Patent Description:
The human heart can suffer from various valvular diseases, which can result in significant malfunctioning of the heart and ultimately require replacement of the native heart valve with an artificial valve. There are a number of known artificial valves and a number of known methods of implanting these artificial valves in humans.

One method of implanting an artificial heart valve in a human patient is via open-chest surgery, during which the patient's heart is stopped and the patient is placed on cardiopulmonary bypass (using a so-called "heart-lung machine"). In one common surgical procedure, the diseased native valve leaflets are excised and a prosthetic valve is sutured to the surrounding tissue at the native valve annulus. Because of the trauma associated with the procedure and the attendant duration of extracorporeal blood circulation, some patients do not survive the surgical procedure or die shortly thereafter. It is well known that the risk to the patient increases with the amount of time required on extracorporeal circulation. Due to these risks, a substantial number of patients with defective native valves are deemed inoperable because their condition is too frail to withstand the procedure.

Because of the drawbacks associated with conventional open-chest surgery, percutaneous and minimally-invasive surgical approaches are in some cases preferred. In one such technique, a prosthetic valve is configured to be implanted in a much less invasive procedure by way of catheterization. For instance, <CIT> <CIT>, and <CIT> describe collapsible transcatheter prosthetic heart valves that can be percutaneously introduced in a compressed state on a catheter and expanded to a functional size at the desired position by balloon inflation or by utilization of a self-expanding frame or stent.

<CIT> discloses a prosthetic cardiac valve that comprises an anchor having an atrial skirt, an annular region, and a ventricular skirt. The prosthetic valve also has a plurality of prosthetic valve leaflets each having a first end and a free end. The first end is coupled with the anchor and the free end is opposite the first end. The prosthetic cardiac valve has an open configuration in which the free ends of the prosthetic valve leaflets are disposed away from one another to allow antegrade blood flow therepast, and a closed configuration in which the free ends of the prosthetic valve leaflets engage one another and substantially prevent retrograde blood flow therepast. The anchor has a collapsed configuration for delivery to the heart and an expanded configuration for anchoring the prosthetic cardiac valve to a patient's heart.

<CIT> relates to prosthetic cardiac and venous valves and a single catheter device and minimally invasive techniques for percutaneous and transluminal valvuloplasty and prosthetic valve implantation.

<CIT> discloses a heart valve prosthesis comprising a supported valve that includes a biological valve portion mounted within a support structure. The supported valve is configured to provide for substantially unidirectional flow of blood through the supported valve. The supported valve has inflow and outflow ends that are spaced axially apart from each other. A fixation support member includes inflow and outflow portions. The inflow portion of the fixation support member extends from a radially inner contact surface of the fixation support member radially outwardly and axially in a direction of the inflow end of the supported valve. The outflow portion of the fixation support member extends from the radially inner contact surface radially outwardly and axially in a direction away from the inflow portion of the fixation support member. The radially inner contact surface is attached to a radially outer surface of the supported valve adjacent the inflow end of the supported valve. The supported valve and the fixation support member are deformable between a reduced cross-sectional dimension and an expanded cross-sectional dimension thereof, whereby implantation of the heart valve prosthesis is facilitated.

<CIT> discloses an apparatus for replacing a native cardiac valve. The native cardiac valve has at least one leaflet and is surrounded by a native cardiac valve annulus having superior and inferior aspects. The apparatus comprises a barbell-shaped, expandable anchoring member including first, second, and main body portions extending between the end portions. The main body portion includes a channel defined by inner and outer surfaces. Each of the first and second end portions has a diameter greater than the diameter of the main body portion. The first and second end portions are sized to respectively contact the superior and inferior aspects of the native cardiac valve annulus when the expandable anchoring member is in an expanded configuration. The apparatus also includes an expandable support member operably disposed within the main body portion of the expandable anchoring member, and a prosthetic cardiac valve secured within the expandable support member.

<CIT> discloses an apparatus for endovascularly replacing a patient's heart valve, including: a delivery catheter having a diameter of <NUM> or less; an expandable anchor disposed within the delivery catheter; and a replacement valve disposed within the delivery catheter.

An implantable prosthetic valve comprises a radially collapsible and radially expandable, annular, main body defining a lumen therethrough, a first flange coupled to the main body and extending radially away from the main body, the first flange comprising a plurality of radially extending first protrusions, a second flange coupled to the main body and extending radially away from the main body, the second flange comprising a plurality of radially extending second protrusions, and a valve member supported within the lumen of the frame, wherein the first flange and the second flange are closer to one another when the main body is in a radially expanded configuration than when the main body is in a radially collapsed configuration, and wherein each of the first protrusions and each of the second protrusions can comprise a first radial strut coupled to a first node of the main body and extending radially away from the main body, a second radial strut coupled to a second node of the main body and extending radially away from the main body, a first angled strut coupled at an angle to the first radial strut, and a second angled strut coupled at an angle to the second radial strut and coupled to the first angled strut.

The valve member defines an inlet end and an outlet end of the implantable prosthetic valve, and the first flange and the second flange are coupled to the main body at locations located closer to the inlet end than to the outlet end of the implantable prosthetic valve. In some embodiments, the distance between the first flange and the second flange when the prosthetic valve is in the radially collapsed configuration is larger than the thickness of the native human mitral valve annulus, and the distance between the first flange and the second flange when the prosthetic valve is in the radially expanded configuration is smaller than the thickness of the native human mitral valve annulus. In some embodiments, the first protrusions are angularly offset from the second protrusions.

In some embodiments, the main body has a first end and a second end, and comprises a network of struts interconnected at a plurality of nodes to form a plurality of open cells; the first protrusions are coupled to first nodes of the main body at the first end of the main body; and the second protrusions are coupled to second nodes of the main body, which are displaced toward the second end of the main body from the first end of the main body by the smallest increment available. In some embodiments, the main body has a first end and a second end, and comprises a network of struts interconnected at a plurality of nodes to form a plurality of open cells; the first protrusions are coupled to first nodes of the main body at the first end of the main body; and the second protrusions are coupled to second nodes of the main body, the second nodes being the closest nodes in the network of struts to the first nodes. In some embodiments, the main body has a first end and a second end, and comprises a network of struts interconnected at a plurality of nodes to form a plurality of open cells; the first protrusions are coupled to first nodes of the main body at the first end of the main body; and the second protrusions are coupled to second nodes of the main body, the first nodes and the second nodes being situated in a single circumferential row of open cells.

In some embodiments, the first flange extends radially away from the main body such that an angle between a side of the main body and the first flange is between about <NUM>° and about <NUM>°, and the second flange extends radially away from the main body such that an angle between a side of the main body and the second flange is between about <NUM>° and about <NUM>°. In some embodiments, the first flange extends radially away from the main body such that an angle between a side of the main body and the first flange is between about <NUM>° and about <NUM>°, and the second flange extends radially away from the main body such that an angle between a side of the main body and the second flange is between about <NUM>° and about <NUM>°. In some embodiments, the first flange extends radially away from the main body such that an angle between a side of the main body and the first flange is about <NUM>°, and the second flange extends radially away from the main body such that an angle between a side of the main body and the second flange is about <NUM>°.

In some embodiments, the first flange extends radially away from the main body parallel to the second flange. In some embodiments, the first flange and the second flange extend radially away from the main body in directions converging toward one another such that an angle between the radially extending flanges is less than about <NUM>°. In some embodiments, the first flange and the second flange extend radially away from the main body in directions diverging away from one another such that an angle between the radially extending flanges is less than about <NUM>°.

A method of implanting a prosthetic apparatus at the native mitral valve region of a heart, which is not covered by the claims, can comprise delivering the prosthetic apparatus to the native mitral valve region within a delivery apparatus, and deploying the prosthetic apparatus from the delivery apparatus, wherein the prosthetic apparatus comprises a main body, a first flange coupled to the main body and extending radially away from the main body perpendicular to a side of the main body, and a second flange coupled to the main body and extending radially away from the main body perpendicular to the side of the main body, and wherein deploying the prosthetic apparatus from the delivery apparatus allows the prosthetic apparatus to radially expand, such that a distance between the first flange and the second flange decreases and the first flange and the second flange pinch a native mitral valve annulus between them.

The frames described herein can be used to provide structure to prosthetic valves designed to be implanted within the vasculature of a patient. The frames described herein can be particularly advantageous for use in prosthetic valves to be implanted within a patient's native mitral valve, but can be used in prosthetic valves to be implanted in various other portions of a patient's vasculature (e.g., another native valve of the heart, or various other ducts or orifices of the patient's body). When implanted, the frames described herein can provide structural support to a leaflet structure and/or other components of a prosthetic valve such that the prosthetic valve can function as a replacement for a native valve, allowing fluid to flow in one direction through the prosthetic valve from an inlet end to an outlet end, but not in the other or opposite direction from the outlet end to the inlet end. Details of various prosthetic valve components can be found in <CIT>, <CIT>, <CIT>, and <CIT>.

The frames described herein can be configured to be radially collapsible to a collapsed or crimped state for introduction into the body on a delivery catheter and radially expandable to an expanded state for implanting a prosthetic valve at a desired location in the body (e.g., the native mitral valve). The frames can be made of a plastically-expandable material that permits crimping of the prosthetic valve to a smaller profile for delivery and expansion of the prosthetic valve using an expansion device such as the balloon of a balloon catheter. Suitable plastically-expandable materials that can be used to form the frames include, without limitation, stainless steel, cobalt-chromium, nickel-based alloy (e.g., a nickel-cobalt-chromium alloy), polymers, or combinations thereof. In particular embodiments, the frames are made of a nickel-cobalt-chromium-molybdenum alloy, such as MP35N® alloy (SPS Technologies), which is equivalent to UNS R30035 (covered by ASTM F562-<NUM>). MP35N® alloy/UNS R30035 comprises <NUM>% nickel, <NUM>% cobalt, <NUM>% chromium, and <NUM>% molybdenum, by weight. It has been found that the use of MP35N® alloy to form a frame provides superior structural results over stainless steel. In particular, when MP35N® alloy is used as the frame material, less material is needed to achieve the same or better performance in radial and crush force resistance, fatigue resistances, and corrosion resistance. Moreover, since less material is required, the crimped profile of the frames can be reduced, thereby providing a lower profile prosthetic valve assembly for percutaneous delivery to the treatment location in the patient's body.

Alternatively, any of the frames described herein can be a so-called self-expanding frame wherein the frame is made of a self-expanding material such as nitinol. A prosthetic valve incorporating a self-expanding frame can be crimped to a smaller profile and held in the crimped state with a restraining device such as a sheath covering the prosthetic valve. When the prosthetic valve is positioned at or near a target site within the patient's vasculature, the restraining device can be removed to allow the prosthetic valve to self-expand to its expanded, functional size.

<FIG> illustrate an exemplary prosthetic heart valve frame <NUM>. Frame <NUM> includes a main body <NUM>, a first flange <NUM>, and a second flange <NUM>. The main body <NUM> can be formed from a plurality of struts <NUM> coupled to one another at a plurality of nodes <NUM> to form a network of struts <NUM> defining a plurality of open cells <NUM>. The main body <NUM> can have a first end portion <NUM>, which can be referred to as an atrial end portion <NUM> or an inlet end portion <NUM>, and a second end portion <NUM>, which can be referred to as a ventricular end portion <NUM> or an outlet end portion <NUM>, and can include three commissure attachment posts <NUM>, each including a plurality of openings <NUM> to allow other components such as prosthetic valve leaflets to be coupled (e.g., stitched) to the frame <NUM>. Suitable components and methods for coupling the other components to the frame <NUM> are known in the art. The first flange <NUM> can be referred to as the atrial flange <NUM>, and the second flange <NUM> can be referred to as the ventricular flange <NUM>, due to their relative locations with respect to one another and the left atrium and the left ventricle when the frame is implanted in the native mitral valve.

The main body <NUM> and flanges <NUM>, <NUM> have generally circular shapes in the illustrated embodiment. In alternative embodiments, the main body and flanges of a prosthetic mitral valve frame can have non-circular shapes, for example, to accommodate the non-circular shape of the native mitral valve annulus. In certain embodiments, the main body and flanges of a prosthetic mitral valve frame can be generally oval-shaped, ellipse-shaped, kidney-shaped, or D-shaped.

The atrial flange <NUM> and the ventricular flange <NUM> are coupled to the main body <NUM> at respective locations located nearer to the atrial end <NUM> of the main body <NUM> than to the ventricular end <NUM>. More specifically, the atrial flange <NUM> is coupled to the nodes 110A of the main body <NUM> which are closest to the atrial end portion <NUM> of the main body <NUM>. The ventricular flange <NUM> is coupled to the nodes 110B of the main body <NUM> which are displaced toward the ventricular end <NUM> of the main body <NUM> from the atrial flange <NUM> by the smallest increment available. That is, the nodes 110B are the closest nodes <NUM> in the network of struts <NUM> to the nodes 110A. In other embodiments, the nodes 110B are not the closest nodes <NUM> to the nodes 110A, for example, the second closest or third closest nodes, or another set of nodes. In alternative embodiments, the atrial and ventricular flanges <NUM>, <NUM> can be coupled to the main body <NUM> at any suitable locations, which need not be at nodes <NUM>. For example, one or both of the flanges <NUM>, <NUM> can be coupled to the mid-points of struts <NUM> of the main body <NUM> rather than to nodes <NUM>.

As shown in <FIG>, in the illustrated configuration, the atrial flange <NUM> comprises nine atrial protrusions <NUM>, and the ventricular flange <NUM> comprises nine ventricular protrusions <NUM>. In alternative embodiments, the atrial flange can comprise more than or fewer than nine atrial protrusions and the ventricular flange can comprise more than or fewer than nine ventricular protrusions. In some embodiments, the atrial and/or the ventricular flange can include at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least twelve, at least fifteen, or at least twenty protrusions. In the illustrated embodiment, the atrial protrusions <NUM> are slightly larger than the ventricular protrusions <NUM>. In alternative embodiments, the protrusions <NUM>, <NUM> can be about the same size, or the ventricular protrusions <NUM> can be larger than the atrial protrusions <NUM>. In the illustrated embodiment, the atrial protrusions <NUM> are angularly offset from the ventricular protrusions <NUM>. In alternative embodiments, the protrusions <NUM>, <NUM> can be angularly aligned with one another. Other embodiments include at least one set of protrusions <NUM>, <NUM> that is angularly aligned and at least one set of protrusions <NUM>, <NUM> that is not angularly aligned. Each atrial protrusion <NUM> comprises a first radial strut <NUM> coupled to a node 110A (<FIG>) and extending radially outward from the main body <NUM>, and a second radial strut <NUM> coupled to a node 110A and extending radially outward from the main body <NUM>. Each protrusion <NUM> further comprises a first angled strut <NUM> coupled to the first radial strut <NUM> at a node <NUM>, and a second angled strut <NUM> coupled to the second radial strut <NUM> at a node <NUM>. Each first angled strut <NUM> is coupled to each second angled strut <NUM> at a respective radial node <NUM>.

Each ventricular protrusion <NUM> similarly comprises a first radial strut <NUM> coupled to a node 110B (<FIG>) and extending radially outward from the main body <NUM>, and a second radial strut <NUM> coupled to a node 110B and extending radially outward from the main body <NUM>. Each protrusion <NUM> further comprises a first angled strut <NUM> coupled to the first radial strut <NUM> at a node <NUM>, and a second angled strut <NUM> coupled to the second radial strut <NUM> at a node <NUM>. Each first angled strut <NUM> is coupled to each second angled strut <NUM> at a respective radial node <NUM>. Thus, the protrusions <NUM> and <NUM> each comprise a series of struts forming a loop coupled to and extending radially away from the main body <NUM>.

The nodes <NUM> and <NUM> of the protrusions <NUM> and <NUM>, respectively, comprise generally U-shaped crown structures or crown portions. Crown structures can each include a horizontal portion extending between and connecting the adjacent ends of the struts such that a gap is defined between the adjacent ends and the crown structure connects the adjacent ends at a location offset from the struts' natural point of intersection. The nodes <NUM> and <NUM>, and <NUM> and <NUM> of the protrusions <NUM> and <NUM>, respectively, also comprise stepped portions that are shaped to connect the adjacent ends of the struts at a location offset from the struts' natural point of intersection. Crown structures and stepped portions, both individually and in combination, can significantly reduce strain on the frame <NUM> during crimping and expanding of the frame <NUM>. Further details regarding crown structures are available in <CIT>.

Also shown in <FIG> are three prosthetic valve leaflets <NUM> coupled to the frame <NUM> at the commissure attachment posts <NUM>. <FIG> also illustrates that a prosthetic valve can include a first fabric layer <NUM> covering the ventricular protrusions <NUM> and a second fabric layer <NUM> covering the atrial protrusions <NUM>, as well as a third fabric layer <NUM> covering the main body <NUM> of the frame <NUM>. The fabric layers can improve the seal formed between the prosthetic valve and the surrounding native tissues of a native heart valve when the prosthetic valve is implanted. The fabric layers <NUM>, <NUM>, <NUM> can also reduce trauma to native tissues caused by the implantation of the prosthetic valve, and can help to promote tissue ingrowth into the prosthetic valve. The fabric layers <NUM>, <NUM>, <NUM> can be made from any of various suitable fabrics, including polyethylene terephthalate (PET).

In the illustrated embodiment, the commissure attachment posts <NUM> are coupled to radial struts <NUM>, <NUM> of ventricular protrusions <NUM>, but not to radial struts <NUM>, <NUM> of atrial protrusions <NUM>. Also in the illustrated embodiment, the commissure attachment posts <NUM> are angularly aligned about a central longitudinal axis of the frame <NUM> with radial nodes <NUM> of atrial protrusions <NUM>, but not with radial nodes <NUM> of ventricular protrusions <NUM>. In alternative embodiments, the commissure attachment posts <NUM> can be coupled to radial struts <NUM>, <NUM> of atrial protrusions <NUM>, and angularly aligned about the central longitudinal axis with radial nodes <NUM> of ventricular protrusions <NUM>.

As explained above, a prosthetic valve frame can be radially collapsible to a collapsed or crimped state for introduction into the body, and radially expandable to an expanded state for implantation at a desired location in the body. <FIG> illustrate a frame <NUM> from side views (<FIG>) and atrial end views (<FIG>) with a main body <NUM> of the frame <NUM> in expanded (<FIG>) and crimped (<FIG>) configurations. Frame <NUM> includes main body <NUM>, an atrial flange <NUM>, and a ventricular flange <NUM>. The main body <NUM> has a diameter Di in the expanded configuration and a diameter D<NUM> in the crimped configuration. The flanges <NUM>, <NUM> have a diameter or width W<NUM> in the expanded configuration of the main body and a diameter or width W<NUM> in the crimped configuration of the main body. In the illustrated embodiments, the flanges <NUM>, <NUM> have the same widths W<NUM> and W<NUM>; as discussed above, in other embodiments, the flanges <NUM>, <NUM> have different widths. The flanges <NUM>, <NUM> are spaced apart from one another by a spacing Si in the expanded configuration and by a spacing S<NUM> in the crimped configuration.

In some embodiments, Si can be between about <NUM> and about <NUM>, with about <NUM> being one possible specific dimension. In some embodiments, S<NUM> can be between about <NUM> and about <NUM>, with about <NUM> being one possible specific dimension. In some embodiments, W<NUM> can be between about <NUM> and about <NUM>, with about <NUM> being one possible specific dimension. In some embodiments, W<NUM> can be between about <NUM> and about <NUM>, with about <NUM> being one possible specific dimension. In some embodiments, Di can be between about <NUM> and about <NUM>, with about <NUM> being one possible specific dimension. In some embodiments, D<NUM> can be between about <NUM> and about <NUM>, with about <NUM> being one possible specific dimension.

As illustrated in <FIG>, as the main body of the frame <NUM> collapses from the expanded configuration to the crimped configuration, the diameter of the main body <NUM> decreases significantly (from Di to D<NUM>), the width of the flanges <NUM>, <NUM> decreases (from W<NUM> to W<NUM>), and the spacing between the flanges <NUM>, <NUM> increases (from Si to S<NUM>). Further, as the main body of the frame <NUM> collapses from the expanded configuration to the crimped configuration, the protrusions making up the flanges <NUM>, <NUM> are compressed angularly such that they transition from a series of relatively wide-and-short radially-extending protrusions to a series of relatively narrow-and-long radially-extending protrusions. As shown in <FIG>, an angle between the main body <NUM> and the radially extending flanges <NUM>, <NUM> can be about <NUM>°. In alternative embodiments, an angle between the side of the main body <NUM> and the radially extending flanges <NUM>, <NUM>, can be between about <NUM>° and about <NUM>°, or between about <NUM>° and about <NUM>°, or between about <NUM>° and about <NUM>°.

As shown in <FIG>, the radially extending flanges <NUM>, <NUM> can extend away from the main body <NUM> in directions generally parallel to one another. In alternative embodiments, the radially extending flanges <NUM>, <NUM> can extend away from the main body <NUM> in directions converging toward one another such that an angle between the radially extending flanges is less than about <NUM>°, or less than about <NUM>°, or less than about <NUM>°, or less than about <NUM>°, or less than about <NUM>°, or less than about <NUM>°, or less than about <NUM>°, or less than about <NUM>°. In other embodiments, the radially extending flanges <NUM>, <NUM> can extend away from the main body <NUM> in directions diverging away from one another such that an angle between the radially extending flanges is less than about <NUM>°, or less than about <NUM>°, or less than about <NUM>°, or less than about <NUM>°, or less than about <NUM>°, or less than about <NUM>°, or less than about <NUM>°, or less than about <NUM>°.

The frame <NUM> can be used as the frame of a prosthetic valve to be implanted at the native mitral valve of a human heart. As shown in <FIG>, the native mitral valve <NUM> of the human heart connects the left atrium <NUM> to the left ventricle <NUM>. The native mitral valve <NUM> includes a native mitral valve annulus <NUM>, which is an annular portion of native tissue surrounding the native mitral valve orifice, and a pair of leaflets <NUM> coupled to the native mitral valve annulus <NUM> and extending ventricularly from the annulus <NUM> into the left ventricle <NUM>. As described in more detail below, in one exemplary method, a prosthetic valve including the frame <NUM> can be compressed to a crimped configuration, loaded into a delivery system, and introduced into the region of the native mitral valve of a patient's heart. With the frame in the crimped configuration and thus the spacing between the atrial and ventricular flanges <NUM>, <NUM> maximized, the prosthetic valve can be positioned so that the native mitral valve annulus <NUM> is situated between the flanges <NUM>, <NUM>. The prosthetic valve can then be expanded to the expanded configuration such that the spacing between the flanges <NUM>, <NUM> is reduced to less than the native thickness of the native mitral valve annulus <NUM>. The flanges <NUM>, <NUM> can then retain the prosthetic valve in place in the native mitral valve by compressing or pinching the annulus <NUM>. By pinching the native mitral valve annulus, the flanges <NUM>, <NUM> can also maintain a continuous seal between the native tissue and the prosthetic valve around the exterior of the prosthetic valve, thereby preventing blood from flowing between the outside of the prosthetic valve and the surrounding annulus, and allowing the prosthetic valve to control the flow of blood between the left atrium and the left ventricle.

This method takes advantage of the relative movement of the nodes of the prosthetic valve frame in a direction aligned with the central longitudinal axis of the prosthetic valve. In particular, as a prosthetic valve frame such as frame <NUM> or frame <NUM> is radially expanded, nodes aligned with one another along an axis parallel to the central longitudinal axis move toward one another. Thus, by coupling a pair of flanges such as flanges <NUM> and <NUM>, or flanges <NUM> and <NUM> to nodes spaced apart from each other axially, the flanges can be made to approach one another as the prosthetic valve expands.

<FIG> illustrate components of an exemplary delivery system <NUM> (<FIG>) which can be used to deliver a prosthetic valve including a frame such as frame <NUM> or frame <NUM> to a native heart valve. <FIG> illustrates an outer sheath <NUM> of the delivery system <NUM>. Outer sheath <NUM> is a hollow sheath which surrounds the remaining components of the delivery system <NUM> and the prosthetic valve being delivered. <FIG> illustrates a slotted sheath <NUM> of the delivery system <NUM>. Slotted sheath <NUM> includes a plurality of distal extensions <NUM> separated by a plurality of distal slots <NUM>. The slotted sheath <NUM> can include at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least twelve, at least fifteen, or at least twenty slots <NUM>. The number of slots <NUM> in the slotted sheath <NUM> can correspond to a number of atrial protrusions, and/or a number of ventricular protrusions in a frame of a prosthetic valve, and/or a sum of the number of atrial protrusions and the number of ventricular protrusions. Slotted sheath <NUM> has an outside diameter slightly smaller than the inside diameter of the outer sheath <NUM> so that the slotted sheath <NUM> can fit within the outer sheath <NUM>.

<FIG> illustrates a nosecone <NUM> coupled to an inner shaft <NUM> of the delivery system <NUM>. The nosecone is hollow and includes an inner recess <NUM>. The nosecone <NUM> can have an outer diameter matching that of the outer sheath <NUM>, and the recess <NUM> can have a diameter slightly larger than the outer diameter of the slotted sheath <NUM> so that a distal end portion of the slotted sheath <NUM> can fit within the recess <NUM>. <FIG> illustrates an inner pusher shaft <NUM> of the delivery system <NUM>. The pusher shaft <NUM> can have an outside diameter smaller than an inside diameter of the slotted sheath <NUM> so that the pusher shaft <NUM> can fit within the slotted sheath <NUM>. The pusher shaft <NUM> can also have an internal lumen <NUM> through which the inner shaft <NUM> can fit. When assembled, the delivery system <NUM> can include, from center to exterior, the inner shaft <NUM>, the pusher shaft <NUM>, the slotted sheath <NUM>, and the outer sheath <NUM>.

<FIG> illustrate an exemplary delivery sequence of a radially self-expanding prosthetic heart valve frame <NUM> from delivery system <NUM>. <FIG> illustrates the delivery system <NUM> in a closed, delivery configuration in which the frame <NUM> is retained within the system <NUM> (the prosthetic valve can be retained in a radially compressed state within an annular space defined between the slotted sheath <NUM> and the inner shaft <NUM> and the nosecone <NUM>). As shown in <FIG>, the outer sheath <NUM> can be retracted proximally to expose the distal extensions <NUM> of the slotted sheath <NUM>. As shown in <FIG>, the inner shaft <NUM> and nosecone <NUM> can be extended distally to expose the distal end portion of the slotted sheath <NUM>.

As shown in <FIG>, the inner shaft <NUM> and nosecone <NUM> can be further extended distally to provide sufficient space for the prosthetic valve frame <NUM> to be pushed out of the slotted sheath <NUM>. The pusher shaft <NUM> can then be extended distally while the slotted sheath <NUM> is retracted proximally so that the prosthetic valve frame <NUM> is pushed distally through the slotted sheath <NUM> until the prosthetic valve frame <NUM> becomes partially exposed and begins to radially self-expand. As shown in <FIG>, the inner shaft <NUM> and nosecone <NUM> can be further extended distally to provide additional space for the prosthetic valve frame <NUM> to be pushed out of the slotted sheath <NUM>. The pusher shaft <NUM> can then be further extended distally while the slotted sheath <NUM> is further retracted proximally so that the prosthetic valve frame <NUM> is pushed distally through the slotted sheath <NUM> until the prosthetic valve frame <NUM> becomes completely exposed from the system <NUM> and radially self-expands to a fully expanded configuration.

The protrusions of a flange of a prosthetic valve frame, such as the protrusions of flanges <NUM>, <NUM>, <NUM>, or <NUM>, or protrusions <NUM> of prosthetic valve frame <NUM>, can fit within or extend through the distal slots <NUM> of the slotted sheath <NUM>. As described above, as prosthetic valve frames <NUM>, <NUM>, <NUM> are compressed to a crimped configuration, the respective protrusions are compressed angularly such that they transition from a series of relatively wide and short, radially-extending protrusions to a series of relatively narrow and long, radially-extending protrusions. Thus, the protrusions can be configured to fit within the distal slots <NUM> when a frame is in the crimped configuration. Loading a prosthetic valve into a delivery system can include crimping the prosthetic valve to a compressed configuration, inserting the compressed prosthetic valve into the slotted sheath <NUM> such that the angularly compressed protrusions fit within the distal slots <NUM> of the slotted sheath <NUM>, and then adjusting the protrusions so they lie flat against the outside of the slotted sheath <NUM>, or so they lie flat within the slots <NUM> and against the outside of the main body of the prosthetic valve, so the prosthetic valve and slotted sheath <NUM> can be contained within the outer sheath <NUM> and recess <NUM> of the nosecone <NUM>. The protrusions of one of the flanges can be contained within the nosecone <NUM>, and the protrusions of the other flange can be contained within the outer sheath <NUM>. Adjusting the protrusions so they lie flat against the outside of the slotted sheath, or so they lie flat within the slots <NUM> and against the outside of the main body of the prosthetic valve, can include bending the protrusions of the atrial flange so they point either toward or away from the protrusions of the ventricular flange, and bending the protrusions of the ventricular flange so they point either toward or away from the protrusions of the atrial flange.

<FIG> illustrate an exemplary delivery sequence of the prosthetic heart valve frame <NUM> from the delivery system <NUM>. <FIG> shows the frame <NUM> in a compressed configuration with protrusions 422A and 422B lying flat against a main body <NUM> of the frame <NUM>, such that the frame <NUM> can be situated within the delivery system <NUM> in the configuration shown in <FIG>. <FIG> shows the main body <NUM> of the frame <NUM> in a compressed configuration with protrusions 422B lying flat against the main body <NUM> of the frame <NUM>, and with the protrusions 422A extending radially outward from the main body <NUM> of the frame <NUM>, such that the frame <NUM> can be situated within the delivery system <NUM> and the protrusions 422A can extend through the slots <NUM> of the delivery system <NUM> in the configuration shown in <FIG>. <FIG> shows the main body <NUM> of the frame <NUM> in a compressed configuration with protrusions 422A and the protrusions 422B extending radially outward from the main body <NUM> of the frame <NUM>, such that the frame <NUM> can be situated within the delivery system <NUM> and the protrusions 422A, 422B can extend through the slots <NUM> of the delivery system <NUM> in the configuration shown in <FIG>.

<FIG> shows the main body <NUM> of the frame <NUM> in a partially expanded configuration in which a first end <NUM> of the frame <NUM> is in a compressed configuration and a second end <NUM> of the frame <NUM> is in an expanded configuration, such that the frame <NUM> can be situated within the delivery system <NUM> in the configuration shown in <FIG>. <FIG> shows the main body <NUM> of the frame <NUM> in a fully expanded configuration in which the first end <NUM> and the second end <NUM> are in expanded configurations, such that the frame <NUM> can be situated on the delivery system <NUM> in the configuration shown in <FIG>.

<FIG> illustrates an exposed distal end portion of a slotted sheath <NUM> having a plurality of distal extensions <NUM>, an outer sheath <NUM>, and a retaining element <NUM>. Small holes extend through the distal extensions <NUM> so that the retaining element <NUM>, which can be wire, string, and/or suture, can be threaded through the holes. In some cases, the retaining element <NUM> can extend from a proximal end portion of the outer sheath <NUM>, where it can be controlled by a physician, along the length of the outer sheath <NUM>, and into a first hole through a first distal extension 506A. The retaining element <NUM> can then be threaded through the holes of successive distal extensions <NUM> in a coiled or helical configuration until it extends out of a final hole through a final distal extension 506B. Alternatively, a retaining element can extend into the first hole of the first distal extension 506A, extend through the holes of successive distal extensions <NUM> in a plurality of circles, and extend out of the final hole of the final distal extension 506B. In some cases, a tension force can be applied to the retaining element <NUM>. The retaining element <NUM> can help to restrain the distal extensions <NUM> against radial expansion from the expansion force of a prosthetic valve retained within the extensions <NUM>.

<FIG> illustrate an alternative retaining element <NUM> which can be used in combination with the outer sheath <NUM>, slotted sheath <NUM>, and distal extensions <NUM>, either in place of, or in addition to, the retaining element <NUM>. Retaining element <NUM> includes a sheath <NUM> having a distal end portion comprising a plurality of teeth <NUM> and a plurality of gaps <NUM> between the teeth <NUM>. In use in a delivery system including outer sheath <NUM>, slotted sheath <NUM>, and distal extensions <NUM>, as shown in <FIG>, the retaining element <NUM> can be situated between the outer sheath <NUM> and the slotted sheath <NUM>. The teeth <NUM> can have a one-to-one correspondence with the distal extensions <NUM>, and each tooth <NUM> can be rotationally offset with respect to a respective distal extension <NUM> so as to form a protrusion-receiving opening <NUM>.

Loading a prosthetic valve including a frame such as frame <NUM>, frame <NUM>, or frame <NUM> into the delivery system can proceed according to similar methods, but is described herein with reference to frame <NUM> for convenience. Loading a prosthetic valve including frame <NUM> into the delivery system can include crimping the prosthetic valve to a compressed configuration, in which the protrusions 422A, 422B of the frame are angularly compressed, as described above. The compressed prosthetic valve can then be inserted into the slotted sheath <NUM> such that the angularly compressed protrusions 422A, 422B fit within slots <NUM> between the extensions <NUM>, such that the protrusions 422A are proximal to the protrusions 422B, and such that the proximal set of angularly compressed protrusions 422A extend through the slots <NUM> and the openings <NUM>. The retaining element <NUM> can then be rotated in the opposite direction shown by arrow <NUM>, so as to pinch the proximal set of angularly compressed protrusions 422A between the teeth <NUM> and the extensions <NUM>. The angularly compressed protrusions 422A and 422B can then be adjusted so they lie flat against the outside of the slotted sheath <NUM>, or so they lie flat within the slots <NUM> and against the outside of the main body <NUM> of the prosthetic valve frame <NUM>. The outer sheath <NUM> can then be actuated to move distally with respect to the slotted sheath <NUM> to enclose the slotted sheath <NUM>, the retaining element <NUM>, and the prosthetic valve.

Deployment of the prosthetic valve from the delivery system can generally progress as described above with reference to <FIG> and <FIG>, and can include proximally retracting the outer sheath <NUM> with respect to the slotted sheath <NUM> to reveal the slotted sheath <NUM> and the prosthetic valve, such that the angularly compressed protrusions 422A, 422B extend radially outward through the slots <NUM> between the extensions <NUM> and the proximal angularly compressed protrusions 422A extend radially through the openings <NUM>. A pusher shaft of the delivery system can then be actuated to push the prosthetic valve distally through the slotted sheath <NUM>, and the retaining element <NUM> can be actuated to move distally over the slotted sheath <NUM> with the prosthetic valve. In this way, the proximal set of angularly compressed protrusions 422A can remain pinched between the teeth <NUM> and the extensions <NUM> as the prosthetic valve is deployed. When the prosthetic valve approaches the distal end of the extensions <NUM>, the retaining element <NUM> can be rotated, for example, in the direction shown by the arrow <NUM> (<FIG>), such that it no longer pinches or holds (e.g., it releases) the proximal protrusions 422A. In some cases, releasing the proximal protrusions 422A in this way allows the proximal protrusions 422A to more fully radially extend outward through the openings <NUM>. Thus, while the distal and proximal protrusions 422B, 422A are deployed, the main body <NUM> remains in a radially compressed state within the slotted sheath <NUM>. In some cases, the retaining element <NUM> can then be retracted proximally with respect to the prosthetic valve to allow a controlled expansion of the prosthetic valve and a controlled release of the prosthetic valve from the extensions <NUM>. As the main body <NUM> is deployed, the distal and proximal protrusions 422B, 422A can slide axially in the distal direction through the distal openings <NUM> of the slots <NUM>.

The retaining element <NUM> can provide substantial benefits to the delivery system. For example, the retaining element <NUM> can help to restrain the distal extensions <NUM> against radial expansion from the expansion force of the prosthetic valve retained within the extensions <NUM>. In particular, as the prosthetic valve moves distally through the extensions <NUM>, the extensions <NUM> can tend to splay farther and farther apart. The retaining element can help to reduce this effect by maintaining a ring of material (e.g., the distal end portion of the sheath <NUM>) in proximity to the proximal end of the prosthetic valve as the prosthetic valve moves through the extensions <NUM>. This can provide an operator with a greater degree of control over the delivery system and the deployment of the prosthetic valve therefrom.

<FIG> illustrate an alternative retaining element <NUM> which can be used in combination with the outer sheath <NUM>, slotted sheath <NUM>, and distal extensions <NUM>, either in place of, or in addition to, the retaining element <NUM>. Retaining element <NUM> includes a sheath <NUM> having a distal end portion comprising a plurality of L-shaped teeth <NUM> and gaps <NUM> between the teeth <NUM>. The L-shaped teeth <NUM> can include a longitudinal portion 522A, a corner portion 522B, and a circumferential portion 522C. In use in a delivery system including outer sheath <NUM>, slotted sheath <NUM>, and distal extensions <NUM>, as shown in <FIG>, the retaining element <NUM> can be situated between the outer sheath <NUM> and the slotted sheath <NUM>. The teeth <NUM> can have a one-to-one correspondence with the distal extensions <NUM>, and each tooth <NUM> can be rotationally offset with respect to a respective distal extension <NUM> so as to form an enclosed, protrusion-receiving opening <NUM>.

Loading a prosthetic valve including a frame such as frame <NUM> or frame <NUM> into the delivery system can generally progress as described above, and such that a proximal set of angularly compressed protrusions 422A of a prosthetic valve frame fit within the openings <NUM>. The retaining element <NUM> can be rotated in the opposite direction shown by arrow <NUM> so as to capture the proximal set of angularly compressed protrusions 422A in the enclosed openings <NUM>. Deployment of the prosthetic valve from the delivery system can generally progress as described above. When the prosthetic valve approaches the distal end of the extensions <NUM>, the retaining element <NUM> can be rotated in the direction shown by the arrow <NUM> such that it no longer captures or constrains (e.g., it releases) the proximal protrusions 422A.

The retaining element <NUM> can provide substantial benefits to the delivery system, as described above with regard to retaining element <NUM>. In some cases, the retaining element <NUM> can be easier to manufacture than the retaining element <NUM>. In some cases, the retaining element <NUM> provides better performance than the retaining element <NUM> because the teeth form enclosed openings and capture the proximal protrusions rather than pinching the proximal protrusions.

<FIG> illustrate delivery approaches by which the delivery system <NUM> can be used to deliver a prosthetic valve to a patient's native mitral valve. <FIG> and <FIG> illustrate that delivery from the ventricular side of the native mitral annulus <NUM> can be accomplished via transventricular and transfemoral approaches, respectively. To deliver a prosthetic valve including frame <NUM> to a patient's native mitral valve from the ventricular side of the native mitral annulus <NUM>, the prosthetic valve can be loaded into the delivery system <NUM> so that the atrial end portion <NUM> of the frame is positioned nearer to the distal end of the delivery system <NUM> than the ventricular end portion <NUM> of the frame is. When the prosthetic valve is delivered to and deployed within the native mitral valve, the atrial end portion <NUM> is situated within the left atrium <NUM> and the ventricular end portion <NUM> is situated within the left ventricle <NUM>.

A prosthetic valve including protrusions fitted within the distal slots of a slotted sheath such as slotted sheath <NUM> can be deployed from a delivery system incorporating a retaining element such as retaining element <NUM>, retaining element <NUM>, or retaining element <NUM>, approaching the native mitral valve from the ventricular side of the native mitral valve annulus <NUM>. The prosthetic valve can be compressed to a crimped configuration and loaded into the delivery system such that the protrusions of an atrial flange are retained within the nosecone <NUM> of the delivery system and the protrusions of a ventricular flange are retained within the outer sheath <NUM> of the delivery system. The delivery system can then advance the prosthetic valve to the native mitral valve from the ventricular side of the native mitral valve annulus via either a transventricular or a transfemoral approach. In the transventricular approach, the delivery system desirably is inserted through a surgical incision made on the bare spot on the lower anterior ventricle wall.

As shown in <FIG>, the outer sheath <NUM> can then be retracted to expose the protrusions <NUM> of the ventricular flange <NUM> within the left ventricle <NUM>, and the delivery system can be advanced until the ventricular flange <NUM> is in contact with the native valve leaflets <NUM> and adjacent the ventricular side of the native mitral valve annulus <NUM>. The nosecone <NUM> can then be extended to deploy the protrusions <NUM> of the atrial flange <NUM> into the left atrium <NUM>, across the native mitral valve annulus <NUM> from the protrusions of the ventricular flange <NUM>. In cases where retaining element <NUM> is used, any tension force applied to the retaining element <NUM> can be removed, and the retaining element <NUM> can be actuated (e.g., pulled proximally) so that the retaining element <NUM> migrates through the holes in the distal extensions <NUM> of the delivery system until the retaining element <NUM> is no longer situated within the holes. A pusher shaft <NUM> of the delivery system can then be extended distally while the slotted sheath <NUM> is retracted proximally so that the prosthetic valve is deployed from the delivery system and allowed to radially expand within the native mitral valve. In some cases, retaining element <NUM> or retaining element <NUM> can be used to help restrain the distal extensions of the slotted sheath <NUM> against radial expansion during this step. As the prosthetic valve radially expands within the native mitral valve, the spacing between the atrial and ventricular flanges <NUM>, <NUM>, respectively, decreases and they compress the native mitral valve annulus <NUM>. As the prosthetic valve radially expands, the protrusions also angularly expand to their expanded configuration. The delivery system can then be removed from the patient's vasculature, leaving the prosthetic valve in place in the native mitral valve.

<FIG> and <FIG> illustrate that delivery from the atrial side of the native mitral annulus <NUM> can be accomplished via transeptal or transatrial approaches. To deliver a prosthetic valve including frame <NUM> to a patient's native mitral valve from the atrial side of the native mitral annulus <NUM>, the prosthetic valve can be loaded into the delivery system <NUM> so that the ventricular end portion <NUM> of the frame is positioned nearer to the distal end of the delivery system <NUM> than the atrial end portion <NUM> of the frame is. When the prosthetic valve is delivered to and deployed within the native mitral valve, the atrial end portion <NUM> is situated within the left atrium <NUM> and the ventricular end portion <NUM> is situated within the left ventricle <NUM>.

A prosthetic valve including protrusions fitted within the distal slots of a slotted sheath such as slotted sheath <NUM> can be deployed from a delivery system incorporating a retaining element such as retaining element <NUM>, retaining element <NUM>, or retaining element <NUM>, approaching the native mitral valve from the atrial side of the native mitral valve annulus <NUM>. The prosthetic valve can be compressed to a crimped configuration and loaded into the delivery system such that the protrusions <NUM> of a ventricular flange <NUM> are retained within the nosecone <NUM> of the delivery system and the protrusions <NUM> of an atrial flange <NUM> are retained within the outer sheath <NUM> of the delivery system. The delivery system can then advance the prosthetic valve to the native mitral valve from the atrial side of the native mitral valve annulus via either a transeptal or a transatrial approach.

The nosecone <NUM> can then be extended to deploy the protrusions <NUM> of the ventricular flange <NUM> within the left ventricle <NUM>, and the delivery system can be retracted until the ventricular flange <NUM> is in contact with the native valve leaflets <NUM> and adjacent the ventricular side of the native mitral valve annulus <NUM>. The outer sheath <NUM> can then be retracted to deploy the protrusions <NUM> of the atrial flange <NUM> into the left atrium <NUM>, across the native mitral valve annulus <NUM> from the protrusions of the ventricular flange <NUM>. In cases where retaining element <NUM> (<FIG>) is used, any tensile force applied to the retaining element <NUM> can be removed, and the retaining element <NUM> can be actuated so that the retaining element <NUM> migrates through the holes in the distal extensions <NUM> of the delivery system until the retaining element <NUM> is no longer situated within the holes. The outer sheath <NUM> and slotted sheath <NUM> can then be retracted while a pusher shaft <NUM> of the delivery system is held stationary so that the prosthetic valve is exposed from the delivery system and allowed to radially expand within the native mitral valve. In some cases, retaining element <NUM> or retaining element <NUM> can be used to help restrain the distal extensions of the slotted sheath <NUM> against radial expansion during this step. As the prosthetic valve radially expands within the native mitral valve, the spacing between the atrial and ventricular flanges <NUM>, <NUM> decreases and they compress the native mitral valve annulus <NUM>. As the prosthetic valve radially expands, the protrusions also angularly expand to their expanded configuration. The delivery system can then be removed from the patient's vasculature, leaving the prosthetic valve in place in the native mitral valve.

In cases in which protrusions of the frame of a prosthetic valve extend through the distal slots <NUM> of the slotted sheath <NUM>, the angular compression of the protrusions makes them narrower, and thus easier to navigate to the native mitral valve. For example, the native mitral valve can include chordae tendineae <NUM> (<FIG>), which tether the leaflets <NUM> to the walls of the left ventricle <NUM>. The chordae tendineae <NUM> can interfere with delivery of a prosthetic valve to the native mitral valve (particularly from the ventricular side of the native mitral annulus <NUM>), and angularly compressing the protrusions can facilitate the navigation of the protrusions through the chordae tendineae <NUM>.

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. 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.

Claim 1:
A prosthetic mitral valve for percutaneous delivery to and implantation at a native mitral valve of a heart, the native mitral valve having a native mitral valve annulus, the prosthetic mitral valve comprising a frame (<NUM>) having:
a radially collapsible and radially expandable main body (<NUM>) defining a lumen therethrough;
an atrial flange (<NUM>) coupled to the main body (<NUM>) and extending radially away from the main body (<NUM>), the atrial flange (<NUM>) comprising a plurality of radially extending atrial protrusions (<NUM>) configured to be located in a left atrium of the heart;
a ventricular flange (<NUM>) coupled to the main body (<NUM>) and extending radially away from the main body (<NUM>), the ventricular flange (<NUM>) comprising a plurality of radially extending ventricular protrusions (<NUM>) configured to be located in a left ventricle of the heart; and
three commissure attachment posts (<NUM>) configured to extend into the left ventricle,
the prosthetic mitral valve further comprising a valve member having three prosthetic valve leaflets (<NUM>) supported within the lumen of the main body (<NUM>) by the commissure attachment posts (<NUM>), the valve member defining an inlet end (<NUM>) and an outlet end (<NUM>) of the prosthetic mitral valve,
wherein the atrial flange (<NUM>) and the ventricular flange (<NUM>) are closer to one another when the main body (<NUM>) is in a radially expanded configuration than when the main body (<NUM>) is in a radially collapsed configuration so as to pinch the native mitral valve annulus between the atrial flange (<NUM>) and the ventricular flange (<NUM>), characterised in that the atrial flange (<NUM>) and the ventricular flange (<NUM>) are coupled to the main body (<NUM>) at locations located closer to the inlet end (<NUM>) than to the outlet end (<NUM>) of the prosthetic mitral valve.