Abstract:
A method of delivering a prosthetic mitral valve includes delivering a distal anchor from a delivery sheath such that the distal anchor self-expands inside a first heart chamber on a first side of the mitral valve annulus, pulling proximally on the distal anchor such that the distal anchor self-aligns within the mitral valve annulus and the distal anchor rests against tissue of the ventricular heart chamber, and delivering a proximal anchor from the delivery sheath to a second heart chamber on a second side of the mitral valve annulus such that the proximal anchor self-expands and moves towards the distal anchor to rest against tissue of the second heart chamber. The self-expansion of the proximal anchor captures tissue of the mitral valve annulus therebetween.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application claims priority to U.S. Patent Provisional Application No. 61/847,515, filed on Jul. 17, 2013, entitled “SYSTEM AND METHOD FOR CARDIAC VALVE REPAIR AND REPLACEMENT,” the entirety of which is incorporated by reference herein. 
     
    
     INCORPORATION BY REFERENCE 
       [0002]    All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. 
       FIELD OF INVENTION 
       [0003]    The present invention relates generally to the treatment of cardiac valve disorders, such as mitral valve replacement, using minimally invasive techniques. 
       BACKGROUND 
       [0004]    The mitral valve lies between the left atrium and the left ventricle of the heart. Various diseases can affect the function of the mitral valve, including degenerative mitral valve disease and mitral valve prolapse. These diseases can cause mitral stenosis, in which the valve fails to open fully and thereby obstructs blood flow, and/or mitral insufficiency, in which the mitral valve is incompetent and blood flows passively in the wrong direction. 
         [0005]    Many patients with heart disease, such as problems with the mitral valve, are intolerant of the trauma associated with open-heart surgery. Age or advanced illness may have impaired the patient&#39;s ability to recover from the injury of an open-heart procedure. Additionally, the high costs are associated with open-heart surgery and extra-corporeal perfusion can make such procedures prohibitive. 
         [0006]    Patients in need of cardiac valve repair or cardiac valve replacement can be served by minimally invasive surgical techniques. In many minimally invasive procedures, small devices are manipulated within the patient&#39;s body under visualization from a live imaging source like ultrasound, fluoroscopy, or endoscopy. Minimally invasive cardiac procedures are inherently less traumatic than open procedures and may be performed without extra-corporeal perfusion, which carries a significant risk of procedural complications. 
         [0007]    Minimally invasive aortic valve replacement devices, such as the Medtronic Corevalve or the Edwards Sapien, deliver aortic valve prostheses through small tubes which may be positioned within the heart through the aorta via the femoral artery or through the apex of the heart. However, current cardiac valve prostheses are not designed to function effectively within the mitral valve. Further, current cardiac valve prostheses delivered via a minimally invasive device are often difficult to place correctly within the native valve, difficult to match in size to the native valve, and difficult to retrieve and replace if initially placed incorrectly. 
         [0008]    Accordingly, it is desirable to have a mitral valve replacement that solves some or all of these problems. 
       SUMMARY OF THE DISCLOSURE 
       [0009]    In general, in one embodiment, a prosthetic mitral valve includes a proximal anchor, a distal anchor, and a central portion therebetween. The proximal and distal anchors each include a first outer frame and a second outer frame. The first outer frame includes a plurality of first arcs joined together, and the second outer frame includes a plurality of second arcs joined together. The plurality of first arcs are out of phase relative to the plurality of second arcs. 
         [0010]    This and other embodiments can include one or more of the following features. The first plurality of arcs can be movable relative to the second plurality of arcs. The first and second outer frames can be substantially circular. The plurality of first arcs can be disposed around substantially the entire first outer frame, and the plurality of second arcs can be disposed around substantially the entire second outer frame. The plurality of first arcs can lie substantially in a first plane, and the plurality of second arcs can lie substantially in an adjacent second plane. The first and second arcs can be approximately 90 degrees out of phase. The first and second outer frames can be made of wire rope. The wire rope of the first outer frame can have an opposite lay than a lay of the wire rope of the second outer frame. The proximal anchor and distal anchor can be substantially parallel to one another. The central portion can include substructures connecting the proximal and distal anchors. The substructures can be hexagonal. The proximal anchor, distal anchor, and central portion can be configured to expand from a constrained configuration to an expanded configuration. The device can be configured to foreshorten upon expansion of the proximal anchor, distal anchor, and central portion from the constrained configuration to the expanded configuration. The proximal anchor and the distal anchor can each have a diameter in the expanded configuration that is greater than a diameter of the central portion in the expanded configuration. 
         [0011]    In general, in one embodiment, a prosthetic mitral valve includes a valve frame comprising a proximal anchor, a distal anchor, and a central portion therebetween. The valve frame is configured to expand from a constrained configuration to an expanded configuration. A plurality of struts is attached to the central portion and extends distally past the distal anchor. A plurality of leaflets are secured to the plurality of struts such that at least a portion of each leaflet extends distally past the distal anchor. 
         [0012]    This and other embodiments can include one or more of the following features. The valve frame can be configured to self-expand. The plurality of leaflets can be attached to the central portion. The plurality of leaflets can include a biomaterial or a polymer. The proximal anchor can be covered with a skirt configured to seal the prosthetic valve. The skirt can include a biomaterial or polymer. The outer perimeter of the proximal anchor can be substantially circular when covered with the skirt. The plurality of leaflets can be arranged to fill an inner diameter of the mitral valve prosthetic. The ratio of the inner diameter to a height of the plurality of struts can be approximately 2:1. The valve frame can be configured to foreshorten upon expansion of the valve frame from the constrained configuration to the expanded configuration. The proximal anchor and the distal anchor can each have a diameter in the expanded configuration that can be greater than a diameter of the central portion in the expanded configuration. 
         [0013]    In general, in one embodiment, a prosthetic mitral valve includes a valve frame having a proximal anchor, a distal anchor, and a central portion therebetween. The valve frame is configured to expand from a constrained configuration to an expanded configuration. The ratio of an outer diameter of the central portion to a length of the valve frame in the expanded configuration is at least 1.1. 
         [0014]    This and other embodiments can include one or more of the following features. The valve frame can be configured to self-expand. The ratio can be less than or equal to 2. The ratio of the outer diameter of the proximal anchor or the distal anchor to the length of the device can be greater than or equal to 2. The outer diameter of the central portion can be between 25 and 40 mm. The length can be less than or equal to 22 mm. The proximal and distal anchors can extend radially outward from the central portion. The outer diameter of the proximal and distal anchors can be at least 38 mm. 
         [0015]    In general, in one embodiment a method of delivering a prosthetic mitral valve includes delivering a distal anchor from a delivery sheath such that the distal anchor self-expands inside a first heart chamber on a first side of the mitral valve annulus, pulling proximally on the distal anchor such that the distal anchor self-aligns within the mitral valve annulus and the distal anchor rests against tissue of the ventricular heart chamber, and delivering a proximal anchor from the delivery sheath to a second heart chamber on a second side of the mitral valve annulus such that the proximal anchor self-expands and moves towards the distal anchor to rest against tissue of the second heart chamber. The self-expansion of the proximal anchor captures tissue of the mitral valve annulus therebetween. 
         [0016]    This and other embodiments can include one or more of the following features. The first heart chamber can be a ventricular heart chamber, and the second heart chamber can be an atrial heart chamber. 
         [0017]    In general, in one embodiment, a method of delivering a prosthetic mitral valve includes securing a prosthetic valve within a delivery device by extending a plurality of wires of the delivery device through a proximal anchor so as to collapse the proximal anchor, extending the prosthetic delivery device into a heart with the prosthetic valve covered by a sheath of the delivery device, pulling the sheath proximally to expose a distal anchor of the prosthetic valve, thereby allowing the distal anchor to self-expand into place on a first side of the mitral valve annulus, pulling the sheath proximally to expose the proximal anchor, loosening the wires of the delivery device so as to allow the proximal anchor to self-expand into place on a second side of the mitral valve annulus, and removing the delivery device from the heart. 
         [0018]    This and other embodiments can include one or more of the following features. The method can further include tightening the wires after loosening the wires so as to collapse the proximal anchor again, repositioning the proximal anchor to a second location on the second side of the mitral valve annulus and loosening the wires of the delivery device so as to allow the proximal anchor to self-expand into place at the second location on the second side of the mitral valve annulus. Extending a plurality of wires of the delivery device through a proximal anchor so as to collapse the proximal anchor and can include extending a plurality of wires through arcs of the proximal anchor. Neighboring retention wires can extend through neighboring arcs. The method can further include extending a guidewire down a central lumen of the delivery device before extending the prosthetic delivery device into the heart. Tightening and loosening the wires of the delivery device can be performed with a control on a handle of the delivery device. 
         [0019]    In general, in one embodiment, a delivery device includes a central longitudinal structure having a plurality of tubes extending therethrough, a retention wire extending within each tube, a sheath, a handle, and a control on the handle. Each tube has a tubular wall and an aperture in the tubular wall. Each retention wire configured to extend through a portion of a medical device at the aperture. The sheath is configured to fit over and slide relative to the central longitudinal structure and the medical device. The handle is connected to the central longitudinal structure. The control on the handle is configured to tighten the wires to collapse at least a portion of the medical device and to loosen the wires to expand the portion of the medical device. 
         [0020]    This and other embodiments can include one or more of the following features. The delivery device can further include a central lumen extending through the central longitudinal structure. The central lumen can be configured to house a guidewire. The retention wires can be made of nitinol or liquid crystal polymer fiber. There can be between 4 and 20 retention wires and tubes. The delivery device can further include a tapered distal tip connected to the central longitudinal structure. The control can be further configured to retighten the wires after loosening to collapse the portion of the medical device again. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0021]    The novel features of the invention are set forth with particularity in the claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which: 
           [0022]      FIGS. 1A-1E  are various view of a compliant, self-centering valve prosthesis structure suitable for delivery via minimally invasive surgical techniques.  FIGS. 1A and 1B  are isometric views of the prosthesis.  FIG. 1C  is a proximal view of a proximal anchor of the prosthesis.  FIG. 1D  is a proximal view of the prosthesis.  FIG. 1E  is a side view of the prosthesis. 
           [0023]      FIGS. 2A-2C  show an exemplary prosthesis with leaflets attached thereto.  FIG. 2A  is an isometric view of the prosthesis.  FIG. 2B  is a distal view of the prosthesis.  FIG. 2C  is a section view of the prosthesis. 
           [0024]      FIGS. 3A-3B  show the prosthesis of  FIGS. 1A-1E  with various dimensions marked thereon.  FIG. 3A  is a proximal view of the prosthesis.  FIG. 3B  is a side view of the prosthesis. 
           [0025]      FIG. 4A  shows a delivery device with a prosthesis fully loaded therein.  FIG. 4B  shows the delivery device with the prosthesis deployed. 
           [0026]      FIGS. 5A-5D  shows exemplary steps for delivery a valve prosthesis.  FIG. 5A  shows a delivery device housing the prosthesis.  FIG. 5B  shows the distal anchor of the prosthesis deployed with the proximal anchor folded up therearound.  FIG. 5C  shows the sheath of the delivery device pulled back to expose the retention wires of the delivery device.  FIG. 5D  shows the valve prosthesis fully deployed around the delivery device. 
           [0027]      FIGS. 6A-6D  show placement of a prosthesis within the mitral valve using a delivery device. 
           [0028]      FIG. 7  shows a valve prosthesis structure with integral folding hooks for gripping cardiac tissue. 
           [0029]      FIGS. 8A-9B  show various wire rope configurations. 
           [0030]      FIGS. 10A-10B  show a mechanism for releasing the retention wires of a delivery device by pulling proximally on the retention wires. 
           [0031]      FIGS. 11A-11B  show a mechanism for loosening the retention wires of a delivery device by pushing distally on the retention wires. 
           [0032]      FIGS. 12A-12B  show an exemplary mechanism for looping the proximal anchor with the retention wires of a delivery device.  FIG. 12A  shows the use of twelve retention wires.  FIG. 12B  shows the use of six retention wires. 
           [0033]      FIG. 13  shows an alternative mechanism for looping the proximal anchor over a delivery device. 
       
    
    
     DETAILED DESCRIPTION 
       [0034]    Described herein is a flexible, self-orienting cardiac valve prosthesis configured to be delivered through minimally invasive techniques. The prosthesis can include a proximal anchor (e.g., configured to be placed in the ventricle), a distal anchor (e.g., configured to be placed in the atrium), a central portion or column between the anchors, a plurality of struts extending distally (e.g., into the ventricle), and a plurality of leaflets attached to the struts. The prosthesis can be self-expanding, such as be made of super elastic nickel titanium (nitinol). In some embodiments, the prosthesis can be made of woven stranded nitinol. 
         [0035]    The prosthesis described herein can be delivered to a cardiac valve orifice, such as the mitral valve, by using minimally invasive techniques to access cardiac valves through small incisions in the patient&#39;s body, passing the prosthesis through the apex of the heart, through the aorta via femoral artery access, through the aorta via an intercostal puncture, through the vena cava via femoral vein access, through the vena cava via jugular access, and through the venous system into the left heart via a transseptal puncture. The flexible prosthesis can be folded and compressed to fit within a delivery tube. The delivery tube can used to position the prosthesis at the treatment site, and if necessary, re-sheath, reposition, and re-deploy the device. 
         [0036]    During deployment, the distal anchor can be deployed first in a cardiac chamber, such as the ventricle, and retracted to a seated position against the valve orifice, such as the mitral valve orifice. Then the center column and proximal anchor may then be deployed in another cardiac chamber, such as the atrium, sandwiching the valve orifice securely between the anchors in opposing cardiac chambers. 
         [0037]    Embodiments of the invention are designed to secure the valve prosthesis in the orifice by applying a radial force from the center column structure of the prosthesis outward against the cardiac orifice and by sandwiching the cardiac orifice between distal and proximal anchors that are larger in diameter than the orifice. Further engagement between the prosthesis and tissue may be added by securing small, curved wire hooks into the sub-structures of the valve prosthesis. 
         [0038]      FIGS. 1A-1E  show an exemplary embodiment of a valve prosthesis  100 . The valve prosthesis includes a proximal anchor  2 , a distal anchor  3 , and a central portion  4  therebetween. A central opening  15  extends through the center of the prosthesis  100 . The central portion  4  can substantially trace the perimeter of the central opening  15  while each anchor  2 ,  3  can extend outwardly therefrom in an annular shape. The proximal anchor  2 , distal anchor  3 , and central portion  4  can be formed of wire, such as nitinol wire rope. Each anchor  2 , 3  can include a first outer frame  122 ,  133  and a second outer frame  222 ,  233 , respectively. In one embodiment, the proximal anchor  2  and distal anchor  3  can be substantially parallel to one another. 
         [0039]    An exemplary proximal anchor  2  is shown in  FIG. 1  C. The first outer frame  122  can sit proximal to the second outer frame  222 , and the first outer frame  122  can sit in a plane substantially parallel to the plane of the second outer frame  222 . Further, each frame  122 ,  222  can include a plurality of arcs  111 ,  211  (which can also be referred to as arcuate portions, curved portions, or petals), such as between 4 and 10 or between 5 and 8 arcs, joined together at joints  16 ,  26 , respectively. For example, outer frame  122  can include six arcs  111   a,b,c,d,e,f  while outer frame  222  can also include six arcs  211   a,b,c,d,e,f.  The arcs  111  of the outer frame  122  can be connected together, and the arcs  211  of the outer frame  222  can be connected together, so as to form a substantially circular outer perimeter for each of the frames  122 ,  222 . 
         [0040]    Each joint  16 ,  26  between neighboring arcs  111  or  211  can be, for example, a crimp that crimps adjacent arcs (e.g.,  111   a  and  111   b ) to one another. As shown in  FIG. 1C , the outer frames  122 ,  222  can be positioned relative to one another such that the arcs  111 ,  211  are out of phase relative to one another. For example, the arcs  111  can be approximately 90 degrees out of phase relative to the arcs  211 . That is, the arcs  111  of the first outer frame  122  can overlap with the arcs  211  of the second outer frame  222  such that, for example, a single arc  111   a  of the first outer frame  122  overlaps with half of two underlying arcs  211   f ,  211   a  of the second outer frame  222 . In some embodiments, only some arcs are out of phase with one another while other arcs are in-phase with one another. The second outer frames  133 ,  233  can likewise include arcs as described with respect to the first outer frame  122 ,  222 . 
         [0041]    As shown in  FIGS. 1A and 1E , the first outer frame  122 ,  133  and the second outer frame  222 ,  233  of each anchor  2 ,  3  can be connected to one another through the central portion  4 . The central portion  4  can extend from the crimps  16 ,  26  of the proximal anchor  2  to the corresponding crimps of the distal anchor  3 . The central portion  4  can include substructures or wire segments  44  that form a pattern, such as a hexagonal pattern (see  FIG. 1E ). For example, two wire segments  44 a,b of the central portion  4  can extend at an angle from the crimp  16   a  (see  FIGS. 1D ,  1 E), such as to form an angle of approximately 120 degrees relative to one another. Each of the wire segments  44   a,b  can then meet adjacent wire segments within the central portion  4  (e.g., segment  44   b  meets segment  44   c ). The adjacent wire segments (e.g.,  44   b  and  44   c ) can then be joined together at a joint  46  (e.g., joint  46   a ). The joint  46   a  can form a column substantially parallel to a central axis  110  of the prosthesis  100 . This pattern can extend throughout the entire prosthesis to form a number of joints  46 , such as twelve joints  46 . The joints  46  can not only fix the position of the outer frames of a single anchor together, but also fix the proximal and distal anchors  2 ,  3  together. The hexagonal structure of the segments  44  and joints  46  can advantageously provide radial and vertical strength as well as stability to the prosthesis  100 . 
         [0042]    In some embodiments (as shown in  FIG. 1D ), parts of the central portion  4  can be formed of the same wire or wire rope as the outer frames of the anchors  2 , 3  and/or the outer frames of the anchors  2 , 3  can be formed of the same wire or wire rope as one another. For example, two single strands of wire, such as two 22-inch long strands of wire, can be used to form the anchors  2 ,  3  and the central portion  4 . As shown in  FIGS. 1D and 1E , a single strand  191  (darkened in the picture relative to the opposite strand  193  for clarity) can form an arc  111   a  (see  FIG. 1D ) of the first outer frame  122  of proximal anchor  2 , extend through a joint  16   a  to form wire segment  44   b  of the central portion  4 , extend through joint  46   a  to form wire segment  44   d  (see  FIG. 1D ), then form an arch of the second outer frame  233 , extend through another joint to form wire segment  44   e  (see  FIG. 1D ), extend around in a similar fashion to form wire segment  44   f  (see  FIG. 1D ), and continue winding in a similar fashion until all of the outer frames  122 ,  233  have been formed from the single strand  191 . The ends of the strand  191  can then be attached to one another, such as through splicing crimps, butt joint crimps, welding, riveting, or weaving. The second strand  193  can be wound similarly to form the second outer frame  222  of the proximal anchor  2  and the first outer frame  133  of the distal anchor  3 . 
         [0043]    By joining the first outer frame  122 ,  133  to the second outer frame  222 ,  233  of each anchor  2 ,  3 , as described above, the arcs of each outer frame can be movable relative to one another. For example, the arc  111   a  can be movable relative to the arcs  211   f ,  211   a  that it overlaps (see  FIG. 1C ). That is, the outer perimeter of the arc  111   a  can flex along the central axis and/or translate relative to the arcs  211   f,    211   a  (while the inner perimeter is fixed at the joints  46 ). 
         [0044]    Advantageously, the large arc structure of the anchors can provide flexibility and compliance for the portions of the prosthesis intended to be placed in the chambers of the heart. In contrast, in the stiffer tissue of the valve orifice, the hexagonal sub-structures of the central portion can provide higher radial stiffness and strength. 
         [0045]    Further, by using wire rope, the prosthesis can advantageously be foldable and strong while the individual fibers, because they are small in diameter, can maintain resistance to fatigue and fracture. In some embodiments, the two frames of a single anchor can be formed of wire rope of opposite lays. For example, the wire of one frame (e.g. strand  193 ) can be made of a rope twisted to the left while the wire of another frame (e.g. strand  191 ) can be made of a rope twisted to the right. Using wires of opposite lays can allow the wires to compensate for one another as they compress, thereby maintaining relative positioning during expansion or contraction/folding of the device (as opposed to twisting of the entire device). Various possibilities for winding the wire rope are shown in  FIGS. 8A-9B . 
         [0046]    As shown in  FIGS. 1A and 1E , struts  5  can extend distally from the distal anchor  3  and/or the central portion  4  and be configured to hold leaflets (shown in  FIGS. 2A-2C ). The struts  5  can be formed, for example, of wire rope. Further, in one example, each strut  5  can include a plurality of wire components  55 , such as three wire components  55 . Each of the three wire components  55  of a single strut  5  can extend from neighboring joints  46  and come together at a joint  56 , thereby forming triangular struts  5 . In some embodiments, additional supporting structures, such as tubes, can be placed over or around the struts to increase the stiffness. The triangular struts  5  can provide vertical strength and lateral flexibility. 
         [0047]    In one embodiment, there can be three struts  5  located approximately 120 degrees away from one another around the circumference of the prosthesis  100 . The joints  56  can be, for example, crimps. As shown in  FIGS. 1A and 1E , in one embodiment, the center strut member  55   a  of a three-strut support can be substantially straight and connected to two outside, curved strut members  55   b,    55   c  to form a structure comprised of two substantially triangular sub-structures, each with the center member as a common triangle leg. This center member may be made of a thin element of material which provides strength in tension as the pressurized leaflets are pushed toward the center of the valve, while providing flexion in compression to allow the valve prosthesis to be folded for delivery and to allow the prosthesis to conform to tissue when placed within the heart. 
         [0048]    The various crimps used for the joints of the prosthesis  100  may be made of a suitable implantable material, such as platinum, tantalum, or titanium. Further, in place of crimps, braids, weaves, or welding can be used. 
         [0049]    Referring to  FIGS. 2A-2C , the valve prosthesis  100  can include integral valve leaflets  511  attached, such as sewn, to the struts  5 . There can be three integral valve leaflets  511 , and the leaflets  511  can form a pressure actuated valve that provides uni-directional flow occlusion when the prosthesis  100  is implanted in a valve orifice. The leaflets can be constructed of bio-materials, such as bovine or porcine pericardium, or polymer materials. 
         [0050]    In one embodiment (shown in  FIGS. 2B-2C ), the proximal anchor  2  can include a cover or skirt  12  thereon or therearound formed of a biomaterial or thin polymer material. The skirt  12  can advantageously help seal the prosthesis  100  against the cardiac tissue when implanted. 
         [0051]    The prosthesis  100  can be configured to be placed in a cardiac valve orifice such that the central portion  4  lines the orifice while the proximal and distal anchors  2 ,  3  sit within the chambers of the heart and pinch tissue of the orifice therebetween. 
         [0052]    In some embodiments, the prosthesis  100  can be sized and configured for use in the mitral valve orifice (shown in  FIG. 6D ). Referring to  FIGS. 3A-3B , to ensure that the prosthesis  100  fits properly within the valve, the diameter d o  of the central opening  15  can be greater than a length l of the device when fully expanded. For example, the ratio d o /l can be greater than or equal to 1.1, such as greater than or equal to 1.2 or greater than or equal to 1.3. Further, the ratio d o /l can be less than 2.0. In one embodiment, the diameter d o  is between 25 mm and 40 mm, such as approximately 28 mm. Further, in one embodiment, the length l is less than or equal to 22 mm, or less than or equal to 20 mm, such as approximately 14 mm. Further, to ensure that the proximal and distal anchors have enough tissue to grab onto, a ratio of the outer diameter of the anchors, d T , to the length l can be greater than or equal to 2.0. In one embodiment, an outer diameter of anchors, d T , can be at least 38 mm, such as greater than or equal to 40 mm. Further, in one embodiment, the anchors can extend out at a radius r a  of greater than 10 mm, such as approximately 12 mm. Finally, a ratio d o  to a length of the struts l s  can be approximately 1.5 to 3.0, such as 2.1. A radio of d o /l s  within this range can advantageously ensure that there is enough leaflet material to allow the leaflets to oppose and seal under stress while maintaining a small enough length to fit properly within the valve. In one embodiment, the struts have a length l s  of between 8 and 16 mm, such as approximately 14 mm. Further, l c  can be approximately 4-10 mm, such as 6 mm. 
         [0053]    In one exemplary embodiment, d o  is 28 mm, r a  is 12 mm, l c  is 6 mm, l s  is 14 mm, d T  is 40 mm, and l  1  is 14 mm. 
         [0054]      FIGS. 4A-4B  show a closed delivery device  200  for delivery of a valve prosthesis  100 . The delivery device  200  can include an outer sheath  13  and a multi-lumen central longitudinal structure  17  extending therethrough. The valve prosthesis  100  is configured to fit over the central longitudinal structure  17  and within the sheath  13  so as to be fully encapsulated within the delivery device  200 . The lumens in the longitudinal structure  17  can be tubular structures  357  (see  FIGS. 4B and 5C ). Each tubular structure  357  can include a side lumen  355  (see  FIGS. 4B and 10A ) therein, i.e., an aperture disposed on a radial outer portion of the tubular wall. The tubular structures  357  can contain retention members  19  that bind the proximal anchor  2  of the valve prosthesis tightly to the longitudinal structure  17 . The retention members  19  can be made, for example, of a strong, flexible material such as nitinol, nitinol wire rope, or liquid crystal polymer fiber, such as Vectran®. There can be various numbers of retention wires and corresponding tubes  357  and lumens, such as between 4 and 20 or between 6 and 12 retention wires and corresponding tubes/lumens. In one embodiment, there are six retention wires and lumens. In another, there are twelve retention wires and lumens. The delivery device  200  includes a central lumen  15  running therethrough (i.e., through the central longitudinal structure  17 ) configured to pass a standard cardiac guidewire  16 . The guidewire  16  may be used to provide a safe pathway for getting the device  100  to the anatomical target. The delivery device  200  further includes a tapered tip  14  to provide a gradual, atraumatic transition from the guidewire to the outer sheath  13  of the delivery device  200 . 
         [0055]    In some embodiments, the delivery device  200  can be adapted to specific delivery paths and cardiac structures by being provided with pre-shaped bends in the outer sheath  13 . In some embodiments, the delivery device  200  may contain pull-wires integral with the outer wall that may be tensioned to articulate and bend the outer sheath  13 . The pull wires may terminate at the tip of the device to provide a bend starting at the distal tip or may terminate along the longitudinal shaft of the device to provide a more proximal bend location. 
         [0056]      FIGS. 5A-5D  show a multi-stage delivery system for a cardiac valve prosthesis (with the valve leaflets omitted from the drawings for clarity).  FIG. 5A  shows the delivery device  200  having a handle  300  connected thereto to control the delivery of a prosthesis loaded within the device. 
         [0057]      FIGS. 5B and 5C  shows the prosthesis  100  partially deployed. That is, as the sheath  13  is pulled back with a lever  301  on the handle  300 , the distal anchor  3  (previously collapsed into the sheath  11  with the peaks of the arcs extending distally) pops open. The proximal anchor  2 , in turn, can remain connected to the delivery device  100  via the retention wires  19 . That is, the retention wires  19  can pass through the multi-lumen central structure  17 , through the arcs of the outer frame  122 ,  222  at apertures  355 , and back into lumens of the structure  17 . Referring to  FIGS. 10A and 12A , in one embodiment, the proximal anchor  2  can be connected to the retention wires  19  such that neighboring arcs  111   a ,  211   a  of the proximal anchor  2  extend over neighboring retention wires  19   a ,  19   b.  In other embodiments (as shown in  FIG. 12B ), two neighboring arcs  111   a,    211   a  can extend over a single retention wire  19   a.  Referring back to  FIGS. 5B and 5C , as the retention wires  19  are pulled tight, the peaks of the arcs of the proximal anchor  2  will be pulled proximally, thereby causing the proximal anchor  2  to fold or cinch up to form a funnel shape at the proximal end of the distal anchor  3  (crimps  16 ,  26  of the proximal anchor  2  can be seen). 
         [0058]    To expand the proximal anchor  2 , the wires  19  can either be withdrawn or loosened (such as with a lever  303  on the handle), thereby allowing the proximal anchor  2  to self-expand into place, as shown in  FIG. 5D . Referring to  FIGS. 10A-10B , in some embodiments, the wires  19   a  can be withdrawn completely, thereby allowing the proximal anchor  2  to expand. In another embodiment, shown in  FIGS. 11A-11B , the retention wires  19  can be formed of loops that, when loosened, i.e. pushed distally, allow the distal anchor  2  to expand without releasing the anchor  2 . By using such a mechanism, the proximal anchor can be resheathed and moved (by retightening the retention members  19 ) if necessary. A mechanism on the handle can then be used to release the retention members  19  entirely. 
         [0059]    Referring to  FIG. 6A , to deploy the valve prosthesis  100  in a valve (such as the mitral valve), the guidewire  16  and delivery device  200  can be inserted through the native valve. Referring to  FIG. 6B , as the outer sheath  13  of the device  200  is retracted relative to the central longitudinal structure  17 , the distal anchor  3  of the valve prosthesis is exposed and self-expands (such as into the left ventricle). Once expanded, the distal anchor  3  may be retracted proximally against the distal-facing tissue of the cardiac chamber around the orifice, providing positive tactile feedback that the distal anchor  3  is oriented and positioned properly against the distal wall of the cardiac orifice. Further retraction of the sheath  13  exposes the central portion  4  of the valve prosthesis, allowing the central portion  4  to radially expand against the inner wall of the cardiac orifice. 
         [0060]    Referring to  FIG. 6C , to expand the prosthesis  100  on the other side of the cardiac orifice (i.e., in the left atrium), the central retention members  19  of the delivery device can be withdrawn or loosened as described above, thereby expanding the proximal anchor  2 . The expanded proximal anchor  2  provides a second backstop to the valve prosthesis  100 , allowing the prosthesis  100  to sandwich the valve orifice, such as the mitral valve orifice between the proximal and distal anchors  2 ,  3 . As the device  100  expands, it foreshortens, moving the proximal anchor  2  and distal anchor  3  toward each other to provide a compressive force on tissue surrounding the cardiac orifice, such as the valve annulus. 
         [0061]    Thus, in one example, as shown in  FIG. 6D , the prosthesis can be delivered into the mitral valve orifice such that the distal anchor  3  sits within the left ventricle while the proximal anchor  2  sits within the left atrium. The struts  5  and leaflets  511  can extend distally into the left ventricle. Tissue of the mitral valve annulus can be captured between the anchors  2 ,  3 . Further, the size of the prosthesis  100  can be such that the anchors  2 ,  3  extend within the chambers of the heart and much wider than the diameter of the orifice itself, thereby allowing for strong tissue capture and anchoring. In some embodiments, placement of the prosthesis can move the existing leaflets valves out of the way. 
         [0062]    In some embodiments, as described above, the valve prosthesis  100  can be repositioned using the delivery device  200 . That is, by pulling on the retention wires  19 , the proximal anchor  2  can be cinched back down with the proximal arcs extending proximally. The distal anchor  3  can be collapsed into the sheath (with the arcs extending distally) either by pulling proximally on the prosthesis  100  or pushing the sheath  13  distally. 
         [0063]    Use of an alternative delivery device is shown in  FIG. 13 . As shown in  FIG. 13 , rather than including multiple retention wires, the delivery device can include a single elongate member  96  over which all of the arcs  111 ,  211  of the proximal anchor  2  are placed. 
         [0064]      FIG. 7  shows an embodiment of the valve prosthesis  199  where retention hooks  21  are built into the device. The hooks  21  extend from toward the center of the device from the joints (e.g., crimps) of the distal anchor  3 . The hooks may be made of nitinol and are curved so that as the distal anchor  3  is drawn toward the center longitudinal member  17  of the delivery device  200 , the hooks flatten and collapse, allowing the outer sheath  13  of the delivery device  200  to slide smoothly over the hooks  21 . As the outer sheath  13  is removed from the valve prosthesis  100  during delivery and the distal anchor  3  of the valve prosthesis opens, the hooks  21  expand into the tissue of the cardiac orifice. In embodiment, the hooks  21  are only located on the distal anchor  3 , as the distal anchor  3 , when located on the ventricular side of the aorta, undergoes the highest pressure. In other embodiments, the hooks  21  are located on the proximal anchor  2  and/or the central portion  4 . 
         [0065]    In one embodiment, small hooks in the distal anchor  3  may be used to grip the valve leaflets. As the distal anchor  3  is retracted from the ventricle toward the mitral valve annulus, the hooks can pull the leaflets into a folded position just under the ventricular side of the mitral annulus. 
         [0066]    While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.