Abstract:
This document provides methods and materials related to providing a mammal with a replacement valve (e.g., a synthetic or artificial heart valve). For example, synthetic or artificial heart valve that can be delivered in a minimally invasive manner are provided.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application claims the benefit of U.S. Provisional Application Ser. No. 61/354,812, filed Jun. 15, 2010. The disclosure of the prior application is considered part of (and is incorporated by reference in) the disclosure of this application. 
     
    
     TECHNICAL FIELD 
       [0002]    This document relates to synthetic valves that can be delivered in a minimally invasive manner. 
       BACKGROUND 
       [0003]    Heart valves are important components of a heart that allow the heart to function normally. In general, natural heart valves can allow for unidirectional blood flow from one chamber of the heart to another. In some cases, natural heart valves can become dysfunctional to a degree that may require complete surgical replacement of the natural heart valve with a heart valve prostheses. 
       SUMMARY 
       [0004]    This document provides methods and materials related to providing a mammal with a replacement valve (e.g., a synthetic or artificial heart valve). For example, this document provides synthetic or artificial heart valve that can be delivered in a minimally invasive manner. 
         [0005]    In general, one aspect of this document features an artificial heart valve for placement within a mammal. The heart valve comprises, or consists essentially of, (a) at least two struts having a proximal portion and a distal portion, wherein the proximal portion is configured to attach to heart tissue, and wherein the struts, when the heart valve is placed within the mammal, converge towards an axis in a direction from the proximal portion to the distal portion, and (b) a membrane structure attached to the struts and configured to form a wall around the axis, wherein at least a portion of the membrane structure is capable of expanding and collapsing movement, wherein during the expanding movement the portion of the membrane structure moves away from the axis to form a closed position of the heart valve, wherein during the collapsing movement the portion of the membrane structure moves toward the axis to form an opened position of the heart valve, wherein, when the heart valve is placed within the mammal and in the opened position, blood upstream of the heart valve is capable of moving past the heart valve between the membrane structure and the mammal&#39;s heart tissue, and wherein, when the heart valve is placed within the mammal and in the closed position, movement of blood upstream of the heart valve past the heart valve between the membrane structure and the mammal&#39;s heart tissue is limited. The mammal can be a human. The proximal portion of the struts can be configured to attach to heart tissue via an adhesive, clamp, staple, barb, suture, hook, screw, or combination thereof. The membrane structure can comprise flexible biocompatible material. The membrane structure can comprise a polymer. The membrane structure can comprise animal pericardium tissue. The membrane structure can form a conical shape. The membrane structure can form a conical shape defining a lumen comprising an opening at first end and an opening at a second end, wherein the opening at the first end is larger than the opening at the second end. The heart valve can comprise a first end defining a diameter and a second end defining a diameter, wherein the diameter of the first end is larger than the diameter of the second end, and wherein the first end defines an opening. The second end can define an opening, wherein the opening of the second is smaller than the opening at the first end. The struts can comprise flexible material. The struts can comprise a shape memory material. The shape memory material can be nitinol. The heart valve can be capable of being placed within the mammal percutaneously. The heart valve can be capable of moving from a collapsed position during delivery to the mammal to an expanded position after placement within the mammal. The heart valve can comprise a ring structure attached to the proximal portion of the struts. When the heart valve is placed within the mammal and in the opened position, blood upstream of the heart valve can be capable of moving past the heart valve between the membrane structure and the ring structure, and when the heart valve is placed within the mammal and in the closed position, movement of blood upstream of the heart valve past the heart valve between the membrane structure and the ring structure can be limited. The ring structure can comprise a shape memory material biased to promote movement of the proximal portion of the struts away from the axis during placement of the heart valve within the mammal. The heart valve can comprise a ring structure attached to the distal portion of the struts. The heart valve can comprise a tethering cord anchor. The tethering cord anchor can be configured to extend from the heart valve and across at least a portion of the heart chamber downstream of the heart valve when the heart valve is placed within the mammal. The tethering cord anchor can comprise an adhesive, clamp, staple, barb, suture, hook, screw, or combination thereof configured to attach the tethering cord anchor to a wall of the heart chamber. 
         [0006]    Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting. 
         [0007]    Other features and advantages of the invention will be apparent from the following detailed description, and from the claims. 
     
    
     
       DESCRIPTION OF DRAWINGS 
         [0008]      FIGS. 1A-1B  depict a replacement valve configured for minimally invasive delivery to the heart, wherein a membrane material that covers strut supports can collapse around those supports, in accordance with some embodiments. 
           [0009]      FIG. 2  depicts the valve of  FIGS. 1A-1B  deployed in the aortic position, thus replacing the native aortic valve, in accordance with some embodiments. 
           [0010]      FIGS. 3A-3B  depict catheter deployment of the valve of  FIGS. 1A-1B  from a transapical approach, in accordance with some embodiments. 
           [0011]      FIGS. 4A-4C  depict multiple embodiments of a replacement valve. 
           [0012]      FIGS. 5A-5E  depict multiple embodiments of a replacement valve. 
           [0013]      FIG. 6  depicts a replacement valve positioned at the mitral position, in accordance with some embodiments. 
           [0014]      FIG. 7  depicts a replacement valve, including cord anchors, positioned in the aortic position, in accordance with some embodiments. 
           [0015]      FIG. 8  depicts a replacement valve, including artificial chordae anchors, in accordance with some embodiments. 
           [0016]      FIG. 9  depicts an annuloplasty ring positioned in a heart, in accordance with some embodiments. 
           [0017]      FIG. 10  depicts a replacement valve including a two piece design, in accordance with some embodiments. 
           [0018]      FIG. 11  depicts a replacement valve, in accordance with some embodiments. 
           [0019]      FIG. 12  depicts a system for removing native valve tissue and deploying a replacement valve, in accordance with some embodiments. Like reference symbols in the various drawings indicate like elements. 
       
    
    
     DETAILED DESCRIPTION 
       [0020]    Referring now to  FIGS. 1A and 1B , in some embodiments, a minimally invasive valve replacement system  10  includes an implantable valve  100  that further includes collapsible/expandable support struts  110  and a flexible membrane  120  covering the struts  110 . In some embodiments, the implantable valve  100  can include three struts  110  covered by the pliable membrane  120  such that the struts  110  are able to engage the annulus of a native valve. In some cases, the struts can have anchoring devices that can embed into the native tissue. For example, a system provided herein can include self-fixing struts (e.g., struts with hooks or barbs along with helices). The struts  110  can form a generally conical shape, and the membrane  120  can include an opening  121  at the tip of the cone to prevent blood from pooling within the valve body. Once the valve  100  is deployed, the struts  110  can remain in a fixed position while portions of the membrane  120  can move radially in and out over the circumference of the valve  100  to facilitate the passage of fluids in one direction, while preventing or minimizing fluid movement in the opposite direction. 
         [0021]    In some embodiments, the membrane  120  is configured such that it can collapse around the strut supports  110 . For example, during the diastolic portion of the cardiac cycle, the membrane  120  remains expanded (e.g., the valve  100  is in a closed configuration), thus obstructing fluid flow. During the systolic portion of the cardiac cycle, the membrane material  120  can collapse (e.g., the valve  100  is in a open configuration), thus allowing fluid flow past the valve  100 . Near a proximal end  102  of the valve  100 , the struts  110  can be configured to engage native tissue to secure the valve  100 . For example, near the proximal end  102  of the valve  100 , the struts  110  can be configured to attach to native tissue (e.g., native annulus) adhesively, mechanically (e.g., using barbs, clips, hooks, clamps, and the like), chemically, electrically (e.g., “welding”), or using a combination of one or more of these attachment methods. Near a distal end  104  of the valve  100 , the struts  110  can meet at a small opening  116 . The struts  110  can include any rigid biocompatible material (e.g., plastic, metal, ceramic, and the like) or alloy thereof which retains some amount of flexibility to allow for percutaneous (e.g., through a catheter) deployment. For example, the struts  110  can include a shape memory alloy (e.g., Nitinol) that can be collapsed into a catheter during delivery and then assume an open, conical shape after deployment (see  FIG. 3 ). The membrane  120  covering and affixed to the struts  110  can include any biocompatible flexible/compliant material (e.g., polymers, polyethylene, animal pericardium tissue, other biological tissues, and the like). For example, the membrane  120  can include animal pericardial tissue. 
         [0022]    The membrane  120  can have proximal and distal reinforcing regions (e.g., bands, coatings, and the like)  122  and  124 , respectively, around the proximal end  102  and distal end  104  of the membrane to reduce or eliminate ripping and fraying after long-term use. 
         [0023]    The membrane  120  can be affixed to the struts  110  using any suitable attachment means (e.g., adhesives, clips, sutures, clamps, rings, and the like). The membrane  120  can include enough material between struts  110  to allow for collapse of a portion of the membrane  120  toward a central axis  106  of the valve  110  during systole (the open configuration depicted in  FIG. 1B ) and to expand and conform to the outer rim of native tissue during diastole (the closed configuration depicted in  FIG. 1A ). In this way, blood can pass by the valve  110  during systole, but is substantially reduced from passage during diastole. When in the closed configuration, the opening  121  at the distal end  104  of the valve  100  can allow a small amount of fluid to pass through the valve  100  (when compared to when the valve  100  is open) to prevent the pooling of fluid in the bottom (e.g., distal end  104 ) of the valve  100 . This small amount of flow can help to reduce or eliminate the formation of blood clots and to wash the inner surface of the valve  100 . 
         [0024]    Referring now to  FIG. 2 , in some embodiments, the valve  100  can be deployed in the heart  20  of a mammal (e.g., a human). For example, the valve  100  can be deployed in the aortic position, thus replacing the native aortic valve. In this configuration, during systole, the contraction of the left ventricle  22  can create a high amount of pressure on the surface of the membrane  120  causing a portion of the membrane  120  to collapse toward the central axis  106  of the valve  110  during systole (see  FIG. 1B ). This collapse can allow blood to flow around the outer face of the membrane  120  and into the aorta  24 . During diastole, the membrane  120  can expand such that the valve  100  transitions back to the closed configuration due to the loss of pressure as the left ventricle  22  relaxes. This configuration can reduce or eliminate blood from flowing from the aorta  24  into the left ventricle  22 . In some cases, the transition between the open and closed configurations is assisted with the help of an active component around the proximal rim of the membrane  120  that can bias the valve  100  toward the closed configuration (described in more detail in connection with  FIG. 5A ). 
         [0025]    Referring now to  FIGS. 3A-3B , in some embodiments, the valve  100  can be deployed (e.g., minimally-invasively deployed) from a catheter  20  using a transapical approach. The valve  100  can assume a collapsed state when loaded into the deployment catheter  30 , as depicted in  FIG. 3A . This allows the valve  100  to be inserted into the body through a relatively small opening. In another example, the valve  100  can be positioned via a retrograde aortic approach. In some cases, the deployment of the valve can be via a retrograde aortic approach, a percutaneous/transfemoral approach, or an open surgical approach. Once the deployment catheter  30  is positioned near the native valve annulus, the valve  100  can be pushed out of the catheter, assume its conical shape, and be secured to the native annulus tissue, as depicted in  FIG. 3B . 
         [0026]    Referring now to  FIGS. 4A-4B , in some embodiments, an implantable valve can include one or more of struts  110 . For example, as depicted in  FIG. 4A , the valves  100 ,  200 , and  300  can include three struts  110 , four struts  110 , and two struts  110 , respectively. In some embodiments, an implantable valve (e.g., the valve  300 ) can include a support ring  330  that can advantageously provide additional stability for the implantable valve. In some embodiments, an implantable valve can include one or more of a variety of features for permanently securing the valve to native tissue. For example, valve  400  features a design that includes hooks  412  near the proximal end  102  which embed into the valve annulus. In another example, valve  500  features a design that includes barb  512  located on clamps  514  near the proximal end  102  to pinch the annular tissue between each arm. In still another example, valve  600  includes tethering cord anchors  616  which can be used to anchor the valve in distal walls of the heart (see, e.g.,  FIGS. 4C and 7 ). In other examples, valve  700  includes a sewing ring  726  whereby the ring  726  can be directly sutured to the annulus, and valve  800  includes barbs  812  near the proximal end  102 . In other examples, any type of known anchoring system can be used to secure an implantable valve to native tissue, including adhesives, clamps, staples, barbs, sutures, hooks, screws, and combinations thereof. 
         [0027]    Referring now to  FIGS. 5A-5E , in some embodiments, an implantable valve can include features advantageous to the implantable valve. For example,  FIG. 5A  depicts a valve  900  that includes a shape memory ring  940  attached along the outer diameter of the proximal portion of the membrane  120 . The shape memory ring  940  can be biased toward an expanded shape to facilitate expanding membrane  120 , and thus facilitating the transitioning of the valve to the closed configuration during an obstructive portion of the valve functional cycle (e.g., when the closed valve reduces the flow of material past it). This can advantageously encourage the valve  900  to more quickly transition to the closed configuration, for example, during the short periods of the cardiac cycle. This can, for example, be advantageous when the valve  900  is deployed in the aortic valve position. The shape memory ring  940  can be flexible enough to allow the membrane  120  to deform into the collapsed state at pressures normally occurring during contraction of the left ventricle in systole. In some embodiments, the opposite configuration can be used, for example, in some anatomical positions such as replacing the mitral valve. 
         [0028]    Referring to  FIG. 5B , in some embodiments, implantable valves can be configured with different lengths  1008  and  1108 . For example,  FIG. 5B  depicts valves  1000  and  1100  with differing lengths. In some embodiments, a valve can be chosen for an application based on length wherein the valve chosen can be based on, for example, the valve that includes a length that facilitates the smallest conformation in a collapsed state in combination with the smallest internal cone volume to reduce fluid pooling. In some cases, the length can be from 15 mm to 50 mm (e.g., 15 mm to 40 mm, 15 mm to 30 mm, 15 mm to 20 mm, 20 mm to 50 mm, 30 mm to 50 mm, or 40 mm to 50 mm).  FIG. 5C  depicts variations in the distal opening in the cone design to facilitate “washing” of the interior membrane walls and to prevent fluid pooling. For example, valve  1200  includes a smaller diameter opening  1221 , while valve  1300  includes a larger diameter opening  1321 . In some embodiments, a valve can be chosen such that the diameter of the opening can balance washing and prevention of fluid pooling with prevention of regurgitation of fluid into the wrong cardiac chamber. In some cases, the diameter of the opening can be from 10 mm to 40 mm (e.g., 10 mm to 35 mm, 10 mm to 33 mm, 10 mm to 30 mm, 10 mm to 25 mm, 10 mm to 20 mm, 15 mm to 40 mm, 20 mm to 40 mm, or 30 mm to 40 mm).  FIG. 5D  depicts a valve  1400  that include rails  1450  attached to a ring structure  1455  on the membrane  120  which allows the membrane  120  to move back and forth from collapsed and expanded orientations.  FIG. 5E  depicts valves  1500  and  1600  that each include a cover  1560  near the proximal ends  102  of the valves  1500  and  1600 . The covers can include materials that are the same or different than material included in the membrane  120 . In some embodiments, inclusion of the cover on the valves  1500  and  1600  can restrict the flow of blood into the interior of the valves  1500  and  1600 . To facilitate re-expansion during the obstructive portion of a valve cycle, the valves  1500  and  1600  can include the shape memory ring (or other features to encourage expansion of the membrane  120 ). In some embodiments, the valve  1500  can include other features to encourage expansion of the membrane  120 . Expansion features  1570  can include a foam mechanism, a sponge mechanism, a coil mechanism, and the like, within the cone. In some embodiments, the valve  1600  can include mechanical structures  1670  such as springs, coils, shocks, and the like, to encourage expansion of the membrane  120 . 
         [0029]    Referring to  FIG. 6 , in some embodiments, a replacement valve  1700  can be positioned at the mitral position within the heart  20  (e.g., to replace the mitral valve). The valve  1700  can be deployed in the pulmonary or tricuspid position. In the mitral position, the valve  1700  can assume the open configuration (e.g., with the membrane  120  collapsed) during diastole and the closed configuration (e.g., with the membrane  120  expanded) during systole. 
         [0030]    Referring now to  FIG. 7 , in some embodiments, a replacement valve  1800  can include one or more cord anchors  616 , which can be used to assist in securing the valve  1800 . For example, in  FIG. 7 , valve  1800  is positioned in the aortic position of heart  20 , and cord anchors  616  can be attached to the wall of the left ventricle  22 , to the internal papillary muscles of the left ventricle  22 , and the like. Cord anchors  616  can include pledgets  1817  or other features to reduce or eliminate the chances of cords  616  pulling through the wall of the heart. 
         [0031]    Referring now to  FIG. 8 , in some embodiments, replacement valves  1900  and  1950  include artificial chordae anchors that can help to maintain valves  1900  and  1950  correctly positioned. Valves  1900  and  1950  can each be placed at an annulus and then cords  1916  (e.g., including sutures, polymers, nylon, and the like) can be run from the valves  1900  and  1950  to the wall of the heart to anchor valves  1900  and  1950  in place. Cords  1916  can be attached to the heart wall, for example, by pledgettes  1917 , staples, T-tags, helical screws, suture, and the like. The ability to anchor valves  1900  and  1950  with cords  1917  can allow for very low-profile valve designs. Current artificial valves may rely on stents, cages, and the like to hold the valves in position and anchor to the native annulus. By using cords  1916  attached to the heart, less material may be needed for anchoring at the annulus, and therefore valves  1900  and  1950  can be lower profile. This can make valves  1900  and  1950  easier to deliver and place, less obtrusive, and the like. Cord anchored valve designs (e.g., valves  1900  and  1950 ) can include one or more of a ring  1930  and a wing  1935  that rests on the top of the native annulus to provide support, with cords  1916  providing anchoring and stability. Ring  1930  and wings  1935  can each rely on radial force/friction or tissue spikes  1932  to provide further anchoring. Cord-anchoring can be used with the valve designs described herein or with any current or traditional valve designs (e.g., bi-leaflet, mechanical, tissue, collapsible, and the like). Cord anchoring can work for valves placed in any location (e.g., aortic, mitral, tricuspid, pulmonary, and the like). Cords  1916  can include an elastic component to allow some give during the cardiac cycle to lengthen and contract, thus minimizing or eliminating the possibility of damage or tearing out. In some embodiments, any number of cords can be used to anchor valves  1900  and  1950  (e.g., one, two, three four, five, or more cords). 
         [0032]    Referring now to  FIG. 9 , in some embodiments, an annuloplasty ring  2000  can include cords  2016  that can assist in anchoring ring  2000 . Annuloplasty ring  2000  can be secured to the annulus of the native valve. Ring  2000  can include sliding members  2080  and  2085 , which allow ring  2000  to become smaller over time. Anchoring cords  2016  can be used to mechanically slide member  2080  of ring  2000  within member  2085 , thereby tightening and shortening ring  2000  over time. 
         [0033]    Referring now to  FIG. 10 , in some embodiments, a valve  2100  can be configured to include a two-piece design. For example, a lower membrane  2126  can include a similar material to membrane  120  described previously (e.g., compliant and collapsible) whereas an upper membrane  2128  can include a more rigid, stiffer composition (e.g., while still being able to have some give to be compliant with biological tissue). Valve  2100  can function in a similar manner to those described in connection with  FIGS. 1-6  except that the more rigid upper membrane  2128  may be less likely to collapse during systole, thus continuing to hold its expanded shape. During diastole, rigid upper membrane  2128  can provide a surface  2129  for compliant lower membrane  2126  to meet against, which can reduce or eliminate the amount of blood that can leak back. 
         [0034]    Referring now to  FIG. 11 , in some embodiments, valves  2200  and  2300  can be configured such that compliant membrane  120  has an overall area such as to only be able to collapse into valves  2200  and  2300  to a certain amount. For example, the amount of compliant material relative to the diameter of the valve (made up by the struts  110 ) would only allow a certain amount of collapse (e.g., between ⅔ and ¾ of the total circumferential area covered by valves  2200  and  2300 ). This type of design can balance the ability to allow blood to flow past valves  2200  and  2300  during systole while optimizing closing of the valve in diastole. 
         [0035]    In some cases, a system provided herein can be configured to remove natural valve tissue (e.g., diseased or calcified valve leaflets) and deploy an artificial valve provided herein. With reference to  FIGS. 12A-C , system  2500  can include deployment device  2510  configured to deploy valve  2530 . In some cases, system  2500  can be configured to include native valve excision device  2520 . Excision device  2520  can be configured to have blades that are capable of opening and closing, thereby providing the ability to cut or remove native valve tissue  2540 . For example, excision device  2520  can have two blades that can actuate back and forth, thereby having the ability to cut the native leaflets to remove them from, e.g., the valve annulus. The blade movement can be mechanically controlled by a handle (force provided by the surgeon) or by hydraulic pressure (fluid, gas, etc.) in order to provide a quick, forceful cutting motion to remove the leaflets (e.g., diseased leaflets). After the leaflets are cut, the device can be pulled back while simultaneously advancing the new valve forward with the deployment tool. In this way, there is a nearly immediate replacement of the native valve with a new valve. In some cases, the removed native valve tissue  2550  can be retained in the system as it is being removed from the patient. 
         [0036]    A number of embodiments of the invention have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the invention. Accordingly, other embodiments are within the scope of the following claims.