ANTI-THROMBUS FEATURE FOR IMPLANTED MEDICAL DEVICES

A medical device for permanent implantation in a circulatory system of a patient may include an implant configured for percutaneous or minimally-invasive insertion into the patient, at least one connector fixedly attached to the implant and configured to releasably attach to a delivery device, the at least one connector being exposed to blood flow within the circulatory system following implantation, and an anti-thrombus feature configured to transition from an undeployed state to a deployed state.

DETAILED DESCRIPTION

The terms “upstream” and “downstream” refer to a position or location relative to the direction of blood flow through a particular element or location, such as a vessel (i.e., the aorta) or vessel lumen, a heart valve (i.e., the aortic valve), and the like.

All numeric values are herein assumed to be modified by the term “about,” whether or not explicitly indicated. The term “about”, in the context of numeric values, generally refers to a range of numbers that one of skill in the art would consider equivalent to the recited value (i.e., having the same function or result). In many instances, the term “about” may include numbers that are rounded to the nearest significant figure. Other uses of the term “about” (i.e., in a context other than numeric values) may be assumed to have their ordinary and customary definition(s), as understood from and consistent with the context of the specification, unless otherwise specified.

Weight percent, percent by weight, wt %, wt-%, % by weight, and the like are synonyms that refer to the concentration of a substance as the weight of that substance divided by the weight of the composition and multiplied by 100.

The recitation of numerical ranges by endpoints includes all numbers within that range, including the endpoints (e.g. 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, and 5).

The following description should be read with reference to the drawings wherein like reference numerals indicate like elements throughout the several views. The detailed description and drawings are intended to illustrate but not limit the claimed invention. Those skilled in the art will recognize that the various elements described and/or shown may be arranged in various combinations and configurations without departing from the scope of the disclosure. The various individual elements described below, even if not explicitly shown in a particular combination, are nevertheless contemplated as being combinable or arrangable with each other to form other additional embodiments or to complement and/or enrich the described embodiment(s), as would be understood by one of ordinary skill in the art.

Diseases and/or medical conditions that impact the cardiovascular system are prevalent in the United States and throughout the world. Traditionally, treatment of the cardiovascular system was often conducted by directly accessing the impacted part of the system. For example, treatment of a blockage in one or more of the coronary arteries was traditionally treated using coronary artery bypass surgery. As can be readily appreciated, such therapies are rather invasive to the patient and require significant recovery times and/or treatments. More recently, less invasive therapies have been developed, for example, where a blocked coronary artery could be accessed and treated via a percutaneous catheter (e.g., angioplasty). Such therapies have gained wide acceptance among patients and clinicians.

Some relatively common medical conditions may include or be the result of inefficiency, ineffectiveness, or complete failure of one or more of the valves within the heart. For example, failure of the aortic valve can have a serious effect on a human and could lead to a serious health condition and/or death if not dealt with. A human heart includes several different heart valves, including aortic, pulmonary, mitral, and tricuspid valves, which control the flow of blood to and from the heart. Over time, a heart valve may become obstructed, narrowed, and/or less flexible (i.e., stenosed) due to hardening, calcium deposition, or other factors, thereby reducing the flow of blood through the valve and/or increasing the pressure within the chambers of the heart as the heart attempts to pump the blood through the vasculature. One traditional treatment method is valve replacement, where the stenosed valve is removed and a replacement tissue or mechanical valve is implanted via open-heart surgery. Alternative treatments, including percutaneous valve replacement procedures (i.e., transcatheter aortic valve implantation, or TAVI) which may deliver and implant a replacement heart valve (i.e., aortic valve), have been developed which may be much less invasive to the patient.

The occurrence of thrombi in the left atrial appendage (LAA) during atrial fibrillation may be due to stagnancy of the blood pool in the LAA. In an effort to reduce the occurrence of thrombi formation within the left atrial appendage during atrial fibrillation, certain medical devices have been developed that close off the left atrial appendage from the heart and/or circulatory system. By reducing or elimination the stagnant pooling of blood, the formation of thrombi can be significantly reduced or avoided, thereby lowering the risk of stroke due to thrombolytic material entering the blood stream from the left atrial appendage.

Each of the medical devices used above, as well as others, may include connectors that have irregular surfaces and/or open apertures that disrupt the normal flow of blood and/or create areas of stagnant blood. The devices and methods described herein may provide additional desirable features and benefits for use with such devices.

Turning to the drawings,FIG. 1is a partial cross-sectional view of certain elements of a typical human heart10and some immediately adjacent blood vessels. A heart10may include a left ventricle12, a right ventricle14, a left atrium16, and a right atrium18. An aortic valve22is disposed between the left ventricle12and an aorta20. A pulmonary or semi-lunar valve26is disposed between the right ventricle14and a pulmonary artery24. A superior vena cava28and an inferior vena cava30return blood from the body to the right atrium18. A mitral valve32is disposed between the left atrium16and the left ventricle12. A tricuspid valve34is disposed between the right atrium18and the right ventricle14. Pulmonary veins36return blood from the lungs to the left atrium16. A left atrial appendage (LAA)50is attached to and in fluid communication with the left atrium16via an ostium56.

FIG. 2illustrates an example medical device such as an aortic valve replacement device100used in transcatheter aortic valve implantation (TAVI). In some embodiments, an aortic valve replacement device100may include a plurality of valve leaflets110each secured to a cylindrical braid120at a post130. In some embodiments, each post130may be secured to the cylindrical braid120, along an inside surface of the cylindrical braid120for example, with sutures, adhesives, or other suitable means. In some embodiments, each post130may include a connector140positioned adjacent to, longitudinally spaced from, and/or aligned with its respective post130. Each connector140may be secured to the cylindrical braid120, for example, by sutures, adhesives, or other suitable means. In some embodiments, the aortic valve replacement device100may also include a seal150disposed about the cylindrical braid120. In some embodiments, the structure and/or operation of the connector140may be similar to a device disclosed in U.S. Application No. 61/559,941, filed Nov. 15, 2011, and/or U.S. Application No. 61/577,880, filed Dec. 20, 2011, both of which are herein incorporated by reference in their entirety.

In some embodiments, each connector140may be configured to releasably attach to a delivery device (not shown) in an installation condition. The installation condition generally includes the aortic valve replacement device100being disposed in a collapsed and/or elongated state. In the installation condition, the aortic valve replacement device100may be inserted (percutaneously, in some embodiments) into the aortic valve22, where the aortic valve replacement device100may be expanded or actuated into the delivered condition.FIG. 2illustrates the aortic valve replacement device100in a delivered condition. Each connector140may include an irregular shape, as seen inFIG. 2Afor example, configured to matingly align with and/or attach to the delivery device. Upon actuation into the delivered condition, the delivery device may be removed, leaving each connector140with the irregular shape exposed to blood flow through the aortic valve22(and/or the aortic valve replacement device100) and/or the aorta20. With some medical devices, an irregular shape may disrupt blood flow and/or create an area of stagnant blood which may facilitate thrombus formation.

FIG. 3illustrates an example medical device such as an expandable filter device200used to close off a left atrial appendage50from blood flow through the left atrium16. In some embodiments, an expandable filter device200may include a filter membrane210supported on an elastic wire frame220. In some embodiments, the filter membrane210may be impermeable to blood or the filter membrane210may be blood permeable while preventing thrombi or embolic debris from passing through the filter membrane210. In some embodiments, the expandable filter device200may include a connector240having an insert242with a socket244disposed therein. In some embodiments, the socket244may be formed integrally with or directly into the elastic wire frame220, with no insert242present or needed. In some embodiments, the structure and/or operation of the expandable filter device200may be similar to a device disclosed in U.S. application Ser. No. 10/351,736, filed Jan. 24, 2003, which is herein incorporated by reference in its entirety.

In some embodiments, the connector240may be configured to releasably attach to a delivery device (not shown) in an installation condition. The installation condition generally includes the expandable filter device200being disposed in a collapsed and/or elongated state. In the installation condition, the expandable filter device200may be inserted (percutaneously, in some embodiments) into an ostium56of a left atrial appendage50, where the expandable filter device200may be expanded or actuated into the delivered condition.FIG. 3illustrates the expandable filter device200in a delivered condition. In some embodiments, the connector240may be configured to matingly align with and/or attach to the delivery device. Upon actuation into the delivered condition, the delivery device may be removed, leaving the socket244of the connector240empty, as seen inFIG. 3Afor example, and exposed to blood flow through the left atrium16. In some embodiments, the connector240and/or the socket244may include threads, spring clips, notches, and/or other releasable interlocking features disposed therein. With some medical devices, an open aperture or socket244may disrupt blood flow and/or create an area of stagnant blood which may facilitate thrombus formation.

FIG. 4illustrates a portion of an example medical device300including an example connector340consisting of mating pieces of hook-and-loop material, such as Velcro®. As shown inFIG. 4A, the connector340may comprise a first piece of material350including a plurality of hooks352and a second piece of material360including a plurality of loops362. In some embodiments, the medical device300may be inserted (percutaneously, in some embodiments) into a patient in an installation condition, wherein the plurality of hooks352of the first piece of material350is matingly engaged with the plurality of loops362of the second piece of material360. Following insertion, the medical device may be actuated into a delivered condition, wherein the first piece of material350is separated from the second piece of material360. In the delivered condition, the second piece of material360may be removed from the patient, leaving the plurality of hooks352of the first piece of material350exposed to blood flow as an irregular shape, which may disrupt blood flow and/or create an area of stagnant blood which may facilitate thrombus formation. As may be appreciated, in some embodiments, the first piece of material350and the second piece of material360may be reversed, such that the first piece of material350may be removed from the patient, leaving the plurality of loops362of the second piece of material360exposed to blood flow as an irregular shape, which may disrupt blood flow and/or create an area of stagnant blood which may facilitate thrombus formation.

FIG. 5Aillustrates the connector140ofFIGS. 2 and 2Aabove including an anti-thrombus feature400. As illustrated, the anti-thrombus feature400is shown as a thin coating disposed in, on, over, and/or around the irregular shape of the connector140in an undeployed state. In some embodiments, the anti-thrombus feature400may be disposed on surfaces of the connector140that are only exposed, for example to surrounding fluid(s), after the delivery device (not shown) has been detached and/or removed. In some embodiments, the anti-thrombus feature400may include a swellable hydrogel and/or a water-swellable polymer that swells when it becomes hydrated (i.e., when the polymer is exposed to an aqueous environment such as body fluid(s), blood, and/or tissue). Some examples of swellable polymers may include polyvinyl alcohol, polyvinylpyrrolidone (PVP), polyethylene glycol, polyethylene oxide, hydroxypropyl methylcellulose, poly(hydroxyalkyl methacrylate) polyacrylic acid, coatings made of or including charged polymers, and the like. In some embodiments, the anti-thrombus feature400may swell and/or increase in volume upon exposure to fluid(s), such as blood or water, to a deployed state, as may be seen inFIG. 5B. In some embodiments, the anti-thrombus feature400in the deployed state may increase in volume by 50%, 75%, 100%, 200%, 400%, 1000%, or more, upon exposure to fluid(s) compared to the undeployed state. In use, following insertion of aortic valve replacement device100and actuation into the delivered condition, the delivery device (not shown) may be detached from the connector(s)140as seen inFIG. 5A, thereby exposing the anti-thrombus feature400to blood flow. The anti-thrombus feature400may then swell and/or increase in volume, in response to exposure to fluid (i.e., blood), to the deployed state, as may be seen inFIG. 5B, to provide a smooth, protective surface over the irregular shape which may reduce the potential for thrombus formation.

One of skill in the art will appreciate that the anti-thrombus feature400described herein is not limited to use on the connector140, but may be equally applicable to any connector having an irregular shape or open aperture exposed to blood flow. For example,FIGS. 6A-6Cschematically illustrate an anti-thrombus feature500disposed within a blind hole or aperture544of a connector540. As described herein, the connector540may be used in place of or as a substitute for the connector240described above, and thus may be used interchangeably with the connector240and/or the insert242throughout the disclosure, for example. Similarly, the anti-thrombus feature500may be the same as or similar to the anti-thrombus feature400in construction, substance, materials, function, and the like.

For the purpose of illustration, the aperture544ofFIGS. 6A-6Cincludes threads disposed therein. As discussed above with respect to the connector240, other means of securing and/or attaching a delivery device to the connector540are also possible. In some embodiments, a delivery device may include an elongate rod560having a distal end configured to releasably attach to the connector540. In some embodiments, the distal end of the elongate rod560may include threads configured to matingly align with the threads of the aperture544. Similarly, in some embodiments, the distal end of the elongate rod560may include one or more features configured to engage other interlocking features disposed within the blind hole or aperture544.

In some embodiments, the anti-thrombus feature500may be disposed within the aperture544of the connector540, and the delivery device may be releasably attached to the connector540, prior to percutaneous or minimally-invasive insertion, for example, to produce an installation condition of a medical device, such as the expandable filter device200. In the installation condition, the anti-thrombus feature500may be disposed between the connector540and the distal end of the elongate rod560in an undeployed state, as shown inFIG. 6A, such that the anti-thrombus feature500is protected from exposure to fluid (i.e., blood), which may cause the anti-thrombus feature500to swell and/or increase in volume. The skilled artisan will recognize that other arrangements of the anti-thrombus feature500, for example, a coating disposed on the threads of the aperture544, are also possible. Following percutaneous or minimally-invasive insertion of the medical device, the distal end of the elongate rod560may be withdrawn from the aperture544, as seen inFIG. 6B. Following withdrawal and/or removal of the distal end of the elongate rod560from the aperture544, the anti-thrombus feature500may be exposed to blood flow. The anti-thrombus feature500may swell and/or increase in volume, in response to exposure to fluid (i.e., blood), to a deployed state, as may be seen inFIG. 6C, to fill in the aperture544and/or to provide a smooth, protective surface over the aperture544which may reduce the potential for thrombus formation.

FIGS. 7A-7Bschematically illustrate an anti-thrombus feature600disposed over or adjacent to a blind hole or aperture644of a connector640. As described herein, the connector640may be used in place of or as a substitute for the connector240described above, and thus may be used interchangeably with the connector240and/or the insert242throughout the disclosure, for example.

For the purpose of illustration, the aperture644ofFIGS. 7A-7Bincludes threads disposed therein. As discussed above with respect to the connector240, other means of securing and/or attaching a delivery device to the connector640are also possible. In some embodiments, a delivery device may include an elongate rod660having a distal end configured to releasably attach to the connector640. In some embodiments, the distal end of the elongate rod660may include threads configured to matingly align with the threads of the aperture644. Similarly, in some embodiments, the distal end of the elongate rod660may include one or more features configured to engage other interlocking features disposed within the blind hole or aperture644.

In some embodiments, the anti-thrombus feature600may include a self-biased flap attached to the connector640immediately adjacent the aperture644. In some embodiments, the self-biased flap may include or be formed from a polymer, a metallic film or alloy(s) such as stainless steel (e.g. 304v stainless steel or 316L stainless steel), nickel-titanium alloy (e.g., nitinol, such as super elastic or linear elastic nitinol), nickel-chromium alloy, nickel-chromium-iron alloy, cobalt alloy, nickel, titanium, platinum, combinations thereof, or other suitable material(s) that provide sufficient spring force or bias to translate the anti-thrombus feature600from an undeployed state into a deployed state against, or in some embodiments with the assistance of, blood flow over the aperture644of the medical device.

In some embodiments, the delivery device may be releasably attached to the connector640, prior to percutaneous or minimally-invasive insertion, for example, to produce an installation condition of a medical device, such as the expandable filter device200. In the installation condition, the anti-thrombus feature600may be held in the undeployed state by the elongate rod660, as shown inFIG. 7A. Following percutaneous or minimally-invasive insertion of the medical device, the elongate rod660may be withdrawn from the aperture644, permitting the anti-thrombus feature600to translate into the deployed state, wherein the anti-thrombus feature600covers the aperture644, as seen inFIG. 7B. Following withdrawal and/or removal of the elongate rod660from the aperture644, the anti-thrombus feature600may provide a smooth, protective surface over the aperture644which may reduce the potential for thrombus formation.

FIGS. 8A-8Bschematically illustrate an anti-thrombus feature700disposed within a blind hole or aperture744of a connector740. As described herein, the connector740may be used in place of or as a substitute for the connector240described above, and thus may be used interchangeably with the connector240and/or the insert242throughout the disclosure, for example.

For the purpose of illustration, the aperture744ofFIGS. 8A-8Bincludes threads disposed therein. As discussed above with respect to the connector240, other means of securing and/or attaching a delivery device to the connector740are also possible. In some embodiments, a delivery device may include an elongate rod760having a distal end configured to releasably attach to the connector740. In some embodiments, the distal end of the elongate rod760may include threads configured to matingly align with the threads of the aperture744. Similarly, in some embodiments, the distal end of the elongate rod760may include one or more features configured to engage other interlocking features disposed within the blind hole or aperture744.

In some embodiments, the anti-thrombus feature700may include a spring-loaded cap disposed within and secured to the aperture744of the connector740. In some embodiments, the anti-thrombus feature700may include or be formed from a polymer, a metallic film or alloy(s) such as stainless steel (e.g. 304v stainless steel or 316L stainless steel), nickel-titanium alloy (e.g., nitinol, such as super elastic or linear elastic nitinol), nickel-chromium alloy, nickel-chromium-iron alloy, cobalt alloy, nickel, titanium, platinum, combinations thereof, or other suitable material(s), and may include a spring such as a coil spring, a leaf spring, a bi-stable element, or other suitable means that provides sufficient spring force or bias to translate the anti-thrombus feature700from an undeployed state into a deployed state. In some embodiments, the anti-thrombus feature700may include or be formed from a swellable or expandable material such as a hydrogel or other materials similar to the anti-thrombus feature400described above.

In some embodiments, the delivery device may be releasably attached to the connector740, prior to percutaneous or minimally-invasive insertion, for example, to produce an installation condition of a medical device, such as the expandable filter device200. In the installation condition, the anti-thrombus feature700may be held in the undeployed state by the distal end of the elongate rod760, as shown inFIG. 8A. Following percutaneous or minimally-invasive insertion of the medical device, the distal end of the elongate rod760may be withdrawn from the aperture744, permitting the anti-thrombus feature700to translate into the deployed state, as seen inFIG. 8B. Following withdrawal and/or removal of the elongate rod760from the aperture744, the anti-thrombus feature700may provide a smooth, protective surface at a mouth of the aperture744, effectively blocking off the aperture744from blood flow, which may reduce the potential for thrombus formation.

FIG. 9Aillustrates the example connector340ofFIGS. 4 and 4Aabove including an anti-thrombus feature800. As illustrated, the anti-thrombus feature800is shown as a thin coating disposed in, on, over, or around the plurality of hooks352of the first piece of material350, in an undeployed state. In some embodiments, the anti-thrombus feature800may be disposed on surfaces of the connector340that are only exposed after the delivery device (not shown) and/or the second piece of material360has been removed. In some embodiments, the anti-thrombus feature800may include a swellable hydrogel and/or a water-swellable polymer that swells when it becomes hydrated (i.e., when the polymer is exposed to an aqueous environment such as body fluid(s), blood, and/or tissue). Some examples of swellable polymers may include polyvinyl alcohol, polyvinylpyrrolidone (PVP), polyethylene glycol, polyethylene oxide, hydroxypropyl methylcellulose, poly(hydroxyalkyl methacrylate) polyacrylic acid, coatings made of or including charged polymers, and the like. In some embodiments, the anti-thrombus feature800may swell and/or increase in volume upon exposure to fluid(s), such as blood or water, to a deployed state, as may be seen inFIG. 9B. In some embodiments, the anti-thrombus feature800in the deployed state may increase in volume by 50%, 75%, 100%, 200%, 400%, 1000%, or more, upon exposure to fluid(s) compared to the undeployed state. In use, following insertion of the medical device300and actuation into the delivered condition, wherein the first piece of material350is separated from the second piece of material360, as seen inFIG. 9A, the anti-thrombus feature800may be exposed to fluid(s)/blood flow. In the delivered condition, the second piece of material360may be removed from the patient, leaving the plurality of hooks352of the first piece of material350exposed to blood flow as an irregular shape. The anti-thrombus feature800may then swell and/or increase in volume, in response to exposure to fluid (i.e., blood), to the deployed state, as may be seen inFIG. 9B, to provide a smooth, protective surface over and/or around the plurality of hooks352and/or the irregular shape which may reduce the potential for thrombus formation. As may be appreciated, in some embodiments, the first piece of material350and the second piece of material360may be reversed, such that in the delivered condition, the first piece of material350may be removed from the patient, leaving the plurality of loops362of the second piece of material360exposed to blood flow as an irregular shape. The anti-thrombus feature800may then swell and/or increase in volume, in response to exposure to fluid (i.e., blood), to the deployed state, to provide a smooth, protective surface over and/or around the plurality of loops362and/or the irregular shape which may reduce the potential for thrombus formation.

FIGS. 10A-10Bschematically illustrate a connector940having a blind hole or aperture944disposed therein. In some embodiments, an anti-thrombus feature900may be inserted, applied, or added to the connector940in vivo, or while the connector940is disposed within a patient. As described herein, the connector940may be used in place of or as a substitute for the connector240described above, and thus may be used interchangeably with the connector240and/or the insert242throughout the disclosure, for example. Similarly, an anti-thrombus feature900may be the same as or similar to the anti-thrombus feature400in construction, substance, materials, function, and the like.

For the purpose of illustration, the aperture944ofFIGS. 10A-10Bincludes threads disposed therein. As discussed above with respect to the connector240, other means of securing and/or attaching a delivery device to the connector940are also possible. In some embodiments, a delivery device may include an elongate rod960having a distal end configured to releasably attach to the connector940. In some embodiments, the distal end of the elongate rod960may include threads configured to matingly align with the threads of the aperture944. Similarly, in some embodiments, the distal end of the elongate rod960may include one or more features configured to engage other interlocking features disposed within the blind hole or aperture944. In some embodiments, the elongate rod960may include a lumen962extending therethrough, the lumen962being in fluid communication with the aperture944and a source (not shown) of the anti-thrombus feature900.

In some embodiments, the delivery device may be releasably attached to the connector940, prior to percutaneous or minimally-invasive insertion, for example, to produce an installation condition of a medical device, such as the expandable filter device200. In the installation condition, the anti-thrombus feature900may not be present within the connector940, and thus in an undeployed state, as shown inFIG. 10A, the anti-thrombus feature900is protected from exposure to fluid (i.e., blood) which may cause the anti-thrombus feature900to swell and/or increase in volume. Following percutaneous or minimally-invasive insertion of the medical device, the distal end of the elongate rod960may be withdrawn from the aperture944, as seen inFIG. 10B. During withdrawal and/or removal of the distal end of the elongate rod960from the aperture944, the anti-thrombus feature900may be transferred from the source of the anti-thrombus feature900, through the lumen962, and into the aperture944. Following withdrawal and/or removal of the elongate rod960from the aperture944, the anti-thrombus feature900may be exposed to fluid/blood flow in a deployed state. In some embodiments, the anti-thrombus feature900may additionally swell and/or increase in volume, in response to exposure to fluid (i.e., blood), to define the deployed state. In the deployed state, the anti-thrombus feature900may fill in the aperture944and/or provide a smooth, protective surface over the aperture944which may reduce the potential for thrombus formation, similar to or the same as may be seen inFIG. 6C.

In some embodiments, the anti-thrombus feature(s) described herein may be mixed with, loaded with, doped with, coated with, or otherwise include a pro-healing agent or drug (i.e., Annexin A5, etc.), an anti-thrombogenic substance (i.e., heparin, heparin derivatives, etc.), urokinase, D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone (PPACK), or other suitable treatment agents.

It should be understood that although the above discussion was focused on medical devices and methods of use within the vascular system of a patient, other embodiments of medical devices or methods in accordance with the disclosure can be adapted and configured for use in other parts of the anatomy of a patient. For example, devices and methods in accordance with the disclosure can be adapted for use in the digestive or gastrointestinal tract, such as in the mouth, throat, small and large intestine, colon, rectum, and the like. For another example, devices and methods can be adapted and configured for use within the respiratory tract, such as in the mouth, nose, throat, bronchial passages, nasal passages, lungs, and the like. Similarly, the apparatus and/or medical devices described herein with respect to percutaneous deployment may be used in other types of surgical procedures as appropriate. For example, in some embodiments, the medical devices may be deployed in a non-percutaneous procedure, such as an open-heart procedure. Devices and methods in accordance with the invention can also be adapted and configured for other uses within the anatomy.

It should be understood that this disclosure is, in many respects, only illustrative. Changes may be made in details, particularly in matters of shape, size, and arrangement of steps without exceeding the scope of the invention. The invention's scope is, of course, defined in the language in which the appended claims are expressed.