Patent Description:
More specifically, the invention relates to occlusion devices that prevent the dispersal of thrombi formed in an atrial appendage into the blood circulation system. In particular, the invention relates to devices having a cage-like structure that are adapted for implantation into the left atrial appendage and prevent blood clots formed therein from being released into the left atrium as well as methods for manufacturing such devices.

Structural heart disease or other cardiac conditions can result in atrial fibrillation, which in turn may cause blood to pool or stagnate in the patient's atrial appendage. Thrombi (i.e. blood clots) are prone to form in the atrial appendages with stagnant blood. The blood clots may subsequently break off and migrate to the brain leading to stroke, or to other parts of the body causing loss of circulation to the affected organ. The left atrial appendage (LAA), which is a pouch-like extension of the left atrium, happens to be a particularly likely site for harmful blood clot formation. Thromboembolic events such as strokes are frequently traced to blood clots from the LAA. Clinical studies show that the majority of blood clots in patients with atrial fibrillation are found in the LAA.

The risk of stroke in patients with atrial fibrillation may be reduced by drug therapy, for example, by using blood thinners such as Coumadin. However, not all patients can tolerate or handle the blood thinning drugs effectively. Alternative methods for reducing the risk of stroke involve surgery to remove or obliterate the LAA. Other proposed methods include using mechanical devices to occlude the atrial appendage opening and thereby stop or filter blood flow from the atrial appendage into its associated atrium.

A need exists for improved filtration or occlusions devices for use in the atrial appendages.

<CIT> forms part of the prior art according to Art. <NUM>(<NUM>) EPC and discloses an occlusion device (e.g., for treatment of the left atrial appendage) that includes a framework and a biocompatible covering disposed over at least a part of the framework.

A need exists for improved filtration or occlusions devices for use in the atrial appendage as well as for improved methods for manufacturing such devices.

<CIT> discloses an occlusion device (e.g., for treatment of the left atrial appendage) that includes a framework and a biocompatible covering disposed over at least a part of the framework.

<CIT> and <CIT> disclose devices for treatment of a patient's vasculature configured for delivery with a microcatheter for treatment of the cerebral vasculature of a patient.

<CIT> discloses a blood filtration system for filtering blood flow from an atrial appendage, comprising, i. , a filter device that is configured for deployment in the atrial appendage to intercept blood flow, wherein the filter device has an elastic structure that expands to its natural size from a compressed state when the device is unconstrained.

The invention is directed to an occlusion device for an atrial appendage. The device has proximal and distal ends and a central axis and comprising a cage-like structure formed of struts. The struts have proximal strut ends and distal strut ends. At the proximal end of the device, the struts extend towards the central axis and are connected to each other at their proximal strut ends. At least some of the struts are connected to each other at their distal strut ends within the cage-like structure so that the struts form an atraumatic distal end of the device.

The cage-like structure is cut from a unitary tubular body.

The struts may have a substantially polygonal cross section. It is also within the scope of the invention to utilize struts with other shaped cross sections. The struts may form a plurality of closed polygonal cells having vertices where the struts merge into each other at said vertices. It is also within the scope of the invention for the struts to form other shape cells.

The atraumatic distal end of the device comprises inwardly bent struts. At least some of the ends of the bent struts point in a direction towards the proximal end of the cage-like structure. Typically, at least some of the struts are bent such that their distal strut ends extend substantially parallel to the central axis.

At least some of the distal strut ends may optionally provide an anchor. Typically, at least some of the struts providing the anchor extend through the cage-like structure.

Typically, at least some of the distal strut ends are connected to proximal strut ends.

The proximal strut ends may be connected to each other outside of the cage-like structure or within the cage-like structure. Optionally, the proximal strut ends may be connected to each other by a proximal collar formed integrally therewith.

The distal strut ends may be connected to each other by one or a combination of a tube that is crimped on and/or welded to the distal strut ends, a collar comprising several openings for receiving the distal strut ends, welding, soldering, and adhesive.

It is within the scope of the invention for the distal strut ends to differ in part or completely in wall thickness and/or a strut width from the other struts of the cage-like structure.

The cage like structure may be formed of a single cut structure.

Optionally, the occlusion device may further comprise a filter.

The occlusion device may further comprise a threaded insert at the proximal end.

The Figures described below disclose embodiments of the invention for illustrational purposes only. In particular, the disclosure provided by the Figures is not meant to limit the scope of protection conferred by the invention. The Figures are schematic drawings only and embodiments shown may be modified in many ways within the scope of the claims. In the context of the disclosure, like references numerals in the Figures refer to the same or corresponding features.

In the context of the present disclosure, the terms "distal" and "proximal" are used according to their established meaning in the field of percutaneous endovascular devices. As such, the term "proximal" refers to those parts of the device which, when following a delivery catheter or delivery instrument during regular percutaneous delivery, are closer to an end of the catheter or instrument that is configured for manipulation by the user (e.g., a physician). In contrast, the term "distal" is used to refer to those parts of the device that are more distant from the end of the catheter or instrument that is configured for manipulation by the user and/or that are inserted further into the body of a patient. Accordingly, in a device for use in the atrial appendage the proximal end may face towards the atrium when the device is deployed in an auricle.

<FIG> shows a side elevational view of an expanded occlusion device <NUM> according to an embodiment of the invention. As shown, the device <NUM> comprises a proximal end <NUM> and a distal end <NUM> as well as a central axis L and a cage-like structure <NUM> formed of struts <NUM>. The struts <NUM> are formed from a cut structure so that they are integrally connected with each other. As such, the struts <NUM> may form generally polygonal cells with vertices <NUM> at which the struts <NUM> merge into each other. It is also within the scope of the invention for the struts to form cells of other shapes. The struts <NUM> may have a substantially polygonal cross section although struts with cross-sections having non-polygonal shapes may also be used.

The cage-like structure <NUM> forms a closed three dimensional frame, i.e., a frame closed on both ends <NUM>, <NUM>. The struts 18at the proximal end <NUM>, i.e., proximal strut ends <NUM>, which may be somewhat S-shaped, extend to the central axis L and are connected to each other. In case of the illustrative embodiment, the proximal strut ends <NUM> are connected at a proximal collar or hub <NUM>. When the device is produced by cutting a tubular structure or a planar sheet, such proximal collar <NUM> may be provided by ending the cuts between the struts <NUM> at a sufficient distance from the proximal end <NUM> so as to define a collar between the ends of the cuts and the proximal end <NUM>. Thus, at least some or all of the struts <NUM> forming the proximal strut ends <NUM> of the device <NUM> are attached at the collar <NUM>. The proximal collar <NUM> is provided with an insert <NUM> for attaching the device <NUM> to a device tether or shaft (e.g., a tether wire).

Moreover, as also illustrated in the sectional view of <FIG>, distal strut ends <NUM> are connected to each other within the cage-like structure <NUM>. At least some of the distal strut ends <NUM> are bent inwardly so as to point in a direction towards the proximal end <NUM> of the cage-like structure <NUM>. In the illustrated embodiment, the distal-most part of the distal strut ends <NUM> extend substantially parallel to the central axis L. The bent distal strut ends <NUM> thus form an atraumatic distal end <NUM> of the device <NUM>. The struts <NUM> are bent such that the distal end <NUM> of the device is atraumatic, preferably in both the constrained and the deployed state of the device.

As further shown in <FIG>, the cage-like structure <NUM> may have a tapered shape. For example, at least a segment of the cage-like structure <NUM> may taper towards the distal end <NUM>. In some embodiments, the device may have a generally cone-like, for example, frusto-conical, or cylindrical shape. Such shapes may allow the device <NUM> to accommodate more closely to the natural shape of the LAA while exerting a tolerable outward contact pressure against the walls of the atrial appendage in order to provide an interference-like fit and hold the device <NUM> in place. The outward contact pressure may result from the designed springiness or elasticity of the cage-like structure.

In order to stabilize the position of the device <NUM> following implantation, the device can also comprise one or more anchors, which may have any suitable form. As illustrated in <FIG> and <FIG>, the anchor may be pins or barbs 28adapted for engaging the wall of the atrial appendage. The barbs <NUM> may extend from the struts <NUM> delimiting an outer perimeter of the cage-like structure <NUM>. The barbs <NUM> can be formed integrally with the struts <NUM>, e.g., by laser cutting. Barbs <NUM> may also be seen in the expanded occlusion device <NUM> of <FIG>. The device may have as many as <NUM>, <NUM>, <NUM>, <NUM> or any other suitable number of anchors.

As further shown in <FIG>, the distal strut ends <NUM> are connected to each other by a tube <NUM> that is crimped to the distal strut ends <NUM>. Alternatively or additionally, the tube <NUM> may be fixed to the distal strut ends <NUM> by welding, soldering or adhesives. The strut ends may be secured to the tube at either end of the tube. The struts may extend the entire length of the tube or only part of the length of the tube. As shown in <FIG>, a centering pin <NUM> may be inserted into the tube <NUM> along with the ends of the distal strut ends <NUM> in order to arrange the ends around the inner wall of the tube <NUM>. In some embodiments, at least six, more typically at least ten, even more typically at least twelve or more struts <NUM> may be connected within the cage-like structure <NUM> to form the distal end <NUM> of the device. <FIG>, which depicts a top elevational view of the device <NUM> illustrated in <FIG>, for example, shows eighteen distal strut ends <NUM> connected within the cage-like structure <NUM>.

<FIG> shows a side elevational view of an expanded occlusion device <NUM> according to an embodiment of the present invention. The device <NUM> includes a filter comprising a filter membrane <NUM> supported on the outer surface of the cage-like structure <NUM>. More specifically, the filter membrane <NUM> is affixed at the proximal end <NUM> of the device. It should be noted, however, that, alternatively or additionally, a filter membrane may be provided at the distal end <NUM>. Furthermore, the filter membrane(s) <NUM> may be provided along the outside of the cage-like structure <NUM> or therein.

The filter membrane may be attached to the cage like structure <NUM> by any suitable technique, including hooks or barbs provided at the cage-like structure <NUM> and/or, as in the exemplary embodiment illustrated in <FIG>, one or several filaments <NUM>. Filaments <NUM> may be threaded through holes in the filter membrane <NUM> and tied to the struts <NUM> in order to secure the filter membrane <NUM> to the cage-like structure <NUM>.

As mentioned above, the filter membrane may be made of a blood-permeable material having fluid conductive holes or channels extending across the membrane. The filter membrane may be fabricated from any suitable biocompatible material. These materials include, for example, ePFTE (e.g., Gore-Tex®), polyester (e.g., Dacron®), PTFE (e.g., Teflon®), silicone, urethane, metal fibers, and other biocompatible polymers. The hole sizes in the blood-permeable material may be chosen to be sufficiently small so that harmful-size emboli are filtered out from the blood flow between the appendage and the atrium. Suitable hole sizes may range, for example, from about <NUM> to about <NUM> microns in diameter. In embodiments, the filter membrane may be made of polyester (e.g., Dacron®) weave or knit having a nominal hole size of about <NUM> microns. The open area of the filter membrane (i.e., the hole density) may be selected or tailored to provide adequate flow conductivity for emboli-free blood to pass through the atrial appendage ostium. Further, portions of filter membrane may be coated or covered with an anticoagulant, such as heparin or another compound, or otherwise treated so that the treated portions acquire antithrombogenic properties to inhibit the formation of hole-clogging blood clots.

<FIG> depicts a perspective view of the device <NUM> illustrated in <FIG>. As shown therein, the insert <NUM> has a threaded socket A tether wire <NUM> having a threaded fixture for engaging the insert <NUM> may be threaded into the socket in order to manipulate the device <NUM>. The threaded socket may be suitable for rotatably engaging and/or releasing the occlusion device <NUM>. An embodiment of an inventive occlusion device <NUM> with a tether wire <NUM> having a threaded fixture <NUM> is also shown at <NUM> in <FIG> and <FIG>. It should be noted that, additionally or alternatively, any other suitable attachment may be provided.

The device <NUM> shown in <FIG> is a self-expanding device and is shown in its natural unconstrained expanded state. The cage-like structure <NUM> of the device <NUM> may be fabricated in different-sizes as necessary or appropriate for use in different sizes of atrial appendages. The illustrated structure may be, for example, about <NUM> (about one inch) in diameter and about <NUM> (about one inch) long in its natural expanded state. For delivery (e.g., percutaneous delivery), the device <NUM> may be compressed to a narrow diameter tubular shape and fitted into a narrow diameter catheter or delivery sheath. Preferably, the device may be compressed to a diameter of less than <NUM>, more preferably of less than <NUM> and recover to its natural shape subsequently upon release from the sheath. For applications in small vessels, the device may be compressed to a diameter of less <NUM> or less while for larger diameter vessels such as the aortic valve, the device may be compressed to a diameter of less than <NUM>.

The struts <NUM> of the cage-like structure <NUM> may be made of any suitable elastic material, for example, nitinol or spring steel. In the case of shape memory materials such as nitinol, the device may be provided with a memorized shape and then deformed to a reduced diameter shape. The device may restore itself to its memorized shape upon being heated to a transition temperature and/or having any restraints removed therefrom.

Depending on the specific embodiments and the requirements for the intended use, the device may also be made from any other suitable biocompatible material including one or more polymers, one or more metals or combinations of polymer(s) and metal(s). Examples of suitable materials include biodegradable materials that are also biocompatible. In this context, the term "biodegradable" is used to denominate a material that undergoes breakdown or decomposition into harmless compounds as part of a normal biological process. Suitable biodegradable materials include polylactic acid, polyglycolic acid (PGA), collagen or other connective proteins or natural materials, polycaprolactone, hylauric acid, adhesive proteins, copolymers of these materials as well as composites and combinations thereof and combinations of other biodegradable polymers. Other polymers that may be used include polyester and polycarbonate copolymers. Examples of suitable metals include, but are not limited to, stainless steel, titanium, tantalum, platinum, tungsten, gold and/or alloys of any of the above-mentioned metals. Examples of suitable alloys may include platinum-iridium alloys, cobalt-chromium alloys (e.g., Elgiloy and Phynox, MP35N), nickel-titanium alloys and nickel-titanium-platinum alloys.

<FIG>, <FIG> and <FIG> illustrate further features that may be provided in conjunction with the device <NUM> of <FIG>. In order to avoid repetitions, only those features differing from the device described above will be addressed. Like reference numbers denominate the same or corresponding features.

<FIG> shows a schematic sectional view illustrating an embodiment of the cage-like structure <NUM> for devices <NUM> according to the invention. As shown therein, at least some or all of the proximal strut ends <NUM> may be connected within the cage like-structure <NUM>. For example, separate struts may be formed at the proximal end of the tubular structure when cutting it, which may then be bent towards the inside of the cage-like structure <NUM> and connected therein.

The proximal strut ends <NUM> are connected to each other by a tube <NUM> that is crimped on, soldered, adhered and/or welded to the proximal strut ends <NUM>. A centering pin may be used in this context to arrange the proximal strut ends <NUM> evenly at the inner wall of the tube <NUM>. According to other embodiments, a collar comprising several openings for receiving the proximal strut ends <NUM> may be employed.

According to embodiments of the invention schematically illustrated in <FIG>, at least some of the distal strut ends <NUM> may provide anchor <NUM>. As shown, the distal strut ends <NUM> providing the anchor <NUM> extend through the cage-like structure <NUM>, for example, from the inside of the cage-like structure <NUM> towards the outside. As illustrated, the anchor <NUM> may be provided in a central or distal part of the cage-like structure <NUM>, for example, within the distal half or the most distal third thereof relative to the entire length of the cage-like structure <NUM> along the central axis L. It should be noted that such anchor are optional. They may be provided alternatively or additionally to the anchor <NUM> described above.

<FIG> depicts an embodiment of the cage-like structure <NUM> wherein some of the distal strut ends (i.e., distal strut ends <NUM>) extend partially along the central axis L through the cage-like structure <NUM> towards the proximal end <NUM> of the device <NUM> to the proximal strut ends <NUM>. The distal strut ends <NUM> may be connected to the proximal strut ends <NUM>, for example, at a location where the proximal strut ends <NUM> are connected to each other (e.g., at the proximal collar <NUM>). In certain embodiments, some or all of the distal strut ends <NUM> may extend through the cage like structure <NUM>.

<FIG> shows a schematic sectional view illustrating the cage-like structure of another occlusion <NUM> device according to the invention. In this embodiment, the distal strut ends <NUM> are connected by a distal collar <NUM> comprising several openings <NUM> (see <FIG>) for receiving the distal strut ends <NUM>. As further shown in <FIG>, which depict schematic cross sectional and side elevational views of the distal collar <NUM>, the openings <NUM> provided around the circumference of the distal collar <NUM> may extend at an angle α with respect to the central axis C of the collar <NUM>. Axis C may be concentric with the central axis L of the device <NUM>. The angle α may be between <NUM>° and <NUM>°. The distal collar <NUM> may be substantially cylindrical and/or may be provided with, for example, six, ten, twelve or eighteen or more openings <NUM>, corresponding to the number of distal strut ends <NUM> to be attached to the collar. In some embodiments, a similar structure may be used to connect at least some of the proximal strut ends <NUM>.

<FIG> show different stages of a method for manufacturing an occlusion device <NUM>. <FIG> illustrates a tubular structure <NUM> having a proximal end <NUM> and a distal end <NUM> and comprising a plurality of struts. The struts form loose distal strut ends <NUM> at the distal end of the device <NUM>. The tubular structure <NUM> is produced by cutting a tubular nitinol body (not shown).

As illustrated in <FIG>, the tubular structure may subsequently be heat treated and expanded by means of a mandrel (not shown) in order to provide a preform <NUM>. A forming tool (not shown) may be used to provide the proximal strut ends <NUM> of the preform <NUM> with a desired shape, for example, the S-shape illustrated in <FIG>. The proximal strut ends <NUM> are connected to each other at the proximal end <NUM>.

The loose distal strut ends <NUM> are then bent such that they have a directional component towards the proximal end <NUM>. As shown in <FIG>, the distal strut ends <NUM> may be bent towards the inside of the preform <NUM>, such that the loose distal strut ends <NUM> point in a direction towards the proximal end <NUM> of the preform <NUM>. A tube <NUM> (e.g., a hypotube) is introduced through the proximal end <NUM> (e.g., through a proximal collar <NUM>) and the loose distal strut ends <NUM> are inserted into the tube <NUM>. The hypotube <NUM> is then crimped and/or welded to the distal strut ends <NUM> in order to connect the ends to each other in a fixed manner. As further illustrated, the hypotube <NUM> is then cut and pulled back through the proximal end <NUM>. The remaining crimped portion <NUM> holds the loose distal strut ends <NUM> together in a fixed and secure manner. Accordingly, the cage-like structure <NUM> with closed proximal and distal ends <NUM>, <NUM> is formed (see <FIG>). In other embodiments, the loose distal strut ends <NUM> may be connected to each other by welding, soldering and/or by use of an adhesive. The tubular structure may be microblasted and/or electropolished.

Further steps may be performed, inter alia, to provide cage-like structures according to the embodiments shown in <FIG> and <FIG>.

<FIG> shows a tubular structure <NUM> that may be used for manufacturing an occlusion device <NUM>. The structure is illustrated in an unrolled and flattened state in order to depict the pattern formed by the struts. The tubular structure <NUM> is produced by laser cutting a tubular body or other suitable processes such as rolling an etched and/or cut sheet of material.

As mentioned above, the tubular structure <NUM> comprises struts <NUM> that may be adapted and configured to form the struts <NUM> of the device <NUM> illustrated in <FIG>. According to the invention, the struts <NUM> extend from a proximal end <NUM> of the tubular structure <NUM> to a distal end <NUM> of said tubular structure <NUM>. At the proximal end <NUM>, the proximal ends <NUM> of the struts <NUM> are configured and adapted to form the proximal end <NUM> of an occlusion device <NUM> according to the invention. As shown, the cuts between the proximal strut ends <NUM> of the struts <NUM> end at a distance from the proximal end <NUM> in order to leave a proximal collar <NUM>, which integrally connects the proximal strut ends <NUM>.

At the distal end <NUM>, the tubular structure <NUM> comprises distal strut ends <NUM>. The distal strut ends <NUM> may terminate in loose ends at or proximate the distal end <NUM>, which are indicated at <NUM> in <FIG>. It should be noted in this context that <FIG> provides a schematic representation and does not show the entire length of distal strut ends <NUM>, which may, optionally, account for approximately <NUM>% to <NUM>%, preferably approximately <NUM>% to <NUM>%, more preferably approximately <NUM>% to <NUM>%, and most preferably approximately <NUM>% of the length of the tubular structure. As mentioned above with respect to the device <NUM> shown in <FIG>, the tubular structure <NUM> may comprise at least <NUM>, at least <NUM>, at least <NUM>, or <NUM> or more loose distal strut ends.

In some embodiments of the invention, the struts forming the loose distal strut ends <NUM> may differ in wall thickness and/or strut width along their entire length or a section thereof. As such, the distal strut ends <NUM>, for example, may have a first section <NUM> that is wider than a second section <NUM> (see <FIG>). In other embodiments, a middle or a distal end section of distal strut ends <NUM> may be provided with a larger or smaller wall thickness and/or strut width. Varying the wall thickness and/or the strut width may allow configuring the bending properties of the distal strut ends <NUM>, thereby determining, inter alia, the shape of the distal end <NUM> of device <NUM> as well as its radial stability.

Anchoring struts <NUM> are optional and may be configured and adapted to provide the anchor <NUM> described above. The anchoring struts <NUM> may be formed when providing the tubular structure and may be integrally connected to struts <NUM>.

The invention is directed to an occlusion device having proximal and distal ends and a central axis and comprising a cage-like structure formed of struts. The struts have proximal strut ends and distal strut ends. At the proximal end of the device, the struts extend towards the central axis and are connected to each other at their proximal strut ends. At the distal end of the device, at least some of the struts are invaginated inward toward the central axis and the proximal end, and are connected to each other at their distal strut ends such that the distal strut ends are located proximal to the distal most part of the device.

The invention is directed to an occlusion device having proximal and distal ends and a central axis and comprising a cage-like structure formed of struts. The struts have proximal strut ends and distal strut ends. At the proximal end of the device, the struts extend towards the central axis and are connected to each other at their proximal strut ends. At the distal end of the device, at least some of the struts extend toward the central axis and the proximal end, and are connected to each other at their distal strut ends such that the distal strut ends are located proximal to the distal most part of the device.

The invention relates to an occlusion device for use in an atrial appendage of a patient. The device may filter or otherwise modify or even block blood flow between an atrial appendage and the associated atrium. The device may be configured and adapted for deployment into an atrial appendage, i.e., the LAA. However, it will be understood that the device can also be placed across other apertures in the body, e.g., apertures through which blood flows. The device may also be adapted for use for RF based ablation.

The device has a proximal end and a distal end as well as a central axis and a cage-like structure formed of struts. The struts each have a proximal strut end and a distal strut end. At the proximal end of the device the struts extend towards the central axis and are connected to each other at their proximal strut ends. Further, at least some of the struts are connected to each other at their distal strut ends within the cage-like structure so that the struts form an atraumatic distal end of the device.

The device may be self-expanding, i.e., it may form an elastic structure that expands from a compressed state to a predetermined expanded state when being unconstrained. In a compressed state, the device may take a narrow diameter tubular shape that is convenient for fitting the device into a narrow diameter catheter or delivery tube for percutaneous delivery. The cage-like structure typically forms a mesh or frame that is closed at both ends and surrounds a three dimensional space when the device is in an expanded state. Alternatively or additionally, the device may be designed to be expandable by means of an expansion mechanism for expanding the device in situ, for example, an inflatable balloon.

The atraumatic distal end of the device according to the invention is atraumatic at least in its constrained delivery state, and more typically both in the constrained and a deployed state. As such, the atraumatic distal end may be configured to enhance structural compatibility of the device with the atrial appendage during deployment as well as after implantation of the device. This could, desirably, reduce the risk of perforation. Also, it could allow for one or more recaptures of the device in the catheter and for full recapturability of the device by the catheter while having a lower likelihood for strut entanglement.

The occlusion devices of the invention may be formed in several ways. According to the invention, the device is cut from a tubular body so as to provide the plurality of struts. The cuts may be formed in the tubular body, for example, by laser cutting, etching or other cutting techniques know in the art, particularly in the art of stent manufacturing. The struts of the device forming the cage-like structure may have a substantially polygonal cross-section or a cross-section of other, non-polygonal, shapes.

The device, in some embodiments of the invention, may also be characterized in that the struts form a plurality of closed polygonal cells having vertices, the struts merging into each other at said vertices. In other embodiments, non-polygonal cells may be provided. According to the invention, the cage-like structure may be formed from a single cut structure, e.g., a single tubular body. In this way all struts are integrally connected with each other so that the cage-like structure represents a unitary body.

In accordance with the invention, the atraumatic distal end of the device comprises inwardly bent struts. In such a design, at least some of the struts at the distal end are bent towards the inside of the cage-like structure. As such, at least some, most or all of the ends or tips of the bent struts may be located inside the cage-like structure when the device is constrained and/or when the device is deployed.

According to the invention, at least some of the ends of the bent struts point in a direction towards the proximal end of the cage-like structure. Preferably, at least some, most or all of the struts are bent such that their distal strut ends extend substantially parallel to the central axis. As discovered by the inventors, such architecture may provide the device with a combination of performance characteristics that are normally difficult to obtain. Inter alia, the device may be constrained to a low profile and have a high radial strength, which may effectively ensure expansion upon deployment and prevent collapse after implantation.

The cage-like structure or frame of the device according to the invention may be fabricated in different sizes, as necessary or appropriate for use in different sizes of atrial appendages or other suitable areas of the body. An exemplary cage-like structure may be about <NUM> (one inch) in diameter and about <NUM> (one inch) long in its natural expanded state. In the constrained state, it may be about <NUM> in diameter and <NUM> in length.

In some embodiments, the cage-like structure may have a tapered shape. For example, the device may be tapered towards the distal end such that an outer diameter proximate the proximal end of the device is larger than an outer diameter proximate the distal end of the device. Thus, the device may have a generally conical, preferably frusto-conical shape. Other shapes, e.g., a generally cylindrical shape, are also feasible.

When the device is expanded in an atrial appendage, it may be held in position by an outwardly directed contact pressure that the cage-like structure exerts against the walls of said atrial appendage, providing an interference-like fit of the device. The contact pressure may result from the designed springiness or elasticity of the cage-like structure or may be the result of plastic deformation.

Alternatively or additionally, the device may comprise one or more anchors, which may engage the wall of the atrial appendage in order to ensure long-term stability in the implanted position. Examples of such tissue-engaging anchors may be hooks, pins, barbs, wires with an atraumatic bulb, tips or other suitable structures. The anchor(s) may be in the form of stubs or barbs extending from the struts forming the cage-like structure and may be formed integrally therewith. For example, the anchor(s) may extend from struts delimiting the outer diameter of the cage-like structure. Alternatively or additionally, at least some of the distal strut ends may provide one or more anchors. In some embodiments of the invention, at least some of the struts providing the anchor(s) may extend from the interior through the cage-like structure outwardly. For example, at least some of the distal strut ends may extend from the inside of the cage-like structure towards the outside in order to provide the anchor(s). The anchor(s) may be provided in the central of distal part of the cage-like structure, for example, within the distal half or the most distal third of the device compared to the overall length from the proximal end to the distal end along the central axis. It should be noted that the anchor(s) are optional and may or may not be provided in the inventive devices according to the specific requirements determined by the intended use.

The proximal strut ends and/or the distal strut ends may be connected to each other by one or a combination of a tube that is crimped on and/or welded to the struts, a collar comprising several openings for receiving the ends of the struts, welding, soldering, use of adhesive, etc. When the struts are connected by means of a tube, a centering pin may be used to arrange the struts at the inner wall of the tube. The struts may also be arranged at the inner wall of the tube via the use of a shrink tube or by attachment with filament such as wire.

Alternatively, the proximal strut ends may be integrally connected with each other. More specifically, the struts at the proximal end may remain connected to each other by a proximal collar or hub formed integrally therewith. When the device is produced by cutting a tubular structure, the cuts between struts forming the proximal end of the device may be ended at a sufficient distance from the proximal end of the tubular structure in order to leave a proximal collar or hub to which at least some or all of the proximal strut ends forming the proximal end of the device are attached.

In some embodiments, at least some or all of the proximal strut ends may be connected to each other within the cage-like structure. For example, separated proximal strut ends may be formed at the proximal end of the tubular structure when cutting it, which may then be bent towards the inside of the cage like structure and connected to each other therein. In one embodiment, some of the proximal strut ends are connected to each other outside the cage-like structure, for example by a proximal collar, while others are connected to each other within said cage-like structure. Accordingly, some of the proximal strut ends may be generally S-shaped while others may be generally C-shaped.

In another embodiment of the invention, at least some struts may extend from the distal end through the cage-like structure to the proximal end of the device, for example, along the central axis. In such an embodiment, the distal strut ends may be connected to the proximal strut ends, for example, where the proximal strut ends at the proximal end of the device are connected to each other. Such architectures may enhance stability of the device.

In some of the embodiments of the invention, the struts forming the distal end of the device may differ in wall thickness, strut width or both from the other struts of the cage-like structure. For example, the wall thickness and/or the width of the struts forming the distal end may be smaller or larger than the wall thickness and/or the width of other struts of the cage-like structure. Alternatively or additionally, a segment of the struts forming the distal end may have a different (e.g., smaller/larger) wall thickness and/or width. The segment may be provided at any suitable location along the struts, for example, at a proximal, a middle or a distal end section thereof. The wall thickness and/or the strut width of the struts that form the distal end of the device may be varied in order to define the bending properties (e.g., the curvature and/or the radial strength) of the struts forming the distal end of the device. In some embodiments, also the wall thickness and/or the strut width of other struts forming the cage-like structure may be varied, for example, along their entire length or a segment thereof.

According to the invention, the device is provided with an insert that is configured for attaching the device to a tether or shaft (e.g., tether wire). For this purpose, the insert may have, for example, a threaded socket so that a tether wire can be releasably attached from a proximal direction. However, other attachment means are likewise feasible and will be apparent to those skilled in the art.

The occlusion device according to the invention may additionally comprise a filter, for example, a filter membrane. The filter may be disposed along at least a portion of the cage-like structure, for example, along an outer or an inner segment thereof. For example, the filter membrane may cover a proximal portion of the cage-like structure (e.g., a proximal "hemisphere" or end thereof). In some embodiments, the filter membrane may span over the atrial facing surface of the device. Additionally or alternatively, the filter may be arranged at the distal portion of the device.

The filter can be attached by any suitable technique. For example, the filter may be supported by hooks or barbs extending from the cage-like structure. Alternatively or additionally, filaments may be used to tie the filter to the cells (e.g., at the vertices). At the proximal end, the filter membrane may be held between struts forming said proximal end and the insert and/or between the proximal collar and the insert.

The filter membrane may be made of a blood-permeable material having fluid conductive holes or channels extending across the membrane. The filter membrane may be fabricated from any suitable biocompatible material. These materials include, for example, ePFTE (e.g., Gore-Tex®), polyester (e.g., Dacron®), PTFE (e.g., Teflon®), silicone, urethane, metal fibers, and other biocompatible polymers. The sizes of the holes in the blood-permeable material may be chosen to be sufficiently small so that harmful-size emboli are filtered out from the blood flow between the appendage and the atrium. Suitable hole sizes may range, for example, from about <NUM> to about <NUM> microns in diameter. In embodiments, the filter membrane may be made of polyester (e.g., Dacron®) weave or knit having a nominal hole size of about <NUM> microns. The open area of the filter membrane (i.e., the hole density) may be selected or tailored to provide adequate flow conductivity for emboli-free blood to pass through the atrial appendage ostium. Further, portions of filter membrane may be coated or covered with an anticoagulant, such as heparin or another compound, or otherwise treated so that the treated portions acquire antithrombogenic properties to inhibit the formation of hole-clogging blood clots. The filter membrane assists in the occlusion of the atrial appendage. In particular, over time, the blood-clots captured by the filter, may lead to occlusion of the ostium of the atrial appendage.

The struts forming the cage-like structure may be made of any suitable elastic material, for example, nitinol or spring steel. Also shape memory materials may be used (e.g., nitinol). In this case, the device may be provided with a memorized shape and then deformed to a reduced diameter shape. The device may restore itself to its memorized shape upon being heated to a transition temperature and having any restraints removed therefrom.

Depending on the specific embodiments and the requirements for the intended use, the device of the invention may also be made from any other suitable biocompatible material including one or more polymers, one or more metals or combinations of polymer(s) and metal(s). Examples of suitable materials include biodegradable materials that are also biocompatible. A "biodegradable" material means that the material will undergo breakdown or decomposition into harmless compounds as part of a normal biological process. Suitable biodegradable materials include polylactic acid, polyglycolic acid (PGA), collagen or other connective proteins or natural materials, polycaprolactone, hylauric acid, adhesive proteins, copolymers of these materials as well as composites and combinations thereof and combinations of other biodegradable polymers. Other polymers that may be used include polyester and polycarbonate copolymers. Examples of suitable metals include, but are not limited to, stainless steel, titanium, tantalum, platinum, tungsten, gold and alloys of any of the above-mentioned metals. Examples of suitable alloys may include platinum-iridium alloys, cobalt-chromium alloys including Elgiloy and Phynox, MP35N alloy, nickel-titanium alloys and nickel-titanium-platinum alloys.

The device of the invention may be provided with a one or more therapeutic agents, whether in coating form or otherwise. As used herein, the terms, "therapeutic agent", "drug", "pharmaceutically active agent", "pharmaceutically active material", "beneficial agent", "bioactive agent", and other related terms may be used interchangeably herein and include genetic therapeutic agents, non-genetic therapeutic agents and cells. A drug may be used singly or in combination with other drugs. Drugs include genetic materials, non-genetic materials, and cells.

A therapeutic agent may be a drug or other pharmaceutical product such as non-genetic agents, genetic agents, cellular material, etc. Some examples of suitable non-genetic therapeutic agents include but are not limited to: antithrombogenic agents such as heparin, heparin derivatives, vascular cell growth promoters, growth factor inhibitors, etc. Where an agent includes a genetic therapeutic agent, such a genetic agent may include but is not limited to: DNA, RNA and their respective derivatives and/or components; hedgehog proteins, etc. Where a therapeutic agent includes cellular material, the cellular material may include but is not limited to: cells of human origin and/or non-human origin as well as their respective components and/or derivatives thereof.

Other active agents include, but are not limited to, antineoplastic, antiproliferative, antimitotic, antiinflammatory, antiplatelet, anticoagulant, antifibrin, antiproliferative, antibiotic, antioxidant, and antiallergic substances as well as combinations thereof.

Examples of antineoplastic/antiproliferative/antimitotic agents include, but are not limited to, paclitaxel (e.g., TAXOL. by Bristol-Myers Squibb Co. , Stamford, Conn. ), the olimus family of drugs including sirolimus (rapamycin), biolimus (derivative of sirolimus), everolimus (derivative of sirolimus), zotarolimus (derivative of sirolimus) and tacrolimus, methotrexate, azathiprine, vincristine, vinblastine, <NUM>-fluorouracil, doxorubicin hydrochloride, mitomycin, cisplatin, vinblastine, vincristine, epothilones, endostatin, angiostatin and thymidine kinase inhibitors.

While the preventative and treatment properties of the foregoing therapeutic substances or agents are well-known to those of ordinary skill in the art, the substances or agents are provided by way of example and are not meant to be limiting. Other therapeutic substances are equally applicable for use with the disclosed methods and compositions. See <CIT>, <CIT>, <CIT> and<CIT>. See also <CIT>, <CIT>, <CIT> and <CIT>.

Derivatives of many of the above mentioned compounds also exist which are employed as therapeutic agents and of course mixtures of therapeutic agents may also be employed.

For application, the therapeutic agent can be dissolved in a solvent or a cosolvent blend, and an excipient may also be added to a coating composition.

Suitable solvents include, but are not limited to, dimethyl formamide (DMF), butyl acetate, ethyl acetate, tetrahydrofuran (THF), dichloromethane (DCM), acetone, acetonitrile, dimethyl sulfoxide (DMSO), butyl acetate, etc..

Suitable excipients include, but are not limited to, acetyl tri-n-butyl citrate (ATBC), acetyl triethyl citrate (ATEC), dimethyl tartarate (D, L, DL), diethyl tartarate (D, L, DL), dibutyl tartarate (D, L, DL), mono-, di- and tri-glycerol such as glycerol triacetate (triacetin), glycerol tributyrate (tributyrin), glycerol tricaprylate (tricarprin), sucrose octa acetate, glucose penta acetate (D, L, DL, and other C6 sugar variations), diethyl oxylate, diethyl malonate, diethyl maleate, diethyl succinate, dimethyl glutarate, diethyl glutarate, diethyl <NUM>-hydroxy glutarate, ethyl gluconate (D, L, DL, and other C6 sugar variations), diethyl carbonate, ethylene carbonate, methyl acetoacetate, ethyl acetoacetate, butyl acetoacetate, methyl lactate, (D, L, or DL), dthyl lactate, (D, L, or DL), butyl lactate (D, L, or DL), methyl glycolate, ethyl glycolate, butyl glycolate, lactide (DD), lactide (LL), lactide (DL), glycolide, etc..

Suitable biodegradable polymeric excipients may include polylactide, polylactide-co-glycolide, polycaprolactone, etc..

Other suitable polymeric excipients include, but are not limited to, block copolymers including styrenic block copolymers such as polystyrene-polyisobutylene-polystyrene triblock copolymer (SIBS), hydrogels such as polyethylene oxide, silicone rubber and/or any other suitable polymer material.

In place of, or in addition to one or more therapeutic agents, the device of the invention may be provided with or more lubricious coatings. Examples of lubricious materials include HDPE (High Density Polyethylene) or PTFE (Polytetrafluoroethylene), or a copolymer of tetrafluoroethylene with perfluoroalkyl vinyl ether (PFA) (more specifically, perfluoropropyl vinyl ether or perfluoromethyl vinyl ether), or the like. Other suitable lubricious polymers may include silicone and the like, hydrophilic polymers such as polyarylene oxides, polyvinylpyrolidones, polyvinylalcohols, hydroxy alkyl cellulosics, algins, saccharides, caprolactones, and the like, and mixtures and combinations thereof. Hydrophilic polymers may be blended among themselves or with formulated amounts of water insoluble compounds (including some polymers) to yield coatings with suitable lubricity, bonding, and solubility. Some other examples of such coatings and materials and methods used to create such coatings can be found in <CIT>, <CIT>, <CIT>, <CIT>, and <CIT>.

These lists are intended for illustrative purposes only, and not as a limitation on the scope of the present disclosure.

According to embodiments, the invention may also relate to tubular structures having patterns configured to form any of the occlusion devices disclosed above.

The tubular structure may be microblasted and/or electropolished in order to enhance surface characteristics, long-term performance and/or biocompatibility.

Further, the present disclosure relates to a method of manufacturing an occlusion device for an atrial appendage. The method comprises the steps of (a) cutting a tubular body having proximal and distal ends to provide a tubular structure having struts, at least some of the struts at the distal end having loose distal strut ends; (b) expanding at least part of the tubular structure; (c) bending at least some of the loose distal strut ends towards the inside of said tubular structure such that the loose distal strut ends point in a direction towards the proximal end of the tubular structure; and (d) connecting at least some of the loose distal strut ends to each other.

The method may further comprise the step of connecting the struts at their proximal strut ends to each other so as to form a cage-like structure. In this context, the cuts may not extend to the proximal end of the tubular body, thereby connecting the struts at the proximal end by a proximal collar that is formed integrally therewith.

The distal strut ends may account for approximately <NUM>% to <NUM>%, preferably approximately <NUM>% to <NUM>%, more preferably approximately <NUM>% to <NUM>%, and most preferably approximately <NUM>% of the length of the tubular structure. The tubular structure may comprise at least <NUM>, at least <NUM>, at least <NUM>, or <NUM> distal strut ends. The struts forming the distal strut ends may differ in wall thickness and/or strut width along their entire length or a section thereof when compared to the other struts forming the tubular structure.

According to the disclosure, laser cutting or other suitable machining processes may be used to cut the tubular body. The tubular structure may also be provided by rolling and welding an etched and/or cut sheet of material.

The tubular structure may be heat treated and shaped over a mandrel in order to expand it and/or in order to provide the struts with a desired geometrical shape. According to an embodiment of the method, a forming tool may be used for this purpose.

In some embodiments, the step of bending at least some of the distal strut ends may comprise inserting the distal struts ends into a tube located within the tubular structure. The tube may be inserted through the proximal end of the cut and expanded tubular structure and cut to length, if necessary. In this case, the step of connecting at least some of the distal strut ends to each other may comprise crimping and/or welding the tube to the loose ends, a type of connection which might be preferable from a manufacturing point of view. Additionally or alternatively, the distal strut ends may be connected to each other by welding, soldering and/or by use of adhesive.

Also, the method may comprise the step of further bending at least some of the bent struts such that the distal strut ends extend to the outside of the tubular structure and form anchor, e.g., in the form of tissue-engaging hooks or barbs.

Further according to the method, at least some of the loose distal strut ends may be connected to the struts at the proximal end. In particular, at least some of the distal strut ends may be connected to the proximal collar.

The method may further comprise the step of bending at least some of the proximal strut ends towards the inside the tubular structure such that the proximal strut ends point in a direction towards the distal end of the tubular structure. At least some of these struts may be connected to each other, for example, inside the tubular structure.

The method may further comprise the step of bending at least some of the struts such that the ends extend to the outside of the tubular structure so as to provide an anchor.

As will be appreciated by those skilled in the art, the sequence of some of the steps described above may be changed in embodiments of the invention. It is noted that the embodiments described above may be combined in any technically feasible manner and that their respective features may be provided in conjunction.

The device of the present invention may be implanted by any of the techniques known in the art, for example by the standard transseptal technique. A detailed description of methods that may be used with the device of the invention is provided, for example, in <CIT>.

The disclosure also may relate to methods for implanting any of the devices described above. Furthermore, the invention relates to a kit for implanting any of these devices, the kit comprising a device according to the invention and a corresponding implantation apparatus (e.g., an apparatus disclosed in <CIT>).

Claim 1:
An occlusion device (<NUM>) for an atrial appendage, the device (<NUM>) having proximal and distal ends (<NUM>, <NUM>) and a central axis (L) and comprising:
a cage-like structure (<NUM>) cut from a unitary tubular body forming struts (<NUM>; <NUM>), the struts (<NUM>; <NUM>) having proximal strut ends (<NUM>; <NUM>) and distal strut ends (<NUM>; <NUM>; <NUM>), wherein at the proximal end (<NUM>) of the device (<NUM>) the struts (<NUM>; <NUM>) extend towards the central axis (L) and are connected to each other by a tube at their proximal strut ends (<NUM>; <NUM>), and
an insert (<NUM>) configured for attaching the device (<NUM>) to a tether or shaft;
characterised in that
at least some of the struts (<NUM>; <NUM>) are connected to each other at their distal strut ends (<NUM>; <NUM>; <NUM>) within the cage-like structure (<NUM>) so that the struts (<NUM>; <NUM>) form an atraumatic distal end (<NUM>) of the device (<NUM>);
wherein the atraumatic distal end (<NUM>) of the device (<NUM>) comprises inwardly bent struts (<NUM>; <NUM>), wherein at least some of the ends of the bent struts (<NUM>; <NUM>) point in a direction towards the proximal end (<NUM>) of the cage-like structure (<NUM>).