Patent Abstract:
A valve prosthesis is adapted to operate in conjunction with native heart valve leaflets. The prosthesis includes an annulus and a skirt extending from the annulus. The skirt may be configured to be positioned through a native heart valve annulus, and the skirt may be movable between an open configuration permitting blood flow through the skirt and a closed configuration blocking blood flow through the skirt in cooperation with opening and closing of the native heart valve leaflets.

Full Description:
CROSS-REFERENCE TO RELATED APPLICATION 
     This application claims the benefit of priority of U.S. provisional patent application No. 61/210,255, entitled “MINIMALLY INVASIVE, SUTURELESS EXPANDABLE HEART VALVE PROSTHESIS WITH A COLLAPSIBLE VALVE,” filed on Mar. 17, 2009; U.S. provisional patent application No. 61/212,459, entitled “MINIMALLY INVASIVE, SUTURELESS EXPANDABLE HEART VALVE PROSTHESIS WITH A COLLAPSIBLE VALVE,” filed on Apr. 13, 2009; U.S. provisional patent application No. 61/215,944, entitled “MINIMALLY INVASIVE SUTURELESS EXPANDABLE HEART VALVE PROSTHESIS WITH A COLLAPSIBLE VALVE AND A METHOD OF DELIVERY,” filed on May 12, 2009; U.S. provisional patent application No. 61/186,100, entitled “A HEART VALVE PROSTHESIS WITH A COLLAPSIBLE VALVE AND A METHOD OF DELIVERY THEREOF,” filed on Jun. 11, 2009; U.S. provisional patent application No. 61/227,193, entitled “A HEART VALVE PROSTHESIS WITH A COLLAPSIBLE VALVE AND A METHOD OF DELIVERY THEREOF,” filed on Jul. 21, 2009; and U.S. provisional patent application No. 61/257,979, entitled “A HEART VALVE PROSTHESIS WITH A COLLAPSIBLE VALVE AND A METHOD OF DELIVERY THEREOF,” filed on Nov. 4, 2009, the disclosures of which are incorporated herein by reference in their entirety as if fully set forth herein. 
    
    
     TECHNICAL FIELD 
     The present disclosure relates to minimally invasive surgical or percutaneous replacement and/or repair of a valve, namely the mitral valve or the tricuspid valve. More particularly, the present disclosure relates to a heart valve prosthesis with a collapsible valve and a method of delivery of the prosthesis. 
     BACKGROUND 
     The mitral valve and tricuspid valve are unidirectional heart valves that separate the atria left and right respectively, from the corresponding heart ventricles. These valves have a distinct anatomical and physiological structure, having two (mitral) or three (tricuspid) sail-like leaflets connected to a subvalvular mechanism of strings (chordae tendinae) and papillary muscles forming a part of the heart&#39;s ventricular shape, function and size. 
     The heart has four chambers: the right and left atria, and the right and left ventricles. The atria receive blood and then pump it into the ventricles, which then pump it out into the body. 
     The synchronous pumping actions of the left and right sides of the heart constitute the cardiac cycle. The cycle begins with a period of ventricular relaxation, called ventricular diastole. The cycle ends with a period of ventricular contraction, called ventricular systole. 
     The heart has four valves that ensure that blood does not flow in the wrong direction during the cardiac cycle; that is, to ensure that the blood does not back flow from the ventricles into the corresponding atria, or back flow from the arteries into the corresponding ventricles. The valve between the left atrium and the left ventricle is the mitral valve. The valve between the right atrium and the right ventricle is the tricuspid valve. The pulmonary valve is at the opening of the pulmonary artery. The aortic valve is at the opening of the aorta. 
     The opening and closing of heart valves occur primarily as a result of pressure differences. For example, the opening and closing of the mitral valve occurs as a result of the pressure differences between the left atrium and the left ventricle. During ventricular diastole, when ventricles are relaxed, the venous return of blood from the pulmonary veins into the left atrium causes the pressure in the atrium to exceed that in the ventricle. As a result, the mitral valve opens, allowing blood to enter the ventricle. As the ventricle contracts during ventricular systole, the intraventricular pressure rises above the pressure in the atrium and pushes the mitral valve shut. 
     As noted above, these valves feature a plurality of leaflets connected to chordae tendinae and papillary muscles, which allow the leaflets to resist the high pressure developed during contractions (pumping) of the left and right ventricles. 
     In a healthy heart, the chords become taut, preventing the leaflets from being forced into the left or right atria and everted. Prolapse is a term used to describe the condition wherein the coaptation edges of each leaflet initially may co-apt and close, but then the leaflets rise higher and the edges separate and the valve leaks. This is normally prevented by contraction of the papillary muscles and the normal length of the chords. Contraction of the papillary muscles is simultaneous with the contraction of the ventricle and serves to keep healthy valve leaflets tightly shut at peak contraction pressures exerted by the ventricle. 
     Valve malfunction can result from the chords becoming stretched, and in some cases tearing. When a chord tears, the result is a flailed leaflet. Also, a normally structured valve may not function properly because of an enlargement of the valve annulus pulling the leaflets apart. This condition is referred to as a dilation of the annulus and generally results from heart muscle failure. In addition, the valve may be defective at birth or because of an acquired disease, usually infectious or inflammatory. 
     Diseases of the valves can cause either narrowing (stenosis) or dilatation (regurgitation, insufficiency) or a combination of those, of the valve. Surgical treatment for repair or replacement of the valves includes an open-heart procedure, extracorporeal circulation and, if replaced, a complete resection of the diseased valve. 
     Currently all available surgical options for valve replacement involve open heart surgery; although minimally invasive methods for valve replacement are more desirable, such methods are still in the experimental stage. 
     Even valves which could theoretically be provided through a non-invasive method, such as those taught by U.S. Pat. No. 7,381,220, have many drawbacks. For example, the taught valves are useful for replacement of the existing valves; however, their installation through non-invasive means is problematic. Furthermore, the valves themselves, even when installed in a manner that supports existing valve tissue, must still withstand very high pressures. Such high pressures can lead to many different types of problems, including reflux as blood returns through heart in a retrograde manner. 
     It may be desirable to provide a valve prosthesis that supports the mitral and/or tricuspid valve without necessarily replacing it, but instead supplements the native valve functionality by providing an adjunctive valve prosthesis, which cooperates together with the native valve for improved functionality. The background art also does not teach or suggest such a valve prosthesis which may optionally be inserted through minimally invasive surgical techniques. 
     SUMMARY OF INVENTION 
     In accordance with various aspects of the disclosure, a valve prosthesis is adapted to operate in conjunction with native heart valve leaflets. The prosthesis includes an annulus and a skirt extending from the annulus. The skirt may be configured to be positioned through a native heart valve annulus, and the skirt may be movable between an open configuration permitting blood flow through the skirt and a closed configuration blocking blood flow through the skirt in cooperation with opening and closing of the native heart valve leaflets. 
     According to various aspects, a novel valve prosthesis, for example, for a tricuspid valve and/or mitral valve, may be inserted through any one or more of a minimally invasive surgical procedure, a “traditional” operative procedure (which may for example involve open heart surgery), or a trans-catheter procedure. 
     The valve prosthesis, in at least some embodiments, is a (optionally non-stented) bioprosthesis attached by means of suture or any other means of bonding, to an expandable, frame (platform), which may be made from a suitable metal, including without limitation an alloy, or any type of suitable composite material (optionally including those that include metal). The frame can be made of self expanding alloy such as Nitinol (nickel/titanium alloy) or made of another metal, such as a cobalt/chrome alloy, expanded by a specialized balloon, or radial expander. 
     The frame engages the tissue at or near or above the top margins of the native valve (annulus). The native valve is not removed, and the ventricular shape and function are preserved. Therefore, the valve prosthesis may not replace the native valve functionality but rather supports its function. 
     By “native valve” or “native valve annulus” it is meant the valve or valve annulus already present in the subject, as opposed to an artificial valve or valve annulus. 
     According to some embodiments, the valve prosthesis comprises a support structure featuring a deployable construction adapted to be initially collapsed (crimped) in a narrow configuration suitable for introduction through a small puncture or incision into the heart cavity such as the left ventricle, the left atrium, the right atrium, the right ventricle and so forth, thereby providing access to the target location. It is further adapted to be deployed by means of removing a radial constriction such as a sheath to allow the platform to self-expand to its deployed state in the target location. 
     In some embodiments, the valve prosthesis optionally features a flexible film made of biological tissue such as pericardia tissue but may also optionally feature one or combination of synthetic materials, additionally or alternatively. The prosthesis may have a funnel like shape that is generally tubular and may have a variable diameter that enables flow in one direction (from the atrium to the ventricle); when the ventricle contracts, the funnel shape valve collapses and blocks any return flow from the ventricle to the atrium. Such retrograde flow is quite dangerous; over a prolonged period of time, it can lead to many deleterious health effects, including on the overall health of the heart muscle. 
     In an exemplary, illustrative configuration, the valve platform of the prosthesis is anchored to the ventricle wall through extensions that pass through the commissures of the native valve or at the plane of the commissures and have hooks at their ends that anchor into the ventricular wall between the chordate attachment to the ventricular wall. Furthermore, in an illustrative example, these extensions have curved ends that can be in any plane (but which may be at a 90 degree angle to the plane of both extensions) that allows a wire or cable to pass through and keep the prosthesis connected to the delivery system as long as this wire or cable is not released. The delivery action of the prosthesis may be reversible. That is, the device may optionally be refolded into the catheter after having being deployed. 
     In an optional embodiment, these extensions should not act on the valve in any way, including not on the valve annulus or surrounding valve tissue, nor should these extensions apply any pressure that may reshape the annulus or deform the leaflet configuration. 
     In an exemplary embodiment, the valve prosthesis features a “skirt” that does not restrict the motion of any of the native valve leaflets but which is situated above such leaflets, for example in the direction of the atrium (by “above” it is meant with regard to the direction of normal, not retrograde, blood flow). If the leaflets prolapse into the atrium, no blood will be able to flow into the atrium because the skirt is situated above the native valve, thus preventing retrograde blood flow into the atrium from the ventricle. 
     In an embodiment, the “skirt” is generally tubular in shape with a diameter that may vary and which is optionally used to complete the incompetent closure of the native valve as a whole. Thus, the skirt specifically and the valve prosthesis generally are not intended to be used as a replacement to the entire valve or in addition to only one native leaflet (in contrast to the apparatus described by Macoviak et al. in U.S. patent application publication number 2008/0065204, for example). In an exemplary embodiment, the valve skirt may be reinforced with at least one reinforcement along at least a portion of its length, for example, along the entirety of its length, in order to prevent prolapse of the skirt into the left atrium. This reinforcement is optionally an extension from the platform. 
     In yet another configuration, the valve “skirt” is connected to the extensions by a cable or wire in order to prevent the prolapsed of the skirt into the left atrium. These connections may optionally be an integral part of the valve platform or alternatively may be connected separately. 
     In an exemplary embodiment, the closing action of the native valve leaflets promotes the collapse of the prosthetic valve (skirt). Thus, during systole function, the native valve may achieve partial closure (i.e function partially) and hence may assist the function of the valve prosthesis. 
     During systole, the action of the native valve leaflets is to close the passage between the left ventricle and the left atrium. In an exemplary embodiment, the leaflets, while acting as such, resist part of the pressure applied by the blood pressure in the ventricle during valve closure as well as reducing the effective area on which the pressure is applied to the valve prosthesis as a whole, thus reducing the total force applied to the prosthesis for migration into the left atrium. Depending on which valve is affected, the present invention is contemplated as a potential treatment for all forms of valvular regurgitation, such as tricuspid regurgitation, pulmonary regurgitation, mitral regurgitation, or aortic regurgitation. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       In the drawings: 
         FIG. 1  shows an exemplary anatomy of a mitral valve (for reference only); 
         FIGS. 2   a - 2   c  show an exemplary valve prosthesis according to some embodiments of the present disclosure;  FIG. 2   a  shows the valve skirt alone, and  FIGS. 2   b  and  2   c  show the valve skirt in place in the heart as an example only; 
         FIG. 3  shows an illustrative embodiment of an exemplary valve prosthesis in accordance with various aspects of the disclosure; 
         FIGS. 4   a - 4   b  show an illustrative configuration of an exemplary valve prosthesis according to some embodiments of the present disclosure; 
         FIG. 5  shows a schematic view of the prosthetic and native mitral valve leaflets during Diastole; 
         FIG. 6  shows a schematic view of the prosthetic and native mitral valve leaflets during Systole; 
         FIG. 7  shows an illustrative embodiment of an exemplary valve prosthesis in accordance with various aspects of the disclosure; 
         FIGS. 8A-8D  show illustrative embodiments of various exemplary valve prostheses in accordance with various aspects of the disclosure; 
         FIG. 9  shows an exemplary frame for a valve prosthesis in accordance with various aspects of the disclosure; 
         FIG. 10  shows an exemplary valve prosthesis in accordance with various aspects of the disclosure; 
         FIG. 11  shows an exemplary frame for a valve prosthesis in accordance with various aspects of the disclosure; 
         FIGS. 12A-12D  show an exemplary prosthesis in its folded state and as it unfolds from a catheter; 
         FIGS. 13  show an exemplary valve prosthesis in accordance with various aspects of the disclosure; 
         FIGS. 14A to 14D  show an exemplary skirt for a valve prosthesis in accordance with various aspects of the disclosure; 
         FIG. 15  shows an exemplary delivery system for a valve prosthesis in accordance with various aspects of the disclosure; 
         FIG. 16  shows a portion of an exemplary delivery system valve prosthesis in accordance with various aspects of the disclosure; 
         FIG. 17  shows a portion of an exemplary delivery system valve prosthesis in accordance with various aspects of the disclosure; 
         FIG. 18  is an exemplary measuring device for use in delivery of a valve prosthesis in accordance with various aspects of the disclosure; 
         FIG. 19  is a flow chart of an exemplary delivery method of a valve prosthesis in accordance with various aspects of the disclosure; and 
         FIG. 20  is a flow chart of an exemplary pre-delivery method of a valve prosthesis in accordance with various aspects of the disclosure. 
     
    
    
     DETAILED DESCRIPTION 
     The disclosure provides, in at least some embodiments, a valve prosthesis and method of insertion thereof which supports the mitral and/or tricuspid valve without replacing it. The valve prosthesis may operate to support the native valve leaflets to provide a functioning heart valve and to prevent retrograde motion of the blood, even if the native valve leaflets alone are unable to completely close and/or to prevent such retrograde motion of the blood. 
       FIG. 1  shows an exemplary anatomy of a native mitral valve (for reference only). As shown, a native valve  100  features an anterior leaflet  102  and a three lobed posterior leaflet  104 , which together comprise the leaflets of native valve  100 , as well as an anterior annulus  106  and a posterior annulus  108 , which together comprise the annulus of native valve  100 . Native valve  100  also features a posterolateral commissure  110  and an anteromedial commissure  112 , one or both of which are optionally used for installation of a valve prosthesis according to some embodiments of the present disclosure. 
     A plurality of chordinae tendinae  116  attach the leaflets to a lateral papillary muscle  118  or a medial papillary muscle  120 . In a healthy heart, chordinae tendinae  116  become taut to prevent retrograde blood flow back through the leaflets. In a non-healthy heart, for a variety of reasons as described above, bloods flow in a retrograde manner through the leaflets. As described in greater detail below, in at least some embodiments of the present disclosure, the leaflets are assisted in their function by a valve prosthesis. 
       FIGS. 2   a - 2   c  show an exemplary valve prosthesis according to some embodiments of the present disclosure. As shown in  FIG. 2   a , a valve prosthesis  200  may comprise a valve skirt  202  and a prosthetic valve annulus  204  according to various aspects of the present disclosure. Although not clearly shown in  FIG. 2   a , in some aspects, the prosthetic valve annulus  204  may have a D-shape configuration. In some aspects, the annulus  204  may have an oval configuration. 
     According to various aspects, the skirt  202  may comprise a biological tissue, such as, for example, an animal (e.g., bovine or porcine tissue) or human pericardium. In some aspects, the skirt  202  may comprise a synthetic material, such as, for example, polyurethane. In various aspects, the skirt  202  may comprise a native mitral valve processed to be biologically compatible for a particular implantation. According to some aspects, the skirt  202  may comprise an ultra-thin sheet of nitinol. According to various aspects of the disclosure, the skirt  202  and/or the prothetic annulus  204  may be coated with various bioactive agents, such as anti-proliferative and/or anti-inflammmatory properties or can have other properties such as antineoplastic, antiplatelet, anti-coagulant, anti-fibrin, antithrombonic, antimitotic, antibiotic, antiallergic, antioxidant as well as cystostatic agents, anti-inflammatory agents (e.g., steroidal anti-inflammatory agent, a nonsteroidal anti-inflammatory agent, or a combination thereof, and anti-proliferative agents (e.g., rapamycin and derivatives of rapamycin; everolimus and derivatives of everolimus; taxoids including taxols, docetaxel, paclitaxel, and related derivatives of taxoids, Biolimus A9, etc.). According to various aspects, the skirt may have a thickness of between about 0.05 mm and about 0.4 mm. 
     According to some aspects, the length of valve prosthesis  200  is at least as long as the native valve leaflets, but is not excessively long so as to avoid disturbing the flow through the aortic or adjacent valve. For example, in some aspects, the length of valve prosthesis  200  is no more than about 120% of the length of the native valve leaflets. According to various aspects, the diameter of the bottom of valve skirt  202  is at least about 80% of the diameter of the native valve area and no more than about 130% of the diameter of the native valve area. 
       FIG. 2   b  shows an exemplary valve prosthesis  200  in place in a mitral valve  100  as an illustrative example only of installation. Valve skirt  202  is shown as well, extending into a ventricle  206 .  FIG. 2   c  shows the view of  FIG. 2   b  in cross-section. Valve skirt  202  is configured and positioned to prevent retrograde flow of blood from the ventricle  206  back into the atrium (not shown) by assisting the function of the natural, native leaflets of the mitral valve  100 . It should be appreciated that the exemplary valve prosthesis  200  may also be placed in a tricuspid valve in accordance with various aspects of the disclosure. 
       FIG. 3  shows an exemplary valve frame, or valve platform, configured to support a valve skirt of a valve prosthesis in accordance with various aspects of the present disclosure. Valve frame  300  may comprise a valve annulus  306 , for example, a D-shaped annulus. According to various aspects, the semi-circular section of the D-shape may have a length at least about 1.1 to 2 times greater than that of the straight section. 
     According to various aspects, the valve frame  300  may comprise a wire having a diameter of about 0.3 mm to about 1.0 mm, although other diameters may be selected depending upon the material chosen for the wire, in order to maintain a desired tensile strength of the valve frame  300 , as well as its ability to be folded and delivered through a catheter at least in some embodiments. Any suitable material may optionally be used for the wire as long as it retains sufficient superelasticity and may also optionally be selected from any material described herein. For example, the valve frame  300  may comprise a nickel titanium alloy (i.e., nitinol). 
     The valve frame  300  may include a pair of reinforcement members  302  extending from the valve annulus  306 . The reinforcement members  302  are configured such that they extend along an interior surface of a valve skirt (not shown) of an exemplary valve prosthesis. The reinforcement members  302  may thus prevent the valve skirt from everting back into the atrium after deployment. The frame  300  may also include two or more hooks  304  extending from the valve annulus  306  and configured to anchor the prosthesis to the ventricle wall. In summary, the frame of valve prosthesis incorporates various anchoring members which provide stability of the valve mechanism during cardiac function, and prevent migration of the valve prosthesis over time relative to its originally deployed anatomic position. For example, the anchoring members can comprise example, hook-like members or barbs disposed at circumferentially-distributed locations along the annulus of the frame, at the distal ends of each reinforcement member. Additionally the anchoring members can also comprise expandable annulus frame designs which ensure fluid tight wall apposition along its outer periphery with the annulus of the native valve, such as by the use of a properly sized, expandable, nitinol frame, or in the alternative, the use of a radially-expandable, plastically deformable, stent-like body which cooperates with the wire frame to ensure wall apposition with the native valve annulus. 
       FIGS. 4   a - 4   c  show an illustrative configuration of an exemplary valve prosthesis in accordance with various aspects of the disclosure. As shown, a valve prosthesis  800  may include a valve annulus  806  with a pair of reinforcing members  802  extending therefrom through a valve skirt  810 . The valve annulus  806  may include a plurality of folded loops  308 . The folded loops  308  may enable the valve prosthesis  800 , including the valve frame, to be folded and collapsed for delivery through a catheter, as described in greater detail below. As shown, a pair of curved, hooked extensions  805  extend from the valve annulus. The extensions  805  may include hooks  804  at its ends opposite to the valve annulus  806 . The extensions may also include eyelets  807  configured to receive a delivery cable  900  ( FIG. 4   b ) therethrough. The delivery cable  900  may pass through the eyelets  807 , circle at least partially around the base of the skirt  810 , and then down through the catheter (not shown), for example for adjustment of the placement of the valve prosthesis  800  at the native valve annulus, by collapsing the valve prosthesis back into the catheter for placement in a different or adjusted location. Upon installation, once the surgeon or doctor has positioned the valve prosthesis correctly, delivery cable  900  may be removed, for example, by being withdrawn through the catheter. 
       FIG. 5  shows a schematic view of an exemplary prosthetic valve and the native mitral valve leaflets during diastole. As shown, a schematic valve prosthesis  1000  with a valve skirt  1002  may be installed in a native valve  1004  having a plurality of native valve leaflets  1006 . The blood flow pressure gradient  1008  is also indicated by an arrow. Native valve leaflets  1006  are open, and the prosthetic valve skirt  1002  is shown as being expanded to permit blood flow. 
       FIG. 6  shows a schematic view of the exemplary prosthetic valve and native mitral valve leaflets during systole, when native valve  1004  should be closed. However, native valve leaflets  1006  are only partially closed due to incomplete coaptation, resulting in valve regurgitation. Blood flow pressure gradient  1008  has now reversed, which could lead to retrograde blood flow, since valve leaflets  1006  are not completely closed. However, such retrograde blood flow is prevented by the collapse of prosthetic valve skirt  1002 . The collapse of prosthetic valve skirt  1002  is assisted by the partial closure of native valve leaflets  1006 . 
     Referring now to  FIG. 7 , an exemplary valve frame for a valve prosthesis in accordance with various aspects of the disclosure is described. As shown, a valve frame  700  may include a valve annulus  706  with a pair of reinforcing members  702  extending therefrom. The reinforcing members are configured to extend downwardly through the interior of a valve skirt (not shown) to prevent eversion of the valve skirt after deployment to a heart valve. The reinforcing members  702  may include eyelets  707  at, for example, the ends of the reinforcing members  702  opposite the valve annulus  706 . It should be appreciated that the valve annulus  706  may include a plurality of folded loops (not shown) to enable the valve prosthesis, including the valve frame  700 , to be folded and collapsed for delivery through a catheter, as described in greater detail below. 
     The valve frame  700  may include a pair of hooks  704  (only one shown in  FIG. 7 ) for anchoring the prosthesis in position relative to the native heart valve. The hooks  704  may be slidable relative to the reinforcing members  702  between an unexposed, delivery position and an exposed, anchoring position. 
     For example, as shown in  FIGS. 8   a  and  8   b , each hook  704  may be slidable within a hollow reinforcing member  702 . The hollow reinforcing member  702  has an opening sized and configured to permit passage of an anchoring portion of the hook  704  curved, while retaining a base portion of the hook  704  that has a larger diameter than the hollow lumen of the reinforcing member. The hook  704  may be pushed out of the reinforcing member  702  by a pusher  709  that is an element of a delivery system which is operable by a user. 
     As shown in  FIGS. 8   c  and  8   d , each reinforcing member  702  may comprise two reinforcing elements  702   a ,  702   b . The hook  704  is coupled to a sliding member  711  coupled to both reinforcing elements  702   a ,  702   b . As shown, the hook  704  may be slidable relative to the reinforcing members  702  between an unexposed, delivery position and an exposed, anchoring position. For example, as shown in  FIGS. 8   c  and  8   d , each hook  704  may be slidable between a pair of reinforcing members  702   a ,  702   b . The reinforcing members  702   a ,  702   b  may include a stop member (not shown) for preventing the hook from being slid off the reinforcing members  702   a ,  702   b . The hook  704  may be pushed to the exposed, anchoring position by a pusher (not shown) that is an element of a delivery system which is operable by a user. 
     Referring now to  FIG. 9 , an exemplary valve frame for a valve prosthesis in accordance with various aspects of the disclosure is described. As shown, a valve frame  1400  may include a valve annulus  1406  with a pair of reinforcing members  1402  extending therefrom. The reinforcing members  1402  may be configured to extend downwardly through the interior of a valve skirt (not shown) to prevent eversion of the valve skirt after deployment to a heart valve. The reinforcing members  1402  may be configured such that the ends of the reinforcing members  1402  distal to the valve annulus  1406  comprise hooks  1404  for anchoring the valve prosthesis, including the valve frame  1400 , in position relative to the native heart valve. 
       FIG. 10  shows an illustrative configuration of an exemplary valve prosthesis in accordance with various aspects of the disclosure. As shown, a valve prosthesis  1500  may include a valve frame annulus  1506  comprising an expandable stent  1502 . According to various aspects, the stent may be self expanding or balloon inflated (e.g., plastically expandable), for example, to hold the valve prosthesis  1500  in position relative to the native heart valve. A valve skirt  1504  may extend from the expandable stent  1502 . 
     Referring now to  FIG. 11 , an exemplary valve frame, or valve platform, configured to support a valve skirt of a valve prosthesis in accordance with various aspects of the present disclosure is described. Valve frame  1100  may comprise a valve annulus  1106 , for example, a D-shaped or oval annulus. According to various aspects, the valve frame  1100  may comprise a wire having a diameter of about 0.3 mm to about 1.0 mm, although other diameters may be selected depending upon the material chosen for the wire, in order to maintain a desired tensile strength of the valve frame  1100 , as well as its ability to be folded and delivered through a catheter at least in some embodiments. Any suitable material may optionally be used for the wire as long as it retains sufficient super-elasticity and may also optionally be selected from any material described herein. For example, the valve frame  1100  may comprise a nickel titanium alloy (i.e., nitinol). 
     The valve frame  1100  may include a pair of reinforcement members  1101  extending from the valve annulus  1106 . The reinforcement members  1101  comprise a wire loop  1102  that extends from the valve annulus  1106  along an interior surface of a valve skirt (not shown) to a distal end of the valve skirt opposite the annulus  1106  along the distal edge of the valve shirt and back to the valve annulus  1106  along an interior surface of the valve skirt. The wire loop  1102  then extends away from the valve annulus  1106  along an interior surface of the valve skirt in a direction toward the distal end of the valve skirt, along the distal edge of the valve skirt, and back to the valve annulus  1106  along an interior surface of the valve skirt to complete the loop. The reinforcement members  1101  may thus prevent the valve skirt from everting back into the atrium after deployment. 
     According to various aspects, the reinforcement members of the disclosure may be secured, for example, by suturing, to the valve skirt at any or all locations coextensive between the reinforcement member and the valve skirt. 
     As shown, a pair of curved, hooked extensions  1103  extend from the valve annulus  1106 . The extensions  1103  may include hooks  1104  at their ends opposite to the valve annulus  1106 . The extensions  1103  may also include eyelets (unnumbered) configured to receive a delivery cable (not shown) therethrough. Alternatively or additionally, the reinforcement members  1101  may include eyelets configured to receive a delivery cable. 
       FIGS. 12   a - 12   d  show the prosthesis in its folded state and as it unfolds from a catheter. As shown in  FIG. 12   a , a valve prosthesis  1200  (shown as the frame only for the purpose of description and without any intention of being limiting) is shown completely folded into a catheter  1202  (it is possible that valve prosthesis  1200  could be so completely collapsed that no portion is visible; however, for a clearer illustration, a part of valve prosthesis  1200  is shown slightly protruding from catheter  1202 ). 
     In  FIG. 12   b , valve prosthesis  1200  starts to emerge from catheter  1202 ; in  FIG. 12   c , valve prosthesis  1200  continues to emerge from catheter  1202 . 
       FIG. 12   d  shows valve prosthesis  1200  completely emerged from catheter  1202  and ready for installation on the native valve annulus. 
     Referring now to  FIGS. 13   a - 13   d , an illustrative configuration of an exemplary valve prosthesis in accordance with various aspects of the disclosure is depicted. As shown, a valve prosthesis  1300  may include a valve annulus  1306  such as, for example, a D-shaped annulus. The valve annulus  1306  may include a plurality of folded loops  1308 . The folded loops  308  may enable the valve prosthesis  800 , including the valve frame, to be folded and collapsed for delivery through a catheter. 
     A first pair of reinforcing members  1302  may extend from the annulus  1306  through an interior of a valve skirt  1310  ( FIG. 13   d ). According to some aspects, the reinforcing members  1302  may extend from each end of the substantially straight portion of the D-shaped annulus  1306 . The extensions may also include eyelets  1307  configured to receive a delivery cable (not shown) therethrough. In some aspects, a pair of hooks  1304  extend from the valve annulus  106  proximate the reinforcing members  1302 . According to various aspects, a third hook  1314  may be provided at a region of the curved portion of the D-shaped annulus  1306  that is furthest from the straight portion of the annulus  1306  or at the approximate midpoint of the curved portion. The hooks  1304 ,  1314  may be configured to anchor the valve prosthesis  1300  in position at the native heart valve. The extensions  805  may include hooks  804  at its ends opposite to the valve annulus  806 . 
     A second pair of reinforcing members  1312  may extend from the valve annulus  1306  along the inner surface of the valve skirt  1310  ( FIG. 13   d ). According to some aspects, the second pair of reinforcing members  1312  may extend from regions of the curved portion of the D-shaped annulus  1306  in opposition to the first pair of reinforcing members  1302 . 
     Referring now to  FIG. 13   d , the valve skirt  1310  may comprise a first skirt portion  1320  and a second skirt portion  1330 . When the valve skirt  1310  is urged to a closed position coaptation by the normal pressure gradient between the ventricle and atrium, the second pair of reinforcing members  1322  cause the second skirt member  1330  to close around the second pair of reinforcing members  1322 , thus giving the appearance from a top view of the valve prosthesis ( FIG. 13   d ) that the valve skirt  1310  has four leaflets instead of two valve skirt portions. 
       FIGS. 14   a - 14   d  illustrate an exemplary valve skirt  1310  of a valve prosthesis in accordance with various aspects of the disclosure.  FIGS. 14   a  and  14   d  illustrate the valve skirt  1310  in a relaxed yet substantially closed configuration, while  FIGS. 14   b  and  14   c  illustrate the valve skirt  1310  in an expanded ex vivo configuration. As shown, the valve skirt  1310  includes a first skirt portion  1320  and a second skirt portion  1330 . As shown in  FIGS. 14   a  and  14   d , the region  1340  of the valve skirt  1310  where the first and second skirt portions  1320 ,  1330  meet in a relaxed yet substantially closed configuration along a curved segment to form a D-shape similar to that of the valve annulus  1306 . Further, the D-shaped annulus  1306  and D-shaped closure region  1340  are similar to those of the native heart valve. 
     Referring now to  FIG. 15 , an exemplary valve prosthesis in accordance with various aspects of the disclosure is described. As shown, the exemplary prosthesis  1700  can be configured from two wires  1701 ,  1702  twisted and wound together. As illustrated, the first wire  1701  may define a portion of the valve annulus  1706  and at least one folded loop  1708  as well as one or more hooks ( 1314 ) at the apex of the curved part of the D-shape. The second wire  1702  may define a further portion of the valve annulus  1706 , one or more hooks  1704 , and one or more reinforcing members  1702 . 
       FIGS. 16 and 17  show portion of an exemplary delivery system for delivering and deploying a valve prosthesis in accordance with various aspects of the disclosure.  FIG. 16  illustrates a delivery system  1600  including an outer sheath  2100 , two inner sheaths  2200 , and two cables or rods  2300 . The inner sheaths  2200  may be disposed in the outer sheath  2100  and may be exposed, for example, by pulling the outer sheath  2100  in a proximal direction relative to the inner sheaths  2200 . Similarly, one cable or rod  2300  may be disposed in each of the inner sheaths  2200 . The cable or rod  2300  may be exposed, for example, by pulling the inner sheath  2200  in a proximal direction relative to the cable or rod  2300 . According to various aspects, the cable or rods  2300  may be coupled to one or more reinforcing members, hooks, and/or extensions of a valve prosthesis, for example, by passing through eyelets provided on the one or more reinforcing members, hooks, and/or extensions of the valve prosthesis. The cables or rods  2300  can operate as pushers for moving hooks from a withdrawn position to an anchoring position in accordance with various aspects of the disclosure. 
     Referring now to  FIG. 17 , any of the aforementioned hooks used for anchoring the valve prosthesis to tissue can be folded for delivery into a tubular sheath  2400 . The various hooks can be pulled into the sheath  2400  by passing a wire or cable  2410  through an eyelet  2420  of the hook  2430  and pulling the hook  2430  into the sheath  2400  with the wire or cable  2410 . The sheath  2400  can be retracted to deploy the hook  2430  upon delivery. 
       FIG. 18  illustrates an exemplary tool, for example, measuring frame  1800 , for use with an exemplary method for delivering a valve prosthesis in accordance with various aspects of the disclosure. The measuring frame  1800  includes a single leg  1810  extending from an annulus  1820 . The annulus  1820  may include markings (not shown) to help size the native valve annulus as described below. Use of the tool is described in connection with the method illustrated in  FIG. 19  below. 
     Referring now to  FIG. 19 , an exemplary pre-delivery procedure is described with respect to the provided flow chart. The pre-delivery process begins at step  1900  where a sheath containing the measuring frame  1800  is inserted into the left atrium from the left ventricle. The process continues to step  1910  where the measuring frame  1800  is advanced from the sheath. Then, in step  1920 , the measuring frame  1800  is deployed such that the leg  1810  is at one commisure of a heart valve. The process proceeds to step  1930 . 
     In step  1930 , the user observes which one of various markers, for example, radiopaque markers, on the annulus  1820  aligns with the second commisure of the heart valve. Next, in step  1940 , the user notes the size of the annulus relative to the measuring frame  1800 . The process concludes in step  1950  where the measuring frame  1800  is retracted into the sheath and the correct size and configuration for a valve prosthesis is selected. 
       FIG. 20  is a flow chart showing an exemplary method for delivering a valve prosthesis in accordance with various aspects of the disclosure. The method begins at step  2000  where a delivery system is inserted into the left atrium from the left ventricle. The process proceeds to step  2010  where the outer sheath  2100  is pulled proximally until a valve annulus is fully deployed. The process then goes to step  2020 . 
     In step  2020 , the delivery system is rotated until a first leg of the valve prosthesis is positioned opposite to one commisure of the heart valve. The process continues to step  2030  where the inner sheath  2200  associated with the first leg is retracted until the first leg is positioned at the commisure. The process then proceeds to step  2040  where the inner sheath  2200  associated with the second leg is retracted until the second leg is positioned at the second commisure. The process continues to step  2050 . 
     Next in step  2050 , the entire delivery system  1600  is retracted proximally until the valve annulus is positioned at the native valve annulus. Then, in step  2060 , the hooks are activated either by being pushed into an anchoring position or by retraction of a tubular sheath enclosed the hooks. The process continues to step  2070  where the device is tested for leakage by observing the flow across the valve using such means as ultrasound. For example, various pre-treatment and post-treatment diagnostic techniques are available for assessing valvular sufficiency and/or leakage, such as transthoracic, echo-Doppler based echocardiography (TTE), and transesophageal, echo-Doppler based echocardiography (TEE); cardiac catherization with radiopaque dye; stress tests; and other known techniques. The process then concludes at step  2080  where the cables  2300  are withdrawn to release the reinforcing members. 
     It would be appreciated by persons skilled in the art that radiopaque markers can be incorporated into the valve prosthesis such as by the use of radiopaque material, for example, tantalum, platinum, and/or gold, which may be physically secured to the valve frame such as by collars crimped or welded on the frame at various locations along the annulus and/or the skirt and/or at the distal ends of the reinforcement members. Alternatively, radiopaque markers can be practice by use of gold thread woven into desired locations of the valve skirt. 
     It will be apparent to those skilled in the art that various modifications and variations can be made to the heart valve prosthesis and method of delivery of the present disclosure without departing from the scope of the invention. Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only.

Technology Classification (CPC): 0