Patent Description:
Prosthetic heart valves that can be delivered percutaneously or less invasively, compared to being implanted via open heart surgery, have gained popularity in recent years, and research and development in this area has increased. Prior to this, conventional heart valve surgery involved accessing the heart through a sternotomy or other incision in the chest, while also having to place the patient on cardiopulmonary bypass. Such procedures were very invasive and complicated, and also required lengthy recovery periods for the patients.

Less invasive devices and methods that can be used to deliver prosthetic valves have since been researched and developed. In some instances, a prosthetic valve is delivered to an implant site at the heart endovascularly. For example, in order to deliver a prosthetic aortic valve to the heart, an access site can be made at a patient's groin area to access the femoral artery, and the prosthetic valve can be delivered endovascularly past the aortic bifurcation, up the aorta, and to the aortic valve of the heart for implantation. In these cases, a prosthetic valve is generally collapsed or crimped to reduce its radial width, and is delivered through a catheter and/or a sheath through the various blood vessels, in order to deliver the replacement valve to the heart. Percutaneous or otherwise less invasive heart valve repair or replacement has therefore become possible using such transcatheter heart valves and associated delivery devices and methods in this manner.

As these transcatheter heart valves and other endovascular devices improve and become more commercially available and competitive, more emphasis has been placed on reducing the profile of the replacement valves in their crimped configurations, since reducing the profile of the devices will ease delivery of the devices to the implant sites. However, there has been limited research directed to whether the devices and techniques used to crimp the replacement valves can be realized without damaging the tissue leaflets, or reducing or compromising other functionality of the replacement valves after the valves have been expanded at the implant sites.

Furthermore, as noted above, different catheters and sheaths can be used in transcatheter surgical procedures to aid in delivery of the replacement valves. Sheaths that extend through at least a portion of the blood vessels can protect the vessels from ends, edges, and other features of the implants or delivery devices that could tear, rupture or otherwise damage the blood vessel walls. In recent times, expandable sheaths have been developed, in order to accommodate advancement of larger prostheses and/or delivery systems through the blood vessels. When a prosthetic or part of a delivery system passes through a portion of the expandable sheath, the expandable sheath can expand locally, via for example various mechanical expanding means, and can abut against the blood vessel walls, and in some cases cause the vessel walls to expand as well in a less traumatic manner, in order to accommodate the larger features passing therethrough. As such, development has moved towards using such expandable sheaths as delivery systems for transcatheter heart valves, over traditional stiff tube sheaths.

There has been little research, however, into how to more effectively introduce a prosthetic replacement valve and/or delivery system into the above-described sheath systems. Furthermore, there has been limited research into different devices and/or methods that can be used in conjunction with the existing expandable sheath systems, to further ease or simplify the delivery or implantation process, or to deal with other issues that can arise during valve delivery.

<CIT> relates to a system for crimping a prosthetic valve that comprises a radially expandable and compressible prosthetic valve, a crimping device positioned around the valve and configured to reduce the diameter of the valve to a delivery configuration, and a sterile package enclosing the valve and the crimping device.

<CIT> relates to an implantable prosthetic valve assembly having a support stent, or frame, having circumferential struts with multiple bends forming obtuse angles when the valve assembly is expanded to its functional size. The frame can be manufactured with one or more of the circumferential struts in a partially collapsed state and a flexible valve member can be mounted to the partially collapsed frame. The partially collapsed struts can be formed with multiple bends having angles selected to facilitate crimping of the frame to a profile suitable for percutaneous delivery.

<CIT> discloses a loading tool for withdrawing, crimping, and loading a stent-mounted valve into a delivery catheter, and for pushing the stent-mounted valve from the delivery catheter into a native heart valve orifice.

<CIT> relates to a prosthetic heart valve and a valve delivery apparatus for delivery of the prosthetic valve to a native valve site via the human vasculature. The delivery apparatus is particularly suited for advancing a prosthetic heart valve through the aorta (i.e., in a retrograde approach) for replacing a diseased native aortic valve.

<CIT> relates to storage and loading systems for expandable intraluminal medical devices. The systems include a container that defines an opening that tapers from a relatively large first diameter to a relatively small second diameter. A neck region includes structure adapted to engage an outer sheath of a delivery system such that an intraluminal medical device within the chamber of the container can be advanced through the tapered opening to effect compression of the intraluminal medical device and, ultimately, loading of the device into the delivery system.

The claimed invention is defined in independent claim <NUM> and relates to a method of crimping a transcatheter heart valve. Preferred configurations of the claimed invention are defined in dependent claims <NUM> to <NUM>.

Also described herein are related aspects, examples, embodiments and arrangements useful for understanding the claimed invention, and which do not necessarily constitute embodiments of the claimed invention. The subject-matter for which protection is sought is defined by the claims.

Herein described is also a loader tube and assembly for a transcatheter delivery system, where a crimped transcatheter heart valve can be loaded into a delivery sheath, and can be retrieved from the delivery sheath and removed from a patient's body without removing the delivery sheath from the access site. Other features of the invention are directed to an assembly and method for more easily facilitated crimping of a transcatheter heart valve prior to loading the replacement valve into the delivery sheath. Still other features of the invention are directed to devices and methods for more effectively crimping a transcatheter heart valve prior to delivery of the replacement valve in order to reduce shrinkage or other deformation or damage that can occur to the leaflet tissue of the valve, and to improve effectiveness of valve operation or functionality after implantation.

Herein described is also a loader assembly for loading a transcatheter heart valve into a delivery sheath for delivering the heart valve into a body of a patient includes a loader tube having a first end, a second end, and a central axis extending through the first and second ends, the loader tube having a tube wall defining a coaxial bore, wherein the tube wall has a first section at the first end with a first diameter, a second section connected to a distal end of the first section and having a second diameter smaller than the first diameter, and a third section connected to a distal end of the second section and having a third diameter greater than the second diameter, and at least one seal configured to maintain hemostasis in the loader tube when the coaxial bore of the loader tube is in communication with a blood vessel of the patient.

Herein described is also a method of using a loader assembly to retrieve a transcatheter heart valve from a body of a patient after the heart valve and a delivery system for the heart valve have been inserted into the body through a delivery sheath that provides access into the body, includes inserting the loader assembly through a hub of the delivery sheath, such that a distal end of the loader assembly extends distally from a hemostatic seal of the hub of the delivery sheath, wherein the delivery system extends through the delivery sheath and the loader assembly, moving the heart valve and a balloon of the delivery system on which the heart valve is positioned towards the loader assembly, moving the heart valve and the balloon into a distal section of the loader assembly, wherein a width of an opening at the distal end of the loader assembly is greater than a width of the heart valve and an axial length of the distal section of the loader assembly is greater than a length of the heart valve when the heart valve is retrieved, and removing the loader assembly from a proximal end of the delivery sheath while the heart valve and the balloon are positioned in the distal section of the loader assembly.

Herein described is also a loader assembly for loading a transcatheter heart valve into a delivery sheath for delivering the heart valve into a body of a patient includes a storage container configured to store the heart valve, a crimping apparatus having a first end connectable to the storage container and a second end, the crimping apparatus being configured to crimp the heart valve from a first expanded configuration to a second crimped position, and a loader tube connectable to the second end of the crimping apparatus and configured to advance the heart valve into the delivery sheath when the heart valve is in the second crimped position.

According to the invention, a method of crimping a transcatheter heart valve having a first end and a second end and including a valve frame and a plurality of valve leaflets, includes crimping the heart valve to a first position where the first end of the heart valve is crimped from a first width to a second width smaller than the first width, while the second end of the heart valve remains at the first width, and packaging the heart valve when the heart valve is in the first position.

According to embodiments of the invention, transcatheter heart valves can more easily and effectively be introduced into an existing delivery sheath system, where the replacement valve can further be retrieved from the delivery sheath system in a more efficient manner. Furthermore, embodiments of the invention can simplify the valve introduction process for a practitioner or other end user, and can also improve operation of the valve once it has been implanted in a patient. According to other embodiments, transcatheter heart valves can be stored in a more effective and efficient manner, to reduce deformation or other damage to the heart valves and to simplify end user requirements.

Further features and advantages of the invention will become apparent from the description of embodiments using the accompanying drawings. In the drawings:.

Disclosed herein are loading assemblies, arrangements, and methods for use with prosthetic heart valves that allow for simplified and improved delivery of the prosthetic valves into delivery sheath devices or other catheter-based access devices, to facilitate endovascular delivery of the prosthetic valves to the heart of a patient.

Some transcatheter heart valves (THV), for example, the Edwards Lifesciences SAPIEN™ valve, are designed to be radially crimped to facilitate endovascular delivery to an implant site at a patient's heart. Once positioned at a native valve annulus, the replacement valve is expanded to an operational state, for example, by an expansion balloon provided in the delivery system. The replacement valve can be crimped off of the balloon, and can be aligned onto the balloon once inside the delivery sheath or after the replacement valve and the balloon have exited a distal end of the delivery sheath. During alignment of the crimped replacement valve onto the balloon, the replacement valve can expand somewhat in order to fit the balloon therethrough.

During some procedures, it may become desirable or necessary to retrieve the replacement valve after the valve has already been radially expanded to accommodate the balloon. Some delivery sheaths have been designed so that the slightly expanded valve and balloon assembly can be retracted back into the distal end of the sheath. However, once the replacement valve is in this slightly expanded state, the valve cannot be completely removed from the delivery sheath and the patient's body, because the larger outer diameter of the slightly expanded valve can get caught on the hemostatic seals in the delivery sheath, potentially damaging the seals and causing a hemostatic leak through the sheath. Under these previous constraints, the physician was therefore required to remove the entire delivery sheath in order to remove the valve.

According to various embodiments, a loading assembly is utilized for loading the prosthetic heart valve through a pre-positioned delivery sheath or catheter at an access site on a patient. The same loading assembly can also later be used to retrieve the replacement valve after the valve has been positioned on a balloon and has been slightly expanded, where the valve and the loading assembly can be removed from the delivery sheath without also having to remove the sheath from the access site on the patient. This will help the physician avoid having to reinsert a delivery sheath or catheter when valve removal is desired.

A loader assembly is illustrated in <FIG> and <FIG>. The loader assembly <NUM> is a generally tubular structure that includes a loader tube <NUM>, a hub <NUM>, and a cap <NUM>. The loader tube <NUM> has a first proximal end <NUM> with an opening for inserting a prosthetic valve in a crimped state, and a second distal end <NUM> with an opening through which the crimped prosthetic valve is advanced into a delivery sheath. The hub <NUM> is attached to the proximal end <NUM> of the loader tube <NUM>, and includes a slot <NUM> that runs longitudinally along a wall of the hub <NUM>, which in some embodiments can be used to facilitate attachment of the hub <NUM> around the loader tube <NUM>. In addition, the cap <NUM> is attachable to the hub <NUM>, for example, by a threaded engagement. The cap <NUM> and/or other portions of the loader assembly <NUM> can form a hemostatic seal to prevent leakage through the loader assembly <NUM> when the loader assembly is inserted into a delivery sheath at an access site of a patient.

Referring now to <FIG>, the loader tube <NUM> includes a tube wall that defines a bore with varying inner diameters extending from the proximal end <NUM> to the distal end <NUM>. At the proximal end <NUM>, the loader tube <NUM> has a tube section <NUM> with an enlarged opening at the proximal end <NUM> and at least one portion <NUM> that reduces in diameter towards the distal end <NUM>, to facilitate guiding and inserting of the delivery system and/or crimped valve through the loader tube. In the embodiment shown, the tube section <NUM> has two such tapering sections <NUM> that reduce in diameter. In a middle portion of the loader tube <NUM>, a middle tube section <NUM> has a reduced inner diameter relative to other portions of the loader tube <NUM>. An inner diameter of the tube section <NUM> is equal to or slightly larger than an outer diameter of a crimped replacement valve that has been crimped off of an expansion balloon, which in some embodiments is the smallest crimped configuration of the valve prosthesis. In this manner, the crimped valve can be temporarily held in the middle tube section <NUM> of the loader tube <NUM> by for example, friction or interference forces against an inner wall of the tube section <NUM>, and the crimped valve is restricted from migrating out of tube section <NUM> absent an additional axial force applied to either the loader assembly <NUM> or the valve. Distal to the tube section <NUM> is an enlarged or flared tube section <NUM> with an enlarged wide-mouth opening at the distal end <NUM>. In the embodiment shown, the opening at the distal end <NUM> is slightly smaller than the opening at the proximal end <NUM>. The flared distal section <NUM> is sized to retrieve and hold a crimped valve that has slightly expanded radial width than its original crimped diameter due, for example, to the valve being aligned onto a balloon. An axial length of the tube section <NUM> is equal to or greater than an axial length of a valve prosthesis when the valve prosthesis is crimped, so that the valve prosthesis can fit fully in the tube section <NUM> during valve retrieval.

The different diameters between the distal tube section <NUM> and the middle tube section <NUM> forms a tapering portion <NUM> which serves as a hard stop for a slightly expanded valve that is being retrieved back into the loader assembly <NUM> through the opening at the distal end <NUM>. The tapering portion <NUM> prevents the retrieved valve from slipping out of the proximal end <NUM> of the loader and potentially breaking any hemostatic seals before the loader and valve have been fully removed from the rest of the delivery system.

Additionally, the loader tube <NUM> can further include one or more trails of etched score marks 18a, 18b in the wall of the loader tube <NUM>. In the embodiment shown, two substantially parallel longitudinal lines of score marks 18a extend from the proximal end <NUM> of the loader tube <NUM>, across the tube section <NUM>, to a transition region between the tube section <NUM> and the tube section <NUM>. An additional trail of score marks 18b extends circumferentially around the loader tube <NUM> approximate the region where the score marks 18a end. In addition, the position of the score mark 18b corresponds to a region of the loader tube <NUM> where the hub <NUM> ends when the hub <NUM> is attached to or bonded to the loader tube <NUM>. Additional features and usage of the score marks 18a, 18b will be discussed in greater detail below with relation to operation of the loader assembly <NUM>.

Referring to Figs. 4A to 4C, the hub <NUM> has a first proximal end <NUM> and a second distal end <NUM>. An axial length of the hub <NUM> corresponds substantially to an axial length of the proximal tube section <NUM> of the loader tube <NUM>, and a shape of a circumferential wall <NUM> of the hub <NUM> corresponds substantially to the shape of the tube section <NUM>, including one of the tapering sections <NUM> in the illustrated embodiment. The wall <NUM> of the hub <NUM> defines a coaxial bore <NUM> that extends through a center of the hub <NUM>. In addition, a slot <NUM> runs longitudinally down one side of the hub <NUM>. A circumferential width of the slot <NUM> is the same as or slightly larger than a distance between the two parallel lines of score marks 18a, so that the score marks 18a are accessible through the slot <NUM> when the loader tube <NUM> and the hub <NUM> are bonded or otherwise assembled together. The hub <NUM> further has an annular lip <NUM> adjacent to the proximal end <NUM> that has a larger diameter than other portions of the hub <NUM>. In the embodiment shown, an outer circumferential surface of the annular lip <NUM> is threaded or otherwise modified to facilitate engagement with the cap <NUM>.

The cap <NUM> is illustrated in <FIG>, and also has a first proximal end <NUM> and a second distal end <NUM>. The cap <NUM> includes a frame <NUM> in the form of an annular ring. The frame <NUM> has a first portion <NUM> adjacent to the proximal end <NUM> with a substantially cylindrical inner surface, and a second portion <NUM> adjacent to the distal end <NUM> with a threaded inner surface. The threaded inner surface of the second portion <NUM> of the cap <NUM> is configured to interact with the threaded outer surface of the annular lip <NUM> of the hub <NUM> to attach the cap <NUM> to the hub <NUM>. Meanwhile, a seal <NUM> is attached to the first portion <NUM> of the frame <NUM>. The seal <NUM> is attached to the first portion <NUM> of the frame <NUM> in one of various manners, for example, via an adhesive or other bonding means. Furthermore, the seal <NUM> can contribute to forming a hemostatic seal of the loader assembly <NUM>. The seal <NUM> includes a centrally located expandable opening <NUM> through which a crimped valve and delivery system can pass, as will be discussed in greater detail below.

<FIG> shows a cross-sectional view of an assembled loader assembly <NUM> according to the first embodiment. As can be seen in <FIG>, the hub <NUM> is bonded or otherwise attached to the proximal section <NUM> of the loader tube <NUM>, where the inner wall of the hub <NUM> substantially corresponds to the outer wall of the proximal section <NUM> of the loader tube <NUM>. The distal end <NUM> of the hub <NUM> is axially aligned with the circumferential trail of score marks 18b extending around the loader tube <NUM>. Additionally, as can best be seen in <FIG>, the slot <NUM> of the hub <NUM> is aligned with the two lines of score marks 18a, so that the score marks 18a are exposed to the outside of the loader assembly <NUM> through the slot <NUM>. Additionally, the cap <NUM> is attached to the proximal end <NUM> of the hub <NUM>. As indicated above, the cap <NUM> includes a seal <NUM>, which can facilitate hemostasis through loader assembly <NUM> during a surgical or other medical procedure. Other seals (not shown) can also be arranged through the loader tube <NUM>, the hub <NUM>, or the cap <NUM>, as needed, for maintaining hemostasis.

Operation of the loader assembly will now be discussed, with reference to <FIG>. <FIG> show steps of inserting a THV and a delivery system into the loader assembly, and of interfacing the loader assembly with a hub of a delivery sheath. In <FIG>, a valve prosthesis delivery system <NUM> includes a delivery catheter <NUM> for supporting and advancing a transcatheter heart valve <NUM> and an expansion balloon <NUM> to an implant site. The delivery catheter <NUM> is generally tubular and has a distal end from which the valve prosthesis <NUM> and the balloon <NUM> extend. Furthermore, a guide wire <NUM> extends through the delivery catheter <NUM>, the valve prosthesis <NUM>, and the balloon <NUM>. The prosthetic valve <NUM> is crimped around the delivery system <NUM>, and for example, a proximal end of the prosthesis <NUM> can abut against an end of a feature or advancing tool of the delivery system <NUM> (not shown). The expandable balloon <NUM> is positioned distal to the crimped valve prosthesis <NUM> on the delivery catheter. The valve prosthesis <NUM> in this embodiment is crimped off of the balloon <NUM>.

The guide wire <NUM>, the uninflated balloon <NUM>, and the crimped valve <NUM> are inserted through the loader assembly <NUM>. The various features of the delivery system <NUM> are first inserted through the opening <NUM> of the cap <NUM>, and then advanced through the middle tube section <NUM> of the loader tube <NUM>. The balloon <NUM> can be collapsed and advanced past the middle section <NUM>, while the crimped valve <NUM> can be positioned in the middle section <NUM>, where, as discussed above, the crimped valve <NUM> can be temporarily held.

In <FIG>, the loader assembly <NUM> holding the delivery system <NUM> and the crimped valve <NUM> is inserted into a proximal hub <NUM> of a delivery sheath device <NUM>. The delivery sheath device <NUM> can be an expandable sheath system, which includes the hub <NUM> and an expandable sheath <NUM> attached to a distal end of the hub <NUM>. The delivery sheath device <NUM> can also include one or more seals <NUM> to help maintain hemostasis when the sheath is positioned at an access site in a patient's body. The loader assembly <NUM> can be configured for use in conjunction with any similar delivery sheath device, and as such, specific details of the sheath device <NUM> that are not associated with interactions with the loader assembly <NUM> have been omitted for ease of description.

In one embodiment, the distal end <NUM> of the loader tube <NUM> is first inserted into the hub <NUM> while the delivery system <NUM> is arranged in the loader assembly <NUM> as previously described and illustrated with respect to <FIG>. Alternatively, in the embodiment shown in <FIG>, the crimped valve <NUM> can first be advanced past the middle tube section <NUM> of the loader tube <NUM> into the enlarged tube section <NUM> and can be positioned on the balloon <NUM>, while also slightly expanding to accommodate the balloon <NUM>. In this manner, the valve <NUM> and balloon <NUM> assembly can be positioned and held in the distal tube section <NUM> when the loader assembly <NUM> is inserted into the hub <NUM> of the sheath device <NUM>.

As can be seen in <FIG>, when the distal end <NUM> of the loader tube <NUM> is approximate the distal end of the hub <NUM>, the relative lengths of the loader assembly <NUM> and the sheath hub <NUM> are such that the middle tube section <NUM> extends out of the proximal end of the hub <NUM>. In this manner, the loader assembly <NUM> can be advanced further distally relative to the sheath device <NUM> when retrieval of a valve prosthesis <NUM> is desired, until the enlarged proximal section <NUM> of the loader tube <NUM> or the hub <NUM> of the loader assembly <NUM> abuts against a proximal end of the hub <NUM>. This allows the enlarged distal section <NUM> of the loader tube <NUM> to extend out of the distal end of the hub <NUM>, and/or any hemostatic seals <NUM> positioned between the hub <NUM> and the sheath <NUM>, and into the sheath <NUM>. This configuration will be discussed in greater detail below with respect to <FIG>, directed to retrieval of the valve prosthesis <NUM>.

After the loader assembly <NUM> is inserted into the hub <NUM>, the loader assembly <NUM> can be held at the position shown in <FIG>, where the distal end <NUM> of the loader tube <NUM> remains in the hub <NUM> of the sheath device <NUM>. Meanwhile, the crimped valve prosthesis <NUM>, as well as the delivery system <NUM> including the catheter <NUM>, the balloon <NUM>, and the guide wire <NUM>, can be aligned with the sheath <NUM> of the sheath device <NUM>, and then advanced through the distal end of the hub <NUM> and into the sheath <NUM>. <FIG> illustrates an example of a valve prosthesis <NUM> positioned on balloon <NUM> being advanced towards the implant site. As can be seen, sheath <NUM> is expandable, and a portion <NUM> of the sheath <NUM> is expanded locally around the prosthesis <NUM> and balloon <NUM> assembly, for accommodating the assembly when it passes through the sheath <NUM>. Meanwhile, the loader assembly <NUM> can be held together with the hub <NUM> in the position shown in <FIG> during the rest of the implantation procedure, or can be pulled proximally out of the proximal end of the hub <NUM>, and held apart from the sheath device <NUM> during the rest of the procedure. It shall be noted that in either of these cases, the delivery catheter <NUM> of the delivery system <NUM> still passes through both the loader assembly <NUM> and the hub <NUM>.

The crimped THV <NUM> can then be advanced and positioned at the implant site, and can be expanded by the balloon <NUM> for final implantation. The sheath <NUM> will only extend to a portion proximal to the implant site (e.g., to a location in the patient's aorta), while the delivery system <NUM> holding the valve prosthesis <NUM> exits a distal end of the sheath <NUM> and advances to the implant site. After the prosthetic valve <NUM> is positioned and expanded at the implant site, the delivery system <NUM> can be retrieved through the sheath <NUM>, and the delivery system <NUM> and the delivery sheath device <NUM> can both be removed from the access site on the patient.

In some situations, retrieval of the valve prosthesis <NUM> may become desirable or necessary. For example, during implantation, the valve <NUM> or part of the delivery system <NUM> can become damaged, the valve <NUM> may not expand correctly, or other errors or malfunctions can occur where the physician deems it necessary to completely remove the valve <NUM> from the patient. Under such circumstances, the loader assembly <NUM> can be used to facilitate retrieval of the valve <NUM>, where the loader assembly <NUM>, the valve <NUM>, and the delivery system <NUM> can be removed from the patient, while the delivery sheath device <NUM> remains in the body. In this manner, reinsertion or repositioning of the sheath device <NUM> at the patient's access site is not needed, and a new delivery system <NUM> and/or valve <NUM> can be delivered through the sheath device <NUM> more quickly and easily. Previously, absent use of the loader assembly <NUM>, removal of the entire sheath device <NUM> would be necessary to remove a partially expanded valve <NUM>, since the valve <NUM> can damage the sheath <NUM> or one or more hemostatic seals <NUM> during the retrieval process.

<FIG> show steps of retrieving a THV <NUM> through the delivery sheath device <NUM> using the loader assembly <NUM>. In <FIG>, the delivery system <NUM>, including the catheter <NUM> and the balloon <NUM>, along with the partially expanded valve <NUM> positioned on the balloon <NUM>, have already been retrieved partially through the sheath <NUM>, but have not yet been pulled back into the hub <NUM>. Meanwhile, the loader assembly <NUM> has been advanced further distally into the hub <NUM>. In cases where the loader assembly <NUM> was pulled proximally out of the hub <NUM> after the valve <NUM> was advanced into the sheath <NUM>, the loader assembly <NUM> can be inserted back into the sheath device <NUM> and advanced to the position illustrated in <FIG> prior to the valve <NUM> being pulled back into the hub <NUM>. In the configuration of <FIG>, the loader assembly <NUM> has been advanced distally through the hub <NUM>, so that the enlarged tube section <NUM> protrudes out of the hub <NUM> and into the sheath <NUM>, where the opening at the distal end <NUM> of the loader tube <NUM> has crossed and is distal to one or more hemostatic seals <NUM> positioned in and/or around the hub <NUM>. A length of the loader assembly <NUM> relative to the hub <NUM> allows for the distal end <NUM> of the loader tube to protrude into the sheath <NUM> before the enlarged proximal portions of the loader assembly <NUM> abut against the proximal end of the hub <NUM>.

In the configuration shown in <FIG>, the balloon <NUM> and the valve prosthesis <NUM> that is partially expanded thereon can be pulled back into the enlarged tube section <NUM> prior to contacting the hub <NUM> and any seals <NUM> associated therewith. The valve <NUM> and balloon <NUM> are held in the enlarged tube section <NUM>, and the tapered section <NUM> acts as a hard stop against pulling the partially expanded valve <NUM> or the balloon <NUM> any further proximally through the loader tube <NUM>. Therefore, a situation where the physician accidentally removes the valve <NUM> and the rest of the delivery system <NUM> through the loader assembly <NUM> before the loader assembly is removed from the sheath device <NUM>, and potentially damaging the seal <NUM> of the loader assembly <NUM>, or any other seals in the loader assembly <NUM> or the sheath device <NUM>, is prevented.

Additionally, since an axial length of the enlarged tube section <NUM> is equal to or greater than an axial length of the crimped valve prosthesis <NUM>, when the valve <NUM> is held in the tube section <NUM>, the tube section <NUM> completely surrounds the valve <NUM> and protects the sheath device <NUM>, and specifically the seals <NUM> and other portions of the hub <NUM>, from being damaged by the valve <NUM> and/or other portions of the delivery device <NUM>.

As shown in <FIG>, an entire system, including the loader assembly <NUM>, the delivery system <NUM>, and the partially expanded valve <NUM>, can then be safely pulled out from the proximal end of the hub <NUM> of the delivery sheath device <NUM>. The enlarged tube section <NUM> protects the seal or seals <NUM> of the hub <NUM> from being damaged by the partially expanded valve <NUM> or the delivery system <NUM>, and the tapered section <NUM> of the loader tube <NUM> keeps the valve <NUM> and balloon <NUM> in place in the tube section <NUM>, thereby also keeping the seal <NUM> of the loader assembly <NUM> from being damaged as well. In this manner, hemostasis can be maintained during removal of the valve <NUM> from the patient's body, and loss of blood through either the loader assembly <NUM> or the sheath device <NUM> can be effectively prevented or minimized.

Since the sheath device <NUM> remains in place in the patient's body during valve removal, a quicker turnaround can be made to prepare and advance a new delivery system <NUM> and/or valve <NUM> assembly through the sheath device <NUM> for implantation of the valve <NUM> in the patient.

As discussed above, the loader assembly <NUM> further includes one or more trails of etched score marks 18a, 18b on the loader tube. The score marks 18a, 18b remain exposed to the outside of the loader assembly <NUM> after the hub <NUM> is attached to the loader tube <NUM>. In some circumstances, for example, when it is apparent that there will be no need to retrieve the valve <NUM> during a procedure, and where the physician requires or would be more comfortable having some additional working length at the proximal side of the hub <NUM> of the sheath device <NUM>, the large tube section <NUM>, the hub <NUM>, and the cap <NUM> of the loader assembly <NUM> can be removed from around the catheter <NUM> of the delivery system <NUM>. The physician can start at the proximal end <NUM> of the loader tube <NUM> and begin peeling away the portion of the loader tube <NUM> defined by the parallel trails of score marks 18a running inside the slot <NUM> of the hub <NUM>, until the circumferential score marks 18b are reached. The physician can then peel off the proximal portion of the loader assembly <NUM> along the score marks 18b, and remove the proximal tube section <NUM>, the hub <NUM>, and the cap <NUM>.

After the proximal portion of the loader assembly <NUM> has been removed from around the delivery system <NUM>, the distal portion of the loader tube <NUM>, including the middle section <NUM> and the distal section <NUM>, for example, can be advanced distally completely into the hub <NUM>, so that the seal <NUM> at the proximal end of the hub <NUM> helps maintain hemostasis in the system. In other embodiments, additional longitudinal score marks can be etched into the middle section <NUM> and distal section <NUM> of the loader tube <NUM>, so that complete removal of the loader assembly <NUM> from around the delivery system <NUM> during a procedure is possible. In other embodiments, the loader tube <NUM> is made of a material that can be peeled apart by the physician, without any etches or score marks made in the loader tube <NUM>.

Referring to <FIG>, a second embodiment of a loader assembly for loading a THV will be described. Similar to the loader assembly discussed with respect to <FIG>, the loader assembly in <FIG> is generally configured for use with heart valve prostheses that can be radially crimped to facilitate endovascular delivery to an implant site at a patient's heart. The loader assembly can be used to more easily and efficiently load the crimped valve into a patient's body through a delivery sheath device or system. However, in the embodiment in <FIG>, the replacement valve can be crimped directly on a balloon expander prior to insertion into the delivery sheath and before the balloon expander has been inflated, where the crimped prosthetic valve and balloon delivery system can be inserted into the delivery sheath at the access site of the patient, and then advanced to the implant site together.

Generally, prior to inserting a valve prosthesis into the patient's body, the valve is retrieved from a storage container or other packaging and prepped for implantation, is radially crimped or collapsed, and is then loaded into the patient's body through a sheath delivery system or other similar means.

Valve prostheses can be individually held in storage jars or containers prior to use. The storage jars generally hold the valve in a glutaraldehyde solution or other similar solution or compound that effectively keeps the valve preserved and sterilized during storage. Once a valve has been selected for implantation, the valve prosthesis is removed from the storage jar and the glutaraldehyde, and is flushed or washed with saline or other similar body-compatible solution. The valve is then placed in a separate crimping device, where radial pressures are applied on the valve to collapse the valve to its crimped orientation. Finally, the crimped valve is inserted through a separate loader tube for introducing the crimped valve into a patient's body through the delivery sheath. Since there are three separate devices for performing these three separate functions, preparation of THVs even prior to introducing the valves into the delivery sheaths is cumbersome and time consuming. Additionally, using so many separate preparatory devices, as well as having to transfer the valves between the respective devices, increases the likelihood and risk of making procedural or other preparatory errors.

A loading assembly is utilized for loading the prosthetic heart valve into a pre-positioned delivery sheath or catheter at an access site on a patient. The system can be assembled together, such that a storage unit, a crimper, and a loader for the valve prosthesis can be combined into a single unit. By using such a loading assembly to prepare and introduce the valve prosthesis into a delivery sheath for implantation, preparation procedures for the valve prior to implantation can be combined and simplified, and the time associated with preparing and manipulating the valve to its crimped state prior to implantation can be reduced.

A loader assembly is illustrated in <FIG> and <FIG>. The loader assembly <NUM> includes a storage jar or container <NUM>, a crimping apparatus or crimper <NUM>, and a loader tube <NUM>. The storage container <NUM> has a first proximal end <NUM> and a second distal end <NUM>. The distal end <NUM> of the storage container <NUM> is connectable to a proximal end <NUM> of the crimper <NUM>, so that a valve prosthesis that is initially housed in the container <NUM> can be advanced directly into the crimper <NUM>. The crimper <NUM> further has a distal end <NUM> that is connectable to the loader tube <NUM>. The loader tube <NUM> has a proximal end <NUM> connectable to the crimper <NUM> and a distal end <NUM> with an opening configured to facilitate advancement of the crimped valve prosthesis into a delivery sheath or other delivery catheter.

Referring to <FIG>, the storage container <NUM> includes a generally cylindrical wall <NUM> extending between the ends <NUM>, <NUM>. In addition, at the proximal end <NUM>, the container <NUM> has an end wall <NUM> that forms a base or bottom of the container <NUM>. Together, the outer wall <NUM> and the end wall <NUM> define a generally cylindrical inner space <NUM> of the container <NUM>. The space <NUM> has a diameter that is greater than a diameter of a fully expanded transcatheter heart valve to be held in the container <NUM>. At a center of the end wall <NUM> is an opening <NUM> that facilitates access into the bore <NUM> from the proximal end <NUM> of the container <NUM>. The opening <NUM> is sized to facilitate insertion of a collapsed balloon expander and a delivery catheter of a valve delivery system therethrough. In some embodiments, an annular ring <NUM> defines the opening <NUM> through the end wall <NUM> and projects slightly into the inner space <NUM> of the container <NUM>. The slightly elongated annular ring <NUM> can serve, for example, as a guide for correctly loading a tip of the expandable balloon, or more generally a distal end of the delivery system, through a center of the expanded valve prosthesis held in the storage container <NUM>, and/or for properly positioning the expandable balloon through the valve prosthesis prior to advancing the valve and balloon assembly into the crimper <NUM>. At the distal end of the container <NUM>, a second opening <NUM> is large enough for the expanded valve prosthesis to advance through. In some embodiments, an attachment feature (not shown) is provided on an inner surface or on an outer surface of the wall <NUM> at the opening <NUM> to facilitate attachment and/or sealing between the container <NUM> and the crimper <NUM>. The attachment feature can be, for example, threads or a lip. Additionally, the same or different engagement features (not shown) can be provided adjacent one or both the opening <NUM> or the opening <NUM> for attaching caps or seals during valve storage, before the particular valve is selected for implantation.

As can be seen in <FIG>, the crimping apparatus <NUM> includes a generally tubular body <NUM> that extends from the first end <NUM> of the crimper <NUM> to the second end <NUM> of the crimper <NUM>. An outer wall of the body <NUM> is generally cylindrical in the embodiment shown, and has openings at both the first and second ends <NUM>, <NUM>. The crimper <NUM> defines a central aperture or bore <NUM> that extends from the first end <NUM> to the second end <NUM> of the crimper <NUM>. In some embodiments, either the outer surface and/or the inner surface of the body <NUM> can also include one or more engagement structures, such as threads (not shown), adjacent to either the first or second ends <NUM>, <NUM>, or both, for engaging other parts of the assembly. On an inner surface of the body <NUM>, there is a crimping device for crimping a transcatheter heart valve. In the embodiment shown, the crimping device includes crimping jaws or a similar mechanism. The crimping jaws are formed by a plurality of wedges <NUM> which define a size of the central bore <NUM>. The central bore <NUM> can be substantially cylindrical, to facilitate placement and crimping of the heart valve prosthetic therein. In the case where wedges <NUM> are used, the sides of the wedges can be substantially flat, so that a polygon with a number of sides equal to the number of wedges <NUM> is formed to approximate a cylindrical shape. The wedges <NUM> articulate relative to one another to increase or decrease a size of the central bore <NUM>. In other embodiments, different known crimping mechanisms can instead be utilized in place of the wedges <NUM>. Meanwhile, a handle or knob <NUM> circumferentially surrounds an outer surface of the tubular body <NUM>. The knob <NUM> can be shaped to include indentations and/or other features that facilitate gripping and rotating around the body <NUM> by a user. The knob <NUM> is mechanically coupled to the wedges <NUM>, such that rotation of the knob <NUM> in one direction will cause the wedges <NUM> to rotate relative to one another (e.g., in the same direction), in order to increase the size of the bore <NUM>, while rotation of the knob <NUM> in the opposite direction will also cause the wedges <NUM> to rotate relative to one another in the opposite direction to decrease the size of the bore <NUM>. In some embodiments, the crimper <NUM> can be configured such that the bore <NUM> decreases in size and then subsequently increases in size in response to rotation of the knob <NUM> in the same direction, in order to simplify operation.

Referring now to <FIG> the loader <NUM> also includes a generally tubular body <NUM> that extends from a first end <NUM> of the body <NUM> to a second end <NUM> of the body <NUM>, and that defines an inner bore <NUM>. The first end <NUM> of the body can include an engagement structure (not shown) for engaging the crimper <NUM>. The engagement structure can be on an outer surface or an inner surface of the loader tube <NUM>, in order to complement a corresponding engagement structure on the crimper <NUM>. The loader tube <NUM> is utilized to correctly orient and position the heart valve before the heart valve is advanced into, for example, a catheter or expandable sheath that has already been positioned in a patient's body, and in some cases, can also further reduce a size of a crimped transcatheter heart valve. As such, the inner bore <NUM> of the loader tube <NUM> gradually reduces in diameter from the first end <NUM> to the second end <NUM>, where a size of the opening at the second end <NUM> can be configured to be slightly larger than a desired diameter of the transcatheter heart valve after it has been crimped (e.g., by crimper <NUM>), or correspond to a diameter of a crimped valve prosthesis that is desired for delivery through the patient's body.

<FIG> illustrate a method of utilizing the loader assembly <NUM> for preparing, crimping, and advancing a THV for delivery through a patient's body via a delivery catheter or sheath. Prior to assembling the various parts of the loader assembly <NUM> as illustrated in <FIG>, the THV can be stored in the storage container or housing <NUM>. Various sealed storage containers <NUM> can, for example, hold different sized or different shaped THVs <NUM>, and can be labeled for easy identification by a practitioner. Prior to use, each of the storage containers <NUM> can be sealed at both ends, with for example, a plug or cap at opening <NUM> (not shown) and a lid or cap at opening <NUM> (not shown). Once a suitable valve <NUM> is selected for a particular procedure, the storage container <NUM> holding the desired valve <NUM> is selected and unsealed, and the glutaraldehyde and/or other preservation/sterilization solutions are drained from the storage container <NUM>. The inside of the container <NUM>, including the valve <NUM>, can also be washed or flushed with saline or other similar solutions to remove residual glutaraldehyde prior to implantation. This flushing step can be streamlined with, for example, tubes and/or stopcocks that easily connect to one or both ends of the storage container <NUM>. In some embodiments, additional openings for more effective flushing and/or draining of the storage container <NUM>, for example, on the sides of the container <NUM>, can also be added.

Once the inside of the storage container <NUM>, including the valve prosthesis <NUM>, has been rinsed or flushed, the storage container <NUM> holding the valve prosthesis <NUM> can be attached to the first end <NUM> of the crimper <NUM>. The loader tube <NUM> can be attached to the second end <NUM> of the crimper <NUM> before or after the storage container <NUM> has been attached to the crimper <NUM>. As shown in <FIG>, the storage container <NUM> is still holding the valve prosthesis <NUM>, while a general pathway is formed between the inner space <NUM> of the storage container <NUM>, the central bore <NUM> of the crimper <NUM>, and the inner bore <NUM> of the loader tube <NUM>, to facilitate advancement of the valve prosthesis <NUM> and the associated delivery system through and out of the distal end of the loading assembly <NUM>, via the opening at second end <NUM> of the loader tube <NUM>. As shown in <FIG>, the wedges <NUM> of the crimper <NUM> are arranged so that the bore <NUM> has a greater diameter than a diameter of the valve prosthesis <NUM> in an expanded configuration, to facilitate advancement of the valve prosthesis <NUM> into the crimper <NUM> prior to being crimped.

In <FIG>, a delivery system <NUM> is advanced into the loading assembly <NUM>. The delivery system <NUM> can include a delivery catheter <NUM> and an expandable balloon <NUM> positioned at or attached to a distal end of the delivery catheter <NUM>. An additional guide wire (not shown) can further be positioned at a distal end of the expandable balloon <NUM>. The delivery system <NUM> can be advanced through the opening <NUM> of the storage container <NUM>, where the opening <NUM> is sized to permit insertion of the expandable balloon <NUM> when it the balloon <NUM> is in a deflated or unexpanded state.

Upon insertion of the balloon <NUM> through the opening <NUM> of the storage container <NUM>, the balloon <NUM> engages the valve prosthesis <NUM>. In some embodiments, the balloon <NUM> engages valve leaflets of the valve prosthesis <NUM>, and can be sized and shaped so that upon engagement or attachment with the valve prosthesis <NUM>, the engagement is strong enough to advance the valve prosthesis <NUM> together with the balloon <NUM> out of the storage container <NUM> and into the bore <NUM> of the crimper <NUM>, as seen in <FIG>. In some embodiments, an additional engagement feature or accessory can be added on either the balloon <NUM> or the prosthetic valve <NUM> (not shown) to more readily facilitate proper engagement between the respective parts. In other embodiments, a frictional force between the balloon <NUM> and the valve prosthesis <NUM> is sufficient to facilitate the engagement. In still other embodiments, the valve prosthesis <NUM> can instead attach to and be crimped along a shaft of the delivery catheter <NUM>, or to another portion of the delivery system <NUM> other than balloon <NUM>, based on the needs and specific operation of the particular delivery system. Alternatively, the loader tube <NUM> can be detached, or can remain detached, from the crimper <NUM>, until a desired positioning of the valve prosthesis <NUM> and/or the delivery system <NUM> in the crimper <NUM> is achieved when viewed from the distal end <NUM> of the crimper <NUM>.

In <FIG> and <FIG>, the valve prosthesis <NUM> and the balloon <NUM> are still positioned in the bore <NUM> of the crimper <NUM>. First, in <FIG>, the knob <NUM> on the crimper <NUM> is turned or rotated about the loading assembly <NUM> by an end user, in order to rotate the wedges <NUM> relative to one another for making the bore <NUM> smaller. The sides of the wedges <NUM> apply inward radial pressure on the valve prosthesis <NUM> during articulation, in order to crimp the valve prosthesis <NUM> to a required or desired crimped or collapsed configuration. Thereafter, in <FIG>, the knob <NUM> on the crimper <NUM> is turned in order to make the wedges <NUM> shift back towards their original positions, in order to increase the size of the bore <NUM> in the crimper <NUM>. Meanwhile, the valve prosthesis <NUM> remains in the collapsed or crimped state around the balloon <NUM> or another corresponding portion of the delivery system <NUM>. In other embodiments, different mechanisms can be used to crimp the valve prosthesis <NUM> via various alternative types of crimpers.

Once the valve prosthesis <NUM> has been crimped and the bore <NUM> of the crimper <NUM> has been expanded back to or near its original expanded size, the delivery system <NUM> along with the valve prosthesis <NUM> can be pushed or otherwise advanced to the loader tube <NUM>, as seen in <FIG>. A distal end <NUM> of the loader tube can be inserted into, for example, a delivery sheath or catheter that is already positioned in and provides access to a patient's body. The loader tube <NUM> directs the delivery system <NUM> and the crimped valve prosthesis <NUM> out through the opening at the distal end <NUM> of the loader tube <NUM> and into the delivery sheath or catheter, and thereafter the valve prosthesis <NUM> and delivery system <NUM> can be advanced to a desired implant site in the patient's body.

In prior situations, various different parts, such as separate jars or storage containers, crimping devices, and loader tubes were needed for preparing a transcatheter heart valve for implantation. Various other parts or assembly devices were also utilized based on each particular clinical situation. The loader assemblies combine three assembly devices into a single integral and easy to use loading device. In some embodiments, different storage containers and/or crimpers can be designed or modified to better interact with one another, and with different loader tubes. In some embodiments, the crimper is designed to interact and connect with and/or seal to an existing loader tube, such that a pre-existing loader tube can be used with the other parts of the loading assembly, without significantly modifying the loader tube.

Furthermore, the loader assembly can be designed to interact with other components used to prepare the valve prosthesis in various other ways, also without having to modify the other devices. For example, the loading assembly can be made to be compatible with existing delivery systems, including existing balloon expanders and delivery catheters. The loading assembly can also be designed to be compatible with other preparatory features or kits, such as the Edwards Qualcrimp™ crimping accessory, or other accessories that, for example, protect the leaflets from pinching on the frame or portions of the crimping tool during valve crimping. Furthermore, while the described loading assemblies are discussed using storage containers that store valve prostheses in glutaraldehyde solutions or similar storage solutions, loading assemblies in other embodiments can be used with dry tissue valve technology or storage devices. In addition, instead of using shelf stored valves (e.g., valves that are stored in expanded configurations), the loading assembly can also be used with valve prostheses that are held or stored in other configurations, for example, valves that have been pre-crimped. Various other features and/or modifications can also be envisioned in other embodiments to accommodate other variations in valves or clinical needs. In this manner, loading assemblies can simplify the pre-implantation procedure, reduce possible errors, and make preparation easier and less time consuming for the end user.

A method for crimping a THV according to another embodiment of the invention will now be discussed with reference to <FIG>. While previous embodiments focused on loading assemblies for preparing and loading a THV into a patient's body, the following method focuses on methods of preparing and packaging a THV prior to delivery to a practitioner or other end user.

Ideally, to reduce preparatory work and to simplify the valve implanting procedure for the end user, and to reduce possible errors by the end user that could potentially damage a valve prosthesis during crimping, it would be desirable to be able to package THVs in their fully crimped configurations and already pre-positioned on a balloon delivery system, so that the valve prosthesis is ready to implant upon opening or removing from storage. However, storing THVs in their crimped or collapsed positions has been found to cause deformation or deterioration of the valve leaflets, and generally reduced performance by the valve leaflets once the valve prosthesis is expanded. Therefore, transcatheter valve prostheses are still generally stored in an open or expanded configuration, and are crimped or collapsed by a practitioner or other end user just prior to implantation into a patient's body, so that the valve prostheses are held in their crimped states for a limited amount of time (e.g., only during delivery of the valve to the implant site).

Recently, research has been devoted to providing THVs that can be packaged or stored directly on balloon and in their crimped states, without damaging or reducing the performance of the valve leaflets. Various treatments could potentially allow for packaging and sterilization of the prosthetic valve in a dry condition, e.g., without the need for a liquid storage solution, which could obviate the need to rinse or otherwise prepare the valve prior to implantation. Some treatments under development focus on providing additional protection for the valve tissue by enhancing anti-calcification properties and improving durability of the valve tissue. However, after crimping and packaging THVs using such dry tissue packaging or other similar dry tissue preparatory processes, problems or issues such as tissue shrinkage and/or other deformation of the leaflets may occur, and as such, the long-term effects these changes would have on the functionality of the THVs remain unknown. For example, studies have shown that exposure to ethylene oxide during sterilization of dry-packaged valves in their crimped states causes approximately <NUM>% shrinkage to the widths of the valve leaflets. Other factors, such as dry packaging conditions or temperature conditioning parameters, can also contribute to tissue shrinkage or degradation.

In an alternate approach, research has been devoted to dry packaging prosthetic valves in their expanded states, together with a low-cost crimping or loading device that is preloaded with each valve, so that an end user can remove the valve with the preloaded crimper from packaging, position the balloon or other portion of the delivery system through the valve, crimp the valve just prior to implantation, and remove and discard the preloaded crimper. In this manner, preparing a THV for implantation can potentially be simplified for the end user. Furthermore, since the valves are stored in their expanded states, the issues with tissue shrinkage or other deformation of the leaflets can potentially be avoided or minimized.

However, this approach has also been met with its own set of drawbacks. Current crimping techniques involving full-size crimping apparatuses typically also require complicated preparation, engagement, and use of a protective sheath or similar crimping accessory to be placed between the prosthetic valve and the crimping apparatus, to assist in the crimping of the prosthetic valve and to protect the leaflets, for example, from pinching against the valve or the frame of the crimping tool during crimping. One such crimping tool is the previously mentioned Edwards Lifesciences Qualcrimp™ crimping accessory. While preloading prosthetic valves with a preloaded or "smart" loader or crimping device can potentially simplify the preparation process for the end user, currently developed preloaded crimping devices still require use of the complex protective crimping accessories for protecting the valve leaflets when the valves are crimped by the end user. As such, the currently developed crimping devices and processes may only be marginally better and/or easier to use than their full-sized counterparts, or do not improve or simplify the process for the end user at all, while increasing manufacturing costs.

According to embodiments of the invention, a method and apparatus for crimping a THV during manufacturing and packaging is provided, so that preparation by an end user is simplified, and possible damage to or deformation of the prosthetic valve can be reduced or minimized. By using the crimping method described herein, a preloaded crimper or loader can be packaged with the valve prosthesis and utilized by the end user prior to implantation, without the need for an additional protective crimping accessory. Furthermore, the crimping method can be applied to valve prostheses with leaflets that have been treated for dry packaging, where the crimping method does not result in shrinkage of the leaflet tissue during packaging or storage of the valve before use. Lastly, the crimping method can be performed on a delivery balloon or other desired portion of a delivery system, to further simplify the preparation process for the end user. In this manner, the end user need only remove the assembly from the packaging, hydrate and/or sterilize the assembly, and then complete the crimping of the valve prosthesis before implanting the valve.

A schematic side view of a THV to which the crimping method according to embodiments of the invention can be applied is illustrated in <FIG>. The valve prosthesis <NUM> has an inflow section <NUM> and an outflow section <NUM>. The valve prosthesis <NUM> includes a valve frame <NUM> that is generally cylindrical in shape and defines a bore extending between the inflow section <NUM> and the outflow section <NUM>. The valve frame <NUM> is collapsible and expandable, so that the outer profile of the valve prosthesis <NUM> can be reduced to facilitate delivery of the valve prosthesis <NUM> to an implant site of a patient, and can thereafter be increased for anchoring the valve prosthesis <NUM> at the implant site. Expansion of the valve frame <NUM> also increases the diameter of the bore through the valve prosthesis <NUM>, and deploys the valve leaflets therein to a final configuration or arrangement for regulating blood flow at the implant site. For simplicity of discussion, the valve leaflets have not been illustrated in the schematic valve illustrations in <FIG>. In addition, an outer skirt or other covering <NUM> can cover at least part of the valve frame <NUM>. The outer skirt <NUM> can seal gaps between the valve prosthesis <NUM> and the native valve annulus at the implant site to reduce or prevent paravalvular leakage, and can also protect the surrounding tissue at the implant site after implantation. In the embodiments shown, the outer skirt <NUM> covers a portion of the inflow section <NUM> of the valve prosthesis <NUM>. The outer skirt has been illustrated in <FIG> as being a transparent layer, so that the portions of the valve frame <NUM> covered by the outer skirt <NUM> can be seen. However, in other embodiments, the outer skirt <NUM> can instead be made of materials such as fabric that are translucent or opaque.

The valve frame <NUM> of the THV <NUM> is designed with two or more rows of diamond-shaped cells at the inflow section <NUM> and one row of elongated hexagonal-shaped cells at the outflow section. The valve frame <NUM> is designed to reduce a delivery profile of the valve prosthesis <NUM>, while being able to maintain radial strength in the valve upon expansion, among other features and properties. One example of a THV with a similar valve frame profile is the Edwards Lifesciences SAPIEN <NUM>™ transcatheter heart valve. However, the crimping methods according to embodiments of the invention are not intended to be limited to prosthetic valves with frames similar to the ones discussed with respect to <FIG>, but rather can generally be applied to any THV with issues similar to those discussed above.

Referring back to the valve prosthesis <NUM> illustrated in <FIG>, in some instances, the variations in frame cell shapes can contribute to different levels of stretching of the valve leaflets that are housed inside the valve frame. For example, when the valve <NUM> is fully crimped, the diamond-shaped cells at the inflow section <NUM> of the valve prosthesis <NUM> can contribute to greater axial stretching of the valve leaflets than the hexagonal-shaped cells at the outflow section <NUM> of the valve prosthesis <NUM>. Such differences in leaflet tissue stretching can lead to additional stresses on the leaflets during packaging or storage if a valve prosthesis <NUM> is stored for extended periods in its crimped state. Consequently, shrinkage or other dimensional deformations of the leaflet tissue can be more severe at the inflow section <NUM> than at the outflow section <NUM> of the prosthetic valve <NUM> if the prosthetic valve <NUM> is stored in the crimped state. In some instances, the shrinkage or other deformation of the leaflet tissue may occur only at or near the inflow section <NUM>, while deformation of the leaflet tissue at or near the outflow section <NUM> is minimal.

<FIG> illustrates a first step of a crimping method according to an embodiment of the invention. As noted above, the crimping method can be employed during manufacturing or packaging of THVs, so that an end user receives the prosthetic valves after the crimping method has already been completed. In <FIG>, the THV <NUM> is inserted into a crimping fixture or holder <NUM>. The holder <NUM> has an outer wall <NUM> that defines an opening <NUM> into which the valve <NUM> is inserted. The opening <NUM> can be slightly larger than a size of the prosthetic valve <NUM> in its expanded state, so that the valve <NUM> can be held snugly in the holder <NUM>. The valve is held in the holder <NUM> such that at least a portion of the outflow section <NUM> of the valve <NUM> still protrudes out of the holder <NUM>. In some embodiments, a portion of the inflow section <NUM> also protrudes out of the holder <NUM>. The holder <NUM> can be constructed with, for example, an inner wall or annular ridge <NUM> that serves as a stop for the valve <NUM>, so that when the end of the valve <NUM> at the inflow section <NUM> abuts the wall or ridge <NUM>, a desired amount of the outflow section <NUM> of the valve <NUM> (and in some embodiments, a part of the inflow section <NUM> as well) remains exposed to the outside of the holder <NUM>. The wall or ridge <NUM> can also define a central through bore <NUM>, to be discussed in greater detail below.

In <FIG>, the exposed portions of the prosthetic valve <NUM> outside of the holder <NUM> are covered by a protective sheath or other protective crimping accessory (not shown). A delivery system <NUM> is then inserted through the THV <NUM> to a desired position. The delivery system can include a delivery catheter <NUM> and a balloon <NUM>. The valve <NUM> can generally be crimped on the balloon <NUM> before the balloon <NUM> is expanded, but can also be crimped on any other suitable or desired portion of the delivery system <NUM>. In embodiments where the holder <NUM> is hollow, or where the inner wall or ridge <NUM> includes the through bore <NUM>, the balloon <NUM> can be advanced through the holder <NUM>, such that a distal end of the balloon <NUM> can extend past a distal end of the valve prosthesis <NUM>, to facilitate more versatile positioning of the balloon <NUM> relative to the valve prosthesis <NUM>. In some embodiments, the valve <NUM> can be crimped off-balloon, so that the valve <NUM> is not crimped on the delivery system.

In <FIG>, the exposed portion of the heart valve <NUM>, along with the protective crimping assembly, are inserted into a bore or aperture of a crimping tool <NUM> until the end of the holder <NUM> is near to or abuts against the crimping tool <NUM>. In some embodiments, for ease of manufacturing, the valve prosthesis <NUM> is first positioned through one end of the aperture of the crimper <NUM>, and the balloon <NUM> of the delivery system <NUM> is then inserted through the valve prosthesis <NUM> via the other end of the aperture of the crimper <NUM> and arranged in a desired position prior to crimping of the valve prosthesis <NUM>. The crimping tool <NUM> is then actuated to reduce the size of the aperture around the exposed portion of the valve <NUM> (e.g., as illustrated by the arrows in <FIG>), in order crimp the exposed portion of the valve <NUM>. The valve prosthesis <NUM> is crimped until the inward pressure from the crimping tool <NUM> is limited or stopped, for example, by the protective crimping assembly positioned around the valve prosthesis <NUM>. In this manner, the crimping assembly can ensure that the prosthetic valve <NUM> is correctly positioned around and is coaxial with the balloon <NUM> or other suitable portion of the delivery system <NUM>, and damage to the valve leaflets during crimping can be avoided. The aperture of the crimper tool <NUM> is then expanded, the entire assembly is removed from the crimper, and the holder <NUM> and protective crimping assembly (not shown) can be removed from around the valve <NUM>, so that the heart valve <NUM> and delivery system <NUM> remain and can be packaged for delivery to an end user.

The resulting assembly, as illustrated in <FIG> and <FIG>, includes a partially crimped THV <NUM> that is crimped in a generally conical or tapered shape and positioned on a balloon catheter delivery system <NUM>. The portion of the valve prosthesis <NUM> that was exposed outside of the holder <NUM> is crimped by the crimper to its collapsed state, while the portion of the valve prosthesis <NUM> that was held in the holder <NUM> remains in the expanded state. A transition region between the expanded and crimped portions of the valve <NUM> can form a substantially tapered or rounded conical shape. Upon partial crimping of the prosthetic valve <NUM>, the valve leaflet tissue is still folded or collapsed down, but stretching of the leaflet tissue in an axial direction can be reduced or minimized (e.g., since the diamond-celled portions of the valve frame <NUM> are not significantly stretched out) to reduce stress on the valve leaflets during storage.

In some embodiments, a preloaded crimper or loader can be placed around at least the remaining expanded portion of the valve prosthesis <NUM>, and the assembly can be packaged together, so that an end user can easily remove the packaging, hydrate and/or sterilize the assembly, and use the preloaded crimper to crimp the rest of the prosthetic valve <NUM> to its fully crimped state around balloon <NUM> (e.g., as schematically illustrated in <FIG>) in preparation for delivery through the patient's body. In some embodiments, additional packaging steps can be applied to further simplify the end user preparation process. Various other ways of packaging the assemblies can also be implemented, for example, to increase shelf life or better protect the valve prostheses during storage, to facilitate easier assembly or preparation by the end user, or based on various other specific needs or requirements of different practitioners and/or patients.

Using crimping methods according to embodiments of the invention, a THV can be partially crimped during manufacturing or packaging using a protective crimping assembly and/or other crimping tools. The prosthetic valve is crimped to a configuration where the protective crimping assembly is no longer needed to crimp the remainder of the prosthetic valve, so that the partially crimped prosthetic valve can be pre-packaged with a preloaded crimper, and without the need for the protective crimping assembly at the end user crimping step. Furthermore, the crimping method at the manufacturing stage can be tailored or adjusted to reduce or prevent shrinkage or other deformations of the leaflet tissues in the valve based on the specific characteristics of the leaflet tissues or the surrounding frame. For example, for the prosthetic valve <NUM>, since the diamond-shaped cells at the inflow section <NUM> cause greater stretching of the valve leaflets than the hexagonal-shaped cells at the outflow section <NUM>, and thereby lead to greater deformation of the leaflets if stored in the crimped state, portions of the inflow section <NUM> of the prosthetic valve <NUM> can be kept in the expanded or partially expanded state until the end user fully crimps the prosthetic valve <NUM>.

Consequently, valves with leaflet tissue that have been treated or conditioned for dry packaging can be packaged in such a partially crimped manner to reduce occurrences of tissue deformation or shrinkage, thereby reducing the possibility of poor valve performance or valve malfunction. For example, in separate laboratory studies, THVs were held in fully crimped and partially crimped states, respectively, and were subjected to heat and ethylene oxide sterilization treatments, as well as shelf life tests including four weeks of aging at room temperature while crimped. The fully crimped valves were then hydrated and expanded, while the partially crimped valves were hydrated, were fully crimped without any additional crimping accessories to simulate the end user preparation and delivery process, and were then expanded. The valve leaflet tissue was removed from the respective frames and their dimensions were measured and further studied using a Keyence measuring system. While the leaflets from the fully crimped valves exhibited approximately <NUM>% decreases in the top width and mid width dimensions compared to typical valves that were stored in their expanded states and only crimped prior to use, the dimensions of the leaflets of the partially crimped valves remained similar to those of their conventionally stored counterparts. Tissue shrinkage in the partially crimped valves was greatly reduced or unobserved when compared to the tissue shrinkage exhibited in the valves that were stored in their fully crimped states.

Valves according to other embodiments can be partially crimped in different ways. For example, where an outflow section of a prosthetic valve can cause more leaflet deformation, the outflow section can be kept expanded, while the inflow section can be crimped instead of the outflow section. In still other embodiments, the entire valve prosthesis can be crimped to varying degrees, where one or more sections is crimped more significantly than other sections, based on the particular properties of each transcatheter heart valve.

Using the manufacturing crimping methods described herein, there will be no need for additional protective sheaths or other extraneous crimping assemblies or tools that an end user will have to learn to use. This would be a significant improvement over the current crimping and preparatory processes that an end user has to perform. The crimping and packaging methods reduces the number of packaging components, reduces the number of preparatory steps needed prior to valve implantation, and reduces the number of operator-dependent skills that an end user needs. Simplifying the end user process will also reduce the potential for preparatory errors, such as aligning or crimping the valve in the wrong direction, or misuse of the various packaging components or assembly tools previously required for crimping the valves prior to implantation.

For purposes of this description, certain aspects, advantages, and novel features of the embodiments of this disclosure are described herein. The disclosed methods, apparatus, and systems should not be construed as being 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 sub-combinations with one another. The methods, apparatus, and systems are not limited to any specific aspect or feature or combination thereof, nor do the disclosed embodiments require that any one or more specific advantages be present or problems be solved.

In view of the many possible embodiments to which the principles of the disclosure 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. Rather, the scope of the disclosure is defined by the following claims.

Claim 1:
A method of crimping a transcatheter heart valve (<NUM>, <NUM>) having a first end (<NUM>) and a second end (<NUM>) and comprising a valve frame (<NUM>) and a plurality of valve leaflets, the method comprising:
crimping the heart valve (<NUM>, <NUM>) to a first position where the first end (<NUM>) of the heart valve (<NUM>, <NUM>) is crimped from a first width to a second width smaller than the first width, while the second end (<NUM>) of the heart valve remains at the first width; and
packaging the heart valve (<NUM>, <NUM>) when the heart valve is in the first position.