow end portion <NUM> to the intermediate section <NUM>, then gradually decreases in diameter from the intermediate section <NUM> to a location on the inflow end portion <NUM>, and then gradually increases in diameter to form a flared portion terminating at the inflow end <NUM>.

When the prosthetic valve is in its expanded state, the intermediate section <NUM> has a diameter D<NUM>, the inflow end portion <NUM> has a minimum diameter D<NUM>, the inflow end <NUM> has a diameter D<NUM>, and the outflow end portion <NUM> has a diameter D<NUM>, where D<NUM> is less than D<NUM> and D<NUM>, and D<NUM> is less than D<NUM>. In addition, D<NUM> and D<NUM> desirably are greater than the diameter of the native annulus in which the prosthetic valve is to be implanted. In this manner, the overall shape of the stent <NUM> assists in retaining the prosthetic valve at the implantation site. More specifically, and referring to <FIG> and <FIG>, the prosthetic valve <NUM> can be implanted within a native valve (the aortic valve in the illustrated example) such that the lower section <NUM> is positioned within the aortic annulus <NUM>, the intermediate section <NUM> extends above the aortic annulus into the sinuses of Valsalva <NUM>, and the lower flared end <NUM> extends below the aortic annulus. The prosthetic valve <NUM> is retained within the native valve by the radial outward force of the lower section <NUM> against the surrounding tissue of the aortic annulus <NUM> as well as the geometry of the stent. Specifically, the intermediate section <NUM> and the flared lower end <NUM> extend radially outwardly beyond the aortic annulus <NUM> to better resist against axial dislodgement of the prosthetic valve in the downstream and upstream directions (toward and away from the aorta). Depending on the condition of the native leaflets <NUM>, the prosthetic valve typically is deployed within the native annulus <NUM> with the native leaflets <NUM> folded upwardly and compressed between the outer surface of the stent <NUM> and the walls of the sinuses of Valsalva <NUM>, as depicted in <FIG>. In some cases, it may be desirable to excise the leaflets <NUM> prior to implanting the prosthetic valve <NUM>.

Known prosthetic valves having a self-expanding frame typically have additional anchoring devices or frame portions that extend into and become fixed to non-diseased areas of the vasculature. Because the shape of the stent <NUM> assists in retaining the prosthetic valve, additional anchoring devices are not required and the overall length L of the stent can be minimized to prevent the stent upper portion <NUM> from extending into the non-diseased area of the aorta, or to at least minimize the extent to which the upper portion <NUM> extends into the non-diseased area of the aorta. Avoiding the non-diseased area of the patient's vasculature helps avoid complications if future intervention is required. For example, the prosthetic valve can be more easily removed from the patient because the stent is primarily anchored to the diseased part of the native valve. Furthermore, a shorter prosthetic valve is more easily navigated around the aortic arch.

In particular embodiments, for a prosthetic valve intended for use in a <NUM>-mm to <NUM>-mm annulus, the diameter D1 is from about <NUM> to about <NUM>, with about <NUM> being a specific example; the diameter D2 is from about <NUM> to about <NUM>, with about <NUM> being a specific example; the diameter D3 is from about <NUM> to about <NUM>, with about <NUM> being a specific example; and the diameter D4 is from about <NUM> to about <NUM>, with about <NUM> being a specific example. The length L in particular embodiments is from about <NUM> to about <NUM>, with about <NUM> being a specific example.

Referring to <FIG>, the stent <NUM> can have a plurality of angularly spaced retaining arms, or projections, in the form of posts <NUM> (three in the illustrated embodiment) that extend from the stent upper portion <NUM>. Each retaining arm <NUM> has a respective aperture <NUM> that is sized to receive prongs of a valve-retaining mechanism that can be used to form a releasable connection between the prosthetic valve and a delivery apparatus (described below). In alternative embodiments, the retaining arms <NUM> need not be provided if a valve-retaining mechanism is not used.

As best shown in <FIG>, the leaflet assembly <NUM> in the illustrated embodiment comprises three leaflets 34a, 34b, 34c made of a flexible material. Each leaflet has an inflow end portion <NUM> and an outflow end portion <NUM>. The leaflets can comprise any suitable biological material (e.g., pericardial tissue, such as bovine or equine pericardium), bio-compatible synthetic materials, or other such materials, such as those described in <CIT>. The leaflet assembly <NUM> can include an annular reinforcing skirt <NUM> that is secured to the inflow end portions of the leaflets 34a, 34b, 34c at a suture line <NUM> adjacent the inflow end of the prosthetic valve. The inflow end portion of the leaflet assembly <NUM> can be secured to the stent <NUM> by suturing the skirt <NUM> to struts <NUM> of the lower section <NUM> of the stent (best shown in <FIG>). As shown in <FIG>, the leaflet assembly <NUM> can further include an inner reinforcing strip <NUM> that is secured to the inner surfaces of the inflow end portions <NUM> of the leaflets.

Referring to <FIG>, the outflow end portion of the leaflet assembly <NUM> can be secured to the upper portion of the stent <NUM> at three angularly spaced commissure attachments of the leaflets 34a, 34b, and 34c. As best shown in <FIG>, each commissure attachment can be formed by wrapping a reinforcing section <NUM> around adjacent upper edge portions <NUM> of a pair of leaflets at the commissure formed by the two leaflets and securing the reinforcing section <NUM> to the edge portions <NUM> with sutures <NUM>. The sandwiched layers of the reinforcing material and leaflets can then be secured to the struts <NUM> of the stent <NUM> with sutures <NUM> adjacent the outflow end of the stent. The leaflets therefore desirably extend the entire length or substantially the entire length of the stent from the inflow end <NUM> to the outflow end <NUM>. The reinforcing sections <NUM> reinforces the attachment of the leaflets to the stent so as to minimize stress concentrations at the suture lines and avoid "needle holes" on the portions of the leaflets that flex during use. The reinforcing sections <NUM>, the skirt <NUM>, and the inner reinforcing strip <NUM> (<FIG>) desirably are made of a bio-compatible synthetic material, such as polytetrafluoroethylene (PTFE), or a woven fabric material, such as woven polyester (e.g., polyethylene terephthalate) (PET), DACRON®).

<FIG> shows the operation of the prosthetic valve <NUM>. During diastole, the leaflets 34a, 34b, 34c collapse to effectively close the prosthetic valve. As shown, the curved shape of the intermediate section <NUM> of the stent <NUM> defines a space between the intermediate section and the leaflets that mimics the sinuses of Valsalva. Thus, when the leaflets close, backflow entering the "sinuses" creates a turbulent flow of blood along the upper surfaces of the leaflets, as indicated by arrows <NUM>. This turbulence assists in washing the leaflets and the skirt <NUM> to minimize or reduce clot formation.

The prosthetic valve <NUM> can be implanted in a retrograde approach where the prosthetic valve, mounted in a crimped state at the distal end of a delivery apparatus, is introduced into the body via the femoral artery and advanced through the aortic arch to the heart, as further described in <CIT>.

<FIG> show a delivery apparatus <NUM>, according to one embodiment, that can be used to deliver a self-expanding prosthetic valve, such as prosthetic valve <NUM> described above, through a patient's vasculature. The delivery apparatus <NUM> comprises a first, outermost or main catheter <NUM> (shown alone in <FIG>) having an elongated shaft <NUM>, the distal end of which is coupled to a delivery sheath <NUM> (<FIG>; also referred to as a delivery cylinder). The proximal end of the main catheter <NUM> is connected to a handle of the delivery apparatus. <FIG> show an embodiment of a handle mechanism having an electric motor for operating the delivery apparatus. The handle mechanism is described in detail below. During delivery of a prosthetic valve, the handle can be used by a surgeon to advance and retract the delivery apparatus through the patient's vasculature. Although not required, the main catheter <NUM> can comprise a guide catheter that is configured to allow a surgeon to guide or control the amount the bending or flexing of a distal portion of the shaft <NUM> as it is advanced through the patient's vasculature, such as further described below. Another embodiment of a guide catheter is disclosed in <CIT>.

As best shown in <FIG>, the delivery apparatus <NUM> also includes a second, intermediate catheter <NUM> (also referred to herein as a torque shaft catheter) having an elongated shaft <NUM> (also referred to herein as a torque shaft) and an elongated screw <NUM> connected to the distal end of the shaft <NUM>. The shaft <NUM> of the intermediate catheter <NUM> extends coaxially through the shaft <NUM> of the main catheter <NUM>. The delivery apparatus <NUM> can also include a third, nose-cone catheter <NUM> having an elongated shaft <NUM> and a nose piece, or nose cone, <NUM> secured to the distal end portion of the shaft <NUM>. The nose piece <NUM> can have a tapered outer surface as shown for atraumatic tracking through the patient's vasculature. The shaft <NUM> of the nose-cone catheter extends through the prosthetic valve <NUM> (not shown in <FIG>) and the shaft <NUM> of the intermediate catheter <NUM>. In the illustrated configuration, the innermost shaft <NUM> is configured to be moveable axially and rotatably relative to the shafts <NUM>, <NUM>, and the torque shaft <NUM> is configured to be rotatable relative to the shafts <NUM>, <NUM> to effect valve deployment and release of the prosthetic valve from the delivery apparatus, as described in detail below. Additionally, the innermost shaft <NUM> can have a lumen for receiving a guide wire so that the delivery apparatus can be advanced over the guide wire inside the patient's vasculature.

As best shown in <FIG>, the outer catheter <NUM> can comprise a flex control mechanism <NUM> at a proximal end thereof to control the amount the bending or flexing of a distal portion of the outer shaft <NUM> as it is advanced through the patient's vasculature, such as further described below. The outer shaft <NUM> can comprise a proximal segment <NUM> that extends from the flex control mechanism <NUM> and a distal segment <NUM> that comprises a slotted metal tube that increases the flexibility of the outer shaft at this location. The distal end portion of the distal segment <NUM> can comprises an outer fork <NUM> of a valve-retaining mechanism <NUM> (<FIG> and <FIG>) that is configured to releasably secure a prosthetic valve <NUM> to the delivery apparatus <NUM> during valve delivery, as described in detail below.

<FIG> is an enlarged view of a portion of the distal segment <NUM> of the outer shaft <NUM>. <FIG> shows the cut pattern that can be used to form the distal segment <NUM> by laser cutting the pattern in a metal tube. The distal segment <NUM> comprises a plurality of interconnected circular bands or links <NUM> forming a slotted metal tube. A pull wire <NUM> can be positioned inside the distal segment <NUM> and can extend from a location <NUM> of the distal segment <NUM> (<FIG> and <FIG>) to the flex control mechanism. The distal end of the pull wire <NUM> can be secured to the inner surface of the distal segment <NUM> at location <NUM>, such as by welding. The proximal end of the pull wire <NUM> can be operatively connected to the flex control mechanism <NUM>, which is configured to apply and release tension to the pull wire in order to control bending of the shaft, as further described below. The links <NUM> of the shaft and the gaps between adjacent links are shaped to allow bending of the shaft upon application of light pulling force on the pull wire <NUM>. In the illustrated embodiment, as best shown in <FIG>, the distal segment <NUM> is secured to a proximal segment <NUM> having a different construction (e.g., one or more layers of polymeric tubing). In the illustrated embodiment, the proximal segment <NUM> extends from the flex control mechanism <NUM> to the distal segment <NUM> and therefore makes up the majority of the length of the outer shaft <NUM>. In alternative embodiments, the entire length or substantially the entire length of the outer shaft <NUM> can be formed from a slotted metal tube comprising one or more sections of interconnected links <NUM>. In any case, the use of a main shaft having such a construction can allow the delivery apparatus to be highly steerable.

The width of the links <NUM> can be varied to vary the flexibility of the distal segment along its length. For example, the links within the distal end portion of the slotted tube can be relatively narrower to increase the flexibility of the shaft at that location while the links within the proximal end portion of the slotted tube can be relatively wider so that the shaft is relatively less flexible at that location.

<FIG> shows an alternative embodiment of a distal segment, indicated at <NUM>', which can be formed, for example, by laser cutting a metal tube. The segment <NUM>' can comprise the distal segment of an outer shaft of a delivery apparatus (as shown in <FIG>) or substantially the entire length of an outer shaft can have the construction shown in <FIG> shows the cut pattern for forming the segment <NUM>'. In another embodiment, a delivery apparatus can include a composite outer shaft comprising a laser-cut metal tube laminated with a polymeric outer layer that is fused within the gaps in the metal layer. In one example, a composite shaft can comprise a laser cut metal tube having the cut pattern of <FIG> and a polymeric outer layer fused in the gaps between the links <NUM> of the metal tube. In another example, a composite shaft can comprise a laser cut metal tube having the cut pattern of <FIG> and a polymeric outer layer fused in the gaps between the links <NUM> of the metal tube. A composite shaft also can include a polymeric inner layer fused in the gaps between the links <NUM> of the metal tube.

Referring to <FIG> and <FIG>, the flex control mechanism <NUM> can comprise a rotatable housing, or handle portion, <NUM> that houses a slide nut <NUM> mounted on a rail <NUM>. The slide nut <NUM> is prevented from rotating within the housing by one or more rods <NUM>, each of which is partially disposed in a corresponding recess within the rail <NUM> and a slot or recess on the inside of the nut <NUM>. The proximal end of the pull wire <NUM> is secured to the nut <NUM>. The nut <NUM> has external threads that engage internal threads of the housing. Thus, rotating the housing <NUM> causes the nut <NUM> to move axially within the housing in the proximal or distal direction, depending on the direction of rotation of the housing. Rotating the housing in a first direction (e.g., clockwise), causes the nut to travel in the proximal direction, which applies tension to the pull wire <NUM>, which causes the distal end of the delivery apparatus to bend or flex. Rotating the housing in a second direction (e.g., counterclockwise), causes the nut to travel in the distal direction, which relieves tension in the pull wire <NUM> and allows the distal end of the delivery apparatus to flex back to its pre-flexed configuration under its own resiliency.

As best shown in <FIG>, the torque shaft catheter <NUM> includes an annular projection in the form of a ring <NUM> (also referred to as an anchoring disc) mounted on the distal end portion of the torque shaft <NUM> adjacent the screw <NUM>. The ring <NUM> is secured to the outer surface of the torque shaft <NUM> such that it cannot move axially or rotationally relative to the torque shaft. The inner surface of the outer shaft <NUM> is formed with a feature, such as a slot or recess, that receives the ring <NUM> in such a manner that the ring and the corresponding feature on the inner surface of the outer shaft <NUM> allow the torque shaft <NUM> to rotate relative to the outer shaft <NUM> but prevent the torque shaft from moving axially relative to the outer shaft. The corresponding feature on the outer shaft <NUM> that receives the ring <NUM> can be inwardly extending tab portions formed in the distal segment <NUM>, such as shown at <NUM> in <FIG>. In the illustrated embodiment (as best shown in <FIG>), the ring <NUM> is an integral part of the screw <NUM> (i.e., the screw <NUM> and the ring <NUM> are portions of single component). Alternatively, the screw <NUM> and the ring are separately formed components but are both fixedly secured to the distal end of the torque shaft <NUM>.

The torque shaft <NUM> desirably is configured to be rotatable relative to the delivery sheath <NUM> to effect incremental and controlled advancement of the prosthetic valve <NUM> from the delivery sheath <NUM>. To such ends, and according to one embodiment, the delivery apparatus <NUM> can include a sheath retaining ring in the form of a threaded nut <NUM> mounted on the external threads of the screw <NUM>. As best shown in <FIG>, the nut <NUM> includes internal threads <NUM> that engage the external threads of the screw and axially extending legs <NUM>. Each leg <NUM> has a raised distal end portion that extends into and/or forms a snap fit connection with openings <NUM> in the proximal end of the sheath <NUM> (as best shown in <FIG>) so as to secure the sheath <NUM> to the nut <NUM>. As illustrated in <FIG> and <FIG>, the sheath <NUM> extends over the prosthetic valve <NUM> and retains the prosthetic valve in a radially compressed state until the sheath <NUM> is retracted by the user to deploy the prosthetic valve.

As best shown in <FIG>, the outer fork <NUM> of the valve-retaining mechanism comprises a plurality of prongs <NUM>, each of which extends through a region defined between two adjacent legs <NUM> of the nut so as to prevent rotation of the nut relative to the screw <NUM> upon rotation of the screw. As such, rotation of the torque shaft <NUM> (and thus the screw <NUM>) causes corresponding axial movement of the nut <NUM>. The connection between the nut <NUM> and the sheath <NUM> is configured such that axially movement of the nut along the screw <NUM> (in the distal or proximal direction) causes the sheath <NUM> to move axially in the same direction relative to the screw and the valve-retaining mechanism. <FIG> shows the nut <NUM> in a distal position wherein the sheath <NUM> (not shown in <FIG>) extends over and retains the prosthetic valve <NUM> in a compressed state for delivery. Movement of the nut <NUM> from the distal position (<FIG>) to a proximal position (<FIG>) causes the sheath <NUM> to move in the proximal direction, thereby deploying the prosthetic valve from the sheath <NUM>. Rotation of the torque shaft <NUM> to effect axial movement of the sheath <NUM> can be accomplished with a motorized mechanism or by manually turning a crank or wheel (e.g., as described in <CIT>).

<FIG> shows an enlarged view of the nose cone <NUM> secured to the distal end of the innermost shaft <NUM>. The nose cone <NUM> in the illustrated embodiment includes a proximal end portion <NUM> that is sized to fit inside the distal end of the sheath <NUM>. An intermediate section <NUM> of the nose cone is positioned immediately adjacent the end of the sheath in use and is formed with a plurality of longitudinal grooves or recessed portions <NUM>. The diameter of the intermediate section <NUM> at its proximal end <NUM> desirably is slightly larger than the outer diameter of the sheath <NUM>. The proximal end <NUM> can be held in close contact with the distal end of the sheath <NUM> to protect surrounding tissue from coming into contact with the metal edge of the sheath. The grooves <NUM> allow the intermediate section to be compressed radially as the delivery apparatus is advanced through an introducer sheath. This allows the nose cone <NUM> to be slightly oversized relative to the inner diameter of the introducer sheath. <FIG> shows a cross-section the nose cone <NUM> and the sheath <NUM> in a delivery position with the prosthetic valve retained in a compressed delivery state inside the sheath <NUM> (for purposes of illustration, only the stent <NUM> of the prosthetic valve is shown). As shown, the proximal end <NUM> of the intermediate section <NUM> can abut the distal end of the sheath <NUM> and a tapered proximal surface <NUM> of the nose cone can extend within a distal portion of the stent <NUM>.

As noted above, the delivery apparatus <NUM> can include a valve-retaining mechanism <NUM> (<FIG>) for releasably retaining a stent <NUM> of a prosthetic valve. The valve-retaining mechanism <NUM> can include a first valve-securement component in the form of an outer fork <NUM> (as best shown in <FIG>) (also referred to as an "outer trident" or "release trident"), and a second valve-securement component in the form of an inner fork <NUM> (as best shown in <FIG>) (also referred to as an "inner trident" or "locking trident"). The outer fork <NUM> cooperates with the inner fork <NUM> to form a releasably connection with the retaining arms <NUM> of the stent <NUM>.

The proximal end of the outer fork <NUM> is connected to the distal segment <NUM> of the outer shaft <NUM> and the distal end of the outer fork is releasably connected to the stent <NUM>. In the illustrated embodiment, the outer fork <NUM> and the distal segment <NUM> can be integrally formed as a single component (e.g., the outer fork and the distal segment can be laser cut or otherwise machined from a single piece of metal tubing), although these components can be separately formed and subsequently connected to each other. The inner fork <NUM> can be mounted on the nose catheter shaft <NUM> (as best shown in <FIG>). The inner fork <NUM> connects the stent to the distal end portion of the nose catheter shaft <NUM>. The nose catheter shaft <NUM> can be moved axially relative to the outer shaft <NUM> to release the prosthetic valve from the valve-retaining mechanism, as further described below.

As best shown in <FIG>, the outer fork <NUM> includes a plurality of angularly-spaced prongs <NUM> (three in the illustrated embodiment) corresponding to the retaining arms <NUM> of the stent <NUM>, which prongs extend from the distal end of distal segment <NUM>. The distal end portion of each prong <NUM> includes a respective opening <NUM>. As best shown in <FIG>, the inner fork <NUM> includes a plurality of angularly-spaced prongs <NUM> (three in the illustrated embodiment) corresponding to the retaining arms <NUM> of the stent <NUM>, which prongs extend from a base portion <NUM> at the proximal end of the inner fork. The base portion <NUM> of the inner fork is fixedly secured to the nose catheter shaft <NUM> (e.g., with a suitable adhesive) to prevent axial and rotational movement of the inner fork relative to the nose catheter shaft <NUM>.

Each prong of the outer fork <NUM> cooperates with a corresponding prong <NUM> of the inner fork to form a releasable connection with a retaining arm <NUM> of the stent. In the illustrated embodiment, for example, the distal end portion of each prong <NUM> is formed with an opening <NUM>. When the prosthetic valve is secured to the delivery apparatus (as best shown in <FIG>), each retaining arm <NUM> of the stent <NUM> extends inwardly through an opening <NUM> of a prong <NUM> of the outer fork and a prong <NUM> of the inner fork is inserted through the opening <NUM> of the retaining arm <NUM> so as to retain the retaining arm <NUM> from backing out of the opening <NUM>. <FIG> also shows the prosthetic valve <NUM> secured to the delivery apparatus by the inner and outer forks before the prosthetic valve is loaded into the sheath <NUM>. The threaded nut <NUM> can be seen positioned between the prongs of the outer fork <NUM>. The prosthetic valve <NUM> is ready to be compressed and loaded into the sheath <NUM> of a delivery apparatus. Retracting the inner prongs <NUM> proximally (in the direction of arrow <NUM> in <FIG>) to remove the prongs from the openings <NUM> is effective to release the prosthetic valve <NUM> from the retaining mechanism. When the inner fork <NUM> is moved to a proximal position (<FIG>), the retaining arms <NUM> of the stent can move radially outwardly from the openings <NUM> in the outer fork <NUM> under the resiliency of the stent. In this manner, the valve-retaining mechanism <NUM> forms a releasable connection with the prosthetic valve that is secure enough to retain the prosthetic valve relative to the delivery apparatus to allow the user to fine tune or adjust the position of the prosthetic valve after it is deployed from the delivery sheath. When the prosthetic valve is positioned at the desired implantation site, the connection between the prosthetic valve and the retaining mechanism can be released by retracting the nose catheter shaft <NUM> relative to the outer shaft <NUM> (which retracts the inner fork <NUM> relative to the outer fork <NUM>).

Once the prosthetic valve <NUM> is loaded in the delivery sheath <NUM>, the delivery apparatus <NUM> can be inserted into the patient's body for delivery of the prosthetic valve. In one approach, the prosthetic valve can be delivered in a retrograde procedure where delivery apparatus is inserted, for example, into a femoral artery and advanced through the patient's vasculature to the heart. Prior to insertion of the delivery apparatus, an introducer sheath can be inserted into the femoral artery followed by a guide wire, which is advanced through the patient's vasculature through the aorta and into the left ventricle. The delivery apparatus <NUM> can then be inserted through the introducer sheath and advanced over the guide wire until the distal end portion of the delivery apparatus containing the prosthetic valve <NUM> is advanced to a location adjacent to or within the native aortic valve.

Thereafter, the prosthetic valve <NUM> can be deployed from the delivery apparatus <NUM> by rotating the torque shaft <NUM> relative to the outer shaft <NUM>. As described below, the proximal end of the torque shaft <NUM> can be operatively connected to a manually rotatable handle portion or a motorized mechanism that allows the surgeon to effect rotation of the torque shaft <NUM> relative to the outer shaft <NUM>. Rotation of the torque shaft <NUM> and the screw <NUM> causes the nut <NUM> and the sheath <NUM> to move in the proximal direction toward the outer shaft (<FIG>), which deploys the prosthetic valve from the sheath. Rotation of the torque shaft <NUM> causes the sheath to move relative to the prosthetic valve in a precise and controlled manner as the prosthetic valve advances from the open distal end of the delivery sheath and begins to expand. Hence, unlike known delivery apparatus, as the prosthetic valve begins to advance from the delivery sheath and expand, the prosthetic valve is held against uncontrolled movement from the sheath caused by the expansion force of the prosthetic valve against the distal end of the sheath. In addition, as the sheath <NUM> is retracted, the prosthetic valve <NUM> is retained in a stationary position relative to the ends of the inner shaft <NUM> and the outer shaft <NUM> by virtue of the valve-retaining mechanism <NUM>. As such, the prosthetic valve <NUM> can be held stationary relative to the target location in the body as the sheath is retracted. Moreover, after the prosthetic valve is partially advanced from the sheath, it may be desirable to retract the prosthetic valve back into the sheath, for example, to reposition the prosthetic valve or to withdraw the prosthetic valve entirely from the body. The partially deployed prosthetic valve can be retracted back into the sheath by reversing the rotation of the torque shaft, which causes the sheath <NUM> to advance back over the prosthetic valve in the distal direction.

In known delivery devices, the surgeon must apply push-pull forces to the shaft and/or the sheath to unsheathe the prosthetic valve. It is therefore difficult to transmit forces to the distal end of the device without distorting the shaft (e.g., compressing or stretching the shaft axially), which in turn causes uncontrolled movement of the prosthetic valve during the unsheathing process. To mitigate this effect, the shaft and/or sheath can be made more rigid, which is undesirable because the device becomes harder to steer through the vasculature. In contrast, the manner of unsheathing the prosthetic valve described above eliminates the application of push-pull forces on the shaft, as required in known devices, so that relatively high and accurate forces can be applied to the distal end of the shaft without compromising the flexibility of the device. In certain embodiments, as much as about <NUM> N (about <NUM> lb) of force can be transmitted to the end of the torque shaft without adversely affecting the unsheathing process. In contrast, prior art devices utilizing push-pull mechanisms typically cannot exceed about <NUM> N (<NUM> lb) of force during the unsheathing process.

After the prosthetic valve <NUM> is advanced from the delivery sheath and expands to its functional size (the expanded prosthetic valve <NUM> secured to the delivery apparatus is depicted in <FIG>), the prosthetic valve remains connected to the delivery apparatus via the retaining mechanism <NUM>. Consequently, after the prosthetic valve is advanced from the delivery sheath, the surgeon can reposition the prosthetic valve relative to the desired implantation position in the native valve such as by moving the delivery apparatus in the proximal and distal directions or side to side, or rotating the delivery apparatus, which causes corresponding movement of the prosthetic valve. The retaining mechanism <NUM> desirably provides a connection between the prosthetic valve and the delivery apparatus that is secure and rigid enough to retain the position of the prosthetic valve relative to the delivery apparatus against the flow of the blood as the position of the prosthetic valve is adjusted relative to the desired implantation position in the native valve. Once the surgeon positions the prosthetic valve at the desired implantation position in the native valve, the connection between the prosthetic valve and the delivery apparatus can be released by retracting the innermost shaft <NUM> in the proximal direction relative to the outer shaft <NUM>, which is effective to retract the inner fork <NUM> to withdraw its prongs <NUM> from the openings <NUM> in the retaining arms <NUM> of the prosthetic valve (<FIG>). Slightly retracting of the outer shaft <NUM> allows the outer fork <NUM> to back off the retaining arms <NUM> of the prosthetic valve, which slide outwardly through openings <NUM> in the outer fork to completely disconnect the prosthetic valve from the retaining mechanism <NUM>. Thereafter, the delivery apparatus can be withdrawn from the body, leaving the prosthetic aortic valve <NUM> implanted within the native valve (such as shown in <FIG> and <FIG>).

The delivery apparatus <NUM> has at its distal end a semi-rigid segment comprised of relatively rigid components used to transform rotation of the torque shaft into axial movement of the sheath. In particular, this semi-rigid segment in the illustrated embodiment is comprised of the prosthetic valve and the screw <NUM>. An advantage of the delivery apparatus <NUM> is that the overall length of the semi-rigid segment is minimized because the nut <NUM> is used rather than internal threads on the outer shaft to affect translation of the sheath. The reduced length of the semi-rigid segment increases the overall flexibility along the distal end portion of the delivery catheter. Moreover, the length and location of the semi-rigid segment remains constant because the torque shaft does not translate axially relative to the outer shaft. As such, the curved shape of the delivery catheter can be maintained during valve deployment, which improves the stability of the deployment. A further benefit of the delivery apparatus <NUM> is that the ring <NUM> prevents the transfer of axial loads (compression and tension) to the section of the torque shaft <NUM> that is distal to the ring.

In an alternative embodiment, the delivery apparatus can be adapted to deliver a balloon-expandable prosthetic valve. As described above, the valve retaining mechanism <NUM> can be used to secure the prosthetic valve to the end of the delivery apparatus. Since the stent of the prosthetic valve is not self-expanding, the sheath <NUM> can be optional. The retaining mechanism <NUM> enhances the pushability of the delivery apparatus and prosthetic valve assembly through an introducer sheath.

<FIG> illustrate the proximal end portion of the delivery apparatus <NUM>, according to one embodiment. The delivery apparatus <NUM> can comprise a handle <NUM> that is configured to be releasably connectable to the proximal end portion of a catheter assembly <NUM> comprising catheters <NUM>, <NUM>, <NUM>. It may be desirable to disconnect the handle <NUM> from the catheter assembly <NUM> for various reasons. For example, disconnecting the handle can allow another device to be slid over the catheter assembly, such as a valve-retrieval device or a device to assist in steering the catheter assembly. It should be noted that any of the features of the handle <NUM> and the catheter assembly <NUM> can be implemented in any of the embodiments of the delivery apparatuses disclosed herein.

<FIG> show the proximal end portion of the catheter assembly <NUM> partially inserted into a distal opening of the handle <NUM>. The proximal end portion of the main shaft <NUM> is formed with an annular groove <NUM> (as best shown in <FIG>) that cooperates with a holding mechanism, or latch mechanism, <NUM> inside the handle. When the proximal end portion of the catheter assembly is fully inserted into the handle, as shown in <FIG>, an engaging portion <NUM> of the holding mechanism <NUM> extends at least partially into the groove <NUM>. One side of the holding mechanism <NUM> is connected to a button <NUM> that extends through the housing of the handle. The opposite side of the holding mechanism <NUM> is contacted by a spring <NUM> that biases the holding mechanism to a position engaging the main shaft <NUM> at the groove <NUM>. The engagement of the holding mechanism <NUM> within the groove <NUM> prevents axial separation of the catheter assembly from the handle. The catheter assembly can be released from the handle by depressing button <NUM>, which moves the holding mechanism <NUM> from locking engagement with the main shaft. Furthermore, the main shaft <NUM> can be formed with a flat surface portion within the groove <NUM>. The flat surface portion is positioned against a corresponding flat surface portion of the engaging portion <NUM>. This engagement holds the main shaft <NUM> stationary relative to the torque shaft <NUM> as the torque shaft is rotated during valve deployment.

The proximal end portion of the torque shaft <NUM> can have a driven nut <NUM> (<FIG>) that is slidably received in a drive cylinder <NUM> (<FIG>) mounted inside the handle. The nut <NUM> can be secured to the proximal end of the torque shaft <NUM> by securing the nut <NUM> over a coupling member <NUM> (<FIG>). <FIG> is a perspective view of the inside of the handle <NUM> with the drive cylinder and other components removed to show the driven nut and other components positioned within the drive cylinder. The cylinder <NUM> has a through opening (or lumen) extending the length of the cylinder that is shaped to correspond to the flats of the nut <NUM> such that rotation of the drive cylinder is effective to rotate the nut <NUM> and the torque shaft <NUM>. The drive cylinder can have an enlarged distal end portion <NUM> that can house one or more seals (e.g., O-rings <NUM>) that form a seal with the outer surface of the main shaft <NUM> (<FIG>). The handle can also house a fitting <NUM> that has a flush port in communication with the lumen of the torque shaft and/or the lumen of the main shaft.

The drive cylinder <NUM> is operatively connected to an electric motor <NUM> through gears <NUM> and <NUM>. The handle can also house a battery compartment <NUM> that contains batteries for powering the motor <NUM>. Rotation of the motor in one direction causes the torque shaft <NUM> to rotate, which in turn causes the sheath <NUM> to retract and uncover a prosthetic valve at the distal end of the catheter assembly. Rotation of the motor in the opposite direction causes the torque shaft to rotate in an opposite direction, which causes the sheath to move back over the prosthetic valve. An operator button <NUM> on the handle allows a user to activate the motor, which can be rotated in either direction to un-sheath a prosthetic valve or retrieve an expanded or partially expanded prosthetic valve.

As described above, the distal end portion of the nose catheter shaft <NUM> can be secured to an inner fork <NUM> that is moved relative to an outer fork <NUM> to release a prosthetic valve secured to the end of the delivery apparatus. Movement of the shaft <NUM> relative to the main shaft <NUM> (which secures the outer fork <NUM>) can be effected by a proximal end portion <NUM> of the handle that is slidable relative to the main housing <NUM>. The end portion <NUM> is operatively connected to the shaft <NUM> such that movement of the end portion <NUM> is effective to translate the shaft <NUM> axially relative to the main shaft <NUM> (causing a prosthetic valve to be released from the inner and outer forks). The end portion <NUM> can have flexible side panels <NUM> on opposite sides of the handle that are normally biased outwardly in a locked position to retain the end portion relative to the main housing <NUM>. During deployment of the prosthetic valve, the user can depress the side panels <NUM>, which disengage from corresponding features in the housing and allow the end portion <NUM> to be pulled proximally relative to the main housing, which causes corresponding axial movement of the shaft <NUM> relative to the main shaft. Proximal movement of the shaft <NUM> causes the prongs <NUM> of the inner fork <NUM> to disengage from the apertures <NUM> in the stent <NUM>, which in turn allows the retaining arms <NUM> of the stent to deflect radially outwardly from the openings <NUM> in the prongs <NUM> of the outer fork <NUM>, thereby releasing the prosthetic valve.

<FIG> shows an alternative embodiment of a motor, indicated at <NUM>, that can be used to drive a torque shaft (e.g., torque shaft <NUM>). In this embodiment, a catheter assembly can be connected directly to one end of a shaft <NUM> of the motor, without gearing. The shaft <NUM> includes a lumen that allows for passage of an innermost shaft (e.g., shaft <NUM>) of the catheter assembly, a guide wire, and/or fluids for flushing the lumens of the catheter assembly.

Alternatively, the power source for rotating the torque shaft <NUM> can be a hydraulic power source (e.g., hydraulic pump) or pneumatic (air-operated) power source that is configured to rotate the torque shaft. In another embodiment, the handle can have a manually movable lever or wheel that is operable to rotate the torque shaft <NUM>.

In another embodiment, a power source (e.g., an electric, hydraulic, or pneumatic power source) can be operatively connected to a shaft, which is turn is connected to a prosthetic valve <NUM>. The power source is configured to reciprocate the shaft longitudinally in the distal direction relative to a valve sheath in a precise and controlled manner in order to advance the prosthetic valve from the sheath. Alternatively, the power source can be operatively connected to the sheath in order to reciprocate the sheath longitudinally in the proximal direction relative to the prosthetic valve to deploy the prosthetic valve from the sheath.

Referring to <FIG>, there is shown a prosthetic aortic heart valve <NUM>, according to another embodiment. Similar to the prosthetic valve <NUM>, the prosthetic valve <NUM> includes an expandable frame member, or stent, <NUM> that supports an expandable valve member, which in the illustrated embodiment comprises a flexible leaflet section <NUM>. Also, the prosthetic valve <NUM> is radially compressible to a compressed state for delivery through the body to a deployment site and expandable to its functional size shown in <FIG> at the deployment site. In certain embodiments, the prosthetic valve <NUM> is self-expanding; that is, the prosthetic valve can radially expand to its functional size when advanced from the distal end of a delivery sheath. In other embodiments, the prosthetic valve can be a balloon-expandable prosthetic valve that can be adapted to be mounted in a compressed state on the balloon of a delivery catheter. The prosthetic valve can be expanded to its functional size at a deployment site by inflating the balloon, as known in the art. Apparatuses particularly suited for percutaneous delivery and implantation of the prosthetic valve <NUM> (such as those described herein) are also suitable for percutaneous delivery and implantation of the prosthetic valve <NUM>. The illustrated prosthetic valve <NUM> is adapted to be deployed in the native aortic annulus, although it also can be used to replace the other native valves of the heart (the mitral, tricuspid and pulmonary valves). Moreover, the prosthetic valve <NUM> can be adapted to replace other valves within the body, such venous valves.

The frame member <NUM> of the prosthetic valve <NUM> can have the same overall shape and construction as the frame member <NUM> of the prosthetic valve <NUM>. Thus, similar to the frame member <NUM>, the frame member <NUM> can be formed from a plurality of longitudinally extending, generally sinusoidal shaped frame members, or struts, <NUM>. Referring to <FIG>, the stent <NUM> has an inflow end <NUM> and an outflow end <NUM>, and the mesh structure formed by the struts <NUM> comprises a generally cylindrical "upper" or outflow end portion <NUM>, an outwardly bowed or distended intermediate section <NUM>, and an inwardly bowed "lower" or inflow end portion <NUM>. Further, the stent <NUM> can have a plurality of angularly spaced retaining arms, or projections, in the form of posts <NUM> (three in the illustrated embodiment) that extend from upper portion of the stent <NUM>. Each retaining arm <NUM> has a respective aperture <NUM> that is sized to receive prongs of a valve-retaining mechanism that can be used to form a releasable connection between the prosthetic valve and a delivery apparatus (described above). In alternative embodiments, the retaining arms <NUM> need not be provided if a valve-retaining mechanism is not used. In further embodiments, the retaining arms <NUM> can extend from the lower portion of the stent <NUM>, for example, for applications involving antegrade implantation of the valve (e.g., the delivery apparatus is inserted through a surgical opening in the wall of the left ventricle of the heart in a transventricular approach, such as an opening made at the bare spot on the lower anterior ventricle wall).

The leaflet assembly <NUM> of the prosthetic aortic heart valve <NUM> is similar to the leaflet assembly <NUM> of the prosthetic aortic heart valve <NUM>, although there are several differences, described below. For example, with reference to <FIG> and <FIG>, the leaflet assembly <NUM> comprises three leaflets 434a, 434b, 434c made of a flexible material. Each leaflet has an inflow end portion <NUM> and an outflow end portion <NUM>. The leaflets can comprise any suitable biological material (e.g., pericardial tissue, such as bovine or equine pericardium), bio-compatible synthetic materials, or other such materials, such as those described in <CIT>. The leaflet assembly <NUM> can include an annular reinforcing skirt assembly <NUM> that is secured to the inflow end portions of the leaflets 434a, 434b, 434c at a suture line <NUM> adjacent the inflow end of the prosthetic valve. The inflow end portion of the leaflet assembly <NUM> can be secured to the stent <NUM> by suturing the skirt assembly <NUM> to the struts <NUM> of the lower section <NUM> of the stent (best shown in <FIG>).

With reference to <FIG>, the skirt assembly <NUM> can include an upper skirt <NUM> and a lower skirt <NUM>. The inflow end portions <NUM> of the leaflets 434a, 434b, and 434c can be positioned between an upper portion <NUM> of the lower skirt <NUM> and a lower portion <NUM> of the upper skirt <NUM>, with the upper skirt desirably having an outward placement compared to the lower skirt. The upper skirt <NUM>, the inflow end portions <NUM> of the leaflets 434a, 434b, 434c, and the lower skirt <NUM> can be secured by sutures along a scalloped or undulating suture line <NUM> adjacent the inflow end of the prosthetic valve (<FIG>). The inflow end portion of the leaflet assembly <NUM> can be secured to the stent <NUM> by suturing the upper skirt <NUM>, the lower skirt <NUM>, or both the upper skirt <NUM> and the lower skirt <NUM> to the struts <NUM> of the lower section <NUM> of the stent via sutures <NUM> (best shown in <FIG>). The skirt assembly <NUM> (including the upper skirt <NUM> and the lower skirt <NUM>), desirably can be made of a bio-compatible synthetic material, such as polytetrafluoroethylene (PTFE), or a woven fabric material, such as woven polyester (e.g., polyethylene terephthalate) (PET), DACRON®). The upper skirt <NUM> and the lower skirt <NUM> can be made of the same, or different, material.

As best shown in <FIG>, the outflow end portion of upper skirt <NUM> can be shaped to substantially align with the undulating or zigzag shape formed by the struts <NUM> of the lower section <NUM> of the stent, e.g., for ease of securing the upper skirt to the struts of the stent by suture. For example, the upper skirt <NUM> can include an upper edge <NUM> shaped to correspond to the shape of the second lowermost row of cells of the frame member <NUM>. The inflow end portion of upper skirt <NUM> can have an undulating lower edge <NUM> that substantially aligns with the undulating suture line <NUM> and the scalloped or undulating shape of the inflow portions of the leaflets 443a, 443b, and 443c. The outflow end portion of the lower skirt <NUM> can be shaped to have an undulating shape that substantially corresponds with the undulating suture line <NUM>. The inflow end portion <NUM> of the upper skirt <NUM> and the outflow end portion <NUM> of the lower skirt <NUM> overlap each other on opposite sides of the leaflet inflow end portions at least enough to secure the upper skirt and lower skirt by sutures along the suture line <NUM>. The inflow end portion of the lower skirt <NUM> typically extends to the inflow end <NUM> of the stent, although other configurations are possible. For example, the inflow end portion of the lower skirt <NUM> can be shaped to include a lower edge shaped to correspond to the shape of a lowermost row of cells of the frame.

The outflow end portion of the leaflet assembly <NUM> can be secured to the upper portion of the stent <NUM> at three angularly spaced commissure attachments of the leaflets 434a, 434b, 434c, in a manner similar to the configuration used to secure the outflow end portion of the leaflet assembly <NUM> to the upper portion of the stent <NUM> at three angularly spaced commissure attachments of the leaflets 34a, 34b, 34c (as best shown in <FIG>).

<FIG> shows the operation of the prosthetic valve <NUM>. During diastole, the leaflets 434a, 434b, 434c collapse to effectively close the prosthetic valve. As shown, the curved shape of the intermediate section <NUM> of the stent <NUM> defines a space between the intermediate section and the leaflets that mimics the sinuses of Valsalva. Thus, when the leaflets close, backflow entering the "sinuses" creates a turbulent flow of blood along the upper surfaces of the leaflets, as indicated by arrows <NUM>. This turbulence assists in washing the leaflets and the skirt assembly <NUM> to minimize clot formation.

Referring to <FIG> and <FIG>, the prosthetic valve <NUM> can further include a sealing skirt <NUM> positioned at the lower section <NUM> of the stent. The sealing skirt <NUM> provides an additional barrier against paravalvular leakage following implantation of the stent in a subject by providing material at the inflow end portion of the stent that protrudes outwardly through the openings of the cells of the frame and contacts surrounding tissue of the native annulus, thereby minimizing or reducing paravalvular leakage. The sealing skirt is desirably supported by the upper skirt <NUM> and the lower skirt <NUM>, which prevent the sealing skirt <NUM> from contacting the leaflets 434a, 434b, and 434c of the leaflet assembly <NUM>. The upper skirt <NUM> and the lower skirt <NUM> additionally provide support to ensure that the material of the sealing skirt <NUM> extends outwardly between cells formed by the struts <NUM> of the stent <NUM> to seal against the surrounding annulus.

<FIG> depicts an embodiment of the sealing skirt <NUM> prior to attachment to the stent. The outflow end portion <NUM> of the sealing skirt <NUM> can have an undulating or zigzag shape that has an upper edge shaped to correspond to the shape of the upper boundary of a lower most row of cells of the frame formed by the struts <NUM> of the stent <NUM>. In alternative embodiments, the outflow end portion <NUM> of the sealing skirt <NUM> can have a substantially straight edge that does not align with the undulating or zigzag shape formed by the struts <NUM> of the stent <NUM>; instead the outflow end portion <NUM> of the sealing skirt <NUM> can transect the lower most row of cells of the frame formed by the struts <NUM> of the stent <NUM> (see, e.g., <FIG>). The inflow end portion <NUM> of the sealing skirt <NUM> typically extends to the inflow end <NUM> of the stent (see, e.g., <FIG>), although other configurations are possible. For example, the sealing skirt <NUM> can have an upper edge and a lower edge shaped to correspond to the shape of a lower most row of cells formed by the struts <NUM> of the inflow end <NUM> of the stent such that the sealing skirt <NUM> only occludes the openings in the lowermost row of cells (see, e.g., <FIG>). In additional embodiments, the inflow end portion of the sealing skirt <NUM> can be constructed to extend beyond the inflow end <NUM> of the stent (see, e.g., <FIG>). In several embodiments, the inflow end portion <NUM> of the sealing skirt <NUM> can be shaped to substantially align with the inflow end portion of the lower skirt <NUM>.

Referring to <FIG>, the sealing skirt <NUM> can be secured to the struts <NUM> of the lower portion of the stent <NUM> with sutures <NUM>. The sutures <NUM> can secure the sealing skirt <NUM> to the struts <NUM> of the lower portion of the stent <NUM>, and optionally can also secure the upper skirt <NUM> and/or the lower skirt <NUM> to the struts <NUM> of the lower portion of the stent <NUM>. The sealing skirt <NUM> desirably is made of a bio-compatible synthetic material, such as polytetrafluoroethylene (PTFE), or a woven fabric material, such as woven polyester (e.g., polyethylene terephthalate) (PET), DACRON®). In several embodiments, the sealing skirt comprises a plush or pile material, such as a loop yarn, which functions as a filler material in that fibers of the sealing skirt can extend outwardly through openings in the frame and fill spaces between the frame and the native annulus. The plush or pile material is also compressible, thus minimizing the crimp profile of the sealing skirt <NUM>. In some embodiments, the sealing skirt can be made of a PET loop yarn or polyester <NUM>/<NUM> textured yarn. In additional embodiments, the sealing skit can be made of polyester multifilament partially oriented yarn (poy); a polyester <NUM>-ply multifilament yarn; a polyester film; a knitted polyester; a woven polyester; and/or a felted polyester. Such materials are available commercially, for example, from Biomedical Structures (Warwick, RI) and ATEX Technologies (Pinebluff, NC).

With reference to <FIG>, the illustrated embodiment of the sealing skirt <NUM> can be made of a relatively less bulky, non-plush or non-pile material (e.g., woven PET fabric) and secured (e.g., with sutures <NUM>) to the frame member <NUM> such that portions of the sealing skirt protrude radially outwardly through the cells of the frame member <NUM> to seal against the surrounding annulus. In such embodiments, the sealing skirt can be secured by sutures <NUM> such that slack material of sealing skirt <NUM> bulges or protrudes through the lowermost cells formed by the struts <NUM> of the frame member <NUM>. The lower skirt <NUM> supports the sealing skirt <NUM> (and can be secured to the frame member <NUM> with the same sutures <NUM> as used to secure the sealing skirt <NUM>) to prevent the slack material of the sealing skirt from protruding inwardly towards the longitudinal axis of the valve <NUM> and contacting the leaflets. In such embodiments, the length of the sealing skirt <NUM> is typically longer than that of the inner circumference of the lower portion of the frame member <NUM>. <FIG> provides a perspective view depicting a portion of the frame member <NUM> and the sealing skirt <NUM>; however, for clarity of illustration, the upper skirt <NUM>, the lower skirt <NUM> and the leaflet assembly <NUM> are not depicted.

The dimensions of the sealing skirt <NUM> can be adjusted to obtain the desired amount of material protruding from an expanded annular frame, depending on the type of material used for the sealing skirt. For example, in embodiments where the sealing skirt <NUM> is constructed of a plush or pile material (such as a loop yarn) having fibers that protrude outwardly between the cells of the frame member <NUM>, the length of the sealing skirt (in an unrolled or flattened configuration prior to mounting on the frame) can be substantially the same as the circumference of the lower portion of the frame member <NUM>. In other embodiments, the length of the sealing skirt prior to mounting on the annular frame is at least about <NUM>% (such as at least about <NUM>%, at least about <NUM>%, at least about <NUM>%, at least about <NUM>%) longer than the circumference of the expanded annular frame of the stent, to allow for additional material to protrude between the cells of the frame member <NUM>.

Although description of the sealing skirt <NUM> above is made with reference to prosthetic heart valve <NUM>, the sealing skirt can also be included on prosthetic heart valve <NUM>, for example, by modifying the dimensions of the sealing skirt <NUM> as needed to secure the sealing skirt <NUM> to skirt assembly <NUM> of heart valve <NUM>.

The prosthetic valve <NUM> can be implanted in a retrograde approach where the prosthetic valve, mounted in a crimped state at the distal end of a delivery apparatus (e.g., the delivery apparatus <NUM>), is introduced into the body via the femoral artery and advanced through the aortic arch to the heart, as further described in <CIT>. The prosthetic valve <NUM> can also be implanted in a retrograde approach where the prosthetic valve, mounted in a crimped state at the distal end of a delivery apparatus (e.g., the delivery apparatus <NUM>), is introduced into the body via the left or right subclavian artery and advanced to the heart. In further embodiments, the prosthetic valve <NUM> can be implanted in an antegrade approach where the prosthetic valve, mounted in a crimped state at the distal end of a delivery apparatus, is introduced into the body and advanced transventricularly (see, e.g., <CIT>). For transventricular implant applications, the retaining arms <NUM> can be included on the lower portion of the stent.

Prior to insertion of the delivery apparatus, an introducer sheath can be inserted into the artery followed by a guide wire, which is advanced through the patient's vasculature through the aorta and into the left ventricle. The delivery apparatus can then be inserted through the introducer sheath and advanced over the guide wire until the distal end portion of the delivery apparatus containing the prosthetic valve <NUM> is advanced to a location adjacent to or within the native aortic valve.

Known introducer sheaths typically employ a sleeve made from polymeric tubing having a radial wall thickness of from about <NUM> (about <NUM> inch) to about <NUM> (about <NUM> inch). <FIG> shows an embodiment of an introducer sheath, indicated at <NUM>, that employs a thin metallic tubular layer that has a much smaller wall thickness compared to known devices. In particular embodiments, the wall thickness of the sheath <NUM> is from about <NUM> (about <NUM> inch) to about <NUM> (about <NUM> inch). The introducer sheath <NUM> includes a proximally located housing or hub <NUM> and a distally extending sleeve or cannula <NUM>. The housing <NUM> can house a seal or a series of seals as known in the art to minimize blood loss. The sleeve <NUM> comprises a tubular layer or sleeve <NUM> that is formed from a metal or metal alloy, such as Nitinol or stainless steel, and desirably is formed with a series of circumferentially extending or helically extending slits or openings to impart a desired degree of flexibility to the sleeve.

As shown in <FIG>, for example, the tubular layer <NUM> is formed (e.g., laser cut) with an "I-beam" pattern of alternating circular bands <NUM> and openings <NUM> with axially extending connecting portions <NUM> connecting adjacent bands <NUM>. Two adjacent bands <NUM> can be connected by a plurality of angularly spaced connecting portions <NUM>, such as four connecting portions <NUM> spaced about <NUM> degrees from each other around the axis of the sleeve, as shown in the illustrated embodiment. The sleeve <NUM> exhibits sufficient flexibility to allow the sleeve to flex as it is pushed through a tortuous pathway without kinking or buckling. <FIG> shows another pattern of openings that can be laser cut or otherwise formed in the tubular layer <NUM>. The tubular layer in the embodiment of <FIG> has a pattern of alternating bands <NUM> and openings <NUM> with connecting portions <NUM> connecting adjacent bands <NUM>, the openings <NUM> and connecting portions <NUM> each arranged in a helical pattern along the length of the sleeve. In alternative embodiments, the pattern of bands and openings and/or the width of the bands and/or openings can vary along the length of the sleeve in order to vary stiffness of the sleeve along its length. For example, the width of the bands can decrease from the proximal end to the distal end of the sleeve to provide greater stiffness near the proximal end and greater flexibility near the distal end of the sleeve.

As shown in <FIG>, the sleeve <NUM> can have a thin outer layer or liner <NUM> extending over the tubular layer <NUM>, the outer layer <NUM> made of a low friction material to reduce friction between the sleeve and the vessel wall into which the sleeve is inserted. The sleeve <NUM> can also have a thin inner layer or liner <NUM> covering the inner surface of the tubular layer <NUM> and made of a low friction material to reduce friction between the sleeve and the delivery apparatus that is inserted into the sleeve. The inner and outer layers can be made from a suitable polymer, such as PET, PTFE, FEP, and/or polyether block amide (PEBAX®). The inner and outer liners, and the tubular layer, are sized appropriately for the desired application of the introducer sheath <NUM>. In particular embodiments, the inner liner <NUM> can have a radial wall thickness in the range of from about <NUM> (about <NUM> inch) to about <NUM> (about <NUM> inch) (such as from about <NUM> (about <NUM> inch) to about <NUM> (<NUM> inch), for example about <NUM> (about <NUM> inch)). In particular embodiments, the outer liner <NUM> has a radial wall thickness in the range of about from about <NUM> (<NUM> inch) to about <NUM> (about <NUM> inch) (such as from about <NUM> (about <NUM> inch) to about <NUM> (<NUM> inch), for example about <NUM> (about <NUM> inch)). In particular embodiments, the tubular layer <NUM> can have a radial wall thickness in the range of from about <NUM> (about <NUM> inch) to about <NUM> (about <NUM> inch) (such as from about <NUM> (about <NUM> inch) to about <NUM> (about <NUM> inch), for example about <NUM> (about <NUM> inch) or about <NUM> (about <NUM> inch)).

Together, the inner liner <NUM>, the tubular layer <NUM>, and the outer layer <NUM>, have a wall thickness that can vary based on the desired final product. In some embodiments, the inner liner <NUM>, the tubular layer <NUM>, and the outer layer <NUM>, together can have a radial wall thickness in the range of from about <NUM> (about <NUM> inch) to about <NUM> (about <NUM> inch) (such as from about <NUM> (about <NUM> inch) to about <NUM> (about <NUM> inch). As such, the sleeve <NUM> can be provided with an outer diameter that is about <NUM>-<NUM> Fr smaller than known devices. The relatively smaller profile of the sleeve <NUM> improves ease of use, lowers risk of patient injury via tearing of the arterial walls, and increases the potential use of minimally invasive procedures (e.g., heart valve replacement) for patients with highly calcified arteries, tortuous pathways or small vascular diameters.

The inner liner <NUM> can be applied to the interior of the tubular layer <NUM>, for example, using a two-stage molding process. In one step, a preform, cylindrical polymer tube or parison <NUM> (<FIG>) with an open end <NUM> and a closed end <NUM> is formed, e.g., by an injection molding or extrusion process. The tube <NUM> has an outer diameter less than that of the inner diameter of the tubular layer <NUM>, and a wall thickness designed to provide an appropriate thickness for the inner liner <NUM> of the tubular layer <NUM>, following blow molding. In one embodiment, the tube <NUM> can have a wall thickness of from about <NUM> (about <NUM> inch) to about <NUM> (about <NUM> inch) (such as from about <NUM> (about <NUM> inch) to about <NUM> (about <NUM> inch), such as about <NUM> (about <NUM> inch)). Appropriate material for the polymer tube can be selected based on the desired finished product. In some embodiments, the polymer tube <NUM> is made of nylon-<NUM>, polyethylene, fluorinated ethylene propylene, and/or polyether block amide (, e.g., PEBAX® 72D). The length of the tube <NUM> can be varied depending on the length of the tubular layer <NUM>, and is typically longer than that of the tubular layer <NUM>. In another step, heat and pressure are applied to the tube <NUM> to form the inner liner <NUM> by blow molding.

<FIG> depict an exemplary method of using blow molding to apply the tube <NUM> to the tubular layer <NUM> to form the inner liner <NUM>. The tubular layer <NUM> is inserted into mold <NUM>. The mold <NUM>, which has an inner diameter that is slightly larger than the outer diameter of the tubular layer <NUM> such that the sleeve can be easily inserted into and removed from the mold, prevents any appreciable radial expansion of the sleeve during the pressurization step (described below). The mold <NUM> can be constructed to be non-expandable during blow molding of the tube <NUM>. The mold <NUM> can have a cylindrical inner surface <NUM> that corresponds to the shape of the outer surface of the tubular layer <NUM>. Thus, when the tube <NUM> is pressurized (discussed in detail below), the inner surface of the mold prevents the tubular layer <NUM> from expanding/deforming under pressure from the expanding tube <NUM> and prevents portions of the tube <NUM> from expanding radially outwardly through the openings <NUM> in the tubular layer <NUM>.

The tube <NUM> with the open end <NUM> and the closed end <NUM> is inserted into the tubular layer <NUM>, as shown in <FIG>. The closed end <NUM> can extend beyond one end of the tubular layer <NUM>, and the open end <NUM> can extend beyond the other end of tubular layer <NUM>.

Heat and pressure are applied to the tube <NUM> to cause the tube to expand against the inner surface of the tubular layer <NUM> to form an expanded polymer tube <NUM>. The heat and pressure can be applied sequentially (e.g., heat is applied, then pressure), or simultaneously. For example, the heat and pressure can be applied simultaneously by injecting heated compressed gas or liquid into the open end <NUM> of the tube <NUM>. Alternatively, the heat can be applied by heating the mold <NUM>, and the tube <NUM> can be pressurized by injecting compressed gas or liquid into the open end <NUM> of the tube <NUM>. For example, the entire assembly including the mold <NUM>, the tubular layer <NUM>, and the tube <NUM> can be immersed in a heated fluid. In this regard, the wall of the mold can have one or more apertures that allow the heated fluid (e.g., a heated liquid such as water) to flow through the apertures and contact the tube <NUM> to facilitate heating of the tube. Various other types of heat sources, such as resistive, conductive, convective, and infrared heat sources, can be used to apply heat to the tube <NUM>. Optionally, the tube <NUM> can be stretched axially concurrently with heating and/or pressurizing, or in one or more separate stretching steps performed at separate times from heating and/or pressurizing.

Portions of the expanded tube <NUM> extending beyond the either end of tubular layer <NUM> can be trimmed to form the inner liner <NUM> of tubular layer <NUM>. In some embodiments, the inner liner <NUM> can expand into the openings <NUM> of the tubular layer <NUM> during the molding process, and remain in the openings following the molding process. In other embodiments, the inner liner <NUM> does not expand into and/or remain into the openings <NUM> of the tubular layer <NUM> during the molding process. The specific heat and pressure conditions (including the duration for which the heat and pressure should be applied, as well as cooling conditions) for blow molding the inner liner <NUM> of the tubular layer <NUM> can be varied as desired, and typically will depend on the starting materials and desired finished product. In some embodiments, the tube <NUM> is heated to about <NUM> (about <NUM> °F) and pressurized to about <NUM> kPa (about <NUM> psi) for a period of time sufficient to form inner liner <NUM>. Further, general methods of blow molding are known to the person of ordinary skill in the art (see, e.g., <CIT>).

The outer layer <NUM> of the sheath can be applied over and secured to the outer surface of the tubular layer <NUM> using conventional techniques or mechanisms (e.g., using an adhesive or by thermal welding). In one embodiment, the outer layer is formed by shrink wrapping a polymer tubular layer to tubular layer <NUM>. Appropriate material for the outer layer <NUM> can be selected based on the desired finished product. In some embodiments, the outer layer <NUM> is made of nylon-<NUM>, polyether block amide (PEBAX®, e.g., PEBAX® 72D), and/or polyethylene. The outer layer <NUM> can be applied to the tubular layer <NUM> before or after the inner layer <NUM> has been formed using the molding process described above.

In a modification of the introducer sheath <NUM>, the sheath can have inner and outer layers <NUM>, <NUM>, respectively, which are secured to a metal sleeve (e.g., sleeve <NUM>) only at the proximal and distal ends of the metal sleeve. The inner and outer polymeric layers can be bonded to the metal sleeve (or to each other through the gaps in the metal sleeve), for example using a suitable adhesive or by thermal welding. In this manner, the metal sleeve is unattached to the inner and outer polymeric layers between the proximal and distal ends of the sleeve along the majority of the length of the sleeve, and therefore is "free-floating" relative to the polymeric layers along the majority of the length of the sleeve. This construction allows the adjacent bands of metal to bend more easily relative to the inner and outer layers, providing the sheath with greater flexibility and kink-resistance than if the inner and outer layers were bonded along the entire length of the sleeve.

<FIG> shows a segment of an alternative metal sleeve, indicated at <NUM>, that can be used in the introducer sheath <NUM>. The sheath <NUM> in this embodiment desirably includes inner and outer polymeric layers, which desirably are secured to the metal sleeve only at its proximal and distal ends as discussed above. The sleeve <NUM> includes a plurality of circular bands or rings <NUM> interconnected by two links, or connecting portions, <NUM>, extending between each pair of adjacent rings. Each pair of links connecting two adjacent bands <NUM> desirably are spaced about <NUM> degrees from each other and desirably are rotationally offset by about <NUM> degrees from an adjacent pair of links, which allows for multi-axial bending.

<FIG> shows side view of a segment of another embodiment of a metal sleeve, indicated at <NUM>, that can be used in the introducer sheath <NUM>. The sleeve <NUM> has the same cut pattern as the sleeve <NUM>, and therefore has circular bands <NUM> and two links <NUM> connecting adjacent bands, and further includes two cutouts, or apertures, <NUM> formed in each band <NUM> to increase the flexibility of the sleeve. The cutouts <NUM> desirably have a generally elliptical or oval shape, but can have other shapes as well. Each cutout <NUM> desirably extends about <NUM> degrees in the circumferential direction of the sleeve and desirably is rotational offset by about <NUM> degrees from a cutout <NUM> in an adjacent band <NUM>.

In particular embodiments, the metal sleeve of an introducer sheath has a wall thickness in the range of from about <NUM> (about <NUM> inch) to about <NUM> (about <NUM> inch). In one implementation, a sheath has a metal sleeve having a wall thickness of about <NUM> (about <NUM> inch) and an inner diameter of about <NUM> (about <NUM> inch), an inner polymeric layer having a wall thickness of about <NUM> (about <NUM> inch), an outer polymeric layer having a wall thickness of about <NUM> (about <NUM> inch), and a total wall thickness (through all three layers) of about <NUM> (about <NUM> inch). In another implementation, a sheath has a metal sleeve having a wall thickness of about <NUM> (about <NUM> inch) and an inner diameter of about <NUM> (about <NUM> inch), an inner polymeric layer having a wall thickness of about <NUM> (about <NUM> inch), an outer polymeric layer having a wall thickness of about <NUM> (about <NUM> inch), and a total wall thickness (through all three layers) of about <NUM> (about <NUM> inch). <FIG> shows the cut pattern for forming the metal sleeve <NUM> of <FIG> shows the cut pattern for forming the metal sleeve <NUM> of <FIG> shows a cut pattern similar to the cut pattern of <FIG>, but including cutouts <NUM> that are narrower than the cutouts shown in <FIG>.

Table <NUM> above demonstrates the bend performance of several metal sleeves. Each metal sleeve had an inner diameter of about <NUM> (about <NUM> inch). Each sleeve was formed with the cut pattern shown in <FIG>, except for the last sleeve in Table <NUM>, which was formed with the cut pattern shown in <FIG>. All of the sleeves in Table <NUM> provide device deliverability at a relatively small bend radius (<NUM>, <NUM> inch). Furthermore, it was found that the metal sleeves recover their circular cross-sectional shapes even after passing a delivery device through a visibly kinked section of the sleeve.

In view of the many possible embodiments to which the principles of the disclosed invention may be applied, it should be recognized that the illustrated embodiments are only preferred examples and should not be taken as limiting the scope of the disclosure. Moreover, additional embodiments are disclosed in <CIT> (<CIT>) and <CIT> (<CIT>). Accordingly, the scope of the disclosure is defined by the following claims. We therefore claim all that comes within the scope of these claims.

Claim 1:
A prosthetic heart valve (<NUM>), comprising:
a collapsible and expandable annular frame (<NUM>) that is configured to be collapsed to a radially collapsed state for mounting on a delivery apparatus and expanded to a radially expanded state inside the body, the frame (<NUM>) having an inflow end (<NUM>), an outflow end, and a longitudinal axis extending from the inflow end (<NUM>) to the outflow end, the frame (<NUM>) comprising a plurality of struts (<NUM>) defining a plurality of rows of a plurality of cells;
a collapsible and expandable valve member mounted within the annular frame (<NUM>); and
a collapsible and expandable sealing skirt (<NUM>) sutured to the struts (<NUM>) at an inflow end portion (<NUM>) of the annular frame (<NUM>), wherein the sealing skirt (<NUM>) comprises a plush or pile fabric and can contact tissue surrounding the prosthetic valve (<NUM>) when the prosthetic valve (<NUM>) is implanted within a native valve annulus.